Adolescent Major Depressive Disorder: Neuroimaging Evidence of Sex Difference during an Affective Go/No-Go Task

Abstract

Compared to female major depressive disorder (MDD), male MDD often receives less attention. However, research is warranted since there are significant sex differences in the clinical presentation of MDD and a higher rate of suicide in depressed men. To the best of our knowledge, this is the first functional magnetic resonance imaging (fMRI) study with a large sample addressing putative sex differences in MDD during adolescence, a period when one of the most robust findings in psychiatric epidemiology emerges; that females are twice as likely to suffer from MDD than males. Twenty-four depressed and 10 healthy male adolescents, together with 82 depressed and 24 healthy female adolescents, aged 11-18 years, undertook an affective go/no-go task during fMRI acquisition. In response to sad relative to neutral distractors, significant sex differences (in the supramarginal gyrus) and group-by-sex interactions (in the supramarginal gyrus and the posterior cingulate cortex) were found. Furthermore, in contrast to the healthy male adolescents, depressed male adolescents showed decreased activation in the cerebellum with a significant group-by-age interaction in connectivity. Future research may consider altered developmental trajectories and the possible implications of sex-specific treatment and prevention strategies for MDD.

Keywords: adolescent major depressive disorder; affective go/no-go task; cerebellum; sex difference; supramarginal gyrus.

Figure 1

The inter-block interval was 12 s with the first 4 s of each block used to present the instructions (in this case, “Press for happy words. Ignore sad words.”). Each word was presented for 450 ms with a 750 ms interstimulus interval. Participants were asked to press a button when presented with a target word (in this case, happy words) and inhibit responses to distractor words (in this case, sad words).

Figure 2

Older participants had longer reaction times responding to the sad distractor contrast. There were no significant group (depressed/healthy) or sex effects. Female patients, female controls, male patients, and male controls all showed similar patterns.

Figure 3

Significant mean activation, sex effect (A) and group-by-sex interaction (B) responding to the sad distractor contrast in all participants. Box plots depicted estimated marginal means of the percent signal changes extracted from the regions showing significant sex effect in the supramarginal gyrus (A), and a group-by-sex interaction in the supramarginal gyrus, precuneus cortex, lateral occipital cortex, and the posterior cingulate cortex (B).

Figure 4

Significant brain activation responding to the sad distractor contrast in the male adolescents. Significant mean activation (A–D) and significant case–control difference of these mean activation regions (E). A box plot showed higher brain activation (extracted percent signal change) in the male controls’ cerebellum when compared with the male patients.

Figure 5

Significant group × age interaction of the psychophysiological interaction (PPI) connectivity between the cerebellum seed and superior frontal gyrus is shown. With age, connectivity increases in strength in male controls but decreases in strength in males with major depressive disorder.