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J Affect Disord. 2017 Nov;222:7-13. doi: 10.1016/j.jad.2017.05.051. Epub 2017 Jun 23.

Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder.

Author information

1
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, United States; Pediatric Bipolar Disorders Program, Stanford University School of Medicine, United States. Electronic address: kchang88@stanford.edu.
2
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, United States; Pediatric Bipolar Disorders Program, Stanford University School of Medicine, United States; Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, United States.
3
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, United States; Pediatric Bipolar Disorders Program, Stanford University School of Medicine, United States.
4
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, United States; Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, United States.
5
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, United States.

Abstract

OBJECTIVE:

Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD.

METHODS:

We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene.

RESULTS:

While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex CONCLUSIONS: Similar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD.

KEYWORDS:

Bipolar; Children; Functional connectivity; Risk; Serotonin transporter gene; fMRI

PMID:
28667891
DOI:
10.1016/j.jad.2017.05.051
[Indexed for MEDLINE]

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