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Schizophrenia - New Concept

Dr.K.R.MANSOOR ALI BHMS,MD(Hom) Govt.Homeopathic Medical College. Calicut Approved practitioner,Ministry Of Health,UAE Email : "Schizophrenia is a cruel disease. The lives of those affected are often chronicles of constricted experiences, muted emotions, missed opportunities, unfulfilled expectations. It leads to a ill light existence, a twentieth-century underground man...It is in fact the single biggest blemish on the face of contemporary medicine and social services; when the social history of our era is written, the plight of persons with schizophrenia will be recorded as having been a national scandal."

CONTENTS An overview of schizophrenia Etiology of schizophrenia Diagnostic criteria MRI scan of schizophrenia Inflammatory basis of schizophrenia Simple blood test for schizophrenia Chewing betel nut _ A therapeutic Associated features Differential diagnosis Classification in detail Paranoid schizophrenia Hebephrenic schizophrenia Catatonic schizophrenia Undifferianted schizophrenia Post schizophrenic depression Residual schizophrenia Simple schizophrenia Simple blood test to schizophrenia Betel chewing & schizophrenia Associated features of schizophrenia Differential diagnosis The future of schizophrenia Symptoms are typically divided into positive and negative symptoms ) because of their impact on diagnosis and treatment Positive symptoms are those that appear to reflect an excess or distortion of normal functions The diagnosis of schizophrenia, according to DSM-IV, requires at least 1-month duration of two or more positive symptoms, unless hallucinations or delusions are especially bizarre, in which case one alone suffices for diagnosis. Negative symptoms are those that appear to reflect a diminution or loss of normal functions These often persist in the lives of people with schizophrenia during periods of low (or absent) positive symptoms. Negative symptoms Schizophrenia interferes with a persons ability to think clearly, manage emotions, make decisions, and relate to others. Specific abnormalities that can be noted in individuals with

schizophrenia include: Delusions and hallucinations; Alterations of the senses; An inability to sort and interpret incoming sensations, and an inability therefore to respond appropriately; An altered sense of self; and Changes in emotions, movements and behavior. Schizophrenia is a neurological brain disorder that affects 2.2 million Americans today, or approximately one percent of the population. Schizophrenia can affect anyone at any age, but most cases develop between ages 16 and 30. In summary, schizophrenia does not follow a single pathway. Rather, like other mental and somatic disorders, course and recovery are determined by a constellation of biological, psychological, and sociocultural factors. That different degrees of recovery are attainable has offered hope to consumers and families. Gender and Age at onset There appear to be gender differences in the course and prognosis of schizophrenia. Women are more likely than men to experience later onset, more pronounced mood symptoms, and better prognosis (DSM-IV), although the prognosis difference recently has come under question. Symptoms of Schizophrenia: In healthy people, the brain functions in such a way that incoming stimuli are sorted and interpreted, followed by a logical response (e.g., saying "thank you" after a gift is given, realizing the potential outcome of arriving late to work, etc.). Conversely, the inability of patients with schizophrenia to sort and interpret stimuli and select appropriate responses is one of the hallmarks of the disease. The symptoms of schizophrenia are generally divided into three categories, including positive, disorganized, and negative symptoms. Overt Symptoms, or "psychotic" symptoms, include delusions, hallucinations and disorganized thinking because the patient has lost touch with reality in certain important ways. Delusions cause the patient to believe that people are reading their minds or plotting against them, that others are secretly monitoring and threatening them, or that they can control other peoples thoughts. Hallucinations cause people to hear or see things that are not there. Approximately three-fourths of individuals with schizophrenia will hear voices (auditory hallucinations) at some time during their illness. Disorganized thinking, speech, and behavior affect most people with this illness. For example, people with schizophrenia sometimes have trouble communicating in coherent sentences or carrying on conversations with others; move more slowly, repeat rhythmic gestures or make movements such as walking in circles or pacing; and have difficulty making sense of everyday sights, sounds and feelings. Negative Symptoms include emotional flatness or lack of expression, an inability to start and follow through with activities, speech that is brief and lacks content, and a lack of pleasure or interest in life. "Negative" does not, therefore, refer to a persons attitude, but

