Risk and protective factors across the schizophrenia spectrum

The study of schizotypal personality disorder (SPD), the prototype of the schizophrenia-related personality disorders, provides an opportunity to identify risk and protective factors for the schizophrenic disorders while minimizing confounding artifacts such as long-term neuroleptic treatment, institutionalization, and psychosis. SPD patients share with schizophrenic patients a core cognitive impairment in working memory, verbal learning, and attention on the Continuous Performance Task (CPT) compared to other personality disorder patients and normal control comparison groups (p < 0.05). Working memory deficits are associated with reduced frontal volume on MRI, deficit-like symptoms, and reductions in plasma HVA, although preliminary results suggested increased frontal volumes in the SPD group compared to the comparison groups. Verbal learning deficits appears to be associated with reduced superior temporal gyrus (STG) volume on MRI and cognitive disorganization (p < 0.05). PET studies using a similar verbal learning task suggest abnormal temporal lobe function. Psychotic-like symptoms are associated in preliminary data with increased left putamen volume and increases in plasma HVA. Working memory and attentional deficits in SPD patients seem to be, however, partially reversible with amphetamine (p < 0.05) and possibly with physostigmine. Psychotic-like symptoms were not observed, however, following amphetamine in the SPD patients. These results suggest that cognitive impairment and associated brain dysfunction constitute a core risk factor for the spectrum in SPD patients and may be partially reversible. SPD patients may be protected against “spreading” of central nervous system damage from temporal regions by increases in frontal volume and/or better buffered in their subcortical dopaminergic activity in the face of frontal deafferentation.