Male Major Depressive Disorder Patients Research Articles

The relationship between plasma interleukin-6 and cognition based on curve correlation in drug-naïve patients with major depressive disorder

BackgroundThe effect of interleukin-6 (IL-6) on cognition in patients with major depressive disorder (MDD) remains unclear. The aim of the present study was to investigate for the first time the non-linear relationship between plasma IL-6 and cognition and its sex-specific associations in patients with drug-naïve MDD. MethodsA total of 326 participants, including 237 drug-naïve MDD patients and 89 healthy controls (HCs), were included in this study. All participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and fasting venous blood was collected for IL-6 measurement. Patients with MDD completed the Hamilton Depression Scale-17 (HAMD-17) and the Hamilton Anxiety Scale-14 (HAMA-14) assessments. Two-way analysis of variance and curve estimation analyses were used to explore the effects of IL-6 on cognition and its sex differences. ResultsWe found that IL-6 and cognition were associated in different patterns in HCs and MDD patients. The best model for curve estimation between IL-6 and attention (F = 2.736, p = 0.045) and HAMA (F = 6.416, p < 0.001) in females with MDD was the cubic model. In male MDD patients, the best model for curve estimation between IL-6 and immediate memory was the cubic model (F = 3.077, p = 0.034). However, in HCs, the best model for curve estimation analysis between IL-6 and language was the quadratic model (F = 3.803, p = 0.026). LimitationsThe main limitations were cross-sectional design. ConclusionThere was a non-linear and sex-specific relationship between IL-6 levels and cognition in patients with MDD.

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.

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.

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.

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.

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.

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.

Preliminary Study on Changes of Sleep EEG Power and Plasma Melatonin in Male Patients With Major Depressive Disorder After 8 Weeks Treatment.

Objective: To clarify the effects of escitalopram on sleep EEG power in patients with Major depressive disorder (MDD).Method: Polysomnography (PSG) was detected overnight, and blood samples were collected at 4 h intervals over 24 h from 13 male healthy controls and 13 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included plasma melatonin levels, sleep architecture, and the sleep EEG power ratio.Results: Compared with healthy controls, MDD patients presented abnormalities in the diurnal rhythm of melatonin secretion, including peak phase delayed 3 h and a decrease in plasma melatonin levels at night and an increase at daytime, accompanied by sleep disturbances, a decrease in low-frequency bands and an increase in high-frequency bands, and the dominant right-side brain activity. Several of these abnormalities (abnormalities in the diurnal rhythm of melatonin secretion, partial sleep architecture parameters) persisted for at least the 8-week testing period.Conclusions: Eight weeks of treatment with escitalopram significantly improved subjective sleep perception and depressive symptoms of patients with MDD, and partially improved objective sleep parameters, while the improvement of circadian rhythm of melatonin was limited.

Gender differences in prevalence and clinical correlates of anxiety symptoms in first-episode and drug-naïve patients with major depressive disorder

AimGender differences in major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) patients with major depressive disorder remain unclear. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid anxiety in FEDN patients with MDD. MethodsA cross-sectional study was conducted with1718 FEDN patients with MDD. Patients' demographic and clinical data were collected and analyzed using standardized clinical evaluation forms. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depression, anxiety and psychotic symptoms, respectively. ResultsThere were no gender-based differences in the comorbidity rates of MDD and anxiety disorders (male: 10.2% vs. female:12.7%, P = 0.123). The prevalence of MDD with severe anxiety symptoms in male patients was similar to that of female patients (80.8%vs. 80.1%, P = 0.749). Male MDD patients were younger, had earlier age of onset, and were less likely to be married. In both the male and female groups, HAMD scores, HAMA scores, suicide attempts, and psychotic symptoms in patients with severe anxiety symptoms were higher than those patients without severe anxiety symptoms (all p ≤ 0.001). Furthermore, binary logistic regression analysis showed that psychotic symptoms and suicide attempts significantly predicted severe anxiety symptoms in both male and female patients with MDD, while body mass index(BMI)significantly predicted severe anxiety symptoms in MDD females only. ConclusionOur study showed that there were no gender differences in the prevalence of comorbid anxiety in FEDN patients with MDD. Suicide attempts and psychiatric symptoms were associated with severe anxiety symptoms in both men and women with MDD, whereas BMI was only correlated with severe anxiety symptoms in women.

