This study aimed to characterise neurometabolic differences between bipolar disorder I (BD-I) and bipolar disorder II (BD-II), and to examine their associations with cognitive function. A total of 50 patients diagnosed with BD-I, 80 patients with BD-II, and 50 healthy controls (HCs) were recruited for this study. Metabolite concentrations—specifically N-acetylaspartate (NAA) and choline-containing compounds (Cho)—were measured in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), and thalamus through proton magnetic resonance spectroscopy (¹H-MRS). Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). When compared to HCs, patients with BD-II showed significantly higher Cho/Cr ratios in the right PWM and left ACC, along with lower NAA/Cr ratios in the right thalamus; compared to BD-II patients, those with BD-I exhibited higher Cho/Cr ratios in the right PWM and lower NAA/Cr ratios in the right thalamus; among BD-I patients, the Cho/Cr ratio in the left ACC was negatively correlated with measures of information processing speed and attentional vigilance. This study demonstrates that BD-II patients exhibit greater cholinergic dysregulation in the left ACC and the right PWM, whereas BD-I patients show more pronounced neuronal dysfunction in the right thalamus. Furthermore, the left ACC Cho/Cr ratio was specifically associated with cognitive impairments in information processing speed and attentional vigilance, but only among patients with BD-I. This suggests that subtype-specific mechanisms underlie the relationship between neurometabolic abnormalities and cognitive deficits. Not applicable.

Dysregulation of copper (Cu) metabolism may contribute to the pathogenesis of major depressive disorder (MDD) by disrupting hippocampal function. The aim of this study is to elucidate the neurobiological mechanisms through integrated clinical and animal experiments. A total of 85 MDD patients and 65 healthy controls (HCs) were recruited for this study. Serum Cu, ceruloplasmin (Cp) levels, and the relative mRNA expression of ATPase copper-transporting alpha (Atp7a) were measured. All participants underwent resting-state functional magnetic resonance imaging, and the Amplitude of Low-Frequency Fluctuation (ALFF) was calculated using subdivisions of the hippocampus (HPC). Cognitive function across seven domains was also assessed. In animal studies, mice were subjected to a chronic unpredictable mild stress (CUMS) model to develop depression. The Cu chelator tetrathiomolybdate (TTM) was then administered to investigate its impacts on Cu-related biochemical indices and brain structure in the HPC of the test group. We found that MDD patients exhibited increased serum Cu2+ levels, and decreased Cp level and Atp7a mRNA expression compared to HCs. A significant reduction in ALFF was observed in the right rostral hippocampus (rHPC) of MDD patients. Animal studies showed depressive-like mice had high Cu levels and Atp7a mRNA expression, with low Cp levels in HPC, accompanying hippocampal cytoarchitectural impairments. Systemic administration of Cu TTM effectively counteracted and reversed both the Cu dyshomeostasis and hippocampal structural damage associated with depression. Patients with MDD exhibit Cu metabolism dysregulation, with excess Cu²⁺ harming hippocampal neurons and contributing to the pathogenesis of depression. Consequently, modulating Cu homeostasis may represent a novel therapeutic target for MDD.

BACKGROUND:Early-onset depression (EOD) and late-onset depression (LOD) are prevalent subtypes of major depressive disorder (MDD), but the clinical distinction between EOD and LOD remains blurred due to nonspecific symptoms and lack of biomarkers. This study aims to elucidate the characteristics in cognitive function and biochemical metabolism of EOD and LOD, and to identify biological factors influencing age of onset (AOO). METHODS:Seventy patients with MDD (40 with EOD and 30 with LOD) and sixty-eight age-matched healthy controls (HC) were included in this study. Participants were evaluated for clinical features, cognitive function, and serum trace elements levels. Proton magnetic resonance spectroscopy (1H-MRS) was employed to quantify neurometabolites levels, including N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr). RESULTS:Patients with LOD experienced more episodes and severe depressive symptoms than those with EOD (p = 0.025, p < 0.001). EOD patients performed significantly worse than LOD patients on social cognition (p = 0.005), while LOD patients performed worse than EOD patients on reasoning and problem solving (p = 0.005). Additionally, LOD patients displayed higher ceruloplasmin (Cp) levels compared to EOD patients (p = 0.004), but no difference was found in neurometabolic levels between EOD and LOD. Multiple linear regression indicated a positive correlation between serum Cp levels and AOO of depression (p < 0.001), while bilateral thalamic NAA/Cr showed a negative correlation with AOO (p = 0.012, p = 0.016). CONCLUSIONS:Patients with EOD were characterized by social cognition impairments, while patients with LOD were marked by reasoning and problem-solving deficits. Serum Cp levels demonstrated an AOO-related effect and served as a positive predictor for the AOO of depression. Furthermore, a negative correlation has been established between bilateral thalamic NAA/Cr and the AOO of MDD. LIMITATIONS:The limited sample size and the challenge in distinguishing whether observed results are attributed to age or AOO effects.

