Schizophrenics

In January 1903 Einstein married Mileva Marie, (of Grcck-Catholic Serbian descent), a fellow student at the ETI I. In 1902 the couple had a daughter out of wedlock, Lieserl, whose fate remains unknown, and after marriage they had two sons, Hans Albert (1904), who became a distinguished professor of hydraulic engineering in Berkeley, California, and Eduard (1910), a gifted child who became a student of medicine in Zurich but who then turned severely schizophrenic and died in a psychiatric hospital. 

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The first three characteristics are considered to be the positive symptoms of the disorder. The fourth are described as negative symptoms although they can be divided into true negative symptoms, i.e. diminished emotions and speech and reactive ones, i.e. social apathy and withdrawal brought on by the positive symptoms. Schizophrenics do not have a split personality. Normally their reaction to the positive symptoms is to withdraw quietly but occasionally they will react violently to the voices they hear and shout at them. 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

Hallucinations Increased Decrease hallucinations in schizophrenics Reduced ... 

There is no evidence of a general overactivity in DA function in schizophrenic patients. Plasma prolactin is not reduced, so the DA inhibitory control of its release is normal there is no recorded increase in DA turnover as CSF and plasma levels of its major metabolite HVA are normal and dyskinesias, which would reflect increased DA activity, are rare. PM studies have shown no consistent increases in DA brain levels, although some reports show an increase in the left amygdala, or in the activity of enzymes involved in its synthesis (tyrosine hydroxylase) or metabolism (MAO). For a review of the neurochemistry see Reynolds (1995). 

Sometimes (2) and (3) are grouped together and called the mesocorticolimbic pathway. It is not clear which pathway is responsible for which schizophrenic symptom. 

The prefrontal cortex (PFQ and in particular the dorsal lateral part (DLPFQ appear to be particularly important in schizophrenia (Kerwin 1992). Lesions there are known to produce functional defects in humans reminiscent of many of the negative symptoms of schizophrenia, such as attention and cognitive defects and withdrawal. Despite this, no specific pathology is seen in the DLPFC in schizophrenics although there is some atrophy and neuronal loss which are normally old and could be congenital. That being so, it is necessary to explain why the symptoms become apparent only in adolescence. 

Although there is no evidence that the DA afferents to DLPFC are damaged in schizophrenics, if the cortical pathology does reduce the ability of DA to function there, this would be equivalent to deafferentation and, as in the experimental studies, lead to increased subcortical mesolimbic activity and positive symptoms (Fig. 17.3). Unfortunately there is no good evidence that the nucleus accumbens is more active in schizophrenics or is even the origin of positive symptoms (but see Animal models ). Nevertheless it is a useful working hypothesis. 

While there are some reports of increased NMDA and non-NMDA receptor number in various cortical regions of schizophrenics including the prefrontal cortex, there are also indications of impaired glutamate innervation, such as reduction in its neuronal uptake sites (Ishimaru, Kurumaji and Torn 1994). Also it has been found that levels of the mRNA for the NRI subunit of the NMDA receptor in the hippocampus and its D-aspartate binding sites in the temporal cortex are both reduced more on the left than right side in schizophrenic brain. This is another indication of greater malfunction on the left side of the brain and the possibility that some schizophrenic symptoms arise from an imbalance between cross-cortical activity. 

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