کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4177365 1276417 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hippocampal and Frontolimbic Function as Intermediate Phenotype for Psychosis: Evidence from Healthy Relatives and a Common Risk Variant in CACNA1C
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Hippocampal and Frontolimbic Function as Intermediate Phenotype for Psychosis: Evidence from Healthy Relatives and a Common Risk Variant in CACNA1C
چکیده انگلیسی

BackgroundVariation in CACNA1C has consistently been associated with psychiatric disease in genome-wide association studies. We have previously shown that healthy carriers of the CACNA1C rs1006737 risk variant exhibit hippocampal and perigenual anterior cingulate (pgACC) dysfunction during episodic memory recall. To test whether this brain systems-level abnormality is a potential intermediate phenotype for psychiatric disorder, we studied unaffected relatives of patients with bipolar disorder, major depression, and schizophrenia.MethodsThe study population comprised 188 healthy first-degree relatives of patients with bipolar disorder (n = 59), major depression (n = 73), and schizophrenia (n = 56) and 110 comparison subjects from our discovery study who were genotyped for rs1006737 and underwent functional magnetic resonance imaging while performing an episodic memory task and psychological testing. Group comparisons were analyzed using SPM8 and PASW Statistics 20.ResultsSimilar to risk allele carriers in the discovery sample, relatives of index patients exhibited hippocampal and pgACC dysfunction as well as increased scores in depression and anxiety measures, correlating negatively with hippocampal activation. Carrying the rs1006737 risk variant resulted in a stronger decrease of hippocampal and pgACC activation in relatives, indicating an additive effect of CACNA1C variation on familial risk.ConclusionsOur findings implicate abnormal perigenual and hippocampal activation as a promising intermediate phenotype for psychiatric disease and suggest a pathophysiologic mechanism conferred by a CACNA1C variant being implicated in risk for symptom dimensions shared among bipolar disorder, major depression, and schizophrenia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 76, Issue 6, 15 September 2014, Pages 466–475
نویسندگان
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