Male Major Depressive Disorder Research Articles

Gender differences in plasma S100B levels of patients with major depressive disorder

BackgroundLow concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders.MethodsWe studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov–Smirnov test was used to test the normality of six groups of S100B samples. The Mann–Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis.ResultsAll individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation.ConclusionsIn summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder

BackgroundIt is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. Methods109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. ResultsIn individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. ConclusionsOur findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

Sex-specific resting state brain network dynamics in patients with major depressive disorder.

Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.

Prevalence of sexual dysfunction and its association with psychological symptoms in drug-naive major depressive disorder patients in West China.

Sexual dysfunction is commonly observed in individuals with Major Depressive Disorder (MDD), along with various psychological symptoms such as anxiety, somatic complaints, interpersonal sensitivity, and obsessive-compulsive tendencies. However, there is a research gap in understanding the impact of these psychological symptoms on sexual functioning in MDD. Furthermore, there is limited data on the incidence of sexual dysfunction among drug-naive MDD patients in West China. This study aims to determine the prevalence of sexual dysfunction in this patient population and explore its association with other psychological indicators. We conducted a retrospective analysis of patient data from October 2020 to September 2022 using propensity score matching. A focused group of 165 males and 490 females was selected from a total of 1941 MDD patients. This allowed for a comparative analysis of demographic data, as well as scores from the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Symptom Checklist-90 (SCL-90), the Arizona Sexual Experience Scale (ASEX). Our findings reveal that 46.2% of drug-naive MDD patients experienced sexual dysfunction. Notably, there was a higher prevalence of sexual dysfunction among female patients (50.3%) compared to males (37.5%). MDD patients without sexual dysfunction consistently exhibited higher SDS scores than those with sexual dysfunction (p < 0.01), There were no statistically significant differences between male and female MDD patients with or without concomitant sexual dysfunction in terms of Somatic complaints, Obsessive-compulsive, Interpersonal sensitivity, Anxiety, Phobic anxiety, Paranoid ideation, Psychoticism and Diet/sleep difficulties (p > 0.05). In addition, male MDD patients with sexual dysfunction showed a emerging trend towards elevated Hostility scores on the SCL-90 (p = 0.058), male MDD patients with sexual dysfunction showed an increasing trend in hostility scores on the SCL-90, whereas female MDD patients with sexual dysfunction did not show such a trend. The study highlights a significant gender difference in the prevalence of sexual dysfunction among MDD patients, with females being more susceptible than males. There is a positive correlation between the severity of depression and sexual dysfunction in both genders. Interestingly, male MDD patients demonstrated a potential protective effect of hostility against sexual dysfunction, which was not observed in female patients.

Exploring specific associations of childhood maltreatment with social cognition in drug-naive first-episode major depressive disorder: a sex-centric approach.

Childhood maltreatment (CM) has been linked to social cognition deficits in major depressive disorder (MDD), but little is known about sex-specific effects. This study aimed to investigate the sex-specific associations of CM with social cognition in first-episode drug-naive patients with MDD. A total of 117 first-episode drug-naive patients with MDD and 134 healthy controls (HCs) were recruited and assessed for demographic and clinical characteristics. All participants completed the Childhood Trauma Questionnaire (CTQ), Toronto Alexithymia Scale (TAS-20), Interpersonal Reactivity Index-C (IRI), and Facial Emotion Recognition Test. Partial correlation analysis was used to explore the sex-specific association of CM with social cognition. Our findings revealed significant differences in the associations of CM with social cognition between males and females in MDD patients. In comparison to HCs, the associations of CM with social cognition displayed distinct and even contrasting sex-specific patterns in MDD patients. Specifically, male MDD patients exhibited unique imbalanced associations between emotional neglect and alexithymia, while both female and male MDD patients shared imbalanced associations of childhood abuse with empathy. These results emphasize the importance of considering the sex-specific associations of CM with social cognition in MDD and highlight the need for personalized interventions and treatments based on sex for MDD patients with a history of CM.

Loneliness is related to smaller gray matter volumes in ACC and right VLPFC in people with major depression: a UK biobank study.