to a lack of certain characteristics that should be there. Etiology of Schizophrenia The cause of schizophrenia has not yet been determined, although research points to the interaction of genetic endowment and major environmental upheaval. During development of the brain. This section first discusses genetic studies and then turns to the evidence for neurodevelopmental disruption. These lines of research are beginning to converge: neurodevelopment disruption may be the result of genetic and/or environmental stressors early in development, leading to subtle alterations in the brain. Furthermore, environmental factors later in development can either exacerbate or ameliorate expression of genetic or neurodevelopmental defects. The overarching message is that the onset and course of schizophrenia are most likely the result of an interaction between genetic and environmental influences. Family, twin, and adoption studies support the role of genetic influences in schizophrenia . Immediate biological relatives of people with schizophrenia have about 10 times greater risk than that of the general population. Given prevalence estimates, this translates into a 5 to 10 percent lifetime risk for first-degree relatives (including children and siblings) and suggests a substantial genetic component to schizophrenia Current research proposes that schizophrenia is caused by a genetic vulnerability coupled with environmental and psychosocial stressors, the so-called diathesis-stress model Family studies suggest that people have varying levels of inherited genetic vulnerability, from very low to very high, to schizophrenia. Whether or not the person develops schizophrenia is partly determined by this vulnerability. At the same time, the development of schizophrenia also depends on the amount and types of stresses the person experiences over time. An analogy can be drawn to diabetes by virtue of both genetic factors (e.g., family history) and behavioral factors (e.g., diet, exercise, stress) that interact to determine whether or not a given person develops diabetes. Diagnosing Schizophrenia : To be diagnosed with schizophrenia, a patient must have psychotic "loss-of-reality" symptoms for at least six months and show increasing difficulty in functioning normally. Before the six-month period is reached, the person is diagnosed as having a schizophreniform disorder. Prior to a medical diagnosis, it is critically important that a doctor rule out other problems that may mimic schizophrenia, such as psychotic symptoms caused by the use of drugs or other medical illnesses; major depressive episode or manic episode with psychotic features; delusional disorder (no hallucinations, disorganized speech or thought or "flattened" emotions) and autistic disorder or personality disorders (especially schizotypal, schizoid, or paranoid personality disorders) Schizoaffective disorder is a diagnosis used to indicate that the person has an illness with a mix of symptoms of both schizophrenia and bipolar disorder. Although the cause of schizophrenia has not yet been identified, recent research suggests

that schizophrenia is linked to abnormalities of brain chemistry and brain structure. Genes play some role, but the magnitude of that role remains to be ascertained. Abnormalities of neurotransmitters (e.g., dopamine, serotonin) and viruses also are under investigation. The brain changes in some cases as suspected to date to childhood. Brain-imaging technology has demonstrated that schizophrenia is as much an organic brain disorder, as is Multiple Sclerosis, Parkinsons or Alzheimers disease. TREATING SCHIZOPHRENIA While there is no cure for schizophrenia, it is a highly treatable disorder.In fact, according to the National Advisory Mental Health Council, the treatment success rate for schizophrenia is comparable to the treatment success rate for heart disease. It is important to diagnose and treat schizophrenia as early as possible to help people avoid or reduce frequent relapses and re-hospitalizations. Several promising, large-scale studies suggest early intervention may forestall the worst long-term outcomes of this devastating brain disorder. People who experience acute symptoms of schizophrenia may require intensive treatment, sometimes including hospitalization. Hospitalization is necessary to treat severe delusions or hallucinations, serious suicidal inclinations, inability to care for oneself, or severe problems with drugs or alcohol. It is critical that people with schizophrenia stay in treatment even after recovering from an acute episode. About 80 percent of those who stop taking their medications after an acute episode will have a relapse within one year, whereas only 30 percent of those who continue their medications will experience a relapse in the same time period. Medication appears to improve the long-term prognosis for many people with schizophrenia. Studies show that after 10 years of treatment, one-fourth of those with schizophrenia have recovered completely, one-fourth have improved considerably, and one-fourth have improved modestly. Fifteen percent have not improved, and 10 percent are dead. Individuals with schizophrenia die at a younger age than do healthy people. Males have a 5.1 greater than expected early mortality rate than the general population, and females have a 5.6 greater risk of early death. Suicide is the single largest contributor to this excess mortality rate, which is 10 to 13 percent higher in schizophrenia than the general population. Suicide is in fact the number one cause of premature death among people with schizophrenia, with an estimated 10 percent to 13 percent killing themselves. The extreme depression and psychoses that can result due to lack of treatment are the usual culprits in these sad cases These suicides rates can be compared to the general population, which is somewhere around one percent. Other contributors to excess mortality include: Accidents: Although individuals with schizophrenia do not drive as much as other

people, studies have shown that they have double the rate of motor vehicle accidents per mile driven. A significant but unknown number of individuals with schizophrenia also are killed as pedestrians by motor vehicles. Diseases: There is some evidence that individuals with schizophrenia have more infections, heart disease, type II (adult onset) diabetes, and female breast cancer, all of which might increase their mortality rate. Individuals with schizophrenia who become sick are less able to explain their symptoms to medical personnel, and medical personnel are more likely to disregard their complaints and assume that they are simply part of the illness. There also is evidence that some persons with schizophrenia have an elevated pain threshold so they may not complain of symptoms until the disease has progressed too far to be treatable. Homelessness: Although it has not been well studied to date, it appears that homelessness increases the mortality rate of individuals with schizophrenia by making them even more susceptible to accidents and diseases. One of the most effective tools in treating schizophrenia is by Programs for Assertive Community Treatment (PACT), an intensive team effort in local communities to help people stay out of the hospital and live independently.

