Deficits In First-degree Relatives Research Articles

Facial emotion recognition deficits in first-degree relatives of patients with bipolar disorder: a systematic review protocol

IntroductionBipolar Disorder (BD) is one of the most challenging and severe psychiatric disorders. Considerable research in BD patients points to deficits in Facial Emotion Recognition (FER) as a potential BD endophenotype. Accordingly, such deficits have also been found in unaffected BD first-degree relatives, but no study has been conducted to synthetize this evidence.ObjectivesTo conduct a systematic review of studies exploring FER deficits in first-degree relatives of patients with BD.MethodsPRISMA 2020 recommendations will be followed. PubMed, Scopus, Web of Science and SciELO electronic bibliographic databases will be searched, as well as grey literature. Reference lists of the included studies will be hand-searched for additional eligible studies. Search strategy will include key-terms in accordance with the pre-established PICOS definition. No restrictions will apply regarding study design, setting, publication date nor language. Outcomes of interest will be FER deficits. Retrieved studies will be screened for eligibility by two independent reviewers using a two-phase approach. The methodological quality of primary studies will be assessed and data extracted independently using a standardized extraction form.Resultswill be described using narrative and tabular approaches. Studies heterogeneity will be verified and if adequate a meta-analysis will be conducted. Findings will be disseminated through a peer-reviewed publication.ConclusionsIt is expected that this systematic review will support the hypothesis that FER deficits may constitute a potential candidate for a BD endophenotype, which will not only improve the understanding of BD neurobiology, but also enable its identification in earlier stages, allowing timely treatments and better patients’ outcomes.DisclosureNo significant relationships.

Systematic review and meta-analysis of the relationship between genetic risk for schizophrenia and facial emotion recognition

BackgroundRecent research has highlighted that facial emotion recognition deficits are more common in people with schizophrenia, but the reason for this association is not well understood. Comparing facial recognition deficits in unaffected individuals at higher genetic risk for schizophrenia with individuals at lower genetic risk could increase our understanding of this relationship. MethodsWe systematically reviewed studies reporting on the relationship between genetic risk of schizophrenia and facial emotion recognition deficits. Meta-analyses were performed where sufficient data were available, otherwise we conducted narrative summaries. Meta-analyses were performed both for generalised and specific facial emotion recognition deficits. Results34 studies were included in this review with 23 included in meta-analyses. Meta-analysis indicated strong evidence of a deficit in facial emotion recognition in first-degree relatives of people with schizophrenia compared with controls (SMD 0.38 95% CI 0.26 to 0.51, p ≤ 0.001). Further meta-analyses demonstrated strong evidence of a deficit in the recognition of negative valence facial expressions (SMD 0.19 CI 0.06 to 0.32, p = 0.004) but no evidence of deficit in the recognition of neutral or positive valance. ConclusionsThere is strong evidence of facial emotion recognition deficits in first-degree relatives of people with schizophrenia. Our findings suggest that such deficits in people with schizophrenia arise prior to the onset of the disorder, though cannot inform whether that association is causal or due to confounding. Emotion recognition deficits, particularly to negative emotions, might be useful predictors of schizophrenia risk.

F221. Brain Abnormalities and Cognitive Deficits in First-Degree Relatives of Patients With Schizophrenia

F221. Brain Abnormalities and Cognitive Deficits in First-Degree Relatives of Patients With Schizophrenia

Theory of Mind in Euthymic Bipolar Patients and First-Degree Relatives.

The present study analyzed the capacity for mentalization of patients with bipolar disorder (BD) and their first-degree relatives (FDR) and examined the implications of clinical variables and cognitive deficits. The study recruited 31 patients with type I BD, 18 FDR, and 31 paired healthy controls. Their capacity for mentalization was explored by means of first- and second-order false-belief tasks, the hinting task, and the Movie for the Assessment of Social Cognition (MASC). Patients and FDR were found to have a theory of mind (ToM) deficit when they were evaluated with the MASC, which was also related to a worse neurocognitive performance and to being a patient or FDR. The evidence of ToM deficits in FDRs supports the hypothesis that these deficits could be an independent trait marker for cognitive deficit. Further research is needed on FDR of patients with BD, using sensitive ToM assessment instruments such as the MASC.

