Sex Differences of the Functional Brain Activity in Treatment-Resistant Depression: A Resting-State Functional Magnetic Resonance Study

Abstract

The presence of different clinical symptoms in patients with treatment-resistant depression (TRD) of different sexes may be related to different neuropathological mechanisms. A total of 16 male patients with TRD, 18 female patients with TRD, 18 male healthy controls (HCs) and 19 female HCs completed this study. We used the amplitude of low frequency fluctuations (ALFF) method to analyze the results. Moreover, the correlation between abnormal brain areas and clinical symptoms in different sexes of the TRD groups was also analyzed. The effects of the sex-by-group interaction difference in ALFF among the four groups was located in the left middle frontal gyrus, left precentral gyrus and left precuneus. Post hoc comparisons revealed that the male TRD group had lower ALFF in the left middle frontal gyrus and left precentral gyrus compared with the female TRD group. There was a positive correlation between the left middle frontal gyrus, the left precuneus and the 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores, and a negative correlation between the left precentral gyrus and the HAMD-17 scores in the female TRD group. This study will provide some clinical reference value for the sex differences in neuropathological mechanisms of TRD.

Shared and distinct prefrontal cortex activation between genders in depression individuals during verbal fluency task: evidence from one large sample of fNIRS studies

“…Furthermore, amplitude of low-frequency uctuation (ALFF) differences between males and females with MDD was discovered in some brain regions of the frontoparietal network, attention network (left superior temporal pole, left inferior parietal lobule), cerebellum network, and auditory network in a resting-state functional magnetic resonance imaging (fMRI) study. This nding is linked to the varying prevalence rates among the genders (Sun et al, 2022).Another study discovered that the male MDD exhibited lower ALFF of the bilateral caudate nucleus and posterior cingulate gyrus than the female MDD, indicating that the functional brain activity in MDD may differ between the sexes (Yao et al, 2014). Besides, for different severity of depression subtypes, compared with bipolar depression, region-speci c fNIR leads show unipolar depression patients had signi cant lower hemodynamic activation in ventrolateral prefrontal cortex (VLPFC) (Feng et al, 2021).…”

Sex Differences in the Antidepressant and Neurocognitive Effects of Nonconvulsive Electrotherapy in Patients with Treatment-Refractory Depression

“… 10 Additionally, numerous studies have indicated that females with TRD tend to experience more severe depressive and anxiety symptoms than males 11 - 13 due to different neuropathological mechanisms. 18 , 19 Furthermore, a substantial body of evidence indicated that sex-related factors possess the potential to influence the outcomes of treatments (both pharmacological and non-pharmacological treatments) for patients with TRD, 14 - 16 this underscores the significance of taking into account sex disparities when evaluating treatment effectiveness. For instance, males and females with TRD exhibit varying responses to antidepressant augmentation strategies, involving mood stabilizers, antipsychotics, or a combination of both, with females deriving significantly greater benefit in one study.…”

Sex Differences in the Antidepressant Effects of Ketamine

“…A recent study states that regarding symptomatology, female MDD patients scored higher on measures of psychological anxiety, somatic anxiety and guilt than males (Vetter et al, 2021). The likelihood of somatic symptom onset was also increased in female TRD patients compared to male TRD patients (Sun et al, 2022). There are also sex differences in treatment response; female TRD patients respond more strongly than their male counterparts to antidepressant treatment supplemented by an antipsychotic or mood stabilizing drug (Moderie et al, 2022).…”