The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

BackgroundThe Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.MethodWe employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.ResultsIrrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.ConclusionsOur results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

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Evidence for the impact of the CACNA1C risk allele rs1006737 on 2-year cognitive functioning in bipolar disorder

Psychiatric Genetics ◽

10.1097/ypg.0b013e328358641c ◽

2013 ◽

Vol 23 (1) ◽

pp. 41-42 ◽

Cited By ~ 12

Author(s):

Baer Arts ◽

Claudia J.P. Simons ◽

Jim van Os

Keyword(s):

Bipolar Disorder ◽

Cognitive Functioning ◽

Risk Allele ◽

The Impact

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Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder

European Psychiatry ◽

10.1016/j.eurpsy.2010.10.004 ◽

2011 ◽

Vol 26 (3) ◽

pp. 135-137 ◽

Cited By ~ 62

Author(s):

E. Perrier ◽

F. Pompei ◽

G. Ruberto ◽

E. Vassos ◽

D. Collier ◽

...

Keyword(s):

Bipolar Disorder ◽

Emotional Processing ◽

Risk Allele ◽

Anatomical Variation ◽

Brain Structures ◽

Brain Morphology ◽

Healthy Controls ◽

Subcortical Brain ◽

Increased Risk ◽

Subcortical Regions

AbstractBackgroundThe polymorphism rs1006737 within the CACNA1C gene is associated with increased risk for bipolar disorder (BD) and variations in brain morphology and function of subcortical regions. Here we sought to investigate the influence of CACNA1C polymorphism on key subcortical brain structures implicated in the pathophysiology of BD.MethodsStructural magnetic resonance imaging scans were acquired from 41 euthymic patients with BD and 40 healthy controls, who were also genotyped for the CACNA1C rs1006737 polymorphism. The effect of diagnosis, genotype and their interaction was examined in predefined volumes of interest in the basal ganglia, hypothalamus and amygdala extracted using SPM5.ResultsCarriers of the CACNA1C rs1006737 risk allele showed increased grey matter density in the right amygdala and right hypothalamus irrespective of diagnosis. An interaction between genotype and diagnosis was observed in the left putamen which was smaller in BD patients carrying the risk allele than in healthy controls.Conclusions:The CACNA1C rs1006737 polymorphism influences anatomical variation within subcortical regions involved in emotional processing.

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Growth hormone response during OGTT: The impact of assay method, gender and BMI on the estimation of reference values in patients with acromegaly and in healthy controls

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2007-972337 ◽

2007 ◽

Vol 115 (S 1) ◽

Author(s):

AM Arafat ◽

M Möhlig ◽

MO Weickert ◽

FH Perschel ◽

J Purschwitz ◽

...

Keyword(s):

Growth Hormone ◽

Reference Values ◽

Growth Hormone Response ◽

Assay Method ◽

Healthy Controls ◽

Hormone Response ◽

The Impact

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Neuroserpin in Bipolar Disorder

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200131125526 ◽

2020 ◽

Vol 20 (7) ◽

pp. 518-523

Author(s):

Rugül Köse Çinar

Keyword(s):

Gene Expression ◽

Bipolar Disorder ◽

Polymerase Chain Reaction Method ◽

Type I ◽

Healthy Controls ◽

Neuroprotective Effects ◽

Expression Levels ◽

Disease States ◽

Cord Injury ◽

System Functioning

Objective: Neuroserpin is a serine protease inhibitor predominantly expressed in the nervous system functioning mainly in neuronal migration and axonal growth. Neuroprotective effects of neuroserpin were shown in animal models of stroke, brain, and spinal cord injury. Postmortem studies confirmed the involvement of neuroserpin in Alzheimer’s disease. Since altered adult neurogenesis was postulated as an aetiological mechanism for bipolar disorder, the possible effect of neuroserpin gene expression in the disorder was evaluated. Methods: Neuroserpin mRNA expression levels were examined in the peripheral blood of bipolar disorder type I manic and euthymic patients and healthy controls using the polymerase chain reaction method. The sample comprised of 60 physically healthy, middle-aged men as participants who had no substance use disorder. Results: The gene expression levels of neuroserpin were found lower in the bipolar disorder patients than the healthy controls (p=0.000). The neuroserpin levels did not differ between mania and euthymia (both 96% down-regulated compared to the controls). Conclusion: Since we detected differences between the patients and the controls, not the disease states, the dysregulation in the neuroserpin gene could be interpreted as a result of the disease itself.

