Showing posts with label disease. Show all posts
Showing posts with label disease. Show all posts
Saturday, July 12, 2008
kidney disease reference
Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. It is divided in acute and chronic forms; either form may be due to a large number of other medical problems.
Biochemically, it is typically detected by an elevated serum creatinine. In the science of physiology, renal failure is described as a decrease in the glomerular filtration rate. When the kidneys malfunction, problems frequently encountered are abnormal fluid levels in the body, deranged acid levels, abnormal levels of potassium, calcium, phosphate, hematuria (blood in the urine) and (in the longer term) anemia. Long-term kidney problems have significant repercussions on other diseases, such as cardiovascular disease.
Classification
Renal failure can broadly be divided into two categories: acute renal failure and chronic kidney disease.
The type of renal failure (acute vs. chronic) is determined by the trend in the serum creatinine. Other factors which may help differentiate acute and chronic kidney disease include the presence of anemia and the kidney size on ultrasound. Long-standing, i.e. chronic, kidney disease generally leads to anemia and small kidney size.
Acute renal failure
Acute renal failure (ARF) is, as the name implies, a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults,[1] less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); body water and body fluids disturbances; and electrolyte derangement. An underlying cause must be identified to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these fundamental causes. ARF can result from a large number of causes.
Chronic kidney disease
Stage 5 Chronic Kidney Disease (CKD) can either develop slowly and show few initial symptoms, be the long term result of irreversible acute disease or be part of a disease progression. There are many causes of CKD. The most common cause is diabetes mellitus. Stage 1 CKD is mildly diminished renal function, with few overt symptoms. Stage 5 CKD is a severe illness and requires some form of renal replacement therapy (dialysis or kidney transplant).
Acute on chronic renal failure
Acute renal failure can be present on top of chronic renal failure. This is called acute-on-chronic renal failure (AoCRF). The acute part of AoCRF may be reversible and the aim of treatment, as with ARF, is to return the patient to their baseline renal function, which is typically measured by serum creatinine. AoCRF, like ARF, can be difficult to distinguish from chronic renal failure, if the patient has not been monitored by a physician and no baseline (i.e., past) blood work is available for comparison.
Use of the term uremia
Before the advancement of modern medicine, renal failure was often referred to as uremic poisoning. Uremia was the term used to describe the contamination of the blood with urine. Starting around 1847, this term was used to describe reduced urine output, that was thought to be caused by the urine mixing with the blood instead of being voided through the urethra.[citation needed] The term uremia is now used to loosely describe the illness accompanying kidney failure.
Liver disease reference
Liver disease is a broad term describing any number of diseases affecting the liver. Many are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the hemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.
* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
* Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.
* Haemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage.
* Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract).
* Wilson's disease, a hereditary disease which causes the body to retain copper.
* Primary sclerosing cholangitis, an inflammatory disease of the bile duct, likely autoimmune in nature.
* Primary biliary cirrhosis, autoimmune disease of small bile ducts.
* Budd-Chiari syndrome, obstruction of the hepatic vein.
* Gilbert's syndrome, a genetic disorder of bilirubin metabolism, found in about 5% of the population.
* Glycogen storage disease type II,The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
There are also many pediatric liver disease, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, and progressive familial intrahepatic cholestasis, to name but a few.
A number of liver function tests are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products.
Symptoms of a diseased liver
The external signs include a coated tongue, bad breath, skin rashes, itchy skin, excessive sweating, offensive body odour, dark circles under the eyes, red swollen and itchy eyes, acne rosacea, brownish spots and blemishes on the skin, flushed facial appearance or excessive facial blood vessels.[1]
Other symptoms include jaundice, dark urine, pale stool, bone loss, easy bleeding, itching, small, spider-like blood vessels visible in the skin, enlarged spleen, fluid in the abdominal cavity, chills, pain from the biliary tract or pancrea, and an enlarged gallbladder.[2]
The symptoms related to liver dysfunction include both physical signs and a variety of symptoms related to digestive problems, blood sugar problems, immune disorders, abnormal absorption of fats, and metabolism problems.[3]
The malabsorption of fats may lead to symptoms that include indigestion, reflux, hemorhoids, gall stones, intolerance to fatty foods, intolerance to alcohol, nausea and vomiting attacks, abdominal bloating, and constipation.
Nervous system disorders include depression, mood changes, especially anger and irritability, poor concentration and "foggy brain", overheating of the body, especially the face and torso, and recurrent headaches (including migraine) associated with nausea.
The blood sugar problems include a craving for sugar, hypoglycaemia and unstable blood sugar levels, and the onset of diabetes (Type 2).
Abnormalities in the level of fats in the blood stream include elevated LDL cholesterol, reduced HDL cholesterol, elevated triglycerides, clogged arteries leading to high blood pressure heart attacks and strokes, build up of fat in other body organs (fatty degeneration of organs), lumps of fat in the skin (lipomas and other fatty tumors), excessive weight gain (which may lead to obesity), inability to lose weight even while dieting, sluggish metabolism, protuberant abdomen (pot belly), cellulite, fatty liver, and a roll of fat around the upper abdomen (liver roll).[4]
The College of Holistic Medicine lists other symptoms of a diseased liver that include tired eyes, a tendency to have accidents, weak sexual vitality, impotence and prostate problems, a psychologically that you are irritable and get angry easily, devoting far too much attention to trivial details, overeating, stubbornness, prone to anger, highly emotional and hypersensitive, heaviness in the head, poor digestion, hemorrhoids, ovarian problems and cysts, PMS, flatulence and petrifaction of tissues, and possible headaches and migraines.
* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons, autoimmunity or hereditary conditions.
* Cirrhosis is the formation of fibrous tissue in the liver, replacing dead liver cells. The death of the liver cells can for example be caused by viral hepatitis, alcoholism or contact with other liver-toxic chemicals.
* Haemochromatosis, a hereditary disease causing the accumulation of iron in the body, eventually leading to liver damage.
* Cancer of the liver (primary hepatocellular carcinoma or cholangiocarcinoma and metastatic cancers, usually from other parts of the gastrointestinal tract).
* Wilson's disease, a hereditary disease which causes the body to retain copper.
* Primary sclerosing cholangitis, an inflammatory disease of the bile duct, likely autoimmune in nature.
* Primary biliary cirrhosis, autoimmune disease of small bile ducts.
* Budd-Chiari syndrome, obstruction of the hepatic vein.
* Gilbert's syndrome, a genetic disorder of bilirubin metabolism, found in about 5% of the population.
* Glycogen storage disease type II,The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
There are also many pediatric liver disease, including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, and progressive familial intrahepatic cholestasis, to name but a few.
A number of liver function tests are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products.
Symptoms of a diseased liver
The external signs include a coated tongue, bad breath, skin rashes, itchy skin, excessive sweating, offensive body odour, dark circles under the eyes, red swollen and itchy eyes, acne rosacea, brownish spots and blemishes on the skin, flushed facial appearance or excessive facial blood vessels.[1]
Other symptoms include jaundice, dark urine, pale stool, bone loss, easy bleeding, itching, small, spider-like blood vessels visible in the skin, enlarged spleen, fluid in the abdominal cavity, chills, pain from the biliary tract or pancrea, and an enlarged gallbladder.[2]
The symptoms related to liver dysfunction include both physical signs and a variety of symptoms related to digestive problems, blood sugar problems, immune disorders, abnormal absorption of fats, and metabolism problems.[3]
The malabsorption of fats may lead to symptoms that include indigestion, reflux, hemorhoids, gall stones, intolerance to fatty foods, intolerance to alcohol, nausea and vomiting attacks, abdominal bloating, and constipation.
Nervous system disorders include depression, mood changes, especially anger and irritability, poor concentration and "foggy brain", overheating of the body, especially the face and torso, and recurrent headaches (including migraine) associated with nausea.
The blood sugar problems include a craving for sugar, hypoglycaemia and unstable blood sugar levels, and the onset of diabetes (Type 2).
Abnormalities in the level of fats in the blood stream include elevated LDL cholesterol, reduced HDL cholesterol, elevated triglycerides, clogged arteries leading to high blood pressure heart attacks and strokes, build up of fat in other body organs (fatty degeneration of organs), lumps of fat in the skin (lipomas and other fatty tumors), excessive weight gain (which may lead to obesity), inability to lose weight even while dieting, sluggish metabolism, protuberant abdomen (pot belly), cellulite, fatty liver, and a roll of fat around the upper abdomen (liver roll).[4]
The College of Holistic Medicine lists other symptoms of a diseased liver that include tired eyes, a tendency to have accidents, weak sexual vitality, impotence and prostate problems, a psychologically that you are irritable and get angry easily, devoting far too much attention to trivial details, overeating, stubbornness, prone to anger, highly emotional and hypersensitive, heaviness in the head, poor digestion, hemorrhoids, ovarian problems and cysts, PMS, flatulence and petrifaction of tissues, and possible headaches and migraines.
Lymphoma reference
Lymphoma is a type of solid neoplasm that originates in lymphocytes (a type of white blood cell in the vertebrate immune system). This is in contrast to lymphoid leukemia, which is a malignancy of circulating cells.[1]
There are many types of lymphoma. Lymphomas are part of the broad group of diseases called hematological neoplasms.
In the 19th and 20th centuries the affliction was called Hodgkin's Disease, as it was discovered by Thomas Hodgkin in 1832. Colloquially, lymphoma is broadly categorized as Hodgkin's lymphoma and non-Hodgkin lymphoma (all other types of lymphoma). Scientific classification of the types of lymphoma is more detailed.
Although older classifications referred to histiocytic lymphomas, these are recognized in newer classifications as of B, T or NK cell lineage. Histiocytic malignancies are rare and are classified as sarcomas
Prevalence
According to the U.S. National Institutes of Health, lymphomas account for about five percent of all cases of cancer in the United States, and Hodgkin's lymphoma in particular accounts for less than one percent of all cases of cancer in the United States.
Because the whole system is part of the body's immune system, patients with a weakened immune system, such as from HIV infection or from certain drugs or medication, also have a higher incidence of lymphoma.
Classification
The WHO Classification, published in 2001[2], is the latest classification of lymphoma and is based on the "Revised European-American Lymphoma classification" (REAL). This system attempts to group lymphomas by cell type, i.e., the normal cell type that most resembles the tumor. There are three large groups: the B cell, T cell, and natural killer cell tumors. Other less common groups, including Hodgkin lymphoma, are also recognized. (ICD-O codes are provided where available.)
[edit] Mature B cell neoplasms
DNA-microarray analysis of Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) showing differences in gene expression patterns. Colors indicate levels of expression; green indicates genes that are underexpressed in lymphoma cells (as compared to normal cells), whereas red indicates genes that are overexpressed in lymphoma cells.
DNA-microarray analysis of Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) showing differences in gene expression patterns. Colors indicate levels of expression; green indicates genes that are underexpressed in lymphoma cells (as compared to normal cells), whereas red indicates genes that are overexpressed in lymphoma cells.
