15 Thirteen never-psychotic
and non-spectrum disorder relatives of schizophrenic patients and 12 matched normal controls were compared. All subjects were less than 55 years of age and had standard scores on a reading test of at. least 80 (ie, at. least the lownormal range). Relatives were significantly impaired on working memory tasks with interference. The tasks produced activation in the lateral and medial frontal cortex, the posterior parietal and precuneal cortex, and the thalamus in both groups. The most striking finding from these data is the difference in the number of regions activated and the extent of regional activations (number Inhibitors,research,lifescience,medical of “voxels”) in relatives compared with the controls. Across the three tasks, the relatives had a greater number of activations, representing significantly more activated voxels than the controls. On working memory and memory plus interference tasks, activation was more bilaterally distributed in relatives than in controls. As relatives also perform worse on these cognitive tasks, these large Inhibitors,research,lifescience,medical and extraneous activations in relatives may represent: (i) compensatory exertion of inefficient neural circuitry in attempting to perform an effortful task to produce accurate output; and/or (ii) abnormal
connectivity in the circuitry required to perform these tasks. These functional data complement the structural Inhibitors,research,lifescience,medical MRI abnormalities and suggest that adult relatives of schizophrenic patients have brain abnormalities, possibly associated with abnormal genes. Effects of genetic loading on verbal memory and hippocampal volume in relatives Inhibitors,research,lifescience,medical Following up the above findings of stability in measures of verbal memory and attention in nonpsychotic relatives
of schizophrenic patients, we compared individuals with one schizophrenic first-degree relative (simplex families) to individuals with two schizophrenic first-degree relatives (multiplex families).16 Relatives from simplex families performed significantly less well on immediate memory (from the logical memory test) compared with controls, while relatives from multiplex families performed Inhibitors,research,lifescience,medical significantly worse on immediate and delayed logical memory, immediate visual reproductions, and estimated intelligence, compared with controls. Relatives from multiplex families also had a significantly Histone demethylase poorer performance than relatives from simplex families on immediate and delayed logical memories, immediate visual reproductions, and estimated intelligence. These results are consistent with the idea that neuropsychological deficits in relatives of patients with schizophrenia reflect their degree of genetic predisposition to schizophrenia. This relationship was also evident in analyses of structural brain volumes. As described above, relatives show reduced hippocampal Nutlin3a volumes compared with controls.13,17 More recently, we found reductions in left. (but. not right.