STRUCTURAL BRAIN ABNORMALITIES AS INDICATORS OF VULNERABILITY TO SCHIZOPHRENIA

The literature on structural brain abnormalities in schizophrenia is e xamined to determine whether these abnormalities represent viable cand idate markers of vulnerability to the disorder. A majority of studies agree in finding that schizophrenia patients as a group have significa ntly larger ventricles and smaller limbic brain structures than normal control subjects, but about 50 percent of patients fall within the ra nge of control subjects on these measures. This result has been interp reted to suggest that structural abnormalities characterize only a sub group of patients. However, given the substantial degree of normal var iability in brain structure between families, the use of biologically unrelated individuals as controls is misleading. Studies that have com pared schizophrenia patients with their unaffected first-degree relati ves have found a much higher sensitivity rate for ventricular enlargem ent and reduced limbic volumes (i.e., 70%-100%). This high within-fami ly sensitivity, together with evidence from metaanalytic reviews of a substantial relationship between ventricular enlargement and severity of illness, argues in favor of a continuous distribution of the brain pathology in schizophrenia and against a model in which the pathology characterizes only a subgroup of patients. The structural abnormalitie s observed in both younger and older patients have been found to be hi ghly correlated with familial risk for schizophrenia and obstetric com plications, suggesting that some part of the deviance may be present i n the premorbid state and that it may reflect both genetic and environ mental etiologic processes. The evidence for specificity of the defici ts to schizophrenia is equivocal, but no study has yet compared the wi thin-family sensitivities of morphological measures among the major ps ychiatric conditions. Additional studies using first-degree relatives and well-defined neuroanatomical measurements are needed to determine which brain regions have the highest sensitivities as indicators of sc hizophrenia in families.