*
o Chronic lymphocytic leukemia/Small lymphocytic lymphoma
o B-cell prolymphocytic leukemia
o Lymphoplasmacytic lymphoma (such as Waldenström macroglobulinemia)
o Splenic marginal zone lymphoma
o Plasma cell neoplasms
+ Plasma cell myeloma
+ Plasmacytoma
+ Monoclonal immunoglobulin deposition diseases
+ Heavy chain diseases
o Extranodal marginal zone B cell lymphoma, also called MALT lymphoma
o Nodal marginal zone B cell lymphoma (NMZL)
o Follicular lymphoma
o Mantle cell lymphoma
o Diffuse large B cell lymphoma
o Mediastinal (thymic) large B cell lymphoma
o Intravascular large B cell lymphoma
o Primary effusion lymphoma
o Burkitt lymphoma/leukemia
Mature T cell and natural killer (NK) cell neoplasms
*
o T cell prolymphocytic leukemia
o T cell large granular lymphocytic leukemia
o Aggressive NK cell leukemia
o Adult T cell leukemia/lymphoma
o Extranodal NK/T cell lymphoma, nasal type
o Enteropathy-type T cell lymphoma
o Hepatosplenic T cell lymphoma
o Blastic NK cell lymphoma
o Mycosis fungoides / Sezary syndrome
o Primary cutaneous CD30-positive T cell lymphoproliferative disorders
+ Primary cutaneous anaplastic large cell lymphoma
+ Lymphomatoid papulosis
o Angioimmunoblastic T cell lymphoma
o Peripheral T cell lymphoma, unspecified
o Anaplastic large cell lymphoma
Hodgkin lymphoma
*
o Nodular lymphocyte-predominant Hodgkin lymphoma
o Classical Hodgkin lymphoma
+ Nodular sclerosis
+ Mixed cellularity
+ Lymphocyte-rich
+ Lymphocyte depleted or not depleted
Immunodeficiency-associated lymphoproliferative disorders
*
o Associated with a primary immune disorder
o Associated with the Human Immunodeficiency Virus (HIV)
o Post-transplant
o Associated with Methotrexate therapy
Working formulation
The Working Formulation, published in 1982, is primarily descriptive. It is still occasionally used, but has been superseded by the WHO classification, above.
Low grade
* Malignant Lymphoma, small lymphocytic (chronic lymphocytic leukemia)
* Malignant Lymphoma, follicular, predominantly small cleaved cell
* Malignant Lymphoma, follicular, mixed (small cleaved and large cell)
Intermediate grade
* Follicular Large Cell
* Diffuse small cleaved cell
* Diffuse mixed small and large cell
* Diffuse large cell
High grade
* Malignant Lymphoma, large cell, immunoblastic
* Malignant Lymphoma, lymphoblastic
* Malignant Lymphoma, small non-cleaved cells (Burkitt's lymphoma)
Mental disorder reference
Mental disorder or mental illness are terms used to refer to a psychological or physiological pattern that occurs in an individual and is usually associated with distress or disability that is not expected as part of normal development or culture. The recognition and understanding of mental disorders has changed over time. Definitions, assessments, and classifications of mental disorders can vary, but guideline criterion listed in the ICD, DSM and other manuals are widely accepted by mental health professionals. Categories of diagnoses in these schemes may include dissociative disorders, mood disorders, anxiety disorders, psychotic disorders, eating disorders, developmental disorders, personality disorders, and many other categories. In many cases there is no single accepted or consistent cause of mental disorders, although they are widely understood in terms of a diathesis-stress model and biopsychosocial model. Mental disorders have been found to be common, with over a third of people in most countries reporting sufficient criteria at some point in their life. Mental health services may be based in hospitals or in the community. Mental health professionals diagnose individuals using different methodologies, often relying on case history and interview. Psychotherapy and psychiatric medication are two major treatment options, as well as supportive interventions. Treatment may be involuntary where legislation allows. Several movements campaign for changes to mental health services and attitudes, including the Consumer/Survivor Movement. There are widespread problems with stigma and discrimination.
History
Eight women representing prominent mental diagnoses in the nineteenth century.
Eight women representing prominent mental diagnoses in the nineteenth century.
Main article: History of mental disorders
A number of mental disturbances, such as melancholy, hysteria and phobia, were described long ago in Ancient Greece and Rome, while others such as schizophrenia may not have been recognized.[1] Hippocrates considered the idea that mental illness may be related to biology.[2]
Psychiatric theories and treatments for mental illness developed in Muslim psychology and Islamic medicine in the medieval Islamic world from the 8th century, where the first psychiatric hospitals were built.[3] The Baghdad Hospital was run by the Persian physician Rhazes. Unlike most ancient and medieval societies which believed mental illness to be caused by either demonic possession or as punishment from a God, Islamic neuroethics held a more sympathetic attitude towards the mentally ill, as exemplified in Sura 4:5 of the Qur'an, which considers the mentally ill to be unfit to manage property but must be treated humanely and be kept under care by a guardian.[4]
Medieval Europe had focused on demonic possession as the explanation of aberrant behavior.[5] Paracelsus used the word lunatic to describe behavior thought to be caused by the lunar effect.[6] Many other terms for mental disorder that found their way into everyday use have been traced to initial use in the 16th and 17th centuries.[7] Shakespeare and his contemporaries frequently depicted mental disorders in their plays.[8] Conditions of "shell shock" came to be recognized in war veterans. From the early study of mental illness through individuals such as Philippe Pinel, Sigmund Freud, and Alois Alzheimer, much has changed in the development and understanding of mental illness and continues to change today.
At the start of the 20th century there were only a dozen officially recognized mental health conditions.[citation needed]. By 1952 there were 192 and the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) today lists 374.
[edit] Classification
Main article: Classification of mental disorders
The definition and classification of mental disorder is a key issue for the mental health professions and for users and providers of mental health services. Most international clinical documents use the term "mental disorder" rather than "mental illness". There is no single definition and the inclusion criteria are said to vary depending on the social, legal and political context. In general, however, a mental disorder has been characterized as a clinically significant behavioral or psychological pattern that occurs in an individual and is usually associated with distress, disability or increased risk of suffering. There is often a criterion that a condition should not be expected to occur as part of a person's usual culture or religion. The term "serious mental illness" (SMI) is sometimes used to refer to more severe and long-lasting disorder. A broad definition can cover mental disorder, mental retardation, personality disorder and substance dependence. The phrase "mental health problems" may be used to refer only to milder or more transient issues.
There are currently two widely established systems that classify mental disorders - Chapter V of the International Classification of Diseases (ICD-10), produced by the World Health Organization (WHO), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) produced by the American Psychiatric Association (APA). Both list categories of disorder and provide standardized criteria for diagnosis. They have deliberately converged their codes in recent revisions so that the manuals are often broadly comparable, although significant differences remain. Other classification schemes may be in use more locally, for example the Chinese Classification of Mental Disorders. Other manuals may be used by those of alternative theoretical persuasions, for example the Psychodynamic Diagnostic Manual.
Some approaches to classification do not employ distinct categories based on cut-offs separating the abnormal from the normal. They are variously referred to as spectrum, continuum or dimensional systems. There is a significant scientific debate about the relative merits of a categorical or a non-categorical system. There is also significant controversy about the role of science and values in classification schemes, and about the professional, legal and social uses to which they are put.
Disorders
There are many different categories of mental disorder, and many different facets of human behavior and personality that can become disordered.[9][10][11][12]
The state of anxiety or fear can become disordered, so that it is unusually intense or generalized over a prolonged period of time. Commonly recognized categories of anxiety disorders include specific phobia, Generalized anxiety disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, Obsessive-Compulsive Disorder, Post-traumatic stress disorder. Relatively long lasting affective states can also become disordered. Mood disorder involving unusually intense and sustained sadness, melancholia or despair is know as Clinical depression (or Major depression), and may more generally be described as Emotional dysregulation. Milder but prolonged depression can be diagnosed as dysthymia. Bipolar disorder involves abnormally "high" or pressured mood states, known as mania or hypomania, alternating with normal or depressed mood. Whether unipolar and bipolar mood phenomena represent distinct categories of disorder, or whether they usually mix and merge together along a dimension or spectrum of mood, is under debate in the scientific literature.[13]
Patterns of belief, language use and perception can become disordered. Psychotic disorders centrally involving this domain include Schizophrenia and Delusional disorder. Schizoaffective disorder is a category used for individuals showing aspects of both schizophrenia and affective disorders. Schizotypy is a category used for individuals showing some of the traits associated with schizophrenia but without meeting cut-off criteria.
The fundamental characteristics of a person that influence his or her cognitions, motivations, and behaviors across situations and time - can be seen as disordered due to being abnormally rigid and maladaptive. Categorical schemes list a number of different personality disorders, such as those classed as eccentric (e.g. Paranoid personality disorder, Schizoid personality disorder, Schizotypal personality disorder), those described as dramatic or emotional (Antisocial personality disorder, Borderline personality disorder, Histrionic personality disorder, Narcissistic personality disorder) or those seen as fear-related (Avoidant personality disorder, Dependent personality disorder, Obsessive-compulsive personality disorder).
There may be an emerging consensus that personality disorders, like personality traits in the normal range, incorporate a mixture of more acute dysfunctional behaviors that resolve in relatively short periods, and maladaptive temperamental traits that are relatively more stable.[14] Non-categorical schemes may rate individuals via a profile across different dimensions of personality that are not seen as cut off from normal personality variation, commonly through schemes based on the Big Five personality traits.[15]
Other disorders may involve other attributes of human functioning. Eating practices can be disordered, at least in relatively rich industrialized areas, with either compulsive over-eating or under-eating or binging. Categories of disorder in this area include Anorexia nervosa, Bulimia nervosa, Exercise Bulimia or Binge eating disorder. Sleep disorders such as Insomnia also exist and can disrupt normal sleep patterns. Sexual and gender identity disorders, such as Dyspareunia or Gender identity disorder or ego-dystonic homosexuality. People who are abnormally unable to resist urges, or impulses, to perform acts that could be harmful to themselves or others, may be classed as having an impulse control disorder, including various kinds of Tic disorders such as Tourette's Syndrome, and disorders such as Kleptomania (stealing) or Pyromania (fire-setting). Substance-use disorders include Substance abuse disorder. Addictive gambling may be classed as a disorder. Inability to sufficiently adjust to life circumstances may be classed as an Adjustment disorder. The category of adjustment disorder is usually reserved for problems beginning within three months of the event or situation and ending within six months after the stressor stops or is eliminated. People who suffer severe disturbances of their self-identity, memory and general awareness of themselves and their surroundings may be classed as having a Dissociative identity disorder, such as Depersonalization disorder or Dissociative Identify Disorder itself (which has also been called multiple personality disorder, or "split personality".). Factitious disorders, such as Munchausen syndrome, also exist where symptoms are experienced and/or reported for personal gain.
Disorders appearing to originate in the body, but thought to be mental, are known as somatoform disorders, including Somatization disorder. There are also disorders of the perception of the body, including Body dysmorphic disorder. Neurasthenia is a category involving somatic complaints as well as fatigue and low spirits/depression, which is officially recognized by the ICD-10 but not by the DSM-IV.[16] Memory or cognitive disorders, such as amnesia or Alzheimer's disease exist.
Some disorders are thought to usually first occur in the context of early childhood development, although they may continue into adulthood. The category of Specific developmental disorder may be used to refer to circumscribed patterns of disorder in particular learning skills, motor skills, or communication skills. Disorders which appear more generalized may be classed as pervasive developmental disorders (PDD) also known as autism spectrum disorders (ASD); these include autism, Asperger's, Rett syndrome, childhood disintegrative disorder and other types of PDD whose exact diagnosis may not be specified. Other disorders mainly or first occurring in childhood include Reactive attachment disorder; Separation Anxiety Disorder; Oppositional Defiant Disorder; Attention Deficit Hyperactivity Disorder.
