Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives.

OBJECTIVE: Schizophrenia and psychotic bipolar disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. The authors used region-of-interest morphometry to volumetrically assess brain structures frequently implicated in psychotic illness in families affected with schizophrenia or psychotic bipolar disorder. METHOD: Magnetic resonance imaging brain scans were obtained from 243 subjects, comprising 42 patients with schizophrenia or schizoaffective disorder, 57 of their unaffected first-degree relatives, 38 patients with psychotic bipolar disorder, 52 of their unaffected first-degree relatives, and 54 healthy comparison subjects. Most of the families affected with schizophrenia and all of the families affected with bipolar disorder were multiply affected with the illness. Volumetric measurements of the cerebrum, lateral ventricles, third ventricle, and hippocampus were completed with stereological methods. RESULTS: Patients with schizophrenia had increased volume of the lateral and third ventricles and reduced hippocampal volume. None of these volumetric abnormalities was present in psychotic bipolar disorder. Unaffected relatives of patients with schizophrenia from multiply affected families had enlarged lateral ventricles but no other volumetric deviations. Unaffected relatives of patients with bipolar disorder showed preservation of ventricular and hippocampal volume. CONCLUSIONS: Schizophrenia and psychotic bipolar disorder are characterized by morphometric distinctions in ventricular and hippocampal regions. Lateral ventricular enlargement represents a potential morphometric endophenotype for schizophrenia.

The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia.

BACKGROUND: We examined the cerebral correlates of intelligence, memory, and executive processing in 56 patients with schizophrenia or schizoaffective disorder and 90 of their nonpsychotic relatives to establish whether the pattern of structure--function relationships in these two groups was different from that in 55 control subjects. METHODS: Magnetic resonance imaging data were acquired, and volumetric measurements were made for whole brain, prefrontal region, lateral ventricles, third ventricle, temporal lobes, hippocampi, and cerebellum. RESULTS: In the total sample, full intelligence quotient (IQ) and verbal IQ correlated with the volume of the whole brain and right hippocampus; the latter was also associated with performance IQ. Left hippocampal size was associated with verbal IQ and, in control subjects and nonpsychotic relatives only, with estimated full IQ. Delayed verbal memory was linked to cerebellar and inversely to left hippocampal volume. Discrepancies in the relationship pattern emerged in patients with schizophrenia between left hippocampus and measures of IQ and verbal memory. CONCLUSIONS: The latter data indicate a loss of a normal structure--function relationship in schizophrenia and might reflect a functional compensation occurring secondary to early neurodevelopmental impairment.

Normal cerebral asymmetry in familial and non-familial schizophrenic probands and their unaffected relatives.

Loss of normal fronto-occipital cerebral asymmetry has been reported in patients with schizophrenia and also in their well relatives from multiply affected families, suggesting a relationship with susceptibility genes. We sought to confirm this relationship in a family study of patients with schizophrenia and their unaffected relatives of presumed differing genetic risk. MRI scans were carried out on 25 probands from families multiply affected with the disorder, and 36 of their unaffected relatives, 34 probands from families with no other affected members, 42 of their unaffected relatives, and 76 controls. Volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions were obtained from which a measure of fronto-occipital torque was derived. There were no significant differences in measurements of fronto-occipital torque between the subject groups. Both schizophrenic probands and their relatives displayed the normal pattern of cerebral asymmetry, with larger right than left frontal regions and a larger left than right occipitoparietal region. Our findings failed to confirm an association between loss of fronto-occipital torque and genetic liability for schizophrenia and also failed to replicate the previously reported association between loss/reversal of fronto-occipital asymmetry and schizophrenia.

Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives.

Structural brain abnormalities are consistently reported in schizophrenic subjects but the etiology of these abnormalities remains unclear. We tested the contribution of genetic predisposition and obstetric complications to the structural brain abnormalities found in schizophrenic probands and their relatives. MRI scans were carried out on 35 schizophrenic probands from families multiply affected with the disorder, and 63 of their unaffected relatives, including 10 parents who appeared to transmit genetic risk to their children; as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives; and finally 68 controls. Volumetric measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and temporal lobes were completed for each subject. The impact of obstetric complications on brain structure was assessed across the gradient of presumed genetic predisposition. Both groups of schizophrenic probands displayed enlargement of the lateral and third ventricles, and there was a gradient of ventricular enlargement amongst the unaffected relatives in proportion to their likelihood of carrying schizophrenic genes. Ventricular enlargement was largely confined to males in both probands and unaffected relatives. Obstetric complications were associated with ventricular enlargement only in the familial probands. Non-familial probands displayed reduced volume of the temporal lobes bilaterally. In families with several schizophrenic members, ventricular enlargement is a marker for genetic liability, particularly in males. Individuals inheriting the susceptibility to schizophrenia appear particularly prone to develop ventricular enlargement in response to obstetric complications.

Minor physical anomalies and quantitative measures of the head and face in patients with psychosis.

BACKGROUND: The aim of this study was to examine minor physical anomalies and quantitative measures of the head and face in patients with psychosis vs healthy controls. METHODS: Based on a comprehensive prevalence study of psychosis, we recruited 310 individuals with psychosis and 303 controls. From this sample, we matched 180 case-control pairs for age and sex. Individual minor physical anomalies and quantitative measures related to head size and facial height and depth were compared within the matched pairs. Based on all subjects, we examined the specificity of the findings by comparing craniofacial summary scores in patients with nonaffective or affective psychosis and controls. RESULTS: The odds of having a psychotic disorder were increased in those with wider skull bases (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.02-1.17), smaller lower-facial heights (glabella to subnasal) (OR, 0.57; 95% CI, 0.44-0.75), protruding ears (OR, 1.72; 95% CI, 1.05-2.82), and shorter (OR, 2.29; 95% CI, 1.37-3.82) and wider (OR, 2.28; 95% CI, 1.43-3.65) palates. Compared with controls, those with psychotic disorder had skulls that were more brachycephalic. These differences were found to distinguish patients with nonaffective and affective psychoses from controls. CONCLUSIONS: Several of the features that differentiate patients from controls relate to the development of the neuro-basicranial complex and the adjacent temporal and frontal lobes. Future research should examine both the temporal lobe and the middle cranial fossa to reconcile our anthropomorphic findings and the literature showing smaller temporal lobes in patients with schizophrenia. Closer attention to the skull base may provide clues to the nature and timing of altered brain development in patients with psychosis.