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Background: Social capital has long been recognized as a determinant of various health outcomes. However, the existence and magnitude of these associations may vary across different health conditions, different communities, and periods. This study aimed to investigate the association between social capital and major depressive disorder (MDD) among participants of the Persian Youth Cohort (PYC) study. Methods: The PYC study enrolled 11,592 participants aged 15–34 years, from four cities in Iran representing a range of geographic areas. Baseline assessments included measuring lifetime MDD using the Persian version of the Composite International Diagnostic Interview (CIDI-2.1) and a 27-item social capital questionnaire to evaluate voluntary participation, trust, and sense of cohesion. We analyzed the baseline data using logistic regression to identify potential associations. Results: The prevalence of lifetime MDD was 18.3%. The mean social capital-total score was 73.93 (SD = 13.93). A higher social capital-total score was inversely associated with the likelihood of MDD (AOR: 0.70, 95% CI: 0.66–0.74). Moreover, participants with higher scores in voluntary participation (AOR: 0.88, 95% CI: 0.83–0.92), trust (AOR: 0.65, 95% CI: 0.62–0.68), and sense of cohesion (AOR: 0.72, 95% CI: 0.68–0.75) were less probable to suffer from MDD. Conclusion: Our study corroborates the existing evidence of the association between MDD and the three dimensions of social capital- participation, trust, and sense of cohesion- highlighting the consistency of these findings across diverse settings including young adults in Iran. The use of a valid diagnostic tool for assessing MDD adds robustness to our results, offering valuable insights for regions with similar social and cultural contexts. These findings suggest that interventions fostering social capital, particularly trust and cohesion, may help reduce the burden of MDD in youth. [ABSTRACT FROM AUTHOR]

Background: Prior research has established a correlation between childhood maltreatment (CM) and personality traits. The current understanding regarding the potential variability in the relationship between CM and its impact on personality dimensions among those with major depressive disorder (MDD) and healthy controls (HCs) remains elusive. Aims: This study analyzes the association between CM and personality traits in the MDD and HC groups. Methods: The study recruited 188 individuals with MDD and 132 HC. The Childhood Trauma Questionnaire (CTQ) was used to assess CM, and the Sixteen Personality Factor Questionnaire (16PF) was used to assess personality traits. We used a 2*2 analysis of covariance (ANCOVA) of the diagnosis and CM on 16PF, and hierarchical regression explored the association between specific types of CM and 16PF in both groups. Results: The 2*2 ANCOVA results indicated significant interaction effects between CM and diagnosis on personality traits, with CM's impact notably different between groups. In the MDD group, sexual abuse (SA) independently predicted the subscale Q1 (Openness to Change), related to the Big Five's openness. In the HC group, emotional abuse (EA) predicted the subscales C (emotional stability), O (apprehension), and Q4(tension), linked to Big Five's neuroticism. Conclusion: The findings highlight the impact of early adversity on personality development, informing psychology and guiding tailored therapy development. [ABSTRACT FROM AUTHOR]

Background: Atypical antipsychotics are a common treatment for serious mental illness, but many are associated with adverse effects, including weight gain and cardiovascular issues, and real-world experience may differ from clinical trial data. Cariprazine has previously demonstrated a favorable safety and tolerability profile in clinical trials. Here, we evaluated the effects of cariprazine on body weight and blood pressure for bipolar I disorder (BP-I), schizophrenia, or as adjunctive treatment for major depressive disorder (MDD) using real-world data. Methods: Symphony Health's Integrated Dataverse® with electronic medical record access (3/1/2015–10/31/2018) was used to identify adults (≥ 18 years) diagnosed with BP-I depression, BP-I mania/mixed, schizophrenia, or MDD, with ≥ 2 cariprazine dispensings (first dispensing = index) and continuous clinical activity for ≥ 12 months pre-index (baseline) and ≥ 3 months post-index. The on-treatment period spanned from index to cariprazine discontinuation, exposure to another atypical or long-acting injectable antipsychotic, or end of clinical activity/data availability. Outcomes included estimated annual linear trajectories for weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) during baseline and on treatment. Changes were estimated using linear mixed-effects models fitted over measurements pre-index and on treatment; 95% CIs were derived from nonparametric bootstrap procedures. Results: The body weight analysis included 612 patients (BP-I, n = 331 [BP-I depression, n = 172; BP-I mania/mixed, n = 159]; schizophrenia, n = 75; MDD, n = 206). The mean patient age was 43.4 years, 75.2% were female, and the mean (SD) on-treatment period was 219 (185) days. Among patients with measurements before and during cariprazine treatment, estimated annual weight trajectories were + 3.55 (95% CI 2.38, 4.59) kg/year before cariprazine initiation and + 0.91 (− 1.17, 2.82) kg/year during cariprazine treatment. Additionally, annual linear trajectories evaluated across the on-treatment period were + 0.31 (− 0.42, 1.01) kg/m2/year for BMI, − 2.38 (− 4.27, − 0.76) mmHg/year for SBP, and − 0.57 (− 1.75, 0.61) mmHg/year for DBP. Conclusion: In this real-world analysis, cariprazine was associated with an estimated weight gain of + 0.91 kg/year and had minimal impact on BMI and blood pressure when evaluated up to 12 months. [ABSTRACT FROM AUTHOR]