Causes
Numerous factors have been linked to the development of mental disorders. In many cases there is no single accepted or consistent cause currently established. A common view held is that disorders often result from genetic vulnerabilities combining with environmental stressors (Diathesis-stress model). An eclectic or pluralistic mix of models may be used to explain particular disorders. The primary paradigm of contemporary mainstream Western psychiatry is said to be the biopsychosocial (BPS) model - incorporating biological, psychological and social factors - although this may not be applied in practice. Biopsychiatry has tended to follow a biomedical model, focusing on "organic" or "hardware" pathology of the brain. Psychoanalytic theories have been popular but are now less so. Evolutionary psychology may be used as an overall explanatory theory. Attachment theory is another kind of evolutionary-psychological approach sometimes applied in the context for mental disorders. A distinction is sometimes made between a "medical model" or a "social model" of disorder and related disability.
Genetic studies have indicated that genes often play an important role in the development of mental disorders, via developmental pathways interacting with environmental factors. The reliable identification of connections between specific genes and specific categories of disorder has proven more difficult.
Environmental events surrounding pregnancy and birth have also been implicated. Traumatic brain injury may increase the risk of developing certain mental disorders. There have been some tentative inconsistent links found to certain viral infections, to substance misuse, and to general physical health.
Abnormal functioning of neurotransmitter systems has been implicated, including serotonin, norepinephrine, dopamine and glutamate systems. Differences have also been found in the size or activity of certain brains regions in some cases. Psychological mechanisms have also been implicated, such as cognitive and emotional processes, personality, temperament and coping style.
Social influences have been found to be important, including abuse, bullying and other negative or stressful life experiences. The specific risks and pathways to particular disorders are less clear, however. Aspects of the wider community have also been implicated, including employment problems, socioeconomic inequality, lack of social cohesion, problems linked to migration, and features of particular societies and cultures.
Diagnosis
Many mental health professionals, particularly psychiatrists, seek to diagnose individuals by ascertaining their particular mental disorder. Some professionals, for example some clinical psychologists, may avoid diagnosis in favor of other assessment methods such as formulation of a client's difficulties and circumstances.[17] The majority of mental health problems are actually assessed and treated by family physicians during consultations, who may refer on for more specialist diagnosis in acute or chronic cases. Routine diagnostic practice in mental health services typically involves an interview (which may be referred to as a mental status examination), where judgements are made of the interviewee's appearance and behavior, self-reported symptoms, mental health history, and current life circumstances. The views of relatives or other third parties may be taken into account. A physical examination to check for ill health or the effects of medications or other drugs may be conducted. Psychological testing is sometimes used via paper-and-pen or computerized questionnaires, which may include algorithms based on ticking off standardized diagnostic criteria, and in relatively rare specialist cases neuroimaging tests may be requested, but these methods are more commonly found in research studies than routine clinical practice.[18][19] Time and budgetary constraints often limit practicing psychiatrists from conducting more thorough diagnostic evaluations.[20] It has been found that most clinicians evaluate patients using an unstructured, open-ended approach, with limited training in evidence-based assessment methods, and that inaccurate diagnosis may be common in routine practice.[21] Comorbidity is very common in psychiatric diagnosis, i.e. the same person given a diagnosis in more than one category of disorder.
Treatment
Mental health services may be based in hospitals, clinics or the community. Often an individual may engage in different treatment modalities. They may be under case management (sometimes referred to as "service coordination"), use inpatient or day treatment, utilize a psychosocial rehabilitation program, and/or take part in an Assertive Community Treatment program. Individuals may be treated against their will in some cases, especially if assessed to be at high risk to themselves or others. Services in some countries are increasingly based on a Recovery model that supports an individual's journey to regain a meaningful life
Psychotherapy
A major option for many mental disorders is psychotherapy. There are several main types. Cognitive behavioral therapy (CBT) is widely used and is based on modifying the patterns of thought and behavior associated with a particular disorder. Psychoanalysis, addressing underlying psychic conflicts and defenses, has been a dominant school of psychotherapy and is still in use. Systemic therapy or family therapy is sometimes used, addressing a network of significant others as well as an individual. Some psychotherapies are based on a humanistic approach. There are a number of specific therapies used for particular disorders, which may be offshoots or hybrids of the above types. Mental health professionals often employ an eclectic or integrative approach. Much may depend on the therapeutic relationship, and there may be problems with trust, confidentiality and engagement.
Medication
A major option for many mental disorders is psychiatric medication. There are several main groups. Antidepressants are used for the treatment of clinical depression as well as often for anxiety and other disorders. There are a number of antidepressants beginning with the tricylics, moving through a wide variety of drugs that modify various facets of the brain chemistry dealing with intercellular communication. Beta-blockers, developed as a heart medication, is also used as an antidepressant. Anxiolytics are used for anxiety disorders and related problems such as insomnia. Mood stabilizers are used primarily in bipolar disorder. Lithium A (a metal) and Lamictal (an epileptic drug) are notable for treating both mania and depression. The others, mainly targeting mania rather than depression, are a wide variety of epilepsy medications and antipsychotics. Antipsychotics are used for psychotic disorders, notably for positive symptoms in schizophrenia. Stimulants are commonly used, notably for ADHD. Despite the different conventional names of the drug groups, there can be considerable overlap in the kinds of disorders for which they are actually indicated. There may also be off-label use. There can be problems with adverse effects and adherence.
Other
Electroconvulsive therapy (ECT) is sometimes used in severe cases when other interventions for severe intractable depression have failed. Psychosurgery has in the past been synonymous with the "frontal lobotomy." While this form of psychosurgery is no longer used, there are four other techniques that are used today. These methods are used only as a last resort for people who have not responded to medications and therapy, and are functionally crippled by their disorder. The disorders for which psychosurgery has been used for for intractable mood and anxiety disorders, such as Obsessive-Compulsive Disorder.[22]
Psychoeducation may be used to provide people with the information to understand and manage their problems. Creative therapies are sometimes used, including music therapy, art therapy or drama therapy. Lifestyle adjustments and supportive measures are often used, including peer support, self-help and supported housing or employment. Some advocate dietary supplements based on published randomized double-blind, placebo controlled trials.[23] Many things have been found to help at least some people. A placebo effect may play a role in any intervention.
Prevalence
WHO estimated that about 450 million people worldwide currently suffer from some form of mental or behavioural disorder.[26] One in four people will suffer from mental illness at some time in life, according to a report from the WHO.[27][28]
Numerous large-scale surveys of the prevalence of mental disorders in adults in the general population have been carried out since the 1980s based on self-reported symptoms assessed by standardized structured interviews, usually carried out over the phone. Mental disorders have been found to be common, with over a third of people in most countries reporting sufficient criteria at some point in their life.[29] The World Health Organization is currently undertaking a global survey of 26 countries in all regions of the world, based on ICD and DSM criteria.[1] The first published figures on the 14 country surveys completed to date, indicate that, of those disorders assessed, anxiety disorders are the most common in all but 1 country (prevalence in the prior 12-month period of 2.4% to 18.2%) and mood disorders next most common in all but 2 countries (12-month prevalence of 0.8% to 9.6%), while substance disorders (0.1%-6.4%) and impulse-control disorders (0.0%-6.8%) were consistently less prevalent. The United States, Colombia, the Netherlands and Ukraine tended to have higher prevalence estimates across most classes of disorder, while Nigeria, Shanghai and Italy were consistently low, and prevalence was lower in Asian countries in general. Cases of disorder were rated as mild (prevalence of 1.8%-9.7%), moderate (prevalence of 0.5%-9.4%) and serious (prevalence of 0.4%-7.7%).[30] However, these are widely believed to be underestimates, due to poor diagnosis (especially in countries without affordable access to mental health services) and low reporting rates, in part because of the predominant use of self-report data, rather than semi-structured instruments such as the Structured Clinical Interview for DSM-IV (SCID); actual lifetime prevalence rates for mental disorders are estimated to be between 65% and 85%.
A review that pooled surveys in different countries up to 2004 found overall average prevalence estimates for any anxiety disorder of 10.6% (in the 12 months prior to assessment) and 16.6% (in lifetime prior to assessment), but that rates for individual disorders varied widely. Women had generally higher prevalence rates than men, but the magnitude of the difference varied.[31] A review that pooled surveys of mood disorders in different countries up to 2000 found 12-month prevalence rates of 4.1% for major depressive disorder (MDD), 2% for dysthymic disorder and 0.72% for bipolar 1 disorder. The average lifetime prevalence found was 6.7% for MDD (with a relatively low lifetime prevalence rate in higher-quality studies, compared to the rates typically highlighted of 5%-12% for men and 10%-25% for women), and rates of 3.6% for dysthymia and 0.8% for Bipolar 1.[32]
Previous widely cited large-scale surveys in the United States were the Epidemiological Catchment Area (ECA) survey and subsequent National Comorbidity Survey (NCS). The NCS was replicated and updated between 2000 and 2003 and indicated that, of those groups of disorders assessed, nearly half of Americans (46.4%) reported meeting criteria at some point in their life for either a DSM-IV anxiety disorder (28.8%), mood disorder (20.8%), impulse-control disorder (24.8%) or substance use disorders (14.6%). Half of all lifetime cases had started by age 14 years and 3/4 by age 24 years.[33] In the prior 12-month period only, around a quarter (26.2%) met criteria for any disorder - anxiety disorders 18.1%; mood disorders 9.5%; impulse control disorders 8.9%; and substance use disorders 3.8%. A substantial minority (23%) met criteria for more than two disorders. A minority (22.3%) of cases were classed as serious, 37.3% as moderate and 40.4% as mild.[34][35]
A 2004 cross-European study found that approximately one in four people reported meeting criteria at some point in their life for one of the DSM-IV disorders assessed, which included mood disorders (13.9%), anxiety disorders (13.6%) or alcohol disorder (5.2%). Approximately one in ten met criteria within a 12-month period. Women and younger people of either gender showed more cases of disorder[36]
A 2005 review of 27 studies have found that 27% of adult Europeans is or has been affected by at least one mental disorder in the past 12 months. It was also found that the most frequent disorders were anxiety disorders, depressive, somatoform and substance dependence disorders.[37]
A 2005 review of prior surveys in 46 countries on the prevalence of schizophrenic disorders, including a prior 10-country WHO survey, found an average (median) figure of 0.4% for lifetime prevalence up to the point of assessment and 0.3% in the 12-month period prior to assessment. A related figure not given in other studies (known as lifetime morbid risk), reported to be an accurate statement of how many people would theoretically develop schizophrenia at any point in life regardless of time of assessment, was found to be “about seven to eight individuals per 1,000.” (0.7/0.8%). The prevalence of schizophrenia was consistently lower in poorer countries than in richer countries (though not the incidence) but the prevalence did not differ between urban/rural areas or men/women (although incidence did).[38]
Studies of the prevalence of personality disorders (PDs) have been fewer and smaller-scale, but a broader Norwegian survey found a similar overall prevalence of almost 1 in 7 (13.4%), based on meeting personality criteria over the prior five year period. Rates for specific disorders ranged from 0.8% to 2.8%, with rates differing across countries, and by gender, educational level and other factors.[39] A US survey that incidentally screened for personality disorder found an overall rate of 14.79%.[40]
Approximately 7% of a preschool pediatric sample were given a psychiatric diagnosis in one clinical study, and approximately 10% of 1- and 2-year-olds receiving developmental screening have been assessed as having significant emotional/behavioral problems based on parent and pediatrician reports.
