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. 2014 Nov:58:129-36.
doi: 10.1016/j.jpsychires.2014.07.023. Epub 2014 Aug 8.

Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication

Danella M Hafeman  1 , Genna Bebko  2 , Michele A Bertocci  2 , Jay C Fournier  2 , Lisa Bonar  2 , Susan B Perlman  2 , Michael Travis  2 , Mary Kay Gill  2 , Vaibhav A Diwadkar  3 , Jeffrey L Sunshine  4 , Scott K Holland  5 , Robert A Kowatch  6 , Boris Birmaher  2 , David Axelson  7 , Sarah M Horwitz  8 , L Eugene Arnold  7 , Mary A Fristad  7 , Thomas W Frazier  9 , Eric A Youngstrom  10 , Robert L Findling  11 , Wayne Drevets  12 , Mary L Phillips  13
Affiliations

Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication

Danella M Hafeman et al. J Psychiatr Res. 2014 Nov.

Abstract

Previous neuroimaging studies of youth with bipolar disorder (BD) have identified abnormalities in emotion regulation circuitry. Using data from the Longitudinal Assessment of Manic Symptoms Cohort (a clinical sample recruited for behavioral and emotional dysregulation), we examined the impact of BD and medication on activation in these regions. Functional neuroimaging data were obtained from 15 youth with BD who currently were unmedicated with a mood stabilizer or antipsychotic (U-BD), 19 youth with medicated BD (M-BD), a non-bipolar clinical sample with high rates of disruptive behavioral disorders (non-BD, n = 59), and 29 healthy controls (HC) while they were shown task-irrelevant morphing emotional faces and shapes. Whole brain analysis was used to identify clusters that showed differential activation to emotion vs. shapes across group. To assess pair-wise comparisons and potential confounders, mean activation data were extracted only from clusters within regions previously implicated in emotion regulation (including amygdala and ventral prefrontal regions). A cluster in the right inferior frontal gyrus (IFG) showed group differences to emotion vs. shapes (159 voxels, corrected p < .05). Within this cluster, U-BD youth showed decreased activation relative to HC (p = .007) and non-BD (p = .004) youth. M-BD also showed decreased activation in this cluster relative to HC and non-BD youth, but these differences were attenuated. Results were specific to negative emotions, and not found with happy faces. IFG findings were not explained by other medications (e.g. stimulants) or diagnoses. Compared to both HC and a non-BD sample, U-BD is associated with abnormally decreased right IFG activation to negative emotions.

Keywords: Bipolar disorder; Emotion regulation; Functional MRI (fMRI); Neuroimaging; Psychopharmacology.

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Conflict of interest statement

Conflict of Interest: Dr. Arnold received research funding from CureMark, Forest, Lilly, and Shire, advisory board honoraria from Biomarin, Novartis, Noven, Roche, Seaside Therapeutics, and Shire, consulting fees from Tris Pharma, and travel support from Noven. Dr. Frazier received federal funding or research support from, acted as a consultant to, received travel support from, and/or received a speaker's honorarium from the Simons Foundation, Ingalls Foundation, Forest Laboratories, Ecoeos, IntegraGen, Shire Development, Bristol-Myers Squibb, National Institutes of Health, and the Brain and Behavior Research Foundation. Dr. Findling has received research support, acted as a consultant and/or served on a speaker's bureau for Alexza Pharmaceuticals, American Psychiatric Press, AstraZeneca, Bracket, Bristol-Myers Squibb, Clinsys, Cognition Group, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm, Lilly, Lundbeck, Merck, NIH, Novartis, Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Rhodes Pharmaceuticals, Roche, Sage, Seaside Pharmaceuticals, Shire, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Dr. Drevets is a full-time employee of Janssen Pharmaceuticals Research & Development, of Johnson & Johnson, Inc. All other authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Task activation patterns to all emotions vs. shapes across the entire study sample (whole brain, FWE-corrected p<.05). Z-scores are labeled.
Figure 2
Figure 2
a: Cluster showing differential activation across groups with peak voxel in the a priori region of interest (voxelwise p<.01, corrected p<.05). b: Mean activation values across group for the extracted region(159 voxels) for emotions vs. shapes. While both HC and non-BD youth showed significant activation in response to emotions vs. shapes, U-BD showed deactivation; p-values are corrected for multiple comparisons using the Tukey-Kramer method.
Figure 2
Figure 2
a: Cluster showing differential activation across groups with peak voxel in the a priori region of interest (voxelwise p<.01, corrected p<.05). b: Mean activation values across group for the extracted region(159 voxels) for emotions vs. shapes. While both HC and non-BD youth showed significant activation in response to emotions vs. shapes, U-BD showed deactivation; p-values are corrected for multiple comparisons using the Tukey-Kramer method.
See this image and copyright information in PMC

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