Functional magnetic resonance imaging (fMRI) of attention processes in presumed obligate carriers of schizophrenia: preliminary findings

<p>Abstract</p> <p>Background</p> <p>Presumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, although do not exhibit the disorder, are in direct lineage of it. Thus, this subpopulation of first-degree relatives could provide very important information with regard to the investigation of endophenotypes for schizophrenia that could clarify the often contradictory findings in schizophrenia high-risk populations. To date, despite the extant literature on schizophrenia endophenotypes, we are only aware of one other study that examined the neural mechanisms that underlie cognitive abnormalities in this group. The aim of this study was to investigate whether a more homogeneous group of relatives, such as POCs, have neural abnormalities that may be related to schizophrenia.</p> <p>Methods</p> <p>We used functional magnetic resonance imaging (fMRI) to collect blood oxygenated level dependent (BOLD) response data in six POCs and eight unrelated healthy controls while performing under conditions of sustained, selective and divided attention.</p> <p>Results</p> <p>The POCs indicated alterations in a widely distributed network of regions involved in attention processes, such as the prefrontal and temporal (including the parahippocampal gyrus) cortices, in addition to the anterior cingulate gyrus. More specifically, a general reduction in BOLD response was found in these areas compared to the healthy participants during attention processes.</p> <p>Conclusion</p> <p>These preliminary findings of decreased activity in POCs indicate that this more homogeneous population of unaffected relatives share similar neural abnormalities with people with schizophrenia, suggesting that reduced BOLD activity in the attention network may be an intermediate marker for schizophrenia.</p

Does COMT val158met polymorphism influence P50 sensory gating, eye tracking or saccadic inhibition dysfunctions in schizophrenia?

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Genetic overlap between P300, P50, and duration mismatch negativity

Mismatch Negativity (MMN), P300, and P50 suppression event-related potential (ERP) components measure intermediate stages of information processing but little is known of how they relate to each other genetically. The present study used multivariate genetic model fitting analytic techniques in 46 monozygotic and 32 dizygotic twin pairs. P300, P50 suppression, and MMN were recorded using a 19-channel electroencephalograph (EEG). Zygosity was determined using DNA genotyping. Little evidence for either genetic or environmental association between each of the three ERP paradigms was found. This result suggests that P300, MMN, and P50 suppression serve to evaluate different brain information processing functions that may be mediated by distinct neurobiological mechanisms which in turn are influenced by different sets of genes. Within paradigm, P300 amplitude and latency shared about half of their genetic effects

Further evidence for shared genetic effects between psychotic bipolar disorder and p50 suppression:A combined twin and family study

P50 suppression deficit has been reported in patients with psychotic bipolar disorder. In our previous report on twin pairs concordant and discordant for bipolar disorder, we found significant genetic overlap between bipolar disorder and P50 sensory gating. However, the sample size in that study was relatively small. A separate study, the Maudsley Bipolar Family Study, reported diminished P50 gating in unaffected relatives of psychotic bipolar patients. However, genetic and environmental influences are confounded in family studies due to lack of monozygotic (MZ) twin pairs. The current study combines the twin sample and the family sample in order to improve statistical power and study design, with the aims of: (1) substantiating the association between psychotic bipolar disorder and diminished P50 suppression and (2) verifying the genetic overlap between the two traits reported in the twin sample. We also assessed the relationship between bipolar disorder and an alternative suppression index, the P50 Condition-Testing (C-T) amplitude difference. A total of 309 subjects was included in this study, comprising 91 twin pairs, 31 bipolar families, and 45 unrelated healthy controls. Statistical analyses were based on structural equation modeling. Bipolar disorder was significantly associated with a diminished P50 suppression ratio and decreased C-T amplitude difference. Shared genetic factors were the main source of these associations. Suppression impairment was due to larger, poorly gated, T amplitude responses. The results provide further evidence that impaired P50 suppressions are promising endophenotypes for psychotic bipolar disorder. The non-specificity of impaired P50 suppression may reflect the impact of shared psychosis susceptibility genes. © 2008 Wiley-Liss, Inc