Stigma of mental illness
A large proportion of individuals who suffer from the symptoms of a mental illness will avoid seeking treatment for their symptoms because of the social stigma[2] associated with having a mental illness. The US Surgeon General acknowledged this in 1999:
Powerful and pervasive, stigma prevents people from acknowledging their own mental health problems, much less disclosing them to others.[51]
As a result many people feel the need to keep their mental illness a secret, and will deny the symptoms that they are experiencing. Two thirds of the people who would benefit from treatment for a mental illness do not receive treatment.[52] As with many physical illnesses, the prognoses of a mental illness can worsen the longer that a mental illness remains untreated. The added anxiety of fearing a mental illness diagnoses can also be detrimental to an individual's mental health, this effect can greatly exacerbate an anxiety disorder or mood disorder. Efforts are being undertaken worldwide to eliminate the stigma of mental illness.
Violence
The public fear of violence due to mental illness is a contentious topic. One US national survey indicated that a far higher percentage of Americans rated individuals described as displaying the characteristics of a mental disorder (for example Schizophrenia or Substance Use Disorder) as "likely to do something violent to others" compared to those described as being 'troubled'.[70] Research indicates, on balance, a higher than average number of violent acts by some individuals with certain diagnoses, notably antisocial or psychopathic personality disorders, but conflicting findings about specific symptoms (for example links between psychosis and violence in community settings) - but the mediating factors of such acts are most consistently found to be mainly socio-demographic and socio-economic factors such as being young, male, of lower socio-economic status and, in particular, substance abuse (including alcohol).[71][72][24] Findings consistently indicate that it is many times more likely that people diagnosed with a serious mental illness living in the community will be the victim rather than the perpetrator of violence.[71][73] Violence by or against individuals with mental illness typically occurs in the context of complex social interactions (including in atmosphere of mutually high "expressed emotion"), including within a family setting,[74] as well as being an issue in healthcare settings[75] and the wider community.
History
Eight women representing prominent mental diagnoses in the nineteenth century.
Eight women representing prominent mental diagnoses in the nineteenth century.
Main article: History of mental disorders
A number of mental disturbances, such as melancholy, hysteria and phobia, were described long ago in Ancient Greece and Rome, while others such as schizophrenia may not have been recognized.[1] Hippocrates considered the idea that mental illness may be related to biology.[2]
Psychiatric theories and treatments for mental illness developed in Muslim psychology and Islamic medicine in the medieval Islamic world from the 8th century, where the first psychiatric hospitals were built.[3] The Baghdad Hospital was run by the Persian physician Rhazes. Unlike most ancient and medieval societies which believed mental illness to be caused by either demonic possession or as punishment from a God, Islamic neuroethics held a more sympathetic attitude towards the mentally ill, as exemplified in Sura 4:5 of the Qur'an, which considers the mentally ill to be unfit to manage property but must be treated humanely and be kept under care by a guardian.[4]
Medieval Europe had focused on demonic possession as the explanation of aberrant behavior.[5] Paracelsus used the word lunatic to describe behavior thought to be caused by the lunar effect.[6] Many other terms for mental disorder that found their way into everyday use have been traced to initial use in the 16th and 17th centuries.[7] Shakespeare and his contemporaries frequently depicted mental disorders in their plays.[8] Conditions of "shell shock" came to be recognized in war veterans. From the early study of mental illness through individuals such as Philippe Pinel, Sigmund Freud, and Alois Alzheimer, much has changed in the development and understanding of mental illness and continues to change today.
At the start of the 20th century there were only a dozen officially recognized mental health conditions.[citation needed]. By 1952 there were 192 and the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition (DSM-IV) today lists 374.
[edit] Classification
Main article: Classification of mental disorders
The definition and classification of mental disorder is a key issue for the mental health professions and for users and providers of mental health services. Most international clinical documents use the term "mental disorder" rather than "mental illness". There is no single definition and the inclusion criteria are said to vary depending on the social, legal and political context. In general, however, a mental disorder has been characterized as a clinically significant behavioral or psychological pattern that occurs in an individual and is usually associated with distress, disability or increased risk of suffering. There is often a criterion that a condition should not be expected to occur as part of a person's usual culture or religion. The term "serious mental illness" (SMI) is sometimes used to refer to more severe and long-lasting disorder. A broad definition can cover mental disorder, mental retardation, personality disorder and substance dependence. The phrase "mental health problems" may be used to refer only to milder or more transient issues.
There are currently two widely established systems that classify mental disorders - Chapter V of the International Classification of Diseases (ICD-10), produced by the World Health Organization (WHO), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) produced by the American Psychiatric Association (APA). Both list categories of disorder and provide standardized criteria for diagnosis. They have deliberately converged their codes in recent revisions so that the manuals are often broadly comparable, although significant differences remain. Other classification schemes may be in use more locally, for example the Chinese Classification of Mental Disorders. Other manuals may be used by those of alternative theoretical persuasions, for example the Psychodynamic Diagnostic Manual.
Some approaches to classification do not employ distinct categories based on cut-offs separating the abnormal from the normal. They are variously referred to as spectrum, continuum or dimensional systems. There is a significant scientific debate about the relative merits of a categorical or a non-categorical system. There is also significant controversy about the role of science and values in classification schemes, and about the professional, legal and social uses to which they are put.
Disorders
There are many different categories of mental disorder, and many different facets of human behavior and personality that can become disordered.[9][10][11][12]
The state of anxiety or fear can become disordered, so that it is unusually intense or generalized over a prolonged period of time. Commonly recognized categories of anxiety disorders include specific phobia, Generalized anxiety disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, Obsessive-Compulsive Disorder, Post-traumatic stress disorder. Relatively long lasting affective states can also become disordered. Mood disorder involving unusually intense and sustained sadness, melancholia or despair is know as Clinical depression (or Major depression), and may more generally be described as Emotional dysregulation. Milder but prolonged depression can be diagnosed as dysthymia. Bipolar disorder involves abnormally "high" or pressured mood states, known as mania or hypomania, alternating with normal or depressed mood. Whether unipolar and bipolar mood phenomena represent distinct categories of disorder, or whether they usually mix and merge together along a dimension or spectrum of mood, is under debate in the scientific literature.[13]
Patterns of belief, language use and perception can become disordered. Psychotic disorders centrally involving this domain include Schizophrenia and Delusional disorder. Schizoaffective disorder is a category used for individuals showing aspects of both schizophrenia and affective disorders. Schizotypy is a category used for individuals showing some of the traits associated with schizophrenia but without meeting cut-off criteria.
The fundamental characteristics of a person that influence his or her cognitions, motivations, and behaviors across situations and time - can be seen as disordered due to being abnormally rigid and maladaptive. Categorical schemes list a number of different personality disorders, such as those classed as eccentric (e.g. Paranoid personality disorder, Schizoid personality disorder, Schizotypal personality disorder), those described as dramatic or emotional (Antisocial personality disorder, Borderline personality disorder, Histrionic personality disorder, Narcissistic personality disorder) or those seen as fear-related (Avoidant personality disorder, Dependent personality disorder, Obsessive-compulsive personality disorder).
There may be an emerging consensus that personality disorders, like personality traits in the normal range, incorporate a mixture of more acute dysfunctional behaviors that resolve in relatively short periods, and maladaptive temperamental traits that are relatively more stable.[14] Non-categorical schemes may rate individuals via a profile across different dimensions of personality that are not seen as cut off from normal personality variation, commonly through schemes based on the Big Five personality traits.[15]
Other disorders may involve other attributes of human functioning. Eating practices can be disordered, at least in relatively rich industrialized areas, with either compulsive over-eating or under-eating or binging. Categories of disorder in this area include Anorexia nervosa, Bulimia nervosa, Exercise Bulimia or Binge eating disorder. Sleep disorders such as Insomnia also exist and can disrupt normal sleep patterns. Sexual and gender identity disorders, such as Dyspareunia or Gender identity disorder or ego-dystonic homosexuality. People who are abnormally unable to resist urges, or impulses, to perform acts that could be harmful to themselves or others, may be classed as having an impulse control disorder, including various kinds of Tic disorders such as Tourette's Syndrome, and disorders such as Kleptomania (stealing) or Pyromania (fire-setting). Substance-use disorders include Substance abuse disorder. Addictive gambling may be classed as a disorder. Inability to sufficiently adjust to life circumstances may be classed as an Adjustment disorder. The category of adjustment disorder is usually reserved for problems beginning within three months of the event or situation and ending within six months after the stressor stops or is eliminated. People who suffer severe disturbances of their self-identity, memory and general awareness of themselves and their surroundings may be classed as having a Dissociative identity disorder, such as Depersonalization disorder or Dissociative Identify Disorder itself (which has also been called multiple personality disorder, or "split personality".). Factitious disorders, such as Munchausen syndrome, also exist where symptoms are experienced and/or reported for personal gain.
Disorders appearing to originate in the body, but thought to be mental, are known as somatoform disorders, including Somatization disorder. There are also disorders of the perception of the body, including Body dysmorphic disorder. Neurasthenia is a category involving somatic complaints as well as fatigue and low spirits/depression, which is officially recognized by the ICD-10 but not by the DSM-IV.[16] Memory or cognitive disorders, such as amnesia or Alzheimer's disease exist.
Some disorders are thought to usually first occur in the context of early childhood development, although they may continue into adulthood. The category of Specific developmental disorder may be used to refer to circumscribed patterns of disorder in particular learning skills, motor skills, or communication skills. Disorders which appear more generalized may be classed as pervasive developmental disorders (PDD) also known as autism spectrum disorders (ASD); these include autism, Asperger's, Rett syndrome, childhood disintegrative disorder and other types of PDD whose exact diagnosis may not be specified. Other disorders mainly or first occurring in childhood include Reactive attachment disorder; Separation Anxiety Disorder; Oppositional Defiant Disorder; Attention Deficit Hyperactivity Disorder.
Causes
Numerous factors have been linked to the development of mental disorders. In many cases there is no single accepted or consistent cause currently established. A common view held is that disorders often result from genetic vulnerabilities combining with environmental stressors (Diathesis-stress model). An eclectic or pluralistic mix of models may be used to explain particular disorders. The primary paradigm of contemporary mainstream Western psychiatry is said to be the biopsychosocial (BPS) model - incorporating biological, psychological and social factors - although this may not be applied in practice. Biopsychiatry has tended to follow a biomedical model, focusing on "organic" or "hardware" pathology of the brain. Psychoanalytic theories have been popular but are now less so. Evolutionary psychology may be used as an overall explanatory theory. Attachment theory is another kind of evolutionary-psychological approach sometimes applied in the context for mental disorders. A distinction is sometimes made between a "medical model" or a "social model" of disorder and related disability.
Genetic studies have indicated that genes often play an important role in the development of mental disorders, via developmental pathways interacting with environmental factors. The reliable identification of connections between specific genes and specific categories of disorder has proven more difficult.