Serving as a hospital without walls, PACT professionals are available around the clock and meet their clients where they live, providing at-home support at whatever level is needed, for whatever problems need to be solved. Professionals can make sure that clients are taking their medication and help them meet the challenges of daily life every day tasks ranging from grocery shopping and keeping doctor appointments to managing money and getting along with others. While PACT programs are an excellent means for delivering outpatient services, research demonstrates that they improve medication compliance for some, but not all, patients. For example, a recent Baltimore study of 77 homeless individuals with severe mental illness (86 percent with schizophrenia or major affective disorder) were assigned to PACT teams and followed for one year. Medication compliance improved from 29 percent to between 50 percent and 57 percent during the remainder of the year. The study found that approximately one-third of the subjects were noncompliant at any given time during the research year. Antipsychotic Medications Antipsychotic drugs are used in the treatment of schizophrenia. These medications help relieve the delusions, hallucinations, and thinking problems associated with this devastating disorder. Scientists believe the drugs work by correcting imbalances in the chemicals that help brain cells communicate with one another. As with drug treatments for other physical illnesses, many patients with severe mental illnesses may need to try several different antipsychotic medications before they find the one, or the combination of medications, that works best for them. Since these medications do not work immediately, experts recommend that doctors give the antipsychotic time to take effect before switching to another antipsychotic, adjusting the dose, or adding another medication. Possible Side Effects of Antipsychotic Medication As a group, antipsychotic drugs are safe, and serious side effects are relatively rare. Some

people may experience side effects that are inconvenient or unpleasant, but not serious. Most common side effects: dry mouth, constipation, blurred vision, and drowsiness. Less common side effects: decreased sexual desire, menstrual changes, and stiff muscles on one side of the neck and jaw. More serious side effects: restlessness, muscle stiffness, slurred speech, tremors of the hands or feet. Agranulocytosis, a decrease in the production of white blood cells, which occurs only when taking clozapine, requires monitoring of the blood every two weeks. Tardive Dyskinesia is the most unpleasant and serious side effect of antipsychotic drugs causing involuntary facial movements and sometimes jerking or twisting movements of other parts of the body. This condition usually develops in older patients, affecting 15 to 20 percent of those who have taken older antipsychotic drugs for years. In most cases, the tardive dyskinesia slowly goes away when the medication is stopped.

Schizophrenia _ types The schizophrenic disorders are characterized in general by fundamental and characteristic distortions of thinking and perception, and by inappropriate or blunted affect. Clear consciousness and intellectual capacity are usually maintained, although certain cognitive deficits may evolve in the course of time. The disturbance involves the most basic functions that give the normal person a feeling of individuality, uniqueness, and self-direction. The most intimate thoughts, feelings, and acts are often felt to be known to or shared by others, and explanatory delusions may develop, to the effect that natural or supernatural forces are at work to influence the afflicted individual's thoughts and actions in ways that are often bizarre. The individual may see himself or herself as the pivot of all that happens. Hallucinations, especially auditory, are common and may comment on the individual's behavior or thoughts. Perception is frequently disturbed in other ways: colors or sounds may seem unduly vivid or altered in quality, and irrelevant features of ordinary things may appear more important than the whole object or situation. Perplexity is also common early on and frequently leads to a belief that everyday situations possess a special, usually sinister, meaning intended uniquely for the individual. In the characteristic schizophrenic disturbance of thinking, peripheral and irrelevant features of a total concept, which are inhibited in normal directed mental activity, are brought to the fore and utilized in place of those that are relevant and appropriate to the situation. Thus thinking becomes vague, elliptical, and obscure, and its expression in speech sometimes incomprehensible. Breaks and interpolations in the train of thought are frequent, and thoughts may seem to be withdrawn by some outside agency. Mood is characteristically shallow, capricious, or incongruous. Ambivalence and disturbance of volition may appear as inertia, negativism, or stupor. Catatonia may be present. The onset may be acute, with seriously disturbed behavior, or insidious, with a gradual development of odd ideas and conduct. The course of the disorder shows equally great variation and is by no means inevitably chronic or deteriorating (the course is specified by five-character categories). In a proportion of cases, which may vary in different cultures and populations, the outcome is complete, or nearly complete, recovery. The sexes are approximately equally affected by the onset tends to be later in women.