Background: Mirtazapine is used to treat depression worldwide, and the effects of mirtazapine on depression rating scales are well-known. Our primary objective was to assess the risks of adverse events with mirtazapine for major depressive disorder. Methods: We searched relevant sources from inception to 7 March 2024 for randomised clinical trials comparing mirtazapine versus placebo in adults with major depressive disorder. The primary outcomes were suicides or suicide attempts, serious adverse events, and non-serious adverse events. Data were synthesised using meta-analysis and Trial Sequential Analysis. Results: We included 17 trials randomising 2,131 participants to mirtazapine versus placebo. All results were at high risk of bias, and the certainty of the evidence was very low. The included trials assessed outcomes at a maximum of 12 weeks after randomisation. Meta-analysis and Trial Sequential Analysis showed insufficient information to determine the effects of mirtazapine on the risks of suicides or suicide attempts and serious adverse events. Meta-analyses showed that mirtazapine increased the risks of somnolence, weight gain, dry mouth, dizziness, and increased appetite but decreased the risk of headaches. Conclusions: There is a lack of evidence on the effects of mirtazapine on suicides and serious adverse events. Mirtazapine increases the risks of somnolence, weight gain, dry mouth, dizziness, and increased appetite. Mirtazapine might decrease the risk of headaches. The long-term effects of mirtazapine are unknown. Prospero id: CRD42022315395. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed sex differences in the prevalences of both major depressive disorder (MDD) and subclinical hypothyroidism (SCH). This study aimed to further compare the prevalence and correlates of moderate-to-severe SCH between male and female Chinese MDD patients. Methods: A total of 1706 first-episode drug naïve Chinese patients with MDD were recruited. Depressive symptoms were assessed by the 17-item Hamilton Depression Rating Scale, psychotic symptoms by the Positive and Negative Syndrome Scale and anxiety symptoms by the Hamilton Anxiety Rating Scale. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) concentrations were measured by chemiluminescence immunoassay. Moderate-to-severe SCH was defined as serum TSH > 8 mIU/L with normal fT4. Results: The prevalence of moderate-to-severe SCH was 10.4% in male patients and 15.1% in female patients (χ2 = 7.22, p < 0.01). In female patients, binary logistic regression showed that systolic blood pressure (SBP), suicide attempts and psychotic symptoms (all p < 0.001) were associated with moderate-to-severe SCH. In male patients, SBP and psychotic symptoms were associated with moderate-to-severe SCH (both p < 0.001), while suicide attempts and severe anxiety were not (p > 0.05). Conclusions: Our findings reveal a higher prevalence rate of moderate-to-severe SCH in female untreated first-episode MDD patients compared with males. Moreover, there is a positive association between suicide attempts and moderate-to-severe SCH only in female MDD patients. Highlights: 1. Moderate-to-severe subclinical hypothyroidism (SCH) occurred more often in female patients. 2. Suicide attempts were associated with moderate-to-severe SCH only in female patients. 3. Psychotic symptoms were associated with moderate-to-severe SCH in both female and male patients. [ABSTRACT FROM AUTHOR]

Introduction: Psychotic depression (PD) is a highly debilitating disorder characterized by hallucinations and/or delusions accompanied by depression. A variety of neurotransmitters, hormones and corresponding receptors in the endocrine system are involved in the onset and progression of depression, and fasting blood glucose (FBG) can be an important indicator for monitoring the stability of the endocrine system. The aim of this study was to investigate the relationship between FBG and PD in a Chinese population with first-episode drug-naïve (FEDN) major depressive disorder (MDD). Methods: In this study, 1718 outpatient individuals diagnosed with first-episode drug-naïve major depressive disorder (FEDN MDD) were included. The association between PD and FBG levels was identified through multivariable binary logistic regression analysis. To investigate potential non-linear relationships, a two-piecewise linear regression model was utilized. Additionally, interaction and stratified analyses were performed based on gender, educational background, marital status, presence of comorbid anxiety, and history of suicide attempt. Results: Multivariate logistic regression analysis showed that FBG was positively associated with the risk of PD in FEDN MDD patients (OR = 1.68, 95% CI: 1.31 to 2.13; P < 0.05). Smoothed plots showed a non-linear relationship between FBG and PD, while the inflection point of FBG was calculated using a two-segmented logistic regression model to be 6.23 mmol/L. On the right side of the inflection point, the probability of PD increased substantially by 278% (OR = 3.78, 95% CI: 1.75 to 8.18, p < 0.001), while no significant association was observed on the left side of the inflection point (OR = 1.06, 95% CI: 0.73 to 1.52, p = 0.772). Conclusions: Our investigation revealed a nonlinear relationship between FBG and PD in patients with FEDN MDD, thereby informing more effective intervention strategies for managing psychotic symptoms in individuals with depression. [ABSTRACT FROM AUTHOR]