Cognitive deficits in first-degree relatives of bipolar patients: the use of homogeneous subgroups in the search of cognitive endophenotypes.

Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first-degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p=0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary.

Event Related Potentials and its role as Endophenotypes in Psychiatry

Familial segregation is a norm rather than an exception in psychiatry. Genetic research has failed to provide much anticipated unanimous, if not awaited answers to the complex predispositions to psychiatric disorders. Hence, the concept of endophenotype took birth. Endophenotype is an attribute which is hidden phenotype, which is described as internal phenotypes discoverable by biochemical test or microscopic examination. This concept was immediately picked up by psychiatry, giving a totally new direction to the search for root cause of various psychiatric disorders.Cognitive deterioration is inseparable from psychiatric disorders, known since dawn of psychiatry. However, cognitive deficits in FDRs (First Degree Relatives) of psychiatric patients were one of the first endophenotypes noted. Event Related Potential (ERP), a science known to be electrophysiological counterpart of various cognitive processes, was soon incorporated in search of endophenotypes in psychiatry. In schizophrenia reduced amplitude of MMN(Mismatch negativity), impaired suppression of P50 and reduced amplitude of P300; reduced P300 amplitude, impaired P50 suppression in Bipolar Affective Disorders; reduced P300 amplitude in substance dependence disorders have been reported to have endophenotypic values. Various other ERP waves such as CNV, N400 have been investigated but no conclusive reports are out yet. The ultimate goal of this science is to search for genes governing the cognitive processes responsible for ERP waves identified as Endophenotypes for specific psychiatric disorders, and the search has just started.Keywords : Event Related Potential, Endophenotype, Psychiatric Disorder, Mismatch negativity,P 300, P 50, CNV

Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT).

It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia, evident prior to full illness onset and independent of medication. The possibility of genetic overlap between risk for schizophrenia and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with schizophrenia; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of schizophrenia have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of many common SNPs of extremely small effect. Similar results have been reported in GWAS of general cognitive ability. The primary aim of the present study is to provide the first molecular genetic test of the classic endophenotype hypothesis, which states that alleles associated with reduced cognitive ability should also serve to increase risk for schizophrenia. We tested the endophenotype hypothesis by applying polygenic SNP scores derived from a large-scale cognitive GWAS meta-analysis (~5000 individuals from 9 non-clinical cohorts comprising the COGENT consortium) to four schizophrenia case-control cohorts. As predicted, cases had significantly lower cognitive polygenic scores compared to controls. In parallel, polygenic risk scores for schizophrenia were associated with lower general cognitive ability. Additionally, using our large cognitive meta-analytic dataset, we identified nominally significant cognitive associations for several SNPs that have previously been robustly associated with schizophrenia susceptibility. Results provide molecular confirmation of the genetic overlap between schizophrenia and general cognitive ability, and may provide additional insight into pathophysiology of the disorder.

A resting-state functional magnetic resonance imaging study on the first-degree relatives of persons with schizophrenia

In this study, resting state fMRI images and BOLD signals were recorded from 13 first-degree relatives of schizophrenic patients and 13 healthy controls. The data were analyzed with the ReHo approach after realignment, registration, and normalization in statistical parametric mapping 2 (SPM2). A two-sample t-test was used to analyze the ReHo differences between first-degree relatives and healthy controls in a voxel by voxel manner. A combined threshold of p < 0.005 and number of voxels >5 was designated as statistically significant. To evaluate cognitive deficits in first-degree relatives, attention/vigilance and verbal/visual memory were measured. Significant impairments in attention were observed in first-degree relatives compared to healthy controls. Significant abnormalities in ReHo were observed in resting brain in first-degree relatives. Decreased ReHo was found to be distributed over the bilateral middle frontal, middle temporal, cingulate gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and dorsolateral prefrontal cortex. Increased ReHo was found to be distributed in the right precuneus and superior temporal gyrus. These changes in ReHo suggest abnormality in the resting state brain function of first-degree relatives of schizophrenic patients and may be early signs for the development of schizophrenia.