Although no strictly pathognomonic symptoms can be identified, for practical purposes it is useful to divide the above symptoms into groups that have special importance for the diagnosis and often occur together, such as: (a) Thought echo, thought insertion or withdrawal, and thought broadcasting; (b) Delusions of control, influence, or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations; delusional perception; (c) Hallucinatory voices giving a running commentary on the patient's behaviour, or discussing the patient among themselves, or other types of hallucinatory voices coming from some part of the body; persistent delusions of other kinds that are culturally inappropriate and completely impossible, such as religious or political identity, or superhuman powers and abilities (e.g. being able to control the weather, or being in communication with aliens from another world); (e) Persistent hallucinations in any modality, when accompanied either by fleeting or halfformed delusions without clear affective content, or by persistent over-valued ideas, or when occurring every day for weeks or months on end; (f)Breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech, or neologisms; (g) Catatonic behaviour, such as excitement, posturing, or waxy flexibility, negativism, mutism, and stupor; (h) "negative" symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses, usually resulting in social withdrawal and lowering of social performance; it must be clear that these are not due to depression or to neuroleptic medication; (i) a significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal. Diagnostic Guidelines The normal requirement for a diagnosis of schizophrenia is that a minimum of one very clear symptom (and usually two or more if less clear-cut) belonging to any one of the groups listed as (a) to (d) above, or symptoms from at least two of the groups referred to as (e) to (h), should have been clearly present for most of the time during a period of 1 month or more. Conditions meeting such symptomatic requirements but of duration less than 1 month (whether treated or not) should be diagnosed in the first instance as acute schizophrenialike psychotic disorder and are classified as schizophrenia if the symptoms persist for longer periods. Viewed retrospectively, it may be clear that a prodromal phase in which symptoms and behaviour, such as loss of interest in work, social activities, and personal appearance and hygiene, together with generalized anxiety and mild degrees of depression and preoccupation, preceded the onset of psychotic symptoms by weeks or even months. Because of the difficulty in timing onset, the 1-month duration criterion applies only to the specific symptoms listed above and not to any prodromal nonpsychotic phase. The diagnosis of schizophrenia should not be made in the presence of extensive depressive or manic

symptoms unless it is clear that schizophrenic symptoms antedated the affective disturbance. If both schizophrenic and affective symptoms develop together and are evenly balanced, the diagnosis of schizoaffective disorder should be made, even if the schizophrenic symptoms by themselves would have justified the diagnosis of schizophrenia. Schizophrenia should not be diagnosed in the presence of overt brain disease or during states of drug intoxication or withdrawal. Paranoid Schizophrenia This is the commonest type of schizophrenia in most parts of the world. The clinical picture is dominated by relatively stable, often paranoid, delusions, usually accompanied by hallucinations, particularly of the auditory variety, and perceptual disturbances. Disturbances of affect, volition, and speech, and catatonic symptoms, are not prominent. Examples of the most common paranoid symptoms are : (a) delusions of persecution, reference, exalted birth, special mission, bodily change, or jealousy; (b) hallucinatory voices that threaten the patient or give commands, or auditory hallucinations without verbal form, such as whistling, humming,orlaughing; (c) hallucinations of smell or taste, or of sexual or other bodily sensations; visual hallucinations may occur but are rarely predominant. Thought disorder may be obvious in acute states, but if so it does not prevent the typical delusions or hallucinations from being described clearly. Affect is usually less blunted than in other varieties of schizophrenia, but a minor degree of incongruity is common, as are mood disturbances such as irritability, sudden anger, fearfulness, and suspicion. "Negative" symptoms such as blunting of affect and impaired volition are often present but do not dominate the clinical picture. The course of paranoid schizophrenia may be episodic, with partial or complete remissions, or chronic. In chronic cases, the florid symptoms persist over years and it is difficult to distinguish discrete episodes. The onset tends to be later than in the hebephrenic and catatonic forms. Diagnostic Guidelines The general criteria for a diagnosis of schizophrenia must be satisfied. In addition, hallucinations and/or delusions must be prominent, and disturbances of affect, volition and speech, and catatonic symptoms must be relatively inconspicuous. The hallucinations will usually be of the kind described in (b) and (c) above. Delusions can be of almost any kind of delusions of control, influence, or passivity, and persecutory beliefs of various kinds are the most characteristic. inludes: * paraphrenic schizophrenia Differential diagnosis. It is important to exclude epileptic and drug-induced psychoses, and to remember that persecutory delusions might carry little diagnostic weight in people from certain countries or cultures. Hebephrenic Schizophrenia A form of schizophrenia in which affective changes are prominent, delusions and hallucinations fleeting and fragmentary, behavior irresponsible and unpredictable, and