The anterior cingulate cortex (ACC) and right ventrolateral prefrontal cortex (VLPFC) are thought to have important roles in loneliness (feeling of social isolation/exclusion) experience or regulation and in the pathophysiology of their disturbance in major depressive disorder (MDD). However, the structural abnormalities of these regions and the correlates with loneliness in MDD across the healthy population have not fully been clarified. The study analyzed the link between loneliness and gray matter volumes (GMVs) in the ACC and right VLPFC among 1,005 patients with MDD and 7,247 healthy controls (HCs) using UK Biobank data. Significant reductions in GMV in the right VLPFC were found in MDD males compared to HCs. MDD males also showed a higher association between loneliness and reduced GMVs in the right VLPFC and bilateral ACC than HCs. No such associations were found in MDD females. The findings suggest that loneliness may influence brain structures crucial for emotion experience and regulation, particularly in middle-older aged men with MDD. This highlights the potential adverse effects of loneliness on brain structure in MDD and suggests that social engagement could have a positive impact.

Prevalence and associated clinical factors for overweight and obesity in young first-episode and drug-naïve Chinese patients with major depressive disorder.

Obesity and overweight are common in young patients with major depressive disorder (MDD). However, the prevalence and associated clinical factors of obesity/overweight in young first-episode and drug-naïve (FEDN) MDD patients are rarely reported in China. A cross-sectional study of 917 young patients (aged 18-35 years) with FEDN MDD was performed. Demographic and clinical data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. Among the young MDD patients, the prevalence of obesity and overweight was 4.14 and 52.89%, respectively. Compared to normal-weight patients, overweight patients were older, had a greater age of onset, and had higher TSH and TG levels. Male MDD patients had a higher risk of obesity than female patients. Compared to obese patients, normal-weight and overweight patients had significantly lower HAMD scores, TC levels, and rates of TSH abnormalities. Logistic regression analysis showed that age, age of onset, and sex were independently associated with obesity, and TSH was independently associated with both obesity and overweight, in young MDD patients. Our findings suggest a high prevalence of overweight and obesity in young FEDN MDD patients. Several demographic and clinical variables are independently associated with overweight/obesity in these young MDD patients.

Gender differences in the association between anxiety symptoms and thyroid hormones in young patients with first-episode and drug naïve major depressive disorder.

Gender differences are prevalent in major depressive disorder (MDD), but the gender differences in the relationship between comorbid anxiety and thyroid hormones in young first-episode and drug-naive (FEND) MDD patients are unknown. A total of 1,289 young outpatients with FEDN MDD were recruited. Demographic and clinical data were collected for each patient. The patient's blood glucose, blood pressure, thyroid hormone, and thyroid antibody levels were measured. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess patients' depression, anxiety, and positive symptoms, respectively. The prevalence of comorbid anxiety disorders was 80.4 and 79.4% in male and female MDD patients, respectively. Patients with anxiety had higher HAMD and PANSS scores, higher serum thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (A-TG), and thyroid peroxidase antibody (A-TPO) levels, higher blood glucose and blood pressure levels, and more patients with psychotic symptoms and suicide attempts. Male patients were younger and had a younger age of onset. Logistic regression analysis showed that HAMD score and comorbid suicide attempts were significant predictors of anxiety symptoms in both males and females, whereas A-TG predicted anxiety symptoms in female patients only. Limitations: No causal relationship could be drawn due to the cross-sectional design. This study showed gender differences in factors associated with anxiety symptoms in patients with MDD. Some factors were associated with anxiety symptoms in both male and female patients, while A-TG was only associated with anxiety symptoms in female patients.

Gender differences in the prevalence and clinical correlates of thyroid dysfunction in patients with first-episode and drug-naïve major depressive disorder with comorbid suicide attempts: a large cross-sectional study

BackgroundGender differences in patients with major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) MDD patients with comorbid suicide attempts have not been reported. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid abnormal thyroid function (ATF) in FEDN MDD patients with comorbid suicide attempts.MethodsA cross-sectional study of 1718 FEDN MDD patients was conducted. The demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to assess depression, anxiety and psychotic symptoms, respectively. Thyroid function parameters and blood glucose levels were measured.ResultsThere was no gender difference in the prevalence of ATF between male (78.6%, 88/112) and female MDD patients (74.8%, 175/234) with comorbid suicide attempts. In the male and female subgroups, duration of disease, HAMD score, HAMA score, anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), diastolic blood pressure (DBP), systolic blood pressure (SBP), glucose level and the rate of psychotic symptoms were higher in patients with ATF than those without ATF in MDD with comorbid suicide attempt (all P < 0.05). There was a gender main effect only on SBP (F = 7.35, P = 0.007). Furthermore, binary logistic regression analysis showed that HAMD score, DBP and glucose levels were independently with ATF in both male and female MDD patients with comorbid suicide attempts. However, anxiety symptoms, psychotic symptoms and TPOAb levels were significantly associated with ATF only in female MDD patients with comorbid suicide attempts.ConclusionOur study showed no gender differences in the prevalence of ATF in FEDN MDD patients with comorbid suicide attempts. Depression, DBP and glucose levels were associated with ATF in both male and female MDD patients with comorbid suicide attempts, whereas anxiety, psychotic symptoms and TPOAb level were correlated with ATF only in female MDD patients with suicide attempts.

