Table 4.

Overview of fMRI studies on sex differences in depression

Study	Tesla sequence	Brain areas	Connectivity/activation	Task	Methods for Sex Differences Analyses Sex by Diagnosis Effects			Covariates	Results
					Model	Tested?	Findings
Amiri et al., 2021	3 T	SCG VCa NAc ITP LHb	Rs-FC	N/A	Nonparametric permuation	Yes	Yes	N/A	Difference in degree values in the SCG between males and females of the TRD. Higher degree values in all regions in the TRD females except in the R LHb.
Briceño et al., 2015	3 T	Fronto-limbic regions	Activation	Facial emotion perception test	ANOVA	Yes	No	N/A	Among fronto-limbic regions, there were no regions significant for an MDD status by gender interaction.
Chuang et al., 2017	3 T	Whole brain	Activation	Affective go/no-go task	GLM	Yes	Yes	Age	Significant group-by-sex differences in the activation of the supramarginal gyrus and posterior cingulate cortex, as those of male controls were more activated than female controls, but the activation of those in depressed males was lower than in depressed females.
De Almeida et al., 2011	3 T	prefrontal cortical–amygdala neural circuitry	Activation	Facial emotion perception test	Spearman rank correlation tests and Mann–Whitney U-tests	Yes	Yes	N/A	In MDD patients, there were no significant effects of sex on any of the connectivity measures. In between-group analysis, there were abnormal inverse left-sided top-down vmPFC-amygdala connectivity, left-sided sgACC–amygdala connectivity, and reduced positive left-sided vmPFC-sgACC to happy faces in females with MDD when compared to their healthy counterparts. In response to fearful faces, there was an abnormally increased positive left-sided sgACC–amygdala connectivity in MDD females. For males with MDD relative to healthy males, there were no significant abnormal findings.
Dong et al., 2022	3 T	Amygdala, hippocampus, medial orbitofrontal cortex, nucleus accumbens, and dorsolateral prefrontal cortex	Activation	Montreal imaging stress task	GLM	Yes	Yes	Age	Less deactivation in the amygdala, hippocampus, and nucleus accumbens of the female MDD group relative to the female HC group, whereas the male MDD and HC did not differ regarding the deactivation/activation of these regions.
Geng et al., 2019	3 T	Whole brain	Rs-FC	N/A	GLM	Yes	Yes	Age, years of education, disease duration, age at onset, number of depressive episodes, HAMD-17 score	Increased ReHo in the R STG and decreased ReHo in the R MFG in SD women compared to NSD women. Higher ReHo in the L inferior triangular frontal gyrus in both SD and NSD males.
Jenkins et al., 2018	3 T	Whole brain	Activation	Facial emotion perception test	GLM	Yes	Yes	Accuracy for each emotion, site	Greater activity in male HCs and rMDD females compared to their counterparts in either groups in the R thalamic cluster for the neutral contrast and in the R SFG cluster for the sad contrast. The opposite pattern in the L MTG and bilateral midbrain for sad contrast. No significant associations in the amygdala.
Mei et al., 2022	3 T	Whole brain	Rs-FC	N/A	ANOVA	Yes	Yes	N/A	Decreased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus of MDD males compared to MDD females and HC females. Increased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus of MDD females compared to HC males.
Piani et al., 2021	3 T	Whole brain	Activation	Affective go/no-go task	GLM	Yes	Yes	Percent of responses to target stimuli, time of response to target stimuli, and percent of responses to non-target stimuli	More negative responses during the overall task and go/no-go condition in the right parahippocampus of MDD females compared to MDD males and in that of HC males than HC females More negative response during the task in the right calcarine of MDD females compared to MDD males and in that of HC males than HC females
Talishinsky et al., 2022	3 T	Whole brain	Rs-FC	N/A	ANOVA	Yes	Yes	N/A	Increased connectivity in subgenual cingulate and posterior cingulate areas and decreased connectivity in the anterior insula, temporal pole, and lateral prefrontal cortex in MDD males compared to HC males. None were seen in females.
Yao et al., 2014	3 T	Frontoparietal networks and attention network	Rs-FC	N/A	ANOVA	Yes	Yes	N/A	Higher ALFF values in the left postcentral gyrus and right superior temporal gyrus and lower ALFF values in the left superior temporal pole, left superior temporal gyrus, and the left superior frontal gyrus in male MDD patients when compared to female MDD patients
Young et al., 2017	3 T	Whole brain	Activation	Autobiographical memory recall	ANOVA	Yes	Yes	N/A	Increased activity in the right dmPFC of MDD males compared to all other groups during recall of positive memories. Decreased activity in the right caudate of MDD females compared to all other groups during recall of positive memories. Increased activity in PCC and insula of HC females compared to both male groups during recall of negative memories. Decreased activity in precuneus of HC males compared to all other groups during recall of negative memories

Abbreviations: fMRI: Functional magnetic resonance imaging, Rs: Resting state, FC: Functional connectivity, SCG: Subcallosal cingulate gyrus, VCa: Ventral caudate, NAc: Nucleus accumbens, LHb: Lateral habenula, ITP: Inferior thalamic peduncle, ANOVA: analysis of variances, vmPFC: ventromedial prefrontal cortex, sgACC: subgenual anterior cingulate cortex, STG: Superior temporal gyrus, MFG: Middle frontal gyrus, MTG: middle temporal gyrus, SFG: Superior frontal gyrus, ReHo: Regional homogeneity, MDD: major depressive disorder, rMDD: Remitted major depressive disorder, SD: Somatic depression, NSD: Non-somatic depression, TRD: Treatment-resistant depression, ALFF: amplitude of low-frequency fluctuation, dmPFC: dorsomedial prefrontal cortex, PCC: posterior cingulate cortex, HC: Healthy control, HAMD: Hamilton Depression Rating Scale, GLM: General linear model, T: Tesla, N/A: Not applicable, R: Right, L: Left.