Major depressive disorder is a prevalent mental disorder, yet its pathogenesis remains poorly understood. Accumulating evidence implicates dysregulated immune mechanisms as key contributors to depressive disorders. This review elucidates the complex interplay between peripheral and central immune components underlying depressive disorder pathology. Peripherally, systemic inflammation, gut immune dysregulation, and immune dysfunction in organs including gut, liver, spleen and adipose tissue influence brain function through neural and molecular pathways. Within the central nervous system, aberrant microglial and astrocytes activation, cytokine imbalances, and compromised blood-brain barrier integrity propagate neuroinflammation, disrupting neurotransmission, impairing neuroplasticity, and promoting neuronal injury. The crosstalk between peripheral and central immunity creates a vicious cycle exacerbating depressive neuropathology. Unraveling these multifaceted immune-mediated mechanisms provides insights into major depressive disorder's pathogenic basis and potential biomarkers and targets. Modulating both peripheral and central immune responses represent a promising multidimensional therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: The neurasthenia–depression controversy has lasted for several decades. It is challenging to solve the argument by symptoms alone for syndrome-based disease classification. Our aim was to identify objective electroencephalography (EEG) measures that can differentiate neurasthenia from major depressive disorder (MDD). Methods: Both electronic medical information records and EEG records from patients with neurasthenia and MDD were gathered. The demographic and clinical characteristics, EEG power spectral density, and functional connectivity were compared between the neurasthenia and MDD groups. Machine Learning methods such as random forest, logistic regression, support vector machines, and k nearest neighbors were also used for classification between groups to extend the identification that there is a significant different pattern between neurasthenia and MDD. Results: We analyzed 305 patients with neurasthenia and 45 patients with MDD. Compared with the MDD group, patients with neurasthenia reported more somatic symptoms and less emotional symptoms (p < 0.05). Moreover, lower theta connectivity was observed in patients with neurasthenia compared to those with MDD (p < 0.01). Among the classification models, random forest performed best with an accuracy of 0.93, area under the receiver operating characteristic curve of 0.97, and area under the precision-recall curve of 0.96. The essential feature contributing to the model was the theta connectivity. Limitations: This is a retrospective study, and medical records may not include all the details of a patient's syndrome. The sample size of the MDD group was smaller than that of the neurasthenia group. Conclusion: Neurasthenia and MDD are different not only in symptoms but also in brain activities. [ABSTRACT FROM AUTHOR]