Bipolar disorder (BD) is highly comorbid with obsessive-compulsive disorder (OCD), leading to poor treatment outcome and prognosis. However, the neurobiological mechanisms underlying BD comorbid with OCD remain poorly understood. To address it, we recruited 69 untreated patients with bipolar II depression, including 35 comorbid with OCD (BD-II-Depression-OCD) and 34 without OCD (BD-II-Depression-nonOCD), and 38 healthy controls (HC). Serum thyroid hormones levels and neurometabolic ratios, including N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine (Cr), were detected to explore the neuroendocrine and neurometabolic mechanisms of BD-II-Depression-OCD comorbidity. Multivariate logistic regression and restricted cubic spline analyses were performed to identify influential factors for comorbidity and their nonlinear relationships with symptom severity. Our results revealed that patients with BD-II-Depression-OCD demonstrated reduced thyroid-stimulating hormone (TSH) levels, decreased NAA/Cr in the left prefrontal white matter (PWM), and increased Cho/Cr in the right PWM compared to patients without comorbidity. These parameters demonstrated diagnostic potential for distinguishing BD-II-Depression-OCD comorbidity. Furthermore, nonlinear associations were observed between obsessive-compulsive symptom severity and both serum TSH levels and right PWM Cho/Cr ratios among patients with comorbidity. In conclusion, BD-II-Depression-OCD comorbidity is characterized by distinct thyroid dysfunction and neurometabolic alterations. Disruptions in serum TSH levels and bilateral PWM neurometabolism may represent potential mechanisms underlying BD-II-Depression-OCD comorbidity.

Background: It 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. Methods: 109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy ( 1 H-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. Results: In 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. Conclusions: Our 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.

Background: We aimed to examine the influence of gender on serum trace elements and minerals levels in depression, as well as the impact of suicidal ideation (SI) on these gender dimorphisms. Methods: A total of 260 unmedicated patients with a current major depressive episode were enrolled. The Beck Scale for Suicide Ideation was utilized to evaluate SI. The serum levels of copper, zinc, iron, calcium, phosphorus, and magnesium were quantified. Results: Within the non-SI (NSI) group, females exhibited higher levels of copper (p = 0.001) and phosphorus (p = 0.008), and lower levels of zinc (p = 0.022) and calcium (p = 0.008) compared to males. Conversely, no discernible gender disparities were observed in the SI group (all p > 0.05). Also, no group differences in these trace elements/minerals were observed between the SI and NSI groups (all p > 0.05). Notably, serum iron levels exhibited a significant group-by-sex interaction effect (p = 0.024). Further analysis revealed that iron levels were higher in the SI group than in the NSI group among females (p = 0.048), but lower in females than in males within the NSI group (p < 0.001). Moreover, a positive association between the fourth quantile of serum iron and SI was detected in females (odds ratio [OR] = 2.88, 95 % confidence interval [CI]: 1.08-8.11). Conclusions: Gender effects on serum trace element/mineral levels were different in depressed patients with and without SI. Female patients were susceptible to SI when serum iron was at the upper end of normal.

Abstract Background Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression. Method This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted. Result ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression. Conclusion Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

Introduction: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. Methods: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Background While patients with major depressive disorder (MDD) and bipolar disorder (BD) often exhibit aberrant hormones, it is still unknown whether the hormones differ between MDD and BD across the age spectrum. We aimed to investigate the differences in testosterone and stress hormones between depressed patients with MDD and BD in adolescents and adults, and the impact of suicidal ideation on these. Methods A total of 432 depressed patients (270 MDD and 162 BD) were recruited, including 177 adolescents and 255 adults. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol (CORT), testosterone (T), and prolactin (PRL) were measured in all patients. Suicidal ideation was assessed by item 3 of the Hamilton Depression Rating Scale. Results In adolescents, plasma T levels were higher in MDD than in BD (p=0.018), MDD patients with suicidal ideation exhibited higher T levels than BD patients with suicidal ideation (p=0.036), and plasma T levels were associated with diagnosis (ORadjus=0.777, p=0.023). In adults, plasma ACTH levels were elevated in MDD versus BD (p=0.012) and were also diagnosis-related (ORadjus=0.972, p=0.019). Plasma levels of other hormones were not significantly different between MDD and BD in adolescents or adults (all p>0.05). Conclusions There was an age-specific difference in the T and ACTH between depressed patients with MDD and BD. Suicidal ideation was linked to T in adolescents.