More severe sustained attention deficits in nonpsychotic siblings of multiplex schizophrenia families than in those of simplex ones

Sustained attention deficits measured by the Continuous Performance Test (CPT) have been proposed as an endophenotype of schizophrenia. However, little is known about whether sustained attention deficits in first-degree relatives of schizophrenic patients are associated with familial loading for schizophrenia. We examined 107 parents and 84 siblings of simplex schizophrenia families as well as 72 parents and 56 siblings of multiplex schizophrenia families, all nonpsychotic, using the Diagnostic Interview for Genetic Studies and two sessions of the CPT (undegraded and degraded). The effect of perceptual load was assessed using the residual of the regression of the degraded score on the undegraded one. Statistical models that can adjust for familial correlations were used to compare the CPT performance of relatives between the two types of families. Siblings from multiplex families exhibited worse performance on the degraded CPT and less proficiency in processing the perceptual load than those from simplex families. No such difference was observed for the parents on either CPT version. We concluded that sustained attention along with perceptual load processing is more impaired in the siblings of schizophrenic patients with high familial loading and that this finding might be useful for future genetic dissection of schizophrenia.

Amygdala–hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients

Verbal memory deficits have been related to reduced volume of medial temporal structures in several neurological and psychiatric populations, including schizophrenic patients. Impairments in verbal memory have been proposed to be a marker of risk for schizophrenia. Recently, relatives of schizophrenic patients have been reported to have reduced volume of the amygdala–hippocampal complex. In this study, we evaluate the possibility that amygdala–hippocampal volume reductions may constitute one neural substrate of verbal memory deficits in first-degree relatives. Subjects were 20 healthy first-degree relatives of schizophrenic patients and 14 demographically similar controls. Verbal memory was assessed with the Logical Memory Test. Subjects were scanned with high-resolution MRI and the images were transformed into Talairach space. Volumes of interest were amygdala–anterior hippocampus and posterior hippocampus. Relatives of schizophrenic patients had intact immediate verbal memory but significantly poorer delayed verbal memory than controls. Relatives also had significantly reduced amygdala–anterior hippocampus volumes. Across all subjects, delayed verbal memory was significantly correlated with amygdala–anterior hippocampus volume. The magnitude of the correlation did not differ between the groups. These data provide an empirical link between memory performance and volumetric abnormalities in the amygdala–hippocampal complex in the relatives of schizophrenic patients.

Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients: a positron emission tomography study.

Schizophrenia is thought to arise from the interaction of genetically mediated and environmentally triggered abnormalities in brain function. Reduced frontal activation, reported in schizophrenic patients, may be one expression of genetic risk. The present study investigated whether frontal activation in relatives of schizophrenic patients would be related to eye tracking deficits (ETD), which are considered a behavioral marker of risk for schizophrenia. Subjects were first-degree relatives of schizophrenic patients (n = 17) and controls (n = 11). Relatives were divided into those with normal and abnormal pursuit based on qualitative ratings. Subjects were scanned using positron emission tomography and the H(2)15O bolus subtraction technique while performing smooth pursuit and fixation. Brain areas more active in pursuit than fixation were identified in the 3 groups. Correlations were used to investigate the relationship between activation of pursuit regions and pursuit gain in the relatives. Controls significantly activated frontal eye fields (FEFs) and posterior areas, including the motion processing area, V5, and cuneus. The 2 groups of relatives activated the same posterior regions as controls, but differed from each other in activation of FEFs. Relatives with normal tracking activated right dorsal FEFs while relatives with ETD did not. Individual subtractions revealed that 90% of controls and 100% of the relatives with normal tracking activated FEFs during pursuit compared with 42% of relatives with ETD (P = .009). Pursuit gain was significantly and selectively associated with percent activation of right dorsal FEFs (r = 0.74). Subtle frontal dysfunction seems to be a pathophysiological substrate of ETD in relatives of schizophrenic patients, and may be one aspect of genetically mediated differences in brain function relevant to schizophrenia.

Abnormal subjective experiences and neuropsychological deficits in first-degree relatives of schizophrenics

We determined brain density and ventricular measurements with computerized tomography (CT) in 33 depressed patients and compared the results with basal plasma cortisol and its suppressibility by dexamethasone. Mean plasma cortisol was positively related to elevated ventricular brain ratio (VBR). No association could be found between dexamethasone suppression test (DST) status and VBR or any other CT parameter. Elevated plasma cortisol levels and increased VBRs were positively correlated with total scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale and the Bech-Rafaelsen Melancholia Scale, but they were not significantly correlated with total score on the Hamilton Anxiety Scale.