mannerisms common. The mood is shallow and inappropriate and often accompanied by giggling or self-satisfied, self-absorbed smiling, or by a lofty manner, grimaces, mannerisms, pranks, hypochondria cal complaints, and reiterated phrases. Thought is disorganized and speech rambling and incoherent. There is a tendency to remain solitary, and behavior seems empty of purpose and feeling. This form of schizophrenia usually starts between the ages of 15 and 25 years and tends to have a poor prognosis because of the rapid development of "negative" symptoms, particularly flattening of affect and loss of volition. In addition, disturbances of affect and volition, and thought disorder are usually prominent. Hallucinations and delusions may be present but are not usually prominent. Drive and determination are lost and goals abandoned, so that the patient's behavior becomes characteristically aimless and empty of purpose. A superficial and mannerist preoccupation with religion, philosophy, and other abstract themes may add to the listener's difficulty in following the train of thought. Diagnostic Guidelines The general criteria for a diagnosis of schizophrenia must be satisfied. Hebephrenic should normally be diagnosed for the first time only in adolescents or young adults. The premorbid personality is characteristically, but not necessarily, rather shy and solitary. For a confident diagnosis of hebephrenic, a period of 2 or 3 months of continuous observation is usually necessary, in order to ensure that the characteristic behaviors described above are sustained. Catatonic Schizophrenia Prominent psychomotor disturbances are essential and dominant features and may alternate between extremes such as hyperkinesis and stupor, or automatic obedience and negativism. Constrained attitudes and postures may be maintained for long periods. Episodes of violent excitement may be a striking feature of the condition. For reasons that are poorly understood, catatonic schizophrenia is now rarely seen in industrial countries, though it remains common elsewhere. These catatonic phenomena may be combined with a dream-like (aneroid) state with vivid scenic hallucinations. Diagnostic Guidelines The general criteria for a diagnosis of schizophrenia must be satisfied. Transitory and isolated catatonic symptoms may occur in the context of any other subtype of schizophrenia, but for a diagnosis of catatonic schizophrenia one or more of the following behaviors should dominate the clinical picture: a) Stupor (marked decrease in reactivity to the environment and in spontaneous movements and activity) or mutism; (b) Excitement (apparently purposeless motor activity, not influenced by external stimuli); (c) posturing (voluntary assumption and maintenance of inappropriate or bizarre postures) (d) Negativism (an apparently motiveless resistance to all instructions or attempts to be moved, or movement in the opposite Direction (e) Rigidity (maintenance of a rigid posture against efforts to be moved) (f) Waxy flexibility (maintenance of limbs and body in externally imposed positions); (f) Other symptoms such as command automatism (automatic compliance with instructions), and preservation of words and phrases. In uncommunicative patients with behavioral manifestations of catatonic disorder, the diagnosis of schizophrenia may have to be provisional until adequate evidence of the presence of other symptoms is obtained. It is also vital to appreciate that catatonic symptoms are not diagnostic of schizophrenia. A catatonic symptom or symptoms may also

be provoked by brain disease, metabolic disturbances, or alcohol and drugs, and may also occur in mood disorders. Undifferentiated Schizophrenia Conditions meeting the general diagnostic criteria for schizophrenia But not conforming to any of the above subtypes, or exhibiting the features of more than one of them without a clear predominance of a particular set of diagnostic characteristics. This rubric should be used only for psychotic conditions (i.e. residual schizophrenia and post-schizophrenic depression are excluded) and after an attempt has been made to classify the condition into one of the three preceding categories. Diagnostic Guidelines This category should be reserved for disorders that: (a) Meet the diagnostic criteria for schizophrenia (b) do not satisfy the criteria for the paranoid, hebephrenic, or catatonicsubtypes; (c) do not satisfy the criteria for residual schizophrenia or post- schizophrenic depression. Post-Schizophrenic Depression A depressive episode, which may be prolonged, arising in the aftermath of a schizophrenic illness. Some schizophrenic symptoms must still be present but no longer dominate the clinical picture. These persisting schizophrenic symptoms may be "positive" or "negative", though the latter are more common. It is uncertain, and immaterial to the diagnosis, to what extent the depressive symptoms have merely been uncovered by the resolution of earlier psychotic symptoms (rather than being a new development) or are an intrinsic part of schizophrenia rather than a psychological reaction to it. They are rarely sufficiently severe or extensive to meet criteria for a severe depressive episode, and it is often difficult to decide which of the patient's symptoms are due to depression and which to narcoleptic medication or to the impaired volition and affective flattening of schizophrenia itself. This depressive disorder is associated with an increased risk of suicide. Diagnostic Guidelines The diagnosis should be made only if: (a) the patient has had a schizophrenic illness meeting the general criteria for schizophrenia (b) within the past 12 monthssome schizophrenic symptoms are still present; (c) the depressive symptoms are prominent and distressing, fulfilling at least the criteria for a depressive episode, and have been present for at least 2 weeks. If the patient no longer has any schizophrenic symptoms, a depressive episode should be diagnosed. If schizophrenic symptoms are still florid and prominent, the diagnosis should remain that of the appropriate schizophrenic subtype. Residual Schizophrenia A chronic stage in the development of a schizophrenic disorder in which there has been a clear progression from an early stage (comprising one or more episodes with psychotic symptoms meeting the general criteria for schizophrenia described above) to a later stage characterized by long-term, though not necessarily irreversible, "negative" symptoms. Diagnostic Guidelines For a confident diagnosis, the following requirements should be met: (a) prominent "negative" schizophrenic symptoms, i.e. psychomotor slowing, under activity, blunting of affect, passivity and lack of initiative, poverty of quantity or content of speech,