Sex effects on differentiating patients with major depressive disorder from bipolar disorder in depressive state: A fMRI study with follow-up

BackgroundBipolar disorder (BD) is difficult to discriminate from major depressive disorder (MDD) before the appearance of mania or hypomania. This study was designed to identify whether patients with MDD and those who converted to BD are distinguishable using dynamic amplitude low-frequency fluctuations (dALFF) and describe the sex effects on the identification of the two disorders. MethodsWe compared the dALFF values of 35 BD patients who converted from MDD during the 2-year follow-up, 99 MDD patients, and 130 healthy controls (HCs) using two-way ANOVA. Pearson's correlation was used to compare dALFF in dysfunctional brain regions and clinical characteristics. ResultsA main effect of diagnosis was discovered in the frontal and occipital gyrus. For the main effect of sex, both the left middle occipital gyrus and the medial part of the superior frontal gyrus had higher dALFF values in males compared to females. An interaction of sex and diagnosis effect was observed in the right precentral gyrus. Male MDD patients exhibited a higher dALFF value than male BD patients. Additionally, we discovered a higher dALFF value in females than in males in BD patients. WCST scores were positively associated with dALFF values in the frontal and occipital gyrus in MDD patients. Meanwhile, dALFF values in the occipital gyrus positively correlated with WCST in female MDD patients only. LimitationMost of the participants were on medication and the sample size was small. ConclusionsOur study is the first to find the non-neglectable role of sex effects in differentiating BD and MDD at an early stage.

HMGB1/STAT3/p65 axis drives microglial activation and autophagy exert a crucial role in chronic Stress-Induced major depressive disorder

IntroductionNeuroinflammation and autophagy are implicated in stress-related major depressive disorder (MDD), but the underlying molecular mechanisms remain largely unknown. ObjectivesHere, we identified that MDD regulated by HMGB1/STAT3/p65 axis mediated microglial activation and autophagy for the first time. Further investigations were performed to uncover the effects of this axis on MDD in vivo and in vitro. MethodsBioinformatics analyses were used to re-analysis the transcriptome data from the dorsolateral prefrontal cortex (dlPFC) of post-mortem male MDD patients. The expression level of HMGB1 and its correlation with depression symptoms were explored in MDD clinical patients and chronic social defeat stress (CSDS)-induced depression model mice. Specific adeno-associated virus and recombinant (r)HMGB1 injection into the medial PFC (mPFC) of mice, and pharmacological inhibitors with rHMGB1 in two microglial cell lines exposed to lipopolysaccharide were used to analyze the effects of HMGB1/STAT3/p65 axis on MDD. ResultsThe differential expression of genes from MDD patients implicated in microglial activation and autophagy regulated by HMGB1/STAT3/p65 axis. Serum HMGB1 level was elevated in MDD patients and positively correlated with symptom severity. CSDS not only induced depression-like states in mice, but also enhanced microglial reactivity, autophagy as well as activation of the HMGB1/STAT3/p65 axis in mPFC. The expression level of HMGB1 was mainly increased in the microglial cells of CSDS-susceptible mice, which also correlated with depressive-like behaviors. Specific HMGB1 knockdown produced a depression-resilient phenotype and suppressed the associated microglial activation and autophagy effects of CSDS-induced. The effects induced by CSDS were mimicked by exogenous administration of rHMGB1 or specific overexpression of HMGB1, while blocked by STAT3 inhibitor or p65 knockdown. In vitro, inhibition of HMGB1/STAT3/p65 axis prevented lipopolysaccharide-induced microglial activation and autophagy, while rHMGB1 reversed these changes. ConclusionOur study established the role of microglial HMGB1/STAT3/p65 axis in mPFC in mediating microglial activation and autophagy in MDD.

Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes

Major depressive disorder (MDD) is a common, heterogenous, and potentially serious psychiatric illness. Diverse brain cell types have been implicated in MDD etiology. Significant sexual differences exist in MDD clinical presentation and outcome, and recent evidence suggests different molecular bases for male and female MDD. We evaluated over 160,000 nuclei from 71 female and male donors, leveraging new and pre-existing single-nucleus RNA-sequencing data from the dorsolateral prefrontal cortex. Cell type specific transcriptome-wide threshold-free MDD-associated gene expression patterns were similar between the sexes, but significant differentially expressed genes (DEGs) diverged. Among 7 broad cell types and 41 clusters evaluated, microglia and parvalbumin interneurons contributed the most DEGs in females, while deep layer excitatory neurons, astrocytes, and oligodendrocyte precursors were the major contributors in males. Further, the Mic1 cluster with 38% of female DEGs and the ExN10_L46 cluster with 53% of male DEGs, stood out in the meta-analysis of both sexes.

Prevalence and correlates of dyslipidemia in first-episode and drug-naïve major depressive disorder patients with comorbid abnormal glucose metabolism: Sex differences.

Lipid metabolism is associated with glucose metabolism, but whether there are variations between sexes in risk factors and prevalence of abnormal lipid metabolism in major depressive disorder (MDD) patients with glucose metabolism abnormalities remains ambiguous. In the present study, the frequency and risk factors of dyslipidemia in first-episode and drug-naïve (FEDN) MDD patients with dysglycemia were examined according to sex. One thousand seven hundred and eighteen FEDN MDD patients were recruited and their demographic data, clinical data, various biochemical indicators and scale assessment scores including 17-item Hamilton Rating Scale for Depression (HAMD-17), 14-item Hamilton Anxiety Rating Scale (HAMA-14), and positive subscale of the Positive and Negative Syndrome Scale (PANSS) were collected. The prevalence of abnormal lipid metabolism in both male and female MDD patients with abnormal glucose metabolism was higher than that in patients without abnormal glucose metabolism. Among male MDD patients with abnormal glucose metabolism, TC was positively correlated with HAMD score, TSH and TgAb levels, but negatively correlated with PANSS positive subscale scores. LDL-C was positively correlated with TSH and BMI, but negatively correlated with PANSS positive subscale scores. HDL-C was negatively correlated with TSH levels. Among females, TC was positively correlated with HAMD score, TSH, and BMI, but negatively correlated with PANSS positive subscale score. LDL-C was positively correlated with HADM score and negatively correlated with FT3 level. HDL-C was negatively correlated with TSH and BMI levels. There are sex differences in the correlated factors of lipid markers in MDD patients with impaired glucose.

Sex differences in the association of plasma cytokines and neurocognition in first-episode major depressive disorder

BackgroundPeripheral cytokines were found to be involved in the pathophysiology of neurocognition in individuals with major depressive disorder (MDD). However, whether there are sex differences in this association between cytokines and cognition in MDD remains unknown. Our aim is to examine sex differences in the relationship between plasma cytokines and cognition in MDD. MethodOne hundred and twenty-seven first episode drug naïve patients with MDD and sixty healthy controls (HCs) were recruited for present study. The MATRICS Consensus Cognitive Battery was administered to measure the cognition. Plasma concentrations of nineteen cytokines were measured using high sensitivity multiplex bead-based assays. ResultsBoth female and male patients with MDD had significant cognitive impairment in verbal learning and visual learning and had higher levels of a range of cytokines than HCs (all p < 0.05). Female patients performed worse in trail making (F = 4.442, p = 0.018) and had higher concentration of interleukin (IL)-4 (F = 7.775, p = 0.006) than males. In female MDD, a significant positive association between category frequency and level of IL-4 was observed (B = 8.040, p = 0.031). However, this association was not present in male MDD or HCs (p > 0.05). LimitationPresent study used a cross-sectional design. ConclusionFemale MDD patients had worse trail making performance and higher level of IL-4 than males. The elevated IL-4 in female MDD was positively associated with category fluency, suggesting that IL-4 may be involved in the pathophysiology related to specific cognitive domain in female MDD patients.

Association Between Serum Uric Acid Levels and Suicide Attempts in Adolescents and Young Adults with Major Depressive Disorder: A Retrospective Study.

