Neural response during explicit and implicit face processing varies developmentally in bipolar disorder

Abstract

Both children and adults with bipolar disorder (BD) exhibit face emotion labeling deficits and neural circuitry dysfunction in response to emotional faces. However, few studies have compared these groups directly to distinguish effects of age and diagnosis. Such studies are important to begin to elucidate the developmental trajectory of BD and facilitate its diagnosis, prevention and treatment. This functional magnetic resonance imaging study compares 41 individuals with BD (19 children; 22 adults) and 44 age-matched healthy individuals (25 children; 19 adults) when making explicit or implicit judgments about angry or happy face morphs across a range of emotion intensity. Linear trend analyses revealed that BD patients, irrespective of age, failed to recruit the amygdala in response to increasing angry face. This finding was no longer significant when the group was restricted to euthymic youth or those without comorbid attention deficit hyperactivity disorder although this may reflect low statistical power. Deficits in subgenual anterior cingulate modulation were observed in both patient groups but were related to implicit processing for child patients and explicit processing for adult patients. Abnormalities in face emotion labeling and the circuitry mediating it may be biomarkers of BD that are present across development.

Fig. 1

Example of the morphed stimuli used in the experiment from a single female exemplar. Stimulus range from 100% neutral to (A) 100% angry and (B) 100% happy in 25% increments.

Fig. 2

Amygdala ROI from the angry face analysis. (A) Left anatomical ROI used in the analysis; a homologous region from the right hemisphere was also used. (B) BOLD signal at each intensity level for each diagnostic group. (C) Linear trend between BOLD signal and intensity level for each diagnostic group. Note: A25 = 25% angry/75% neutral; A50 = 50% angry/50% neutral; A75 = 75% angry/25% neutral. BD = bipolar disorder and HC = healthy comparison.

Fig. 3

SgACC cluster identified by a Diagnosis × Age × Condition interaction from the whole-brain analysis of angry faces. (A) Cluster identified from the whole-brain analysis (P < 0.005, k ≥ 20). (B) BOLD signal at each intensity level for each participant group and each condition. (C) Linear trend between BOLD signal and intensity level for each participant group and each condition. Solid lines reflect the explicit rating condition (hostility ratings) and dashed lines reflect the implicit rating condition (nose width). Note: A25 = 25% angry/75% neutral; A50 = 50% angry/50% neutral; A75 = 75% angry/25% neutral; child BD = children with bipolar disorder; adult BD = adults with bipolar disorder.

Fig. 4

Cuneus cluster identified by a Diagnosis × Condition interaction from the whole-brain analysis of happy faces. (A) Cluster identified from the whole-brain analysis (P < 0.005, k ≥ 20). (B) BOLD signal at each intensity level for each diagnostic group and each condition. (C) Linear trend between BOLD signal and intensity level for each diagnostic group and each condition. Solid lines reflect the explicit rating condition (hostility ratings) and dashed lines reflect the implicit rating condition (nose width). Note: A25 = 25% angry/75% neutral; A50 = 50% angry/50% neutral; A75 = 75% angry/25% neutral.