Environmental events surrounding pregnancy and birth have also been implicated. Traumatic brain injury may increase the risk of developing certain mental disorders. There have been some tentative inconsistent links found to certain viral infections, to substance misuse, and to general physical health.
Abnormal functioning of neurotransmitter systems has been implicated, including serotonin, norepinephrine, dopamine and glutamate systems. Differences have also been found in the size or activity of certain brains regions in some cases. Psychological mechanisms have also been implicated, such as cognitive and emotional processes, personality, temperament and coping style.
Social influences have been found to be important, including abuse, bullying and other negative or stressful life experiences. The specific risks and pathways to particular disorders are less clear, however. Aspects of the wider community have also been implicated, including employment problems, socioeconomic inequality, lack of social cohesion, problems linked to migration, and features of particular societies and cultures.
Diagnosis
Many mental health professionals, particularly psychiatrists, seek to diagnose individuals by ascertaining their particular mental disorder. Some professionals, for example some clinical psychologists, may avoid diagnosis in favor of other assessment methods such as formulation of a client's difficulties and circumstances.[17] The majority of mental health problems are actually assessed and treated by family physicians during consultations, who may refer on for more specialist diagnosis in acute or chronic cases. Routine diagnostic practice in mental health services typically involves an interview (which may be referred to as a mental status examination), where judgements are made of the interviewee's appearance and behavior, self-reported symptoms, mental health history, and current life circumstances. The views of relatives or other third parties may be taken into account. A physical examination to check for ill health or the effects of medications or other drugs may be conducted. Psychological testing is sometimes used via paper-and-pen or computerized questionnaires, which may include algorithms based on ticking off standardized diagnostic criteria, and in relatively rare specialist cases neuroimaging tests may be requested, but these methods are more commonly found in research studies than routine clinical practice.[18][19] Time and budgetary constraints often limit practicing psychiatrists from conducting more thorough diagnostic evaluations.[20] It has been found that most clinicians evaluate patients using an unstructured, open-ended approach, with limited training in evidence-based assessment methods, and that inaccurate diagnosis may be common in routine practice.[21] Comorbidity is very common in psychiatric diagnosis, i.e. the same person given a diagnosis in more than one category of disorder.
Treatment
Mental health services may be based in hospitals, clinics or the community. Often an individual may engage in different treatment modalities. They may be under case management (sometimes referred to as "service coordination"), use inpatient or day treatment, utilize a psychosocial rehabilitation program, and/or take part in an Assertive Community Treatment program. Individuals may be treated against their will in some cases, especially if assessed to be at high risk to themselves or others. Services in some countries are increasingly based on a Recovery model that supports an individual's journey to regain a meaningful life
Psychotherapy
A major option for many mental disorders is psychotherapy. There are several main types. Cognitive behavioral therapy (CBT) is widely used and is based on modifying the patterns of thought and behavior associated with a particular disorder. Psychoanalysis, addressing underlying psychic conflicts and defenses, has been a dominant school of psychotherapy and is still in use. Systemic therapy or family therapy is sometimes used, addressing a network of significant others as well as an individual. Some psychotherapies are based on a humanistic approach. There are a number of specific therapies used for particular disorders, which may be offshoots or hybrids of the above types. Mental health professionals often employ an eclectic or integrative approach. Much may depend on the therapeutic relationship, and there may be problems with trust, confidentiality and engagement.
Medication
A major option for many mental disorders is psychiatric medication. There are several main groups. Antidepressants are used for the treatment of clinical depression as well as often for anxiety and other disorders. There are a number of antidepressants beginning with the tricylics, moving through a wide variety of drugs that modify various facets of the brain chemistry dealing with intercellular communication. Beta-blockers, developed as a heart medication, is also used as an antidepressant. Anxiolytics are used for anxiety disorders and related problems such as insomnia. Mood stabilizers are used primarily in bipolar disorder. Lithium A (a metal) and Lamictal (an epileptic drug) are notable for treating both mania and depression. The others, mainly targeting mania rather than depression, are a wide variety of epilepsy medications and antipsychotics. Antipsychotics are used for psychotic disorders, notably for positive symptoms in schizophrenia. Stimulants are commonly used, notably for ADHD. Despite the different conventional names of the drug groups, there can be considerable overlap in the kinds of disorders for which they are actually indicated. There may also be off-label use. There can be problems with adverse effects and adherence.
Other
Electroconvulsive therapy (ECT) is sometimes used in severe cases when other interventions for severe intractable depression have failed. Psychosurgery has in the past been synonymous with the "frontal lobotomy." While this form of psychosurgery is no longer used, there are four other techniques that are used today. These methods are used only as a last resort for people who have not responded to medications and therapy, and are functionally crippled by their disorder. The disorders for which psychosurgery has been used for for intractable mood and anxiety disorders, such as Obsessive-Compulsive Disorder.[22]
Psychoeducation may be used to provide people with the information to understand and manage their problems. Creative therapies are sometimes used, including music therapy, art therapy or drama therapy. Lifestyle adjustments and supportive measures are often used, including peer support, self-help and supported housing or employment. Some advocate dietary supplements based on published randomized double-blind, placebo controlled trials.[23] Many things have been found to help at least some people. A placebo effect may play a role in any intervention.
Prevalence
WHO estimated that about 450 million people worldwide currently suffer from some form of mental or behavioural disorder.[26] One in four people will suffer from mental illness at some time in life, according to a report from the WHO.[27][28]
Numerous large-scale surveys of the prevalence of mental disorders in adults in the general population have been carried out since the 1980s based on self-reported symptoms assessed by standardized structured interviews, usually carried out over the phone. Mental disorders have been found to be common, with over a third of people in most countries reporting sufficient criteria at some point in their life.[29] The World Health Organization is currently undertaking a global survey of 26 countries in all regions of the world, based on ICD and DSM criteria.[1] The first published figures on the 14 country surveys completed to date, indicate that, of those disorders assessed, anxiety disorders are the most common in all but 1 country (prevalence in the prior 12-month period of 2.4% to 18.2%) and mood disorders next most common in all but 2 countries (12-month prevalence of 0.8% to 9.6%), while substance disorders (0.1%-6.4%) and impulse-control disorders (0.0%-6.8%) were consistently less prevalent. The United States, Colombia, the Netherlands and Ukraine tended to have higher prevalence estimates across most classes of disorder, while Nigeria, Shanghai and Italy were consistently low, and prevalence was lower in Asian countries in general. Cases of disorder were rated as mild (prevalence of 1.8%-9.7%), moderate (prevalence of 0.5%-9.4%) and serious (prevalence of 0.4%-7.7%).[30] However, these are widely believed to be underestimates, due to poor diagnosis (especially in countries without affordable access to mental health services) and low reporting rates, in part because of the predominant use of self-report data, rather than semi-structured instruments such as the Structured Clinical Interview for DSM-IV (SCID); actual lifetime prevalence rates for mental disorders are estimated to be between 65% and 85%.
A review that pooled surveys in different countries up to 2004 found overall average prevalence estimates for any anxiety disorder of 10.6% (in the 12 months prior to assessment) and 16.6% (in lifetime prior to assessment), but that rates for individual disorders varied widely. Women had generally higher prevalence rates than men, but the magnitude of the difference varied.[31] A review that pooled surveys of mood disorders in different countries up to 2000 found 12-month prevalence rates of 4.1% for major depressive disorder (MDD), 2% for dysthymic disorder and 0.72% for bipolar 1 disorder. The average lifetime prevalence found was 6.7% for MDD (with a relatively low lifetime prevalence rate in higher-quality studies, compared to the rates typically highlighted of 5%-12% for men and 10%-25% for women), and rates of 3.6% for dysthymia and 0.8% for Bipolar 1.[32]
Previous widely cited large-scale surveys in the United States were the Epidemiological Catchment Area (ECA) survey and subsequent National Comorbidity Survey (NCS). The NCS was replicated and updated between 2000 and 2003 and indicated that, of those groups of disorders assessed, nearly half of Americans (46.4%) reported meeting criteria at some point in their life for either a DSM-IV anxiety disorder (28.8%), mood disorder (20.8%), impulse-control disorder (24.8%) or substance use disorders (14.6%). Half of all lifetime cases had started by age 14 years and 3/4 by age 24 years.[33] In the prior 12-month period only, around a quarter (26.2%) met criteria for any disorder - anxiety disorders 18.1%; mood disorders 9.5%; impulse control disorders 8.9%; and substance use disorders 3.8%. A substantial minority (23%) met criteria for more than two disorders. A minority (22.3%) of cases were classed as serious, 37.3% as moderate and 40.4% as mild.[34][35]
A 2004 cross-European study found that approximately one in four people reported meeting criteria at some point in their life for one of the DSM-IV disorders assessed, which included mood disorders (13.9%), anxiety disorders (13.6%) or alcohol disorder (5.2%). Approximately one in ten met criteria within a 12-month period. Women and younger people of either gender showed more cases of disorder[36]
A 2005 review of 27 studies have found that 27% of adult Europeans is or has been affected by at least one mental disorder in the past 12 months. It was also found that the most frequent disorders were anxiety disorders, depressive, somatoform and substance dependence disorders.[37]
A 2005 review of prior surveys in 46 countries on the prevalence of schizophrenic disorders, including a prior 10-country WHO survey, found an average (median) figure of 0.4% for lifetime prevalence up to the point of assessment and 0.3% in the 12-month period prior to assessment. A related figure not given in other studies (known as lifetime morbid risk), reported to be an accurate statement of how many people would theoretically develop schizophrenia at any point in life regardless of time of assessment, was found to be “about seven to eight individuals per 1,000.” (0.7/0.8%). The prevalence of schizophrenia was consistently lower in poorer countries than in richer countries (though not the incidence) but the prevalence did not differ between urban/rural areas or men/women (although incidence did).[38]
Studies of the prevalence of personality disorders (PDs) have been fewer and smaller-scale, but a broader Norwegian survey found a similar overall prevalence of almost 1 in 7 (13.4%), based on meeting personality criteria over the prior five year period. Rates for specific disorders ranged from 0.8% to 2.8%, with rates differing across countries, and by gender, educational level and other factors.[39] A US survey that incidentally screened for personality disorder found an overall rate of 14.79%.[40]
Approximately 7% of a preschool pediatric sample were given a psychiatric diagnosis in one clinical study, and approximately 10% of 1- and 2-year-olds receiving developmental screening have been assessed as having significant emotional/behavioral problems based on parent and pediatrician reports.
Stigma of mental illness
A large proportion of individuals who suffer from the symptoms of a mental illness will avoid seeking treatment for their symptoms because of the social stigma[2] associated with having a mental illness. The US Surgeon General acknowledged this in 1999:
Powerful and pervasive, stigma prevents people from acknowledging their own mental health problems, much less disclosing them to others.[51]
As a result many people feel the need to keep their mental illness a secret, and will deny the symptoms that they are experiencing. Two thirds of the people who would benefit from treatment for a mental illness do not receive treatment.[52] As with many physical illnesses, the prognoses of a mental illness can worsen the longer that a mental illness remains untreated. The added anxiety of fearing a mental illness diagnoses can also be detrimental to an individual's mental health, this effect can greatly exacerbate an anxiety disorder or mood disorder. Efforts are being undertaken worldwide to eliminate the stigma of mental illness.