Sex differences in the association between suicide attempts and glucose disturbances in first-episode and drug naive patients with major depressive disorder

BackgroundGlucose metabolism is related to depression, but the relationship between blood glucose and suicide attempts in patients with major depressive disorder (MDD) remains unclear. This large-scale sample explores the relationship between suicide attempts and fasting blood glucose, in addition to sex differences in first-episode and drug naive (FEDN) MDD patients. Methods1718 FEDN MDD patients diagnosed for the first time were recruited, and their demographic data, clinical data, and blood glucose indicators were collected. 17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety and psychotic symptoms, respectively. ResultsThe depression, anxiety, psychotic symptoms and blood sugar levels of the suicide attempt group were higher than those of the non-suicide attempt group. Correlation analysis showed that blood glucose was significantly associated with suicide attempts in male and female patients. While binary logistic regression showed that blood glucose levels were significantly associated with suicide attempts in male patients, it showed that suicide attempts were not significantly associated with blood glucose levels in female patients. LimitationsThe main limitations are cross-sectional design and inability to control selection bias. ConclusionsIn male MDD patients, fasting blood glucose level is a potential biomarker of suicide attempt, which deserves attention to avoid suicide risk. However, in female patients, fasting blood glucose has no significant correlation to suicide attempts.

BDNF pro-peptide: physiological mechanisms and implications for depression.

Most growth factors are synthesized as precursors and biologically active forms are generated by proteolytic cleavage of the pro-domain. However, the biological functions of pro-domains are ill-defined. New roles were recently reported for the pro-domain of brain-derived neurotrophic factor (BDNF), a well-known growth factor in the brain. Interestingly, the pro-domain of BDNF (BDNF pro-peptide) is localized at presynaptic termini, where it facilitates long-term depression (LTD) in hippocampal slices, implicating it as a novel synaptic modulator. BDNF binds its pro-peptide with high affinity in a pH-dependent manner and when bound to BDNF, the BDNF pro-peptide cannot facilitate hippocampal LTD, representing a new mechanism of regulation. The BDNF pro-peptide is present in human cerebrospinal fluid (CSF) and levels were significantly lower in patients with major depressive disorder (MDD) than in controls. Notably, male MDD patients exhibit significantly lower levels of CSF pro-peptide than females. These findings demonstrate that the BDNF pro-peptide is a biologically important synaptic modulator and is associated with MDD, particularly in males.

Accuracy of brain-derived neurotrophic factor levels for differentiating between Taiwanese patients with major depressive disorder or schizophrenia and healthy controls.

ObjectivesBrain-derived neurotrophic factor (BDNF) has been associated with the psychopathology of both major depressive disorder (MDD) and schizophrenia (SZ). However, studies focusing on the accuracy of BDNF levels to differentiate between these patients and healthy controls (HCs) have been rare.MethodsOver a discrete ten-year period, we investigated serum BDNF levels in patients with MDD or SZ and compared them to HCs.ResultsWe found serum BDNF levels in 224 samples with SZ to be lower than those in 390 HCs samples (p = 0.007), but not lower than those in the 273 samples with MDD. Male MDD patients tended to have lower BDNF levels compared to male HCs (p = 0.083). The receiver operating characteristic curve analysis demonstrated that BDNF levels were moderately accurate in differentiating male MDD patients and female patients with SZ from HCs (AUC = 0.652 and 0.623, respectively). The most adequate cut-off points for BDNF level were 5.11 ng/ml (sensitivity = 81.1%, specificity = 48.5%) and 5.88 ng/ml (sensitivity = 74.1%, specificity = 57.4%), respectively.ConclusionsOur results support that BDNF demonstrated moderate accuracy in distinguishing male patients with MDD and female patients with SZ from HCs. In the future, greater samples would be required to further confirm these results.

Sex differences in gut microbiota in patients with major depressive disorder.

ObjectiveOur previous studies found that disturbances in gut microbiota might have a causative role in the onset of major depressive disorder (MDD). The aim of this study was to investigate whether there were sex differences in gut microbiota in patients with MDD.Patients and methodsFirst-episode drug-naïve MDD patients and healthy controls were included. 16S rRNA gene sequences extracted from the fecal samples of the included subjects were analyzed. Principal-coordinate analysis and partial least squares-discriminant analysis were used to assess whether there were sex-specific gut microbiota. A random forest algorithm was used to identify the differential operational taxonomic units. Linear discriminant-analysis effect size was further used to identify the dominant sex-specific phylotypes responsible for the differences between MDD patients and healthy controls.ResultsIn total, 57 and 74 differential operational taxonomic units responsible for separating female and male MDD patients from their healthy counterparts were identified. Compared with their healthy counterparts, increased Actinobacteria and decreased Bacteroidetes levels were found in female and male MDD patients, respectively. The most differentially abundant bacterial taxa in female and male MDD patients belonged to phyla Actinobacteria and Bacteroidia, respectively. Meanwhile, female and male MDD patients had different dominant phylotypes.ConclusionThese results demonstrated that there were sex differences in gut microbiota in patients with MDD. The suitability of Actinobacteria and Bacteroidia as the sex-specific biomarkers for diagnosing MDD should be further explored.

