Schizophrenia 197Causation
Twin studies suggest that the heritability of schizophrenia is around
80%, that is, genes account for about 80% of the variation between
individuals in their liability to schizophrenia (see Chapter 33 for more
on behavioural genetics and its limitations). Genetic factors may be even
more important in early-onset than adult-onset schizophrenia. Studies
using neuroimaging and neuropathology have demonstrated brain ab-
normalities in schizophrenia such as selective loss of grey matter due to
loss of dendritic spines and synapses. Some brain abnormalities seem to
precede the onset of psychosis, while others abnormalities may develop
subsequently. While there is no doubt that biology plays an important role
in the aetiology of schizophrenia, psychosocial stressors such as migration
can also increase risk. In some instances, genes and environment seem to
interact, for example, adolescent cannabis use may increase the risk of de-
veloping schizophrenia subsequently – but only in genetically vulnerable
individuals.
In the light of growing evidence that schizophrenia is, at least in part,
a neurodevelopmental disorder, why is prepubertal schizophrenia so un-
common? One possible explanation is that although brain abnormalities
arise early in development, these are mostly silent until unmasked by
normaldevelopmental processes such as myelination or the progressive
‘weeding out’ of excessive synapses – processes that continue into puberty
and even beyond. Alternatively, the key neurodevelopmental abnormality
in schizophrenia may beexcessivesynaptic elimination occurring during
adolescence, perhaps most marked in the prefrontal and temporal regions,
resulting in abnormal neuronal connectivity and psychotic symptoms.
Clinical course and treatment
When schizophrenia begins early in life, the onset is often insidious rather
than acute. Psychotic episodes commonly involve between one and six
months of hallucinations, delusions and thought disorder.
Neuoleptic medications (usually referred to as ‘antipsychotics’ in this
context) often reduce the intensity of positive symptoms but do not
necessarily shorten the episode. Many adolescent psychiatrists choose
newer ‘atypical’ antipsychotics such as olanzapine or risperidone as first-
line treatment in preference to traditional ‘typical’ antipsychotics such
as haloperidol or chlorpromazine. Head-to-head comparisons of typicals
and atypicals suggest that they are roughly equally effective as far as
reducing psychotic features are concerned, differing mainly in their ad-
verse effects: typicals are more linked to extrapyramidal side effects (for
example, Parkinsonian symptoms) and atypicals to rapid weight gain
and its metabolic complications. Clozapine is a special atypical that may
be successful when other typical and atypical antipsychotics have failed
Patients on clozapine need regular blood monitoring to reduce the risk