Brain volumes in familial and non‐familial schizophrenic probands and their unaffected relatives

Abstract

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.

Aberrant localization of synchronous hemodynamic activity in auditory cortex reliably characterizes schizophrenia

“…Additional studies will be required to answer this question and to determine whether long-term neuroleptic exposure could produce changes in synchronous activity in auditory cortex. Previous work has indicated structural (McDonald et al 2002;Pantelis et al 2003) and functional (Braus et al 2002) abnormalities in nonpharmacologically treated at-risk relatives of patients; thus, it is not clear at this point whether measures of synchrony will be affected by medications.…”

Compromised small-world efficiency of structural brain networks in schizophrenic patients and their unaffected parents

“…As is often the case in a family study, there may be some heterogeneity of genetic predisposition to schizophrenia in first-degree relatives [58] . To distill this kind of heterogeneity, an obligate carrier study in which the unaffected relatives who appear to transmit a genetic predisposition to their affected children are classified as presumed obligate carriers, has been proposed [59] .…”

Adjudicating neurocognitive endophenotypes for schizophrenia

“…The great promise of endophenotypes for providing insights into the pathophysiology of schizophrenia has led to significant scientific activity and the proposal of numerous potential markers, including neuropsychological impairments [Faraone et al, 1999;Cannon et al, 2000;Egan et al, 2001a;MylesWorsley and Park, 2002;Glahn et al, 2003;Hoff et al, 2005], neuroanatomic abnormalities McDonald et al, 2002;Seidman et al, 2002], and electrophysiological deviations [Myles-Worsley, 2002;Bramon et al, 2005]. However, relatively little research has focused on determining which of these putative endophenotypes are likely to be effective in linkage or association studies, raising the possibility that measures significantly influenced by environmental or epigenetic influences could be employed, leading to ambiguous or spurious findings.…”