BACKGROUND:The clinical characteristics of major depressive disorder (MDD) in adolescents show notable gender-related differences, but the cause of these differences is still not understood. The current research concentrates on the changes in neurometabolism and neuroendocrine function, aiming to identify differences in endocrine function and brain metabolism between male and female adolescents with MDD. METHODS:A total of 121 teenagers diagnosed with MDD (43 males and 78 females) were enlisted as participants. Measurement was conducted on levels of endocrine hormones, which included free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4), thyroid-stimulating hormone (TSH), cortisol, and adrenocorticotropic hormone (ACTH). Obtained through 1H-MRS, the N-acetyl aspartate (NAA) and choline containing compounds (Cho) to creatine (Cr) ratios were acquired for the prefrontal whiter matter (PWM), anterior cingulate cortex (ACC), basal ganglia (BG), thalamus, and cerebellum. RESULT:After adjusting for multiple comparisons, female adolescents with MDD showed lower ACTH levels compared to their male counterparts. An increased lateralization index (LI) was observed in female patients for both the thalamic Cho/Cr ratio and the basal ganglia NAA/Cr ratio. Additionally, an intriguing finding was that in male adolescent patients, TT4 levels were significantly correlated with the Cho/Cr ratio in the left cerebellum. However, no such correlation between hormones and brain metabolism was found in females. CONCLUSIONS:Gender differences in endocrine and neurometabolic abnormalities may contribute to the gender-specific pathophysiology of MDD in adolescent patients. Metabolic abnormalities and lateralization changes are observed in different brain regions for male and female MDD patients.

Objective: Vortioxetine has been shown to improve cognitive performance in people with depression. This study will look at the changes in neurobiochemical metabolites that occur when vortioxetine improves cognitive performance in MDD patients, with the goal of determining the neuroimaging mechanism through which vortioxetine improves cognitive function. Methods: 30 depressed patients and 30 demographically matched healthy controls (HC) underwent MCCB cognitive assessment and 1H-MRS. After 8 weeks of vortioxetine medication, MCCB and 1H-MRS tests were retested in the MDD group. Before and after therapy, changes in cognitive performance, NAA/Cr, and Cho/Cr were examined in the MDD group. Results: Compared with the HC group, the MDD group had significant reduced in verbal learning, social cognition, and total cognition (all p < 0.05). And the MDD group had lower NAA/Cr in Right thalamus and Left PFC; the Cho/Cr in Right thalamus was lower than HC; the Cho/Cr in Left ACC had significantly increase (all p < 0.05). The MDD group showed significant improvements in the areas of verbal learning, attention/alertness, and total cognitive function before and after Vortioxetine treatment (all p < 0.05). The NAA/Cr ratio of the right PFC before and after treatment (t = 2.338, p = 0.026) showed significant changes. Conclusions: Vortioxetine can enhance not just the depression symptoms of MDD patients in the initial period, but also their verbal learning, social cognition, and general cognitive capacities after 8 weeks of treatment. Furthermore, vortioxetine has been shown to enhance cognitive function in MDD patients by altering NAA/Cr and Cho/Cr levels in the frontal-thalamic-ACC.

Cognitive impairment is a common symptom in depression, yet few intervention strategies target adolescents. This study investigated the effects of an attention and working memory cognitive training system based on virtual reality (VRCT) in adolescents with mild to moderate depressive episodes. Adolescents with depression were randomized into a VR training group (VRG, n = 47) or a waitlist control group (WT, n = 46). The VR training consisted of three 10-min tasks per session, conducted three sessions per week for 20 sessions over 7 weeks. Forty-four healthy adolescents participated as a comparison group for baseline cognitive assessment. Cognitive functions and depressive symptoms were assessed using the Das-Naglieri cognitive assessment system, driven by the Planning, Attention, Simultaneous, and Successive (PASS) processing theory, and the Hamilton Depression Rating Scale-24 at pre- and post-intervention. Baseline results indicated significantly lower cognitive scores in patients compared to healthy adolescents. Post-intervention, the VRG demonstrated significant improvements in all four cognitive scales (effect sizes 0.56 to 0.76) and a significant reduction in depressive symptoms compared to the WT. These findings suggest that VRCT holds potential for improving cognitive impairments and alleviating depressive symptoms in adolescents with depression. Further large-scale and follow-up studies are necessary to confirm long-term benefits.