Background: Anhedonia and suicidal ideation are symptoms of major depressive disorder (MDD) that are not regularly captured in structured scales but may be captured in unstructured clinical notes. Natural language processing (NLP) techniques may be used to extract longitudinal data on suicidal behaviors and anhedonia within unstructured clinical notes. This study assessed the accuracy of using NLP techniques on electronic health records (EHRs) to identify these symptoms among patients with MDD. Methods: EHR-derived, de-identified data were used from the NeuroBlu Database (version 23R1), a longitudinal behavioral health real-world database. Mental health clinicians annotated instances of anhedonia and suicidal symptoms in clinical notes creating a ground truth. Interrater reliability (IRR) was calculated using Krippendorff's alpha. A novel transformer architecture-based NLP model was trained on clinical notes to recognize linguistic patterns and contextual cues. Each sentence was categorized into one of four labels: (1) anhedonia; (2) suicidal ideation without intent or plan; (3) suicidal ideation with intent or plan; (4) absence of suicidal ideation or anhedonia. The model was assessed using positive predictive values (PPV), negative predictive values, sensitivity, specificity, F1-score, and AUROC. Results: The model was trained, tested, and validated on 2,198, 1,247, and 1,016 distinct clinical notes, respectively. IRR was 0.80. For anhedonia, suicidal ideation with intent or plan, and suicidal ideation without intent or plan the model achieved a PPV of 0.98, 0.93, and 0.87, an F1-score of 0.98, 0.91, and 0.89 during training and a PPV of 0.99, 0.95, and 0.87 and F1-score of 0.99, 0.95, and 0.89 during validation. Conclusions: NLP techniques can leverage contextual information in EHRs to identify anhedonia and suicidal symptoms in patients with MDD. Integrating structured and unstructured data offers a comprehensive view of MDD's trajectory, helping healthcare providers deliver timely, effective interventions. Addressing current limitations will further enhance NLP models, enabling more accurate extraction of critical clinical features and supporting personalized, proactive mental health care. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a recurrent and persistent mental illness. However, there is a lack of research that distinguishes the severity of comorbid anxiety disorders in MDD, and insufficient evidence exists regarding the prevalence of MDD patients with comorbid moderate-to-severe anxiety in the Chinese population. Methods: The study included 1718 MDD patients (894 with moderate-to-severe anxiety symptoms and 824 without moderate-to-severe anxiety symptoms). Clinical symptoms and development were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale-14 (HAMA-14), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI). The blood pressure and thyroid hormone levels were measured. Results: We found that the incidence of MDD patients with moderate-to-severe anxiety symptoms was 52.04%. The prevalence of recent suicide attempts in MDD comorbid moderate-to-severe anxiety patients was 31.8%, which was 4.24 times higher than that in patients without moderate-to-severe anxiety. Additionally, suicide attempters had elevated levels of thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), systolic blood pressure (SBP), and diastolic blood pressure (DBP) compared to non-suicide attempters. We further identified CGI score, TSH, TPOAb, and DBP as influential factors for recent suicide attempts in MDD individuals who had moderate-to-severe anxiety symptoms. These indexes could distinguish between suicide attempts and non-suicide attempts in MDD patients with moderate-to-severe anxiety symptoms. Conclusions: Our findings mainly indicated a high prevalence of recent suicide attempts in MDD patients with moderate-to-severe anxiety. Several clinical correlates, thyroid hormones, and blood pressure might contribute to recent suicide attempts in MDD patients with moderate-to-severe anxiety symptoms. [ABSTRACT FROM AUTHOR]

Background: Ketamine is a promising therapy for treatment-resistant depression due to its rapid onset, although benefits are often transitory, with patients needing maintenance therapy to prevent relapse. Most data supporting ketamine for treatment-resistant depression refers to the intravenous route of administration, leaving alternative routes lacking in data, especially as maintenance regimens. Moreover, the safety of ketamine maintenance therapy is poorly defined. This report aims to describe and evaluate a novel hospital-to-outpatient intranasal racemic ketamine maintenance therapy program. Methods: This was an observational program evaluation study. Participants were adult inpatients with treatment-resistant depression who had been successfully treated with intranasal racemic ketamine in hospital and were being referred for outpatient maintenance therapy with an intranasal racemic ketamine spray, administered at a specialized community treatment centre. Effectiveness was assessed with the Self-Report Quick Inventory of Depressive Symptomatology, the Quality of Life Scale, and the Clinical Global Impression-Improvement scale. Results: Five patients were enrolled, completing up to 14 treatment sessions over 192 days. The mean dose administered throughout treatment was 220 mg (100 to 400 mg). All patients had decreased (or stable) depressive symptoms and increased (or stable) quality of life. There were no serious adverse events or discontinuations due to adverse effects. Reported adverse effects included anxiety and nausea. Slight blood pressure increases were seen during treatment, none of which required intervention. Conclusions: Intranasal racemic ketamine maintenance therapy for treatment-resistant depression appeared to be feasible and well tolerated, although effectiveness conclusions cannot be drawn from this small pilot study. Further investigations regarding the safety and effectiveness of intranasal ketamine maintenance therapy are warranted. [ABSTRACT FROM AUTHOR]