Sex differences in glutamate receptor gene expression in major depression and suicide.

Accumulating data indicate that the glutamate system is disrupted in major depressive disorder (MDD), and recent clinical research suggests that ketamine, an antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor (GluR), has rapid antidepressant efficacy. Here we report findings from gene expression studies of a large cohort of postmortem subjects, including subjects with MDD and controls. Our data reveal higher expression levels of the majority of glutamatergic genes tested in the dorsolateral prefrontal cortex (DLPFC) in MDD (F21,59=2.32, P=0.006). Posthoc data indicate that these gene expression differences occurred mostly in the female subjects. Higher expression levels of GRIN1, GRIN2A-D, GRIA2-4, GRIK1-2, GRM1, GRM4, GRM5 and GRM7 were detected in the female patients with MDD. In contrast, GRM5 expression was lower in male MDD patients relative to male controls. When MDD suicides were compared with MDD non-suicides, GRIN2B, GRIK3 and GRM2 were expressed at higher levels in the suicides. Higher expression levels were detected for several additional genes, but these were not statistically significant after correction for multiple comparisons. In summary, our analyses indicate a generalized disruption of the regulation of the GluRs in the DLPFC of females with MDD, with more specific GluR alterations in the suicides and in the male groups. These data reveal further evidence that, in addition to the NMDA receptor, the AMPA, kainate and the metabotropic GluRs may be targets for the development of rapidly acting antidepressant drugs.

Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: A model for nitric oxide in major depressive disorder

Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (P<0.001). Plasma CORT levels were increased in male CUS rats (P=0.001), while male MDD patients did not show a significant change in cortisol levels. In conclusion, the changes in plasma and hypothalamic NOS-NO of CUS rats and MDD were similar. The male CUS rat model may thus help us with our investigation of the mechanism underlying NOS-NO alterations in depression.

Gender differences in brain activity and the relationship between brain activity and differences in prevalence rates between male and female major depressive disorder patients: A resting-state fMRI study

ObjectiveWe examined the gender-difference effect on abnormal spontaneous neuronal activity of male and female major depressive disorder (MDD) patients using the amplitude of low-frequency fluctuation (ALFF) and the further clarified the relationship between the abnormal ALFF and differences in MDD prevalence rates between male and female patients. MethodsFourteen male MDD patients, 13 female MDD patients and 15 male and 15 female well matched healthy controls (HCs) completed this study. The ALFF approach was used, and Pearson correlation was conducted to observe a possible clinical relevance. ResultsThere were widespread differences in ALFF values between female and male MDD patients, including some important parts of the frontoparietal network, auditory network, attention network and cerebellum network. In female MDD patients, there was a positive correlation between average ALFF values of the left postcentral gyrus and the severity of weight loss symptom. ConclusionsThe gender-difference effect leading to abnormal brain activity is an important underlying pathomechanism for different somatic symptoms in MDD patients of different genders and is likely suggestive of higher MDD prevalence rates in females. SignificanceThe abnormal ALFF resulting from the gender-difference effect might improve our understanding of the differences in prevalence rates between male and female MDD patients from another perspective.

Diurnal alterations in circadian genes and peptides in major depressive disorder before and after escitalopram treatment

Strong links exist between circadian disturbances and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However, changes in the expression of clock genes or neuropeptides related to the regulation of circadian rhythm that may influence the susceptibility to recurrence after antidepressant treatment in MDD have not been investigated. Blood samples were collected at 4h intervals for 24h from 12 male healthy controls and 12 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included the relative expression of clock gene mRNA (PERIOD1, PERIOD2, PERIOD3, CRY1, BMAL1, NPAS2, and GSK-3β), and the levels of serum melatonin, vasoactive intestinal polypeptide (VIP), cortisol, adrenocorticotropic hormone (ACTH), insulin-like growth factor-1 (IGF-1), and growth hormone (GH). Compared with healthy controls, MDD patients showed disruptions in the diurnal rhythms of the expression of PERIOD1, PERIOD2, CRY1, BMAL1, NPAS2, and GSK-3β and disruptions in the diurnal rhythms of the release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (i.e., PER1, CRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted 8 weeks after escitalopram treatment, similar to the increase in the 24h levels of VIP and decreases in the 24h levels of cortisol and ACTH. These persistent neurobiological changes may play a role in MDD symptoms that are thought to contribute to the vulnerability to recurrence and long-term maintenance therapy.