Violence
The public fear of violence due to mental illness is a contentious topic. One US national survey indicated that a far higher percentage of Americans rated individuals described as displaying the characteristics of a mental disorder (for example Schizophrenia or Substance Use Disorder) as "likely to do something violent to others" compared to those described as being 'troubled'.[70] Research indicates, on balance, a higher than average number of violent acts by some individuals with certain diagnoses, notably antisocial or psychopathic personality disorders, but conflicting findings about specific symptoms (for example links between psychosis and violence in community settings) - but the mediating factors of such acts are most consistently found to be mainly socio-demographic and socio-economic factors such as being young, male, of lower socio-economic status and, in particular, substance abuse (including alcohol).[71][72][24] Findings consistently indicate that it is many times more likely that people diagnosed with a serious mental illness living in the community will be the victim rather than the perpetrator of violence.[71][73] Violence by or against individuals with mental illness typically occurs in the context of complex social interactions (including in atmosphere of mutually high "expressed emotion"), including within a family setting,[74] as well as being an issue in healthcare settings[75] and the wider community.
Multiple sclerosis reference
Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the immune system attacks the central nervous system (CNS), leading to demyelination. It may cause numerous physical and mental symptoms, and often progresses to physical and cognitive disability. Disease onset usually occurs in young adults, is more common in women, and has a prevalence that ranges between 2 and 150 per 100,000 depending on the country or specific population. MS was first described in 1868 by Jean-Martin Charcot.
MS affects the areas of the brain and spinal cord known as the white matter. White matter cells carry signals between the grey matter areas, where the processing is done, and the rest of the body. More specifically, MS destroys oligodendrocytes which are the cells responsible for creating and maintaining a fatty layer, known as the myelin sheath, which helps the neurons carry electrical signals. MS results in a thinning or complete loss of myelin and, less frequently, the cutting (transection) of the neuron's extensions or axons. When the myelin is lost, the neurons can no longer effectively conduct their electrical signals. The name multiple sclerosis refers to the scars (scleroses - better known as plaques or lesions) in the white matter. Loss of myelin in these lesions causes some of the symptoms, which vary widely depending upon which signals are interrupted. However, more advanced forms of imaging are now showing that much of the damage happens outside these regions. Almost any neurological symptom can accompany the disease.
MS takes several forms, with new symptoms occurring either in discrete attacks (relapsing forms) or slowly accumulating over time (progressive forms). Most people are first diagnosed with relapsing-remitting MS but develop secondary-progressive MS (SPMS) after a number of years. Between attacks, symptoms may go away completely, but permanent neurological problems often persist, especially as the disease advances.
Although much is known about the mechanisms involved in the disease process, the cause remains elusive: the most widely-held being that the condition results from attacks to the nervous system by the body's own immune system. Some believe it is a metabolically dependent disease while others think that it might be caused by a virus such as Epstein-Barr. Still others believe that its virtual absence from tropical areas points to a deficiency of vitamin D during childhood.[2]
This disease does not have a cure, but several therapies have proven helpful. Treatments attempt to return function after an attack, prevent new attacks, and prevent disability. MS medications can have adverse effects or be poorly tolerated, and many patients pursue alternative treatments, despite the paucity of supporting scientific study. Many candidate therapies are still under investigation.
The prognosis, or expected course of the disease, depends on the subtype of the disease, the individual patient's disease characteristics, the initial symptoms, and the degree of disability the person experiences as time advances. Life expectancy of patients, however, is nearly the same as that of the unaffected population, and in some cases a near-normal life is possible.
MS presents with a variety of symptoms, including changes in sensation (hypoesthesia), muscle weakness, abnormal muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain syndromes, and bladder and bowel difficulties. Cognitive impairment of varying degrees, or emotional symptomatology in the form of depression or pseudobulbar affect[3] are also common. Neuropathic pain is usual, and this can be in the form of Lhermitte's sign. Neuropathic pain is the most common, distressing and intractable of the pain syndromes in MS. This pain is described as constant, boring, burning or tingling intensely. It usually occurs in the legs. Paraesthesias include pins and needles; tingling; shivering; burning pains; feelings of pressure; and areas of skin with heightened sensitivity to touch. The pains associated with these can be aching, throbbing, stabbing, shooting, gnawing, tingling, tightness and numbness.[4] The main clinical measure of disability progression and severity of the symptoms is the Expanded Disability Status Scale or EDSS.[5]
The initial attacks (also known as exacerbations or relapses) are often transient, mild (or asymptomatic), and self-limited. They often do not prompt a health care visit and sometimes are only identified in retrospect once the diagnosis has been made based on further attacks. The most common initial symptoms reported are: changes in sensation in the arms, legs or face (33%), complete or partial vision loss (optic neuritis) (16%), weakness (13%), double vision (7%), unsteadiness when walking (5%), and balance problems (3%); but many rare initial symptoms have been reported such as aphasia or psychosis.[6][7] Fifteen percent of individuals have multiple symptoms when they first seek medical attention.[8] Optic neuritis or focal leg weakness may lead to falls and other serious accidents.[9] For some people the initial MS attack is preceded by infection, trauma, or strenuous physical effort.
Diagnosis
T1-weighted MRI scans (post-contrast) of same brain slice at monthly intervals. Bright spots indicate active lesions.
T1-weighted MRI scans (post-contrast) of same brain slice at monthly intervals. Bright spots indicate active lesions.
Multiple sclerosis is difficult to diagnose in its early stages. In fact, a definite diagnosis cannot be made until other disease processes (differential diagnoses) have been ruled out and, in the case of relapsing-remitting MS, there is evidence of at least two anatomically separate demyelinating events separated by at least thirty days. In the case of primary progressive, a slow progression of signs and symptoms over at least 6 months is required.
Historically, different criteria were used and the Schumacher and Poser criteria were both popular. Currently, the McDonald criteria represent international efforts to standardize the diagnosis of MS using clinical, laboratory and radiologic data.[10]
* Clinical data alone may be sufficient for a diagnosis of MS. If an individual has suffered two separate episodes of neurologic symptoms characteristic of MS, and the individual also has consistent abnormalities on physical examination, a diagnosis of MS can be made with no further testing. Since some people with MS seek medical attention after only one attack, other testing may hasten the diagnosis and allow earlier initiation of therapy.
* Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of the brain and spine is often used during the diagnostic process. MRI shows areas of demyelination (lesions) as bright spots on the image. Gadolinium can be administered intravenously to highlight active plaques and, by elimination, demonstrate the existence of historical lesions not associated with clinical symptoms. This can provide the evidence of chronic disease needed for a definitive diagnosis of MS.
* Testing of cerebrospinal fluid (CSF) can provide evidence of chronic inflammation of the central nervous system. The CSF is tested for oligoclonal bands, which are immunoglobulins found in 75% to 85% of people with definite MS (but also found in people with other diseases).[11] Combined with MRI and clinical data, the presence of oligoclonal bands can help make a definite diagnosis of MS. Lumbar puncture is the procedure used to collect a sample of CSF.
* The brain of a person with MS often responds less actively to stimulation of the optic nerve and sensory nerves. These brain responses can be examined using visual evoked potentials (VEPs) and somatosensory evoked potentials (SEPs). Decreased activity on either test can reveal demyelination which may be otherwise asymptomatic. Along with other data, these exams can help find the widespread nerve involvement required for a definite diagnosis of MS.[12]
Another test, which may become important in the future, is measurement of antibodies against myelin proteins such as myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). As of 2007, however, there is no established role for these tests in diagnosing MS. Optical coherence tomography of the eye's retina is also under study,[13] mainly as a tool to measure response to medication and axonal degeneration.[14]
The signs and symptoms of MS can be similar to other medical problems, such as neuromyelitis optica, stroke, brain inflammation, infections such as Lyme disease (which can produce identical MRI lesions and CSF abnormalities[15][16][17][18]), tumors, and other autoimmune problems, such as lupus. Additional testing may be needed to help distinguish MS from these other problems.
The course of MS is difficult to predict, and the disease may at times either lie dormant or progress steadily. Several subtypes, or patterns of progression, have been described. Subtypes use the past course of the disease in an attempt to predict the future course. Subtypes are important not only for prognosis but also for therapeutic decisions. In 1996 the United States National Multiple Sclerosis Society standardized the following four subtype definitions:[19]
Relapsing-remitting
Relapsing-remitting describes the initial course of 85% to 90% of individuals with MS. This subtype is characterized by unpredictable attacks (relapses) followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits suffered during the attacks may either resolve or may be permanent. When deficits always resolve between attacks, this is referred to as "benign" MS.
Secondary progressive
Secondary progressive describes around 80% of those with initial relapsing-remitting MS, who then begin to have neurologic decline between their acute attacks without any definite periods of remission. This decline may include new neurologic symptoms, worsening cognitive function, or other deficits. Secondary progressive is the most common type of MS and causes the greatest amount of disability.
Primary progressive
Primary progressive describes the approximately 10% of individuals who never have remission after their initial MS symptoms. Decline occurs continuously without clear attacks. The primary progressive subtype tends to affect people who are older at disease onset.
Progressive relapsing
Progressive relapsing describes those individuals who, from the onset of their MS, have a steady neurologic decline but also suffer superimposed attacks; and is the least common of all subtypes
Nevertheless the earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). In CIS, there is a subacute attack suggestive of demyelination but the person does not fulfill the criteria for multiple sclerosis.[20] Several studies have shown that starting treatment with interferons during the initial attack can decrease the chance that a patient will develop clinical MS.[21][22][23] Cases of MS before the CIS are sometimes found during other neurological inspections and are referred to as subclinical MS.[24] Preclinical MS refers to cases after the CIS but before the confirming second attack.[25]
During the standard clinical course, relapses rate decreases with disease time.[26] Special cases of the disease with non-standard behavior have also been described although many researchers believe they are different diseases. These cases are sometimes referred to as borderline forms of multiple sclerosis and are Neuromyelitis optica (NMO), Balo concentric sclerosis, Schilder's diffuse sclerosis and Marburg multiple sclerosis.[27]
Factors triggering a relapse
Multiple sclerosis relapses are often unpredictable and can occur without warning with no obvious inciting factors. Some attacks, however, are preceded by common triggers. In general, relapses occur more frequently during spring and summer than during autumn and winter. Infections, such as the common cold, influenza, and gastroenteritis, increase the risk for a relapse.[28] Emotional and physical stress may also trigger an attack,[29][30][31] as can severe illness of any kind. Statistically, there is no good evidence that either trauma or surgery trigger relapses.[32] People with MS can participate in sports, but they should probably avoid extremely strenuous exertion, such as marathon running. Heat can transiently increase symptoms, which is known as Uhthoff's phenomenon. This is why some people with MS avoid saunas or even hot showers. However, heat is not an established trigger of relapses.[33]
Pregnancy can directly affect the susceptibility for relapse. The last three months of pregnancy offer a natural protection against relapses. However, during the first few months after delivery, the risk for a relapse is increased 20%–40%. Pregnancy does not seem to influence long-term disability. Children born to mothers with MS are not at increased risk for birth defects or other problems.
Many potential triggers have been examined and found not to influence relapse rates in MS. Influenza vaccination is safe, does not trigger relapses, and can therefore be recommended for people with MS. There is also no evidence that vaccines for hepatitis B, varicella, tetanus, or Bacille Calmette-Guerin (BCG—immunization for tuberculosis) increases the risk for relapse.
