Sex-specific neural responses to acute psychosocial stress in depression

Abstract

Major Depressive Disorder (MDD) is characterized by increased stress sensitivity. Emerging findings in healthy adults suggest that stress responses within limbic/striatal-prefrontal regions are moderated by sex and unfold over time. Thus, we hypothesized that stress response abnormalities in MDD might be affected by sex and stress exposure time. The Montreal Imaging Stress Task was administered to 124 unmedicated patients with first-episode MDD (76 females) and 243 healthy controls (HC; 137 females) during functional magnetic resonance imaging (fMRI). Based on prior studies, amygdala, hippocampus, medial orbitofrontal cortex (mOFC), nucleus accumbens (NAc) and dorsolateral prefrontal cortex (dlPFC) were selected as a priori regions of interest. In a complementary approach, we probed the effects of stress on the frontoparietal network (FPN) and a network including the amygdala, NAc and anterior cingulate cortex (ACC). Across groups, males exhibited higher dlPFC activity and right FPN amplitude than females. Relative to female HCs, the female MDD group had less deactivation in limbic/striatal regions (amygdala, NAc, hippocampus, Amygdala-NAc-ACC network). Furthermore, unlike female HCs, the female MDD group failed to show a significant increase of deactivation over stress exposure time in the amygdala, mOFC and NAc. Our findings confirm the importance of considering sex differences when investigating neural stress responses. Case-control differences in neural stress responses observed in females (but not males) provide insights into sex differences in the etiology and pathophysiology of depression. The failure to deactivate limbic/NAc regions in depressed females point to dysfunction of adaptive stress responses over stress exposure time.

High-frequency repetitive transcranial magnetic stimulation alleviates the cognitive side effects of electroconvulsive therapy in major depression

“…The design of the current study was retrospective, and the sample size is small. A larger and more representative sample is needed to confirm our findings and distinguish the efficacy of HF-rTMS and ECT in female and male MDD patients because fMRI findings have revealed that male MDD patients exhibited increased neural stress responses in the DLPFC and frontoparietal network (PFN), while female MDD patients explored less deactivation in limbic-striatal regions including the amygdala, hippocampus, and nucleus accumbens (NAc) ( 50 ). Moreover, there was a small difference in the variables of family history and duration of illness ( Table 1 ).…”

Brain-based Sex Differences in Depression: A Systematic Review of Neuroimaging Studies

“…Thirty studies were included in our systematic review: 15 MRI studies (Ancelin et al, 2019 ; Carceller-Sindreu et al, 2015 ; Cyprien et al, 2014 ; Furtado et al, 2008 ; Hastings et al, 2004 ; Kong et al, 2013 ; Kronmüller et al, 2009 ; Lavretsky et al, 1998 ; Lewine et al, 1995 ; MacMaster et al, 2006 ; Nielsen et al, 2020 ; Piani et al, 2021 ; Ritter et al, 2021 ; Soriano-Mas et al, 2011 ; Yang et al, 2017 ), 12 fMRI studies (De Almeida et al, 2011 ; Amiri et al, 2021 ; Briceño et al, 2015 ; Chuang et al, 2017 ; Dong et al, 2022 ; Geng et al, 2019 ; Jenkins et al, 2018 ; Mei et al, 2022 ; Piani et al, 2021 ; Talishinsky et al, 2022 ; Yao et al, 2014 ; Young et al, 2017 ), and 4 DTI ones (Ho et al, 2021 ; Kliamovich et al, 2021 ; Lyon et al, 2019 ; Ugwu et al, 2015 ) (One study had assessed both MRI and fMRI findings (Piani et al, 2021 ). The publication year of MRI studies varied from 1995 to 2022.…”

“…Details of medication regimens in depressed subjects were provided in 25 studies. Among these, participants of 12 studies did not take any medications (Dong et al, 2022 ; Hastings et al, 2004 ; Jenkins et al, 2018 ; Kliamovich et al, 2021 ; Kong et al, 2013 ; Lavretsky et al, 1998 ; MacMaster et al, 2006 ; Mei et al, 2022 ; Piani et al, 2021 ; Ritter et al, 2021 ; Yang et al, 2017 ; Yao et al, 2014 ; Young et al, 2017 ). Eleven studies' probands administered antidepressants (De Almeida et al, 2011 ; Ancelin et al, 2019 ; Chuang et al, 2017 ; Cyprien et al, 2014 ; Furtado et al, 2008 ; Geng et al, 2019 ; Kronmüller et al, 2009 ; Lyon et al, 2019 ; Piani et al, 2021 ; Talishinsky et al, 2022 ; Ugwu et al, 2015 ).…”

Bilateral repetitive transcranial magnetic stimulation ameliorated sleep disorder and hypothalamic–pituitary–adrenal axis dysfunction in subjects with major depression

“…For serum COR level, our data did not indicate that there was a significant difference between sham and rTMS stimulation in male MDD participants ( Figure 4C ). Recently, fMRI findings have revealed that male patients with MDD exhibited increased neural stress responses in the DLPFC and frontoparietal network (PFN) relative to females, and less deactivation in limbic-striatal regions, namely, the amygdala, hippocampus, and nucleus accumbens (NAc) was only observed in female patients with MDD ( 44 ). Therefore, the effect of bilateral rTMS over DLPFC on depression and HPA function was only observed in male patients with MDD.…”