Background: It is important to timely capture the fluctuation of the symptoms related to major depressive disorder (MDD). However, most conventionally used assessment tools for MDD symptoms are not designed for real-time assessment. The Immediate Mood Scaler (IMS) is suitable for the real-time evaluation of the mood of patients with MDD. Methods: The original IMS was translated into Chinese and back-translated. At baseline, data from 368 patients with MDD, including demographic information and scores on the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and IMS, were collected. In total, 185 participants completed the retest at Week 2 which included the PHQ-9, GAD-7, and IMS. Internal structural validity, construct validity, and internal consistency were evaluated with the confirmatory factor analysis (CFA), the Pearson correlation, and Cronbach's α, respectively. Responsiveness was anchored by the change of the PHQ-9 total scores from baseline to Week 2 and predictability was tested using the multivariate linear mixed model for repeated measures (MMRM). Results: Two factors with an eigenvalue greater than 1, corresponding to IMS-Depression and IMS-Anxiety subscales, were identified using CFA. The Cronbach's α that evaluated internal consistency was 0.96, 0.95, and 0.92 for the scores of the IMS, IMS-Depression subscale, and IMS-Anxiety subscale at baseline, respectively. The depression and anxiety subscales at baseline showed high subscale-total correlations (r = 0.96 for the depression subscale; r = 0.89 for the anxiety subscale). The test-retest ICC (0.65, 95%CI: 0.53–0.73) of the IMS at baseline and Week 2 show high reliability. The total score of IMS had significant correlations with that of the PHQ-9 (r = 0.52, P < 0.001) and GAD-7(r = 0.43, P < 0.001), indicating good construct validity. In patients with MDD who showed changes in mood, the changes in total scores of the IMS from baseline to the retest were statistically significant with a mean difference of 13.3 (SD: 20.1), an ES of 0.66, and an SRM of 0.3, showing good responsiveness. Also, the baseline IMS-Depression subscale score could predict the change in the PHQ-9 score over the two weeks (t = 2.19, P = 0.029). Conclusions: Study findings suggest that the Chinese version of the IMS is a valid and reliable tool for assessing mood symptoms in patients with MDD in China. Further validation studies of the Chinese version IMS in different regions and at various levels of medical institutions are needed to further confirm the current findings. [ABSTRACT FROM AUTHOR]

Objective: The incidence of suicide is high among adolescents and young adults, especially those suffering from psychiatric diseases. Because of the reported association between depression and suicidality, exploring suicide risk factors in depressed patients is crucial for the identification of those at high risk and preventing suicide. In recent decades, electroencephalography parameters have been considered for identifying biomarkers of suicide ideation and attempts in depressed patients. This study aimed to review the available literature on resting-state EEG for suicidality in depressed patients. Method: A systematic search was performed in five electronic databases, including APA PsycINFO, Embase, Medline (via PubMed), Scopus, and Web of Science. Papers with full text available in English in which resting-state EEG was evaluated in depressed patients with suicide ideation or suicide attempts compared to a control group of healthy subjects or non-suicidal depressed patients were included. The risk of bias was assessed by using the Newcastle–Ottawa scale. Results: A total of 4665 references were retrieved from five electronic databases from which eleven studies were included in this systematic review. A meta-analysis was not performed due to the substantial heterogeneity of the studies. Five of the eleven reviewed papers were classified as high-quality, and six had moderate quality. Conclusions: According to the included studies in this review, the EEG signals of depressed patients with suicide ideation or suicide attempts may be different from patients with low risk of suicidality or healthy subjects. Connectivity measures sound more promising parameters than the power spectral analysis and EEG asymmetry. Protocol registration: The protocol of this review was registered in PROSPERO (No. CRD42024502056). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In observational studies, frailty has been strongly associated with mental disorders. However, the mechanisms underlying the association between frailty and mental disorders remain unclear. Methods: We conducted a two-sample Mendelian randomization (MR) study to assess the causal relationship between frailty, as measured by the frailty index (FI), and ten common mental disorders. The datasets involved European ancestry individuals and included measurements of the FI (N = 175,226), schizophrenia (SCZ; N = 320,404), major depressive disorder (MDD; N = 143,265), bipolar disorder (N = 337,199), insomnia (N = 462,341), obsessive–compulsive disorder (N = 33,925), anxiety disorders (N = 463,010), autism spectrum disorder (N = 46,351), anorexia nervosa (N = 14,477), opioid-related mental and behavioral disorders (N = 215,650), and mental and behavioral disorders due to use of other stimulants including caffeine (N = 215,570). Results: Two-sample MR analyses were performed using inverse variance weighting followed by various sensitivity and validation analyses. Genetically predicted SCZ (odds ratio [OR] = 1.019, 95% confidence interval [CI] 1.005–1.033) and MDD (OR = 1.211, 95% CI 1.092–1.343) had significant causal effects on FI. In the reverse MR analysis, we discovered that MDD was significantly and causally affected by FI (OR = 1.290, 95% CI 1.133–1.469). No causal links were identified between the FI and the other eight common mental disorders. In the Multivariable MR, the estimated MDD effect on FI is comparable to the univariate IVW estimate (OR = 1.298; 95% CI, 1.175 to 1.435), while the estimated SCZ effect on FI fails to be significant compared to the univariate estimate. The results of the sensitivity and validation analyses confirmed stabilization. Conclusions: Our study found evidence of a causal relationship between SCZ, MDD, and frailty and explored the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Sustained attention deficits were reported more significant in patients with major depressive disorder (MDD) than in healthy controls (HCs), and are pivotal in both the development and aggravation of depression. Childhood trauma is also common in MDD and the exposure to childhood trauma may impede sustained attention and increase the treatment resistance in MDD. However, the underlying neuro-mechanisms link the childhood trauma to sustained attention deficits in MDD remain unclear. Methods: We collected resting-state functional magnetic resonance imaging data, and measured childhood trauma severity using the Childhood Trauma Questionnaire and sustained attention using the Continuous Performance Test, Identical Pairs version. After excluding subjects with significant head movement, 45 MDDs and 54 HCs were included in the analysis. We compared fractional amplitude of low-frequency fluctuation (fALFF) between the groups, conducted whole-brain correlation analysis between the fALFF and sustained attention in the MDD group, and defined significant regions as the regions of interest for the seed-to-whole brain functional connectivity (FC) analysis. We further performed mediation analyses to investigate the relationships among the childhood trauma, fALFF and FC values, and the level of sustained attention in the MDD group. Results: Compared with HCs, MDDs exhibited higher fALFF in the right middle frontal gyrus and left inferior frontal gyrus, and lower fALFF in the bilateral insular cortex, left medial orbital superior frontal gyrus and left angular gyrus (ANG.L). Whole-brain correlation analysis showed that impaired sustained attention was associated with increased fALFF in the left postcentral gyrus (PoCG.L), and FC of PoCG.L-left precentral gyrus (PreCG.L) and ANG.L-right superior temporal gyrus (STG.R) in the MDD group. Furthermore, mediation analyses showed that the fALFF in PoCG.L, and FC of PoCG.L-PreCG.L and ANG.L-STG.R mediated the relationship between the childhood trauma and sustained attention in the MDD group. Conclusion: The fALFF in PoCG.L, and FC of PoCG.L-PreCG.L and ANG.L-STG.R might be potential neural substrate in the association between the childhood trauma and poor sustained attention in the MDDs, and might serve as potential intervention targets for the treatment of sustained attention deficits in MDDs with childhood trauma history. [ABSTRACT FROM AUTHOR]