PurposeUric acid (UA) is thought to exert neuroprotective roles. The purpose of this study was to examine the association of serum UA with suicide attempts (SA) in adolescents and young adults with major depressive disorder (MDD).Patients and MethodsWe retrospectively recruited 533 participants with MDD aged 13 to 25 years, of which 168 had a history of SA in the past three months and 365 did not have a history of SA. Serum UA levels were measured using the uricase-peroxidase coupling method. In addition to overall serum UA level comparison in MDD individuals with and without SA, a stratified analysis by biological sex was carried out.ResultsCompared to MDD individuals without a history of SA, serum UA levels were significantly lower in MDD individuals with SA (P < 0.001). Female MDD, but not male MDD individuals, with SA exhibited lower levels of UA than those without SA (P < 0.01). Importantly, serum UA remained significantly associated with SA in MDD individuals (OR = 0.996, 95% CI: 0.993~0.999, P < 0.01) when controlling for possible confounding variables.ConclusionThis research identifies a relationship between serum UA levels and SA in adolescents and young adults with MDD. UA may represent a biological risk marker for SA, in particular for female MDD individuals.

Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression

Major depressive disorder (MDD) is amongst the most devastating psychiatric conditions affecting several millions of people worldwide every year. Despite the importance of this disease and its impact on modern societies, still very little is known about the etiological mechanisms. Treatment strategies have stagnated over the last decades and very little progress has been made to improve the efficiency of current therapeutic approaches. In order to better understand the disease, it is necessary for researchers to use appropriate animal models that reproduce specific aspects of the complex clinical manifestations at the behavioral and molecular levels. Here, we review the current literature describing the use of mouse models to reproduce specific aspects of MDD and anxiety in males and females. We first describe some of the most commonly used mouse models and their capacity to display unique but also shared features relevant to MDD. We then transition toward an integral description, combined with genome-wide transcriptional strategies. The use of these models reveals crucial insights into the molecular programs underlying the expression of stress susceptibility and resilience in a sex-specific fashion. These studies performed on human and mouse tissues establish correlates into the mechanisms mediating the impact of stress and the extent to which different mouse models of chronic stress recapitulate the molecular changes observed in depressed humans. The focus of this review is specifically to highlight the sex differences revealed from different stress paradigms and transcriptional analyses both in human and animal models.

Study of Sex Differences in Unmedicated Patients With Major Depressive Disorder by Using Resting State Brain Functional Magnetic Resonance Imaging.

Some important clinical characteristics of major depressive disorder (MDD) differ between sexes. We explored abnormal spontaneous neuronal activity in MDD patients using the amplitude of low-frequency fluctuation (ALFF) and its relationship to clinical manifestations in male and female patients, to seek the neural mechanisms underlying sex-related differences in depression. Twenty-five male MDD patients, 36 female MDD patients, and 25 male and 36 female matched healthy controls (HC) were included. The ALFF difference was investigated among four groups, and partial correlation analysis was used to explore a possible clinical relevance. The main effect results of sex difference were located in the bilateral caudate nucleus and posterior cingulate gyrus. Post hoc comparisons found that the male MDD patients showed decreased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus when compared with female MDD patients/female HCs, and female MDD patients showed increased ALFF in the bilateral caudate nucleus and posterior cingulate gyrus when compared with male HCs. The average ALFF of the right caudate nucleus was positively correlated with illness duration in female MDD patients. Our results suggest that the sex-specific abnormal brain activity might be a potential pathomechanism of different symptoms in male and female MDD patients.

Associations between Sex Hormones and Circulating Growth Differentiation Factor-15 in Male Patients with Major Depressive Disorder

The interaction between the endocrine system and inflammation is crucial pathogenesis of depression. Our study aimed at exploring the possible relationship between sex hormones and growth differentiation factor-15 (GDF-15), a common indicator of inflammation in male patients with major depressive disorder (MDD). Methods: GDF-15 levels of 121 male MDD patients were compared with 105 healthy subjects with the help of a Cobas 8000 automatic chemiluminescence immunoanalyzer. Results: (1) MDD patients showed higher GDF-15 levels, a lower testosterone (T) level and testosterone/estradiol ratio (T/E2 ratio) than healthy subjects (all p < 0.05). (2) Serum T levels and the T/E2 ratio were inversely associated with GDF-15 serum levels (all p < 0.05). (3) HAMD-24 scores were positively correlated with the levels of GDF-15 (p < 0.01), but not with T levels, estradiol (E2) levels, and the T/E2 ratio (all p > 0.05). Conclusion: The high level of GDF-15 was correlated with a low T/E2 ratio and T deficiency in male MDD patients. The above results demonstrate that up-regulation of serum GDF-15 and down-regulation of T and T/E2 ratio may be correlated with the occurrence and severity of depression. So, changing the level of GDF-15 by regulating the proportion of sex hormones may play a key role in the prognosis and treatment of depression.

Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder

Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.