poor nonverbal communication by facial expression, eye contact, voice modulation, and posture, poor self-care and social performance; (b) evidence in the past of at least one clear-cut psychotic episode meeting the diagnostic criteria for schizophrenia; (c) a period of at least 1 year during which the intensity and frequency of florid symptoms such as delusions and hallucinations have been minimal or substantially reduced and the "negative" schizophrenic syndrome has been present; (d) absence of dementia or other organic brain disease or disorder, and of chronic depression or institutionalism sufficient to explain the negative impairments. If adequate information about the patient's previous history cannot be obtained, and it therefore cannot be established that criteria for schizophrenia have been met at some time in the past, it may be necessary to make a provisional diagnosis of residual schizophrenia Simple Schizophrenia An uncommon disorder in which there is an insidious but progressive development of oddities of conduct, inability to meet the demands of society, and decline in total performance. Delusions and hallucinations are not evident, and the disorder is less obviously psychotic than the hebephrenic, paranoid, and catatonic subtypes of schizophrenia. The characteristic "negative" features of residual schizophrenia (e.g. blunting of affect, loss of volition) develop without being preceded by any overt psychotic symptoms Diagnostic Guidelines Simple schizophrenia is a difficult diagnosis to make with any confidence because it depends on establishing the slowly progressive development of the characteristic "negative" symptoms of residual schizophrenia without any history of hallucinations, delusions, or other manifestations of an earlier psychotic episode, and with significant changes in personal behavior, manifest as a marked loss of interest, idleness, and social withdrawal. Diagnostic Criteria of Schizophrenia Subtypes Paranoid Type A type of Schizophrenia in which the following criteria are met: A. Preoccupation with one or more delusions or frequent auditory hallucinations. B. None of the following is prominent: disorganized speech, disorganized or catatonic behavior, or flat or inappropriate affect. Catatonic Type A type of Schizophrenia in which the clinical picture is dominated by at least two of the following: 1. Motorist immobility as evidenced by catalepsy (including waxy flexibility) or stupor 2. Excessive motor activity (that is apparently purposeless and not influenced by external stimuli) 3. Extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism 4. Peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing 5. Echolalia or echopraxia

Disorganized Type A type of Schizophrenia in which the following criteria are met: A. All of the following are prominent: 1. disorganized speech 2. disorganized behavior 3. flat or inappropriate affect B. The criteria are not met for Catatonic Type. Undifferentiated Type A type of Schizophrenia in which symptoms that meet Criterion A are present, but the criteria are not met for the Paranoid, Disorganized, or Catatonic Type. Residual Type A type of Schizophrenia in which the following criteria are met: A. Absence of prominent delusions, hallucinations, disorganized speech, and grossly disorganized or catatonic behavior. B. There is continuing evidence of the disturbance, as indicated by the presence of negative symptoms or two or more symptoms listed in Criterion A for Schizophrenia, present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences). Associated Features Learning Problem Hypo activity Psychotic Euphoric Mood Depressed Mood Somatic/Sexual Dysfunction Hyperactivity Guilt/Obsession Sexually Deviant Behavior Odd/Eccentric/Suspicious Personality Anxious/Fearful/Dependent Personality Dramatic/Erratic/Antisocial Personality Differential Diagnosis Psychotic Disorder Due to a General Medical Condition, delirium, or dementia; Substance-Induced Psychotic Disorder; Substance-Induced Delirium; Substance-Induced Persisting Dementia; Substance-Related Disorders; Mood Disorder With Psychotic Features; Schizoaffective Disorder; Depressive Disorder Not Otherwise Specified Bipolar Disorder Not Otherwise Specified; Mood Disorder With Catatonic Features; Schizophreniform Disorder; Brief Psychotic Disorder Delusional Disorder; Psychotic Disorder Not Otherwise Specified; Pervasive Developmental Disorders (e.g., Autistic Disorder); childhood presentations combining disorganized speech (from a Communication Disorder) and disorganized behavior (from Attention-Deficit/ Hyperactivity Disorder); Schizotypal Disorder; Schizoid Disorder; Paranoid Personality Disorder.