Background: Insomnia may mediate the association between internet addiction (IA) and suicidal ideation (SI). However, such association has not been thoroughly investigated in adolescents with major depressive disorder (MDD). Thus, our study aimed to explore whether insomnia significantly affects the association between IA and SI in adolescents with MDD, as well as any sex differences. Methods: From January 2021 to September 2023, this cross-sectional study included 502 adolescents with MDD and 123 healthy controls (HCs). The Clinical Global Impression-Severity (CGI-S), the Internet Addiction Test (IAT), the Insomnia Severity Index Scale (ISI) and the Positive and Negative Suicidal Ideation Scale (PANSI) were used to assess subjects' severity of depression, IA, insomnia and SI. And we employed the PROCESS macro program to examine the mediating role of insomnia between IA and SI. Results: Compared to HCs, adolescents with MDD had significantly higher levels of SI and their prevalence of IA and insomnia were 50.0% and 35.7%. In patients, PANSI scores correlated negatively with age and age of onset, and positively with disease duration as well as the scores of the CGI-S, IAT, and ISI (all p < 0.01). Moreover, above-mentioned correlations were more significant in girls. Mediation analyses showed that insomnia mediated the effect of IA on SI, and the total, direct, and indirect effects were 0.197 (95% CI: 0.132—0.262), 0.157 (95% CI: 0.096—0.218) and 0.040 (95% CI: 0.014—0.068), respectively. In female patients, the total, direct, and indirect effects were 0.224 (95% CI: 0.151—0.296), 0.191 (95% CI: 0.124—0.257) and 0.033 (95% CI: 0.002—0.068), respectively. In male patients, insomnia acted as a fully mediated effect between IA and SI, with an effect value of 0.045 (95% CI: 0.008—0.093). Conclusion: Depressed adolescents have higher suicide risk, and SI is significantly associated with IA and insomnia, especially in girls. Moreover, insomnia may mediate the association between IA and SI. However, given the small sample size of this study and the limitations of assessment tools used, the results need to be viewed with caution. Regardless, clinical interventions should be strengthened for IA and insomnia in adolescents with MDD to reduce suicide risk. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is known to be characterized by disrupted brain functional network connectivity (FNC) patterns, while the dynamic change mode of different functional networks is unclear. This study aimed to characterize specific dynamic alterations pattern on intrinsic FNC in MDD by combining static FNC (sFNC) and dynamic FNC (dFNC). Methods: A total of 48 first-episode drug-naïve MDD and 48 matched healthy controls (HCs) were included in this study. The sFNC and dFNC were analyzed using complete time-series and sliding window approach, respectively. Both sFNC and dFNC differences between groups were analyzed and associations between disease severity and aberrant FNC were explored. Results: MDD patients exhibited lower sFNC within and between sensory and motor networks than HC. Four dFNC states were identified, including a globally-weakly-connected state, a cognitive-control-dominated state, a globally-positively-connected state, and an antagonistic state. The antagonistic state was marked by strong positive connections within the sensorimotor domain and their anti-correlations with the executive-motor control domain. Notably, MDD patients exhibited significantly longer dwell time in the globally-weakly-connected state, at the cost of significantly shorter dwell time in the antagonistic state. Further, only the mean dwell time of this antagonistic state was significantly anticorrelated to disease severity measures. Conclusions: Our study highlights the altered dynamics of the antagonistic state as a fundamental aspect of disrupted FNC in early MDD. [ABSTRACT FROM AUTHOR]