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F117EVALUATING THE IMPACT OF NON-RANDOM MATING: PSYCHIATRIC OUTCOMES AMONG THE OFFSPRING OF PAIRS DIAGNOSED WITH SCHIZOPHRENIA AND BIPOLAR DISORDER

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2018.08.197 ◽

2019 ◽

Vol 29 ◽

pp. S1173-S1174

Author(s):

James Crowley ◽

Ashley Nordsletten ◽

Gustaf Brander ◽

Patrick Sullivan ◽

Naomi Wray ◽

...

Keyword(s):

Bipolar Disorder ◽

Random Mating ◽

Psychiatric Outcomes ◽

The Impact

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Response Processes to Looming Appetitive and Aversive Cues in Euthymic Bipolar Patients and Their First-Degree Relatives: An Exploratory Study

Indian Journal of Psychological Medicine ◽

10.1177/0253717620975285 ◽

2020 ◽

pp. 025371762097528

Author(s):

Velprashanth Venkatesan ◽

Christoday R J Khess ◽

Umesh Shreekantiah ◽

Nishant Goyal ◽

K. K. Kshitiz

Keyword(s):

Bipolar Disorder ◽

Healthy Controls ◽

Sensitivity To Reward ◽

Bipolar Group ◽

First Degree Relatives ◽

Vulnerability Model ◽

Increased Sensitivity ◽

Appetitive Cues ◽

Spectrum Disorders ◽

Bipolar Patients

Background: Patients with bipolar disorder demonstrate increased sensitivity to appetitive/rewarding stimuli even during euthymia. On presentation of arousing pictures, they show a peculiar response, suggesting heightened vigilance. While responding to looming arousing cues, studies show subjects with anxiety spectrum disorders exhibit increased reaction time (RT), explained by the “looming-vulnerability model.” This study aimed to investigate the responses to looming arousing cues in euthymic bipolar patients and their first-degree relatives, as compared to healthy controls. Method: A looming appetitive and aversive cue paradigm was designed for assessing the RT of patients to process appetitive and aversive cues. The behavioral inhibition/activation and sensitivity to reward/punishment amongst the groups were also assessed. Results: The bipolar group showed significantly longer RT to process appetitive cues irrespective of the looming condition. Aversive cues elicited significantly longer RT in both the bipolar group and in first-degree relatives, but only when presented with the looming condition. Significant looming bias was elicited in the bipolar group which suggested a particular cognitive style to looming cues. A composite measure of RT along with sensitivity to reward/punishment distinguishes the bipolar group and their first-degree relatives from the healthy controls. Conclusion: The looming vulnerability model may provide important insights for future exploration of cognitive endophenotypes in bipolar disorder.

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Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

Scientific Reports ◽

10.1038/s41598-021-94469-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Asmaa M. Zahran ◽

Azza Shibl ◽

Amal Rayan ◽

Mohamed Alaa Eldeen Hassan Mohamed ◽

Amira M. M. Osman ◽

...

Keyword(s):

T Cells ◽

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Lymphoblastic Leukemia ◽

Critical Role ◽

Suppressor Cells ◽

Healthy Controls ◽

Blast Cells ◽

Cell Acute Lymphoblastic Leukemia ◽

The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

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Association between apolipoprotein gene polymorphisms and hyperlipidemia: a meta-analysis

BMC Genomic Data ◽

10.1186/s12863-021-00968-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xiao-Ning Zhao ◽

Quan Sun ◽

You-Qin Cao ◽

Xiao Ran ◽

Yu Cao

Keyword(s):

Risk Factor ◽

Cerebrovascular Disease ◽

Gene Polymorphisms ◽

Meta Analysis ◽

Control Group ◽

Case Group ◽

Healthy Controls ◽

Ε4 Allele ◽

Different Populations ◽

The Impact

Abstract Background Hyperlipidemia plays an important role in the etiology of cardio-cerebrovascular disease. Over recent years, a number of studies have explored the impact of apolipoprotein genetic polymorphisms in hyperlipidemia, but considerable differences and uncertainty have been found in their association with different populations from different regions. Results A total of 59 articles were included, containing in total 13,843 hyperlipidemia patients in the case group and 15,398 healthy controls in the control group. Meta-analysis of the data indicated that APOA5–1131 T > C, APOA1 -75 bp, APOB XbaI, and APOE gene polymorphisms were significantly associated with hyperlipidemia, with OR values of 1.996, 1.228, 1.444, and 1.710, respectively. All P-values were less than 0.05. Conclusions Meta-analysis of the data indicated that the C allele of APOA5 1131 T > C, the A allele at APOA1-75 bp, the APOB XbaI T allele, and the ε2 and ε4 allele of APOE were each a risk factor for susceptibility for hyperlipidemia.

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