Risk factors, and the neurodevelopmental course of schizophrenia.

From birth to two years, preschizophrenic children show much higher rates of neuromotor abnormalities and negative affective displays than their healthy siblings. Retrospectively, parents reportthat preschizophrenic children show more social and interpersonal problems and more abnormalities of thought. Similar results have been found with adolescents who have schizotypal personality disorder. Adolescence appears to be a critical period for the emergence of psychopathology in general, but especially for psychotic disorders. This may in large part be through the actions of gonadal and adrenal hormones, including cortisol, and in particular their influence on the expression of genes. In the case of schizophrenia, these are presumably the vulnerability genes. Patients with schizophrenia have heightened baseline levels of cortisol, and a heightened cortisol response to some biological challenges. Cortisol levels are positively correlated with symptom severity. In addition, the hippocampus, which modulates the activity of the HPA axis, is abnormal in schizophrenia. The HPA axis and hippocampal complex are modulatory neural systems; in the case of schizophrenia, what they might be modulating is the expression of abnormalities in dopamine neurotransmission. Whilst we assume that schizophrenia has prenatal neurodevelopmental origins, neural maturational processes that occur later in life, especially in adolescence, have significant implications for the expression of the illness. It is likely that preventive interventions for schizophrenia, be they pharmacological or behavioural, will have the best chance of success if they are directed at adolescents who are showing preschizophrenic indicators.