BACKGROUND:Major depressive disorder (MDD) and insomnia have been linked to deficiencies in cognitive performance. However, the underlying mechanism of cognitive impairment in MDD patients with insomnia symptoms (IS) remains unclear. This study aimed to explore the effects of IS in patients with MDD by comparing cognitive function indices among those with IS, those without insomnia symptoms (NIS), and healthy controls (HCs). In addition, we assessed whether the dysfunction of central nervous system (CNS) is one of the important pathophysiologic mechanisms of IS in patients with MDD by comparing the biochemical metabolism ratios in the anterior cingulate cortex (ACC).METHOD:Fifty-five MDD with IS, 39 MDD without IS, and 47 demographically matched HCs underwent the MATRICS Consensus Cognitive Battery (MCCB) assessment and proton magnetic resonance spectroscopy (1H-MRS). MCCB cognitive scores and biochemical metabolism in ACC were assessed and compared between groups.RESULTS:Compared to the HCs group, IS and NIS groups scored significantly lower in seven MCCB cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning problem solving and social cognition). IS group showed a lower speed of processing and lower Cho/Cr ratio in the left ACC vs. NIS group and HCs. Also, in IS group, the Cho/Cr ratio in the left ACC was positively correlated with the composite T-score.CONCLUSION:Patients with comorbidity of MDD with IS may exhibit more common MCCB cognitive impairments than those without IS, particularly speed of processing. Also, dysfunction of ACC may underlie the neural substrate of cognitive impairment in MDD with IS.

OBJECTIVE:Little is known about the pathogenesis underlying cognitive impairment in major depressive disorder (MDD). We aimed to explore the mechanisms of cognitive impairments among patients with MDD by investigating the dynamics of overlapping brain sub-networks.METHODS:Forty unmedicated patients with MDD and 28 healthy controls (HC) were enrolled in this study. Cognitive function was measured using the Chinese versions of MATRICS Consensus Cognitive Battery (MCCB). All participants were scanned using a whole-head resting-state magnetoencephalography (MEG) machine. The dynamism of neural sub-networks was analyzed based on the detection of overlapping communities in five frequency bands of oscillatory brain signals.RESULTS:MDD demonstrated poorer cognitive performance in six domains compared to HC. The difference in community detection (functional integration mode) in MDD was frequency-dependent. MDD showed significantly decreased community dynamics in all frequency bands compared to HC. Specifically, differences in the visual network (VN) and default mode network (DMN) were detected in all frequency bands, differences in the cognitive control network (CCN) were detected in the alpha2 and beta frequency bands, and differences in the bilateral limbic network (BLN) were only detected in the beta frequency band. Moreover, community dynamics in the alpha2 frequency band were positively correlated with verbal learning and reasoning problem solving abilities in MDD.CONCLUSIONS:Our study found that decreasing in the dynamics of overlapping sub-networks may differ by frequency bands. The aberrant dynamics of overlapping neural sub-networks revealed by frequency-specific MEG signals may provide new information on the mechanism of cognitive impairments that result from MDD.

Mood disorders are a group of mental conditions characterized by significant and lasting mood or emotional changes, which seriously affect patients′ normal lives. However, the pathogenesis of mood disorders is still unclear, and the specific biological markers to assist the diagnosis are still not determined, and this affects the diagnosis, treatment and prognosis. With the development of molecular imaging, positron emission tomography (PET) has been widely used in clinical research on mood disorders, which is helpful for their clinical diagnosis and treatment. This paper aims to review the research progress on PET imaging principles, the pathogenesis and treatment mechanism of mood disorders, and to summarize the application prospect of PET in mood disorders.

Abstract Background Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA). Methods Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality. Results Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group. Conclusions Our findings indicated that the dysfunction of insula–cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.

BACKGROUND:Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) both showed cognitive impairment, and the altered neurometabolic may associate with cognitive impairment. However, there are limited comparative working memory (WM) and neuroimaging studies on these two disorders. Therefore, we investigated the characteristics of WM and neurometabolic changes in patients with OCD and MDD.METHODS:A total of 64 unmedicated patients (32 OCD and 32 MDD), and 33 healthy controls (HC) were included to conduct WM assessment comprising Digit Span Test (DST), 2-back task and Stroop Color and Word Test (SCWT). Additionally, all subjects underwent protons magnetic resonance spectroscopy (1H-MRS) to collect neurometabolic ratios of N-acetyl aspartate (NAA) and choline-containing compounds (Cho) to creatine (Cr) in the prefrontal cortex (PFC) and lentiform nucleus (LN). Finally, differential and correlation analysis were conducted to investigate their characteristics and relationships.RESULTS:Compared with HC, both OCD and MDD patients exhibited a lower accuracy rate in the 2-back task, and only MDD patients performed worse in DST scores and longer reaction times in SCWT (all p < 0.05). Both OCD and MDD patients had lower NAA/Cr ratios in bilateral PFC (all p < 0.05). And the decreased NAA/Cr ratios in right PFC were positively correlated to DST scores in MDD group (r = 0.518, p = 0.003).CONCLUSIONS:Both OCD and MDD showed WM impairment and neurometabolic alterations in PFC. Besides, MDD performed more severe and broader WM impairment compared to OCD. Moreover, the dysfunction of PFC may underlie the neural basis of WM impairment in MDD.

