Schizophrenia is perhaps the most intensively studied of the psychiatric disorders, and there is increasing evidence that its pathogenesis involves neurodevelopmental abnormalities. Patients seem to show loss of grey matter, but it is unclear whether this occurs early or late in neural development. Thompson et al. have followed patients with early-onset schizophrenia (starting in childhood or early adolescence) to study the dynamics of this reduction in volume.

Grey matter loss in adolescents with schizophrenia. Warmer colours denote regions with the most significant losses. © 2001 National Academy of Sciences, USA.

The researchers used high-resolution magnetic resonance imaging (MRI) scans to track structural changes in the brains of adolescents with early-onset schizophrenia over five years. The authors compared the scans across the time course of the experiment, and compared schizophrenic patients with control subjects and 'medication-matched' teenagers who had other psychiatric disorders. They found that there was a greater loss of grey matter in patients with schizophrenia than in normal adolescents, and that the loss followed a specific spatial pattern as time progressed.

The control subjects did show some loss of grey matter over the five-year span of the experiment, consistent with previous findings. But this reduction was fairly homogeneous across the brain. By contrast, patients with schizophrenia showed a specific, wave-like pattern of loss that began in the parietal cortices and progressed over the following years to affect frontal and temporal regions. Medication-matched non-schizophrenic patients also showed a greater loss of grey matter than did controls, but the loss was less marked than for the patients with schizophrenia and did not include the temporal cortex.

Previous work has shown that grey matter deficits in some areas of the brain in adult schizophrenic patients and their families are attributable to genetic factors, whereas in other areas they seem to be related to environmental factors. Intriguingly, the parietal cortices, where the dynamic loss in teenagers with schizophrenia begins, fall into the latter category, whereas loss in the frontal and temporal regions, which are affected later, appears to be genetically mediated. The authors comment that these findings are consistent with the idea that an environmental trigger contributes to the onset and initial development of schizophrenia.

Grey matter deficits in different brain areas also show interesting correlations with the clinical progression of the disease. Specifically, faster loss in the temporal cortices is associated with more severe positive symptoms (for example, hallucinations and delusions), whereas loss in the frontal cortices correlates with increased negative symptoms (such as lack of emotional responses and poverty of speech).

Although the causes of schizophrenia are still mysterious, a better understanding of the structural changes that occur during the progression of the disease in these adolescent patients could provide further insight into the mechanisms of the adult-onset form of the disease. And the tight correlations between the pattern of loss and specific symptoms could point towards the mechanisms that underlie these symptoms. However, these findings also indicate that treatments for schizophrenia will need to be aimed at slowing the loss of grey matter, raising another question — just what causes this progressive wave of tissue loss?