Although much is known about how multiple sclerosis causes damage, the reasons why multiple sclerosis occurs are not known.
Multiple sclerosis is a disease in which the myelin (a fatty substance which covers the axons of nerve cells) degenerates. According to the view of most researchers, a special subset of lymphocytes, called T cells, plays a key role in the development of MS.
According to a strictly immunological explanation of MS, the inflammatory process is triggered by the T cells. T cells gain entry into the brain via the blood-brain barrier (a capillary system that should prevent entrance of T-cells into the nervous system). The blood brain barrier is normally not permeable to these types of cells, unless triggered by either infection or a virus, where the integrity of the tight junctions forming the blood-brain barrier is decreased. When the blood brain barrier regains its integrity (usually after infection or virus has cleared) the T cells are trapped inside the brain. These lymphocytes recognize myelin as foreign and attack it as if it were an invading virus. That triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the blood-brain barrier. These leaks, in turn, cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as matrix metalloproteinases. A deficiency of uric acid has been implicated in this process.[36]
It is known that a repair process, called remyelination, takes place in early phases of the disease, but the oligodendrocytes that originally formed a myelin sheath cannot completely rebuild a destroyed myelin sheath. The newly-formed myelin sheaths are thinner and often not as effective as the original ones. Repeated attacks lead to successively fewer effective remyelinations, until a scar-like plaque is built up around the damaged axons, according to four different damage patterns.[37] The central nervous system should be able to recruit oligodendrocyte stem cells capable of turning into mature myelinating oligodendrocytes, but it is suspected that something inhibits stem cells in affected areas.
The axons themselves can also be damaged by the attacks.[38] Often, the brain is able to compensate for some of this damage, due to an ability called neuroplasticity. MS symptoms develop as the cumulative result of multiple lesions in the brain and spinal cord. This is why symptoms can vary greatly between different individuals, depending on where their lesions occur.
Causes
Although many risk factors for multiple sclerosis have been identified, no definitive cause has been found. MS likely occurs as a result of some combination of both environmental and genetic factors. Various theories try to combine the known data into plausible explanations. Although most accept an autoimmune explanation, several theories suggest that MS is an appropriate immune response to one or several underlying conditions (the etiology could be heterogeneous[39]). The need for alternative theories is supported by the poor results of present therapies, since autoimmune theory predicted greater success.[40][41][42]
Environmental
The most popular hypothesis is that a viral infection or retroviral reactivation primes a susceptible immune system for an abnormal reaction later in life. On a molecular level, this might occur if there is a structural similarity between the infectious virus and some component of the central nervous system, leading to eventual confusion in the immune system.
A correlation between clinical MS and presence of an endogenous retrovirus called HERV has been found.[43][44][45][46][47] The strong correlation of MS to HERV infection, suggests that MS patients might benefit from use of HERV targeted antivirals or a gene therapy strategy to neutralize the HERV infection directly.
Since MS seems to be more common in people who live farther from the equator, another theory proposes that decreased sunlight exposure[48] and possibly decreased vitamin D production may help cause MS. This theory is bolstered by recent research into the biochemistry of vitamin D, which has shown that it is an important immune system regulator. A large, 2006 study by the Harvard School of Public Health, reported evidence of a link between vitamin D deficiency and the onset of multiple sclerosis.[2] Other data comes from a 2007 study which concluded that sun exposure during childhood reduces the risk of suffering MS, while controlling for genetic factors.[49]
Other theories, noting that MS is less common in children with siblings, suggest that less exposure to illness in childhood leads to an immune system which is not primed to fight infection and is thus more likely to attack the body. One explanation for this would be an imbalance between the Th1 type of helper T-cells, which fight infection, and the Th2 type, which are more active in allergy and more likely to attack the body[citation needed].
Other theories describe MS as an immune response to a chronic infection. The association of MS with the Epstein-Barr virus suggests a potential viral contribution in at least some individuals.[50] Human endogenous retroviruses could also be involved, specially one called MSRV (MS associated retrovirus)[51]. Still others believe that MS may sometimes result from a chronic infection with spirochetal bacteria, a hypothesis supported by research in which cystic forms were isolated from the cerebrospinal fluid of all MS patients in a small study.[52] When the cysts were cultured, propagating spirochetes emerged. Another bacterium that has been implicated in MS is Chlamydophila pneumoniae; it or its DNA has been found in the cerebrospinal fluid of MS patients by several research laboratories, with one study finding that the oligoclonal bands of 14 of the 17 MS patients studied consisted largely of antibodies to Chlamydophila antigens.[53]. Varicella zoster virus is also suspected to be involved[54].
Severe stress may also be a factor—a large study in Denmark found that parents who had lost a child unexpectedly were 50% more likely to develop MS than parents who had not.[55] Smoking has also been shown to be an independent risk factor for developing MS.[56]
Genetic
MS is not considered a hereditary disease. However, increasing scientific evidence suggests that genetics may play a role in determining a person's susceptibility to MS:
Some populations, such as the Roma, Inuit, and Bantus, rarely if ever develop MS. The indigenous peoples of the Americas and Asians have very low incidence rates.
In the population at large, the chance of developing MS is less than a tenth of one percent. However, if one person in a family has MS, that person's first-degree relatives—parents, children, and siblings—have a one to three percent chance of getting the disease.
For identical twins, the likelihood that the second twin may develop MS if the first twin does is about 30%. For fraternal twins (who do not inherit an identical set of genes), the likelihood is closer to that for non-twin siblings, at about 4%. This pattern suggests that, while genetic factors clearly help determine the risk of MS, other factors such as environmental effects or random chance are also involved. The actual correlation may be somewhat higher than reported by these numbers as people with MS lesions remain essentially asymptomatic throughout their lives.
Further indications that more than one gene is involved in MS susceptibility comes from studies of families in which more than one member has MS. Several research teams found that people with MS inherit certain regions on individual genes more frequently than people without MS. Of particular interest is the human leukocyte antigen (HLA) or major histocompatibility complex region on chromosome 6. HLAs are genetically determined proteins that influence the immune system. However, there are other genes in this region which are not related to the immune system.
The HLA patterns of MS patients tend to be different from those of people without the disease. Investigations in northern Europe and America have detected three HLAs that are more prevalent in people with MS than in the general population. Studies of American MS patients have shown that people with MS also tend to exhibit these HLAs in combination—that is, they have more than one of the three HLAs—more frequently than the rest of the population. Furthermore, there is evidence that different combinations of the HLAs may correspond to variations in disease severity and progression.
A large study examining 334,923 single nucleotide polymorphisms (small variations in genes) in 931 families showed that apart from HLA-DRA there were two genes in which polymorphisms strongly predicted MS; these were the IL2RA (a subunit of the receptor for interleukin 2) and the IL7RA (idem for interleukin 7) genes. Mutations in these genes were already known to be associated with diabetes mellitus type 1 and other autoimmune conditions; the findings circumstantially support the notion that MS is an autoimmune disease.[57]
Studies of families with multiple cases of MS and research comparing proteins expressed in humans with MS to those of mice with EAE suggest that another area related to MS susceptibility may be located on chromosome 5. Other regions on chromosomes 2, 3, 7, 11, 17, 19, and X have also been identified as possibly containing genes involved in the development of MS.
These studies strengthen the theory that MS is the result of a number of factors rather than a single gene or other agent. Development of MS is likely to be influenced by the interactions of a number of genes, each of which (individually) has only a modest effect. Additional studies are needed to specifically pinpoint which genes are involved, determine their function, and learn how each gene's interactions with other genes and with the environment make an individual susceptible to MS.
Treatment
Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS have several adverse effects, and many possible therapies are still under investigation. At the same time different alternative treatments are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study.
Management of acute attacks
During symptomatic attacks administration of high doses of intravenous corticosteroids, such as methylprednisolone,[58][59] is the routine therapy for acute relapses. The aim of this kind of treatment is to end the attack sooner and leave fewer lasting deficits in the patient. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery.[60] Potential side effects include osteoporosis[61] and impaired memory, the latter being reversible.[62]
Disease modifying treatments
Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions at 1-3 month intervals.
Disease-modifying treatments are expensive and most of these require frequent (up-to-daily) injections. Others require IV infusions at 1-3 month intervals.
The earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). Several studies have shown that treatment with interferons during an initial attack can decrease the chance that a patient will develop MS.[63][64][23]
As of 2007, six disease-modifying treatments have been approved by regulatory agencies of different countries for relapsing-remitting MS. Three are interferons: two formulations of interferon beta-1a (trade names Avonex and Rebif) and one of interferon beta-1b (U.S. trade name Betaseron, in Europe and Japan Betaferon). A fourth medication is glatiramer acetate (Copaxone). The fifth medication, mitoxantrone, is an immunosuppressant also used in cancer chemotherapy, is approved only in the USA and largely for SPMS. Finally, the sixth is natalizumab (marketed as Tysabri). All six medications are modestly effective at decreasing the number of attacks and slowing progression to disability, although they differ in their efficacy rate and studies of their long-term effects are still lacking.[65][66][67][68] Comparisons between immunomodulators (all but mitoxantrone) show that the most effective is natalizumab, both in terms of relapse rate reduction and halting disability progression[69]; it has also been shown to reduce the severity of MS[70]. Mitoxantrone may be the most effective of them all;[71] however, it is generally considered not as a long-term therapy as its use is limited by severe cardiotoxicity.[72]
The interferons and glatiramer acetate are delivered by frequent injections, varying from once-per-day for glatiramer acetate to once-per-week (but intra-muscular) for Avonex. Natalizumab and mitoxantrone are given by IV infusion at monthly intervals.
Treatment of progressive MS is more difficult than relapsing-remitting MS. Mitoxantrone has shown positive effects in patients with a secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in patients in short-term follow-up.[68] On the other hand no treatment has been proven to modify the course of primary progressive MS.[73]
As with any medical treatment, these treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the Interferon treatments. Over time, a visible dent at the injection site due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons also produce symptoms similar to influenza;[74] while some patients taking glatiramer experience a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety, which usually lasts less than thirty minutes. More dangerous are liver damage of interferons and mitoxantrone, the immunosuppressive effects and cardiac toxicity of the latter;[79] or the putative link between natalizumab and some cases of progressive multifocal leukoencephalopathy in patients who had taken it in combination with interferons.[80][81]
Management of the effects of MS
Disease-modifying treatments only reduce the progression rate of the disease but do not stop it. As multiple sclerosis progresses, the symptomatology tends to increase. The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and handicap. Management of these deficits is therefore very important. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, even though neither influence disease progression.[82] As for any patient with neurologic deficits, a multidisciplinary approach is key to limiting and overcoming disability; however there are particular difficulties in specifying a ‘core team’ because people with MS may need help from almost any health profession or service at some point.[83] Similarly for each symptom there are different treatment options. Treatments should therefore be individualized depending both on the patient and the physician
Therapies under investigation
Main article: Therapies under investigation for multiple sclerosis
Scientists continue their extensive efforts to create new and better therapies for MS. There are a number of treatments under investigation that may improve function, curtail attacks, or limit the progression of the underlying disease. Many treatments already in clinical trials involve drugs that are used in other diseases or medications that have not been designed specifically for MS. There are also trials involving the combination of drugs that are already in use for multiple sclerosis. Finally, there are also many basic investigations that try to understand better the disease and in the future may help to find new treatments.