Inflammatory basis for schizophrenia? The quest to understand the basis of psychiatric disorders such as schizophrenia may be a step closer to completion. A recent Japanese study has shown that blood levels of interleukin-18 (IL-18) are increased in people with schizophrenia. The findings suggest a role for inflammatory and immunological mechanisms in the development of schizophrenia. Serum IL-18 was measured in 66 people with schizophrenia and the results compared to 66 healthy control people who were matched for age and sex. The results indicated that IL-18 is significantly higher in people with schizophrenia. A variety of neurochemical, biochemical and immunological changes distinguish healthy individuals from people with schizophrenia. Following evidence of an inflammatory mechanism involving the immune system in the pathology of schizophrenia, interest in of a group of chemical called cytokines has expanded. Cytokines are naturally produced in the body as part of the normally functioning immune system. Under normal circumstances they are produced in response to injury and infection. IL-18 is a recently identified chemical that is involved in bodily defences against harmful microbes. Cells called macrophages, which are responsible for attacking alien invaders such as bacteria, produce IL-18. There is speculation whether macrophages could be activated to produce IL-18 inappropriately, and if so, whether this could be an underlying mechanism in the pathology of schizophrenia. For scientists seeking to understand the underlying basis of schizophrenia, the finding that IL-18 is higher in people with schizophrenia is encouraging. However, it is important to be aware of the limitations of the study. The people with schizophrenia who participated had all been receiving antipsychotic drug therapy. It is therefore possible that the observed results arose from the medication rather than the illness. But certain antipsychotics are known to suppress cytokine production; this study reported an opposite trend. Further studies are needed, but the evidence is mounting for an immunological basis to schizophrenia.

Simple blood test for schizophrenia ? Step closer to reality, according to scientists at The Weizmann Institute of Science in Rehovot, Israel. Tal Ilani and colleagues reported that dopamine receptors expressed by white blood cells, which make up the body's immune system, are measurably different in people with schizophrenia, and that this effect is independent of medications used to treat the illness. At the moment, diagnosing schizophrenia is a difficult, unreliable and lengthy procedure. The illness cannot be diagnosed until psychotic symptoms have been present for at least six months, and there are no diagnostic laboratory tests like there are for cancer, for example. In the future, a blood test that can give a simple yes or no answer could offer enormous benefits in terms of preventative treatment and improved long term outcomes for people

with schizophrenia. The research follows the discovery that various receptors for dopamine, as well as playing a more established role in the brain, are also expressed by white blood cells. Dopamine neurotransmitter systems in the brain are implicated in schizophrenia, so it was a logical progression for scientists to query the role of dopamine receptors on white cells. But measuring dopamine receptors themselves is difficult, so instead the team tested for mRNA, the genetic message that says 'make dopamine receptors'. Previous work in this area has been hampered by the fact that antipsychotic medications, the mainstay of treatments for schizophrenia, are known to influence parts of the immune system. Due to this, experimental results from people with schizophrenia could not be guaranteed to reflect real as opposed to drug-induced changes in white cell properties. In this crucial respect the present study differs; the researchers have identified an association that holds true independent of whether people with schizophrenia have received medication. The study suggests that there is a minimum 2-fold increase in mRNA coding for D3 dopamine receptors in the white cells of people with schizophrenia when compared to healthy volunteers. By contrast, D4 and D5 receptors, which are also expressed by white cells, do not alter significantly in their mRNA levels between people with schizophrenia and control subjects. If the results can be corroborated in other research centers, and providing that evidence does not emerge to suggest similar changes could occur to white cells in other disease states (particularly other psychiatric illnesses), this finding could represent a breakthrough in the detection and diagnosis of schizophrenia. Chewing betel nuts MIGHT BE A THERAPEUTIC IN SCHIZOPHRENIA The recently published study by Sullivan into the benefits of chewing betel nuts in people with schizophrenia raises some intriguing questions about how, if at all, betel nut chewing might produce a therapeutic effect. Muscarinic receptors - a betel nut target Chewing betel nut releases chemicals such as arecoline, an alkaloid capable of affecting a number of brain neurotransmitter systems, in particular a group of receptors for acetylcholine - the muscarinic receptors. Muscarinic receptors (and their distant cousins nicotinic receptors) function normally to process the signals that result from the release of acetylcholine during neurotransmission. Neurotransmission involving acetylcholine occurs in both the central and peripheral nervous systems, and plays a key role in many different bodily functions. Five different types of muscarinic receptor (m1-m5) have been identified each subgroup having its own unique distribution in the nervous system. The effects of acetylcholine acting at these various receptor subtypes are diverse and occasionally paradoxical; there remains much to be discovered about their precise functions in both healthy and diseased states. Partial agonism may be the key When neurotransmitters such as acetylcholine act at receptors, they are considered to be agonists. This means that a physiological response that is dose-dependent is observed.