Background: Anhedonia—a core symptom of major depressive disorder (MDD)—is closely related to diminished reward sensitivity. Nonetheless, the psychopathological and computational mechanism underlying anhedonia in young patients with MDD remains unclear. Therefore, this study aims to investigate reward sensitivity in adolescents and young adults with MDD using computational modelling. Methods: Overall, 70 patients with MDD and 54 age- and sex-matched healthy controls (HC) completed a probabilistic reward task (PRT) to assess their general behavioral inclination towards more frequently reinforced stimuli (i.e., "response bias"). Bayesian hierarchical drift diffusion modeling (HDDM) was employed to determine changes in reward sensitivity and computational process during decision-making. Results: Adolescents with depression showed a trend toward reduced response bias compared to those in HC. HDDM analysis revealed wider decision thresholds in both adolescents and young adults with MDD group. Adolescents with MDD exhibited significantly lower drift rates and reduced starting point bias compared to those in HC. Higher anhedonia levels were linked to lower drift rates and wider decision thresholds. Additionally, increased discriminability correlated with higher drift rates, while higher response bias was linked to larger starting points. Conclusions: Our findings suggest that reduced reward sensitivity and slower evidence accumulation during reward learning may serve as potential indicators of anhedonia in adolescents with MDD. These findings provided crucial insights into the dysregulated positive affect model, underscoring a dysfunctional reward system as a key factor in anhedonia developmental psychopathology in depression. [ABSTRACT FROM AUTHOR]

Background: Mobile-based screening interventions to detect and treat Major Depressive Disorder (MDD) at an early stage might be a promising approach for reducing its societal burden. In the present study, we will evaluate the feasibility and effectiveness of screening for MDD using a mobile-based screening protocol. Methods: This study will be a three-arm, parallel randomized control trial (RCT) performed in a multi-ethnic population within the municipality of Rotterdam (the Netherlands). The trial includes two intervention groups that will be screened 4-weekly for MDD for 12 months using the Patient Health Questionnaire (PHQ-9) and a control group who does not receive mobile-based screening for MDD. Participants in the one-test intervention arm will be referred for further diagnosis and treatment, if necessary, after a single positive test score for moderate-severe major depression symptoms (PHQ-9 > 10). Participants in the multiple-test intervention arm will only be referred after three consecutive positive test scores. 1786 eligible participants will be included in the RCT, with 446 and 447 in the one-test and multiple-test referral arms, respectively, and 893 in the control arm. Primary outcome is participants' QoL after 12 months (EQ-5D-5L). Secondary outcomes include participants' QoL after 24 months (EQ-5D-5L), evaluating the occurrence and severity of MDD symptoms (PHQ-9), intervention engagement, and identifying public mental health differences based on sociodemographic characteristics, including age, gender, ethnicity, financial situation, educational background, and living area. Long-term results of the RCT will be incorporated into a microsimulation model to determine the long-term benefits, harms, and costs of MDD screening. Discussion: The information gained from examining the feasibility and (cost-) effectiveness of mobile-based screening for MDD could be of guidance for mental health policy implementations and support the introduction of mobile-based screening for MDD in the Netherlands and/or other nations. Trial registration: ClinicalTrials.gov: NL84280.078.23, NCT05989412, August 8, 2024. [ABSTRACT FROM AUTHOR]

