Schizophrenia etiology clinical features and treatment BY Dr Izharul Hasan

Just under 1 % of the population develop schizophrenia at some point in their lives, a statistic that appears to hold true for all cultures and countries. Chronic major mental illness in people under 65 is due mainly to schizophrenia. Until the move towards community care began, about half of all hospital beds in the UK were in mental hospitals and the majority of these (for the under-65s) were occupied by patients with a schizophrenic illness. As the number of hospital beds has fallen, a significant proportion of the vagrants living in large inner-city hostels and prison recidivists are found to be suffering from schizophrenia.
Etiology
Schizophrenia is the core disorder in adult psychiatry. Much debate has raged about the nature of schizophrenia,
or even whether it is a valid clinical entity. It is probable that schizophrenia is not a single disease but a group of related conditions. Both genetic and environmental factors are important in the aetiology of schizophrenia. It is best seen as a developmental disorder of the brain to which genetic and perinatal factors (birth trauma or maternal viral infection) contribute, but manifesting itself in late adolescence when brain maturation is finally completed. Pathogenic environments contribute to relapse in schizophrenia, but their role in aetiology is uncertain. It is possible that abnormal brain development may result from unstimulating or traumatic environments.
• Twin and adoption studies have demonstrated the role of heredity in schizophrenia. The concordance rate for identical twins is about 50%, that for nonidentical twins around 15%.
• The efficacy of antipsychotic drugs such as chlorpromazine, with its inevitable parkinsonian side-effects, suggests a disturbance of midbrain dopaminergic pathways in schizophrenia (the 'dopamine' hypothesis). There is convincing evidence of increased D2 activity in patients with positive symptoms of schizophrenia. Dopamine abnormality may be the end result of other metabolic aberrations. It seems likely that serotonin (5HT) is also involved, perhaps by increasing D2 levels. Also glutamate, an excitatory neurotransmitter, may behave abnormally, leading to underactivity of Nmethyl- D-aspartate, which in turn may stimulate abnormal dopamine and 5HT activity.
• A subgroup of patients show ventricular abnormalities on CT scan. There is slight ventricular enlargement, a reduction in the normal asymmetry between the cerebral hemispheres and, particularly in males, a reduction in cortical grey matter, especially in the temporal lobes. It has been suggested that structural abnormalities are more common in patients who lack a family history of the illness, suggesting that non-genetic organic factors, perhaps associated with perinatal brain injury, may be important in some cases. Family and social factors have also been shown to be important, although not pathognomonic. In established schizophrenia the relapse rate is high when the patient is living in an over-involved family where there is a negatively charged emotional atmosphere (high 'expressed emotion', or 'EE')
• Schizophrenic patients have a high state of psychophysiological arousal, possibly related to family stress. This may reflect limbic system dysfunction and lead to a difficulty in processing sensory stimuli.

Clinical features
Schizophrenia usually starts in young adulthood (the exception being paraphrenia, a form of paranoid schizophrenia affecting the elderly). There is a slight preponderance of men. The features of the illness can be divided into two parts: the effects on mental processes, and the effects on social functioning.

Mental disturbance
There is a general disturbance of mental functioning in schizophrenia. The normal progression of logical thought is disrupted ('thought disorder'). The privacy of the self is breached. Certain patterns of disorganization of thinking are characteristic of schizophrenia, and are known as Schneider's first-rank symptoms.

Hallucinations
These are usually auditory. Characteristic of schizophrenia are 'third-person' hallucinations, in which more than one person is heard discussing the patient and referring to him as 'he', 'she' or 'it'. Voices commenting on a person's actions like a 'running commentary' are also characteristic, as are voices that echo the patient's thoughts. Tactile or 'kinaesthetic' hallucinations, for example electric-shock feelings in the limbs, are rare but pathognomonic.

Delusions
In schizophrenia these include the feeling that one's thoughts originate from outside ('thought insertion'), that they are being interfered with, removed ('thought block' and 'thought withdrawal') or transmitted to outsiders as though on a loudspeaker ('thought broadcasting'). 'Passivity feelings' are the feeling that one's thoughts or actions are 'made' from outside.

Delusional perception
In delusional perception, a neutral stimulus (e.g. a car number plate or a traffic light) suddenly acquires special and often frightening significance for the patient.

Social deterioration
The second main feature of schizophrenia is social deterioration. This is known as a negative feature of the illness, as opposed to the positive features of thought disorder, delusions and hallucinations. The patient may withdraw from social contact, give up his job, shun his friends and family, and spend many hours in isolation.

Differential diagnosis
An important subtype of schizophrenia is paranoid schizophrenia, characterized by paranoid delusions. Here theonset is later (around 30-40 years of age), social deterioration is much less marked, and the personality is relativelywell preserved. Schizoaffective disorder has features of both schizophrenia and an affective illness, e.g. first-ranksymptoms plus considerable depression. Its diagnosis is intermediate between that of the two 'parent' disorders.Not all madness is schizophrenia. The differential diagnosis includes:
• Organic psychosis, such as acute confusional states and drug- and alcohol-related psychosis;
• Manic or depressive psychosis (in which auditory hallucinations occur but are more often 'second-person', in which voices speak directly to the patient);
• Hysteria;
• Stress-induced or 'psychogenic' psychosis;
• Severe personality disorder.

Prognosis
The course of schizophrenia is very variable. About 30% of patients have only one episode. A good prognosis is more likely if the psychosis has an acute onset, a clear precipitant, florid symptoms, marked mood change in addition to disturbance of thinking, and good previous social adjustment and personality. At the other end of the scale, about 15% remain severely disabled and will still be in institutional care after a year. In these patients the negative features of schizophrenia (withdrawal and inertia) may predominate. In the middle group, representing the majority of patients, the illness has a fluctuating course but relapse and some residual disability are likely to occur.

Management of schizophrenia
• First attack: admit to hospital or day hospital for assessment, confirm diagnosis, establish contact and initiate treatment.
• Treat symptoms with neuroleptics. Chlorpromazine 100mgt.d.s. by mouth
Trifluoperazine 5mg t.d.s. by mouth
Risperidone 2-4 mg b.d. by mouth Examples of
Olanzapine 5-10 mg b.d. by mouth moderate doses
Flupentixol ('Depixol') 40 mg 2-weekly
Fluphenazine ('Modecate') 25 mg 2-weekly
Treat side-effects as necessary with antiparkinsonian agents,
e.g. Kemadrin 5 mg t.d.s.
• Assign 'community key worker' as part of community care programme who will offer supportive psychotherapy and coordinate care package.
• Assess family situation: offer psychoeducational programme to lower 'EE' if indicated.
• Rehabilitation: attend day hospital, day centre, sheltered workshop, live-in hostel, sheltered housing.
• Where resistant to medication consider newer neuroleptics: clozapine and risperidone.

Psychosocial treatment of schizophrenia
Exciting results have recently been claimed for cognitive- behavioural treatment in schizophrenia. Contraryto earlier views, it seems that patients can develop some control and mastery over their symptoms, especiallyabnormal beliefs and auditory hallucinations. Patients can, for example, distract themselves from voices byconcentrating on external tasks, by playing music on Walkman' headphones, or even by 'bargaining' with thevoices so that they confine 'their' attentions to particular times of the day. With the help of a therapist, or evena self-help 'voices' group, patients can also be encouraged to test the validity of delusions, e.g. 'if I go into thatshop I will be killed', and on the basis of the 'results' of these 'tests', modify their beliefs. Early studies of  these approaches are encouraging in producing, for some patients at least, reduced symptoms, improved social functioning and compliance, and reduced drug dosages.


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