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.

The presence of reward deficits in major depressive disorder is associated with abnormal striatal function. However, differences in striatal whole-brain functional between recurrent depressive episode (RDE) and first-episode depression (FDE) have not been elucidated. Thirty-three patients with RDE, 27 with FDE, and 35 healthy controls (HCs) were recruited for this study. A seed-based functional connectivity (FC) method was used to analyze abnormalities in six predefined striatal subregion circuits among the three groups of subjects and to further explore the correlation between abnormal FC and clinical symptoms. The results revealed that compared with the FDE group, the RDE group showed higher FC of the striatal subregion with the left middle occipital gyrus, left orbital area of the middle frontal gyrus, and bilateral posterior cerebellar gyrus, while showing lower FC of the striatal subregion with the right thalamus, left inferior parietal lobule, left middle cingulate gyrus, right angular gyrus, right cerebellum anterior lobe, and right caudate nucleus. In the RDE group, the HAMD-17 scores were positively correlated with the FC between the left dorsal rostral putamen and the left cerebellum posterior lobe. This study provides new insights into understanding the specificity of striatal circuits in the RDE group.

In this study, we observed the sex differences in functional brain activity in patients with recurrent depressive disorder (RDE) and assessed the correlation between abnormal functional brain activity changes and clinical symptoms. A total of 40 patients with RDE (19 male and 21 female) and 42 healthy controls (HCs) (20 male and 22 female) met the inclusion criteria. Analysis of images using regional homogeneity (ReHo) and further analysis of the correlation between abnormal brain areas and clinical symptoms of the different sexes with RDE groups were carried out. For the main effects of sex (male vs. female), there were statistically significant differences in ReHo among the four groups in the right middle temporal gyrus, right thalamus, and left posterior cerebellar lobe. For the effects of the sex-by-group interaction, there were statistically significant differences in ReHo among the four groups in the left middle frontal gyrus, left precentral gyrus, and right insula. Post hoc analyses showed that compared with the female RDE group, the male RDE group had decreased ReHo in the left middle frontal gyrus and right insula. In the female RDE group, the ReHo values of the left middle frontal gyrus were positively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17) scores. This study provides new insights into the clinical targeting of different sexes for RDE.