BACKGROUND:Cognitive impairment has been acknowledged as a core clinical manifestation of bipolar disorder (BD) as well as major depressive disorder (MDD). Determining the prevalence and characteristics of cognitive impairment is important for clinical interventions. This study investigated the prevalence and characteristics of cognitive impairment based on the Measurement and Treatment Research to Improve Cognition Schizophrenia Consensus Cognitive Battery (MCCB) in both BD and MDD. METHOD:One hundred and forty-nine BD II depression, 147 MDD, and 124 demographically matched healthy controls (HC) underwent MCCB cognitive assessment. The prevalence of MCCB cognitive impairment and group difference comparisons were performed. Additionally, association analysis was performed to investigate the relationship between cognitive performance and clinical variables. RESULTS:Compared to the HC group, both BD II depression and MDD groups had a significantly reduced performance for all MCCB cognitive domains (all p < 0.05). The numerical scores for visual learning were lower in the BD II depression group compared to the MDD group. 32.89% of the BD II depression patients had clinically significant impairment (>1.5 SD below the normal mean) in two or more MCCB domains compared to 23.13% for MDD patients. CONCLUSIONS:A high percent of patients in the BD II depression and MDD group exhibited MCCB cognitive impairments with clinical significance. Cognitive impairments were more common in BD II depression patients compared to MDD patients, particularly for visual learning. These findings suggest that clinicians should be aware of the severe cognitive impairment in mood disorders and establish effective cognitive screening and intervention strategies.

Background Obesity not only affects physical and mental conditions, but also influences cognitive function. Endocrine hormones may influence the risk of obesity and severe obesity. Our study investigated the influences of changes in levels of endocrine hormones on cognitive function in patients with obesity and severe obesity. Methods We used the MATRICS Consensus Cognitive Battery (MCCB) to evaluate cognitive function in the groups of healthy control (HC), obesity (OB), and severe obesity (SOB). We detected the levels of endocrine hormones and cortisol at 8:00 am in the three groups. We statistically analyzed differences in cognitive function and levels of endocrine hormones among the three groups, and performed linear correlation analysis of cortisol level and cognitive function. Using mediation analysis, we assessed the influences of body mass index (BMI) on endocrine levels and cognitive function. Results Our findings revealed that OB and SOB groups exhibited a lower level of cortisol than HC group. Among the three groups, we found significant differences in verbal learning (F = 4.433, P = 0.014), social cognition (F = 4.778, P = 0.010), and total cognition (F = 2.989, P = 0.008). After post hoc Bonferroni correction, we noted that SOB group had worse scores in the above-mentioned three areas than OB and HC groups. Moreover, except for working memory and visual cognition, we identified that the degree of cognitive impairment in SOB group was more severe than that in OB group. In our study, mediation analysis showed a mediating effect of BMI on cortisol level and verbal learning. We also found correlations between cortisol level and attention/alertness (r = 0.277, P = 0.003), between cortisol level and verbal learning (r = 0.205, P = 0.030), and between BMI and verbal learning (r = - 0.192, P = 0.043). Conclusion In our study, patients in both OB and SOB groups experienced a widespread cognitive impairment. We also found that patients with severe obesity had more severe cognitive impairment. Cognitive impairment could be mediated by abnormal cortisol metabolism, and BMI could be a mediating factor in regulation of cortisol level.

Major depressive disorder (MDD), is characterized by high incidence rate, high suicide rate, and high disability rate, however, the underlying pathogenesis of MDD is still unclear. Based on the diathesis-stress model of depression, epigenetic mechanisms strongly explain the integration of genes and environment in the development of depression. However, depression has a high degree of clinical heterogeneity, with individuals of different ages presenting different symptoms and epigenetic changes. As a dynamic molecular marker that varies with age and environmental experience, epigenetics helps to elucidate the unique and complex disease pathogenesis of depression at different ages. Therefore, this paper aims to review relevant epigenetic studies of depression at different ages of onset to explore its potential age-specific association mechanism, in order to provide a theoretical basis for the formulation of accurate intervention measures for patients with MDD at different ages.