Beyond a certain dose level, responses cease to be dose-dependent and 'level off'. This is said to be the maximal response. Agonists are said to have efficacy because by occupying receptors they produce cellular responses. Most of the chemicals in the body involved in signalling work as agonists. By contrast, there are many drugs that are antagonists. Such chemicals occupy receptors but do not produce cellular responses. By occupying receptors, they may prevent neurotransmitters and other agonists from working as normal. So although antagonists are said to have zero efficacy, they may elicit indirect pharmacological responses by blocking receptors. A third class of drugs are neither full agonists nor antagonists. Partial agonists behave similarly to agonists in that they occupy receptors and in so doing effect cellular responses in a dose-dependent fashion. But however big the dose, partial agonists never achieve maximal cellular responses. Arecoline is a partial agonist at muscarinic receptors. Muscarinic receptors in the brain In the central nervous system, acetylcholine-containing nerve cells acting at muscarinic receptors are thought to play a key role in the processing of cognitive functions, for example in processing memory and problem solving. Centrally acting muscarinic drugs are associated with a variety of effects ranging from hallucinations to memory loss. But the brain is a highly complex organ; interactions between various neurotransmitter systems preclude the simplistic interpretation of drugs exerting their effects simply through activating or blocking individual receptors More probably, interactions between various transmitter systems determine the net results of neurotransmission events. This is illustrated by studies into the distribution of brain muscarinic receptors Methods have been developed which manipulate the fact that different subtypes of muscarinic receptor are coded for by different genes. The expression of a given gene in a cell can be detected by chemical probes, which attach selectively to the mRNA of the gene in question. By making the probe radioactive, it is possible to record photographically the places where it has attached to the mRNA, for example in slices of brain from laboratory animals. It is also possible to engineer strains of mice which have had specific genes 'knocked out' (eg. the gene for one receptor subtype). Studying the effects that an absent gene causes has greatly enhanced understanding of the function of individual receptor subtypes, although there remains much to do. Using such techniques, it has been shown that various muscarinic acetylcholine receptor subtypes and receptors for dopamine are intimately interconnected, and that drugs affecting one system are likely to influence the other. Thus antipsychotic drugs which act primarily on dopamine systems also influence muscarinic systems and vice-versa. Muscarinic receptors and schizophrenia It has been established that cognitive functions are impaired in people with schizophrenia, and it is probable that given their role in normal cognitive functioning, defects in muscarinic receptors and/or acetylcholine-containing nerves may play a role in the development of schizophrenia. Several laboratory studies also point to a potential role for muscarinic acetylcholine receptors in schizophrenia. They reported behaviour patterns consistent with animal models of schizophrenia, namely

increased locomotor activity and stereotypical behaviour such as sniffing, grooming and self-biting. The muscarinic agonist carbachol and the antipsychotic drug haloperidol relieved the effects of scopolamine. Bymaster conducted animal studies on a new agent (PTAC) with partial agonist activity at muscarinic m2 and m4 receptors. At clinically relevant doses, PTAC demonstrated antipsychotic activity in animal models of schizophrenia without producing the adverse effects associated with less selective muscarinic agents - salivation, catalepsy and tremor. Muscarinic receptors and the acetylcholine system are also involved in the processing of movements that originate with the dopamine-containing nerves of the basal ganglia. For this reason, they may play a role in the extrapyramidal side effects (EPS) associated with many medications used to treat schizophrenia. This has been the rationale for the use of antimuscarinic drugs (such as scopolamine, atropine) for people with schizophrenia who develop movement disorders as result of long-term antipsychotic drug therapy. The future ? The delineation of the various functions of the muscarinic receptor subtypes will lead to a more complete understanding of their roles in health and disease. In parallel, more selective agonists and antagonists will become available and the treatments for disorders such as schizophrenia will be more effective with fewer side effects. But in the meantime, studying natural compounds that display therapeutic effects will yield valuable clues in the search for the origins of diseases like schizophrenia. REFERENCES Kaplan .A concise text book of psychiatry Internet mental health WHO E.F.Xller torreye MD www.mentasl Mental health _ A Report of the surgeon general