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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 health.com
Mental health _ A Report of the surgeon general

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