Alternative treatments
Different alternative treatments are pursued by many patients, despite the paucity of supporting, comparable, replicated scientific study. Examples are dietary regimens,[84] herbal medicine, including the use of medical cannabis to help alleviate symptoms,[85][86] or hyperbaric oxygenation.[87] On the other hand the therapeutic practice of martial arts such as tai chi, relaxation disciplines such as yoga, or general exercise, seem to mitigate fatigue and improve quality of life.[88]
Prognosis
The prognosis (the expected future course of the disease) for a person with multiple sclerosis depends on the subtype of the disease; the individual's sex, race, age, and initial symptoms; and the degree of disability the person experiences. The life expectancy of people with MS, at least for earlier years, is now nearly the same as that of unaffected people. This is due mainly to improved methods of limiting disability, such as physical therapy, occupational therapy and speech therapy, along with more successful treatment of common complications of disability, such as pneumonia and urinary tract infections.[89] Nevertheless, half of the deaths in people with MS are directly related to the consequences of the disease, while 15% more are due to suicide.[90]
* Individuals with progressive subtypes of MS, particularly the primary progressive subtype, have a more rapid decline in function. In the primary progressive subtype, supportive equipment (such as a wheelchair or standing frame) is often needed after six to seven years. However, when the initial disease course is the relapsing-remitting subtype, the average time until such equipment is needed is twenty years. This means that many individuals with MS will never need a wheelchair. There is also more cognitive impairment in the progressive forms than in the relapsing-remitting course.
* The earlier in life MS occurs, the slower disability progresses. Individuals who are older than fifty when diagnosed are more likely to experience a chronic progressive course, with more rapid progression of disability. Those diagnosed before age 35 have the best prognosis. Females generally have a better prognosis than males. Although individuals of African descent tend to develop MS less frequently, they are often older at the time of onset and may have a worse prognosis.
* Initial MS symptoms of visual loss or sensory problems, such as numbness or tingling, are markers for a relatively good prognosis, whereas difficulty walking and weakness are markers for a relatively poor prognosis. Better outcomes are also associated with the presence of only a single symptom at onset, the rapid development of initial symptoms, and the rapid regression of initial symptoms.
* The degree of disability varies among individuals with MS. In general, one of three individuals will still be able to work after 15–20 years. Fifteen percent of people diagnosed with MS never have a second relapse, and these people have minimal or no disability after ten years.[91] The degree of disability after five years correlates well with the degree of disability after fifteen years. This means that two-thirds of people with MS with low disability after five years will not get much worse during the next ten years. It should be noted that most of these outcomes were observed before the use of medications such as interferon, which can delay disease progression for several years.
* Apart from physical disability, cognitive impairment in MS occurs in approximately half of all patients. In its earlier stages, this impairment can include loss of short-term memory, depression and the pseudobulbar affect. As the disease progresess, the impairment can become more profound, ranging from loss of deductive reasoning to dementia.
Currently there are no clinically established laboratory investigations available that can predict prognosis or response to treatment. However, several promising approaches have been proposed. These include measurement of the two antibodies anti-myelin oligodendrocyte glycoprotein and anti-myelin basic protein, and measurement of TRAIL (TNF-related apoptosis-inducing ligand).[92]
Epidemiology
World map showing that risk (incidence) for MS increases with greater distance from the equator
World map showing that risk (incidence) for MS increases with greater distance from the equator
Epidemiology is, among other things, the study of prevalence and incidence of diseases, incidence being the percentage of cases reported each year and prevalence the total percentage of cases in the population. Prevalence is known to depend not only to incidence, but also to survival rate and migrations of affected people[93].
In northern Europe, continental North America, and Australasia, about one of every 1000 people suffers from multiple sclerosis, whereas in the Arabian peninsula, Asia, and continental South America, the frequency is much lower. In sub-Saharan Africa, MS is extremely rare. With important exceptions, there is a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere, with MS being much less common in people living near the equator.[94] Climate, diet, geomagnetism, toxins, sunlight exposure, genetic factors, and infectious diseases have all been discussed as possible reasons for these regional differences. Environmental factors during childhood may play an important role in the development of MS later in life. This idea is based on several studies of migrants showing that if migration occurs before the age of fifteen, the migrant acquires the new region's susceptibility to MS. If migration takes place after age fifteen, the migrant keeps the susceptibility of his home country.[95] However other works suggest that the age/geographical risk for developing multiple sclerosis spans a larger timescale than just the first 15 years of life.[96]
MS occurs mainly in Caucasians. It is twentyfold lower in the Inuit people of Canada than in other Canadians living in the same region. It is also rare in the Native American tribes of North America, Australian Aborigines and the Māori of New Zealand. Scotland appears to have the highest rate of MS in the world.[97] The reasons for this are unknown. These few examples point out that either genetic background or lifestyle and cultural factors play an important role in the development of MS.
As observed in many autoimmune disorders, MS is more common in females than males; the mean sex ratio is about two females for every male. In children (who rarely develop MS) the sex ratio may reach three females for each male. In people over age fifty, MS affects males and females equally. Onset of symptoms usually occurs between fifteen and forty years of age, rarely before age fifteen or after age sixty.
As previously discussed, there is a genetic component to MS. On average one of every 25 siblings of individuals with MS will also develop MS. Almost half of the identical twins of MS-affected individuals will develop MS, but only one of twenty fraternal twins. If one parent is affected by MS, each child has a risk of only about one in forty of developing MS later in life.[98]
Finally, it is important to remark that advances in the study of related diseases have shown that some cases formerly considered MS are not MS at all. In fact, all the studies before 2004 can be affected by the impossibility to distinguish MS and Devic's disease (NMO) reliably before this date. The error can be important in some areas: 30% of cases diagnosed as MS in Japan may have been NMO.
Friday, July 11, 2008
Thyroid disorder reference
The thyroid is one of the largest endocrine glands in the body. This gland is found in the neck inferior to (below) the thyroid cartilage (also known as the Adam's apple in men) and at approximately the same level as the cricoid cartilage. The thyroid controls how quickly the body burns energy, makes proteins, and how sensitive the body should be to other hormones.
The thyroid participates in these processes by producing thyroid hormones, principally thyroxine (T4) and triiodothyronine (T3). These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body. Iodine is an essential component of both T3 and T4. The thyroid also produces the hormone calcitonin, which plays a role in calcium homeostasis.
The thyroid is controlled by the hypothalamus and pituitary. The gland gets its name from the Greek word for "shield", after the shape of the related thyroid cartilage. Hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid) are the most common problems of the thyroid gland.
Anatomy
The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or wings: lobus dexter (right lobe) and lobus sinister (left lobe), connected with the isthmus. The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath. It starts cranially at the oblique line on the thyroid cartilage (just below the laryngeal prominence or Adam's apple) and extends inferiorly to the fourth to sixth tracheal ring[citation needed]. It is difficult to demarcate the gland's upper and lower border with vertebral levels as it moves position in relation to these during swallowing.
The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroidea, composed of an internal and external layer. The external layer is anteriorly continuous with the lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous with the carotid sheath. The gland is covered anteriorly with infrahyoid muscles and laterally with the sternocleidomastoid muscle. Posteriorly, the gland is fixed to the cricoid and tracheal cartilage and cricopharyngeus muscle by a thickening of the fascia to form the posterior suspensory ligament of Berry[1][2]. In variable extent, Zuckerkandl's tubercle, a pyramidal extension of the thyroid lobe, is present at the most posterior side of the lobe[3][4]. In this region the recurrent laryngeal nerve and the inferior thyroid artery pass next to or in the ligament and tubercle. Between the two layers of the capsule and on the posterior side of the lobes there are on each side two parathyroid glands.
The thyroid isthmus is variable in presence and size, and can encompass a cranially extending pyramid lobe (lobus pyramidalis or processus pyramidalis), remnant of the thyroglossal duct. The thyroid is one of the larger endocrine glands, weighing 2-3 grams in neonates and 18-60 grams in adults, and is increased in pregnancy[citation needed].
The thyroid is supplied with arterial blood from the superior thyroid artery, a branch of the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, and sometimes by the thyroid ima artery, branching directly from the aortic arch. The venous blood is drained via superior thyroid veins, draining in the internal jugular vein, and via inferior thyroid veins, draining via the plexus thyroideus impar in the left brachiocephalic vein. Lymphatic drainage passes frequently the lateral deep cervical lymph nodes and the pre- and parathracheal lymph nodes. The gland is supplied by sympathetic nerve input from the superior cervical ganglion and the cervicothoracic ganglion of the sympathetic trunk[citation needed], and by parasympathetic nerve input from the superior laryngeal nerve and the recurrent laryngeal nerve.
In the fetus, at 3-4 weeks of gestation, the thyroid gland appears as an epithelial proliferation in the floor of the pharynx at the base of the tongue between the tuberculum impar and the copula linguae at a point latter indicated by the foramen cecum. Subsequently the thyroid descends in front of the pharyngeal gut as a bilobed diverticulum through the thyroglossal duct. Over the next few weeks, it migrates to the base of the neck. During migration, the thyroid remains connected to the tongue by a narrow canal, the thyroglossal duct. Follicles of the thyroid begin to make colloid in the 11th week and thyroxine by the 18th week.
Physiology
The primary function of the thyroid is production of the hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. Up to 80% of the T4 is converted to T3 by peripheral organs such as the liver, kidney and spleen. T3 is about ten times more active than T4.[5]
Significance of iodine
In areas of the world where iodine (essential for the production of thyroxine, which contains four iodine atoms) is lacking in the diet, the thyroid gland can be considerably enlarged, resulting in the swollen necks of endemic goitre.
Thyroxine is critical to the regulation of metabolism and growth throughout the animal kingdom. Among amphibians, for example, administering a thyroid-blocking agent such as propylthiouracil (PTU) can prevent tadpoles from metamorphosing into frogs; conversely, administering thyroxine will trigger metamorphosis.
In humans, children born with thyroid hormone deficiency will have physical growth and development problems, and brain development can also be severely impaired, in the condition referred to as cretinism. Newborn children in many developed countries are now routinely tested for thyroid hormone deficiency as part of newborn screening by analysis of a drop of blood. Children with thyroid hormone deficiency are treated by supplementation with synthetic thyroxine, which enables them to grow and develop normally.
Because of the thyroid's selective uptake and concentration of what is a fairly rare element, it is sensitive to the effects of various radioactive isotopes of iodine produced by nuclear fission. In the event of large accidental releases of such material into the environment, the uptake of radioactive iodine isotopes by the thyroid can, in theory, be blocked by saturating the uptake mechanism with a large surplus of non-radioactive iodine, taken in the form of potassium iodide tablets. While biological researchers making compounds labelled with iodine isotopes do this, in the wider world such preventive measures are usually not stockpiled before an accident, nor are they distributed adequately afterward. One consequence of the Chernobyl disaster was an increase in thyroid cancers in children in the years following the accident.[10]
The use of iodised salt is an efficient way to add iodine to the diet. It has eliminated endemic cretinism in most developed countries, and some governments have made the iodination of flour mandatory. Potassium iodide and Sodium iodide are the most active forms of supplemental iodine.
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