Background: Although symptoms of depressive episodes in patients with bipolar depressive episodes (BDE) and major depressive disorder (MDD) are similar, the treatment strategies for these disorders are completely different, suggesting that BDE and MDD have different neurobiological backgrounds. In this study, we examined the relationship between brain function and clinical symptoms, particularly cognitive function, in female individuals with bipolar disorder and MDD experiencing depressive episodes. Methods: Regional homogeneity (ReHo) was analyzed in 51 medication-free female patients with BDE, 63 medication-free female patients with MDD, and 45 female healthy controls (HCs). Depressive symptom severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and multidimensional cognitive function was evaluated using the MATRICS Consensus Cognition Battery. Partial correlation analysis was used to explore the links between the brain regions and clinical characteristics. A support vector machine (SVM) was used to assess the classification accuracy. Results: Compared with HCs, patients with BDE and MDD had decreased ReHo in the left lobule VI of the cerebellum and increased ReHo in the left precuneus. Patients with BDE also had reduced ReHo in the left lobules IV–V of the cerebellum and increased ReHo in the right putamen, unlike patients with MDD who had no significant differences in these regions. Patients with BDE exhibited more severe cognitive deficits in processing speed, attention, word learning, and overall cognitive function than those with MDD. In patients with BDE, a significant negative correlation was found between the right putamen and HAMD-24 scores. However, no significant association was observed between abnormal ReHo levels and cognitive function. The SVM effectively differentiated between patients with BDE, MDD, and HCs. Conclusion: Cognitive impairment was more severe in female patients with BDE than in those with MDD. Changes in the ReHo values of the right putamen and left lobules IV–V may serve as unique neuroimaging markers for BDE. Alterations in the ReHo values of the left precuneus and left lobule VI could serve as common pathophysiological mechanisms for BDE and MDD in women and indicate depressive states. [ABSTRACT FROM AUTHOR]

Thyroid dysfunction is commonly seen in major depressive disorder (MDD), and is particularly prevalent in female patients. Moreover, gender differences occur in many aspects of MDD, including suicide attempts (SAs). We aimed to explore gender differences in the prevalence and clinical correlates of SAs in young first-episode drug-naïve MDD patients with thyroid dysfunction, which have not yet been reported. We recruited 509 patients in this study. Demographic and clinical characteristics were collected. We used HAMD-17, HAMA-14, the positive subscale of PANSS, and CGI-S to assess every participant. We found no significant difference in the prevalence of SAs between male and female subgroup. Gender differences in factors associated with SAs were found with anxiety, body mass index, serum anti-thyroid antibodies (A-TPO), and free triiodothyronine levels in male patients and anxiety, CGI-S score, and A-TPO in female patients. We found no gender differences in the prevalence of SAs; however, there were gender differences in several clinical correlates of SAs, highlighting specific strategies to avoid SAs in male and female MDD patients. [ABSTRACT FROM AUTHOR]

Risk and protective factors for psychiatric illnesses are linked to distinct structural and functional changes in the brain. Further, the prevalence of these factors varies across sexes and genders, yet the distinct and joint effects of sex and gender in this context have not been extensively characterized. This suggests that risk and protective factors may map onto the brain and uniquely influence individuals across sexes and genders. Here, we review how specific risk (childhood maltreatment, the COVID-19 pandemic, experiences of racism), and protective factors (social support and psychological resilience) distinctly influence the brain across sexes and genders. We also discuss the role of sex and gender in the compounding effects of risk factors and in the interdependent influences of risk and protective factors. As such, we call on researchers to consider sex and gender when researching risk and protective factors for psychiatric illnesses, and we provide concrete recommendations on how to account for them in future research. Considering protective factors alongside risk factors in research and acknowledging sex and gender differences will enable us to establish sex- and gender-specific brain-behavior relationships. This will subsequently inform the development of targeted prevention and intervention strategies for psychiatric illnesses, which have been lacking. To achieve sex and gender equality in mental health, acknowledging and researching potential differences will lead to a better understanding of men and women, males and females, and the factors that make them more vulnerable or resilient to psychopathology. Plain English summary: Exposure to different environments and distinct lived experiences for individuals across the sexes and genders have unique effects on mental wellbeing, brain structure, and function. These differences in outcomes arise from interdependent effects of biology and socio-culture and can be challenging to separate. This review describes sex- and gender-specific effects of negative and positive environmental experiences, known as risk and protective factors. Specifically, we review current sex- and gender-specific findings for childhood maltreatment, the COVID-19 pandemic, experiences of racism, social support, and resilience. Risk and protective factors, and sex and gender have bidirectional influences, and our review outlines their dynamic, interconnected and intersectional nature. Including sex and gender as a variable of interest will enable us to capture specific effects that may have previously gone undetected. More broadly, implementing the outlined considerations will lead to more inclusive and representative research that can deliver robust findings and meaningfully propel the field forward. Highlights: Unique effects of sex and gender on brain and behavior necessitate the investigation of these factors as a variable of interest in research. Protective factors should be considered alongside risk factors for a more holistic understanding of mental wellbeing. Investigating sex and gender influences will help detect findings that would have otherwise been overlooked. Risk factors, protective factors, sex, and gender all have bidirectional influences on each other. [ABSTRACT FROM AUTHOR]

Background: Epidemiological and other studies have shown correlations among major depressive disorder (MDD), anxiety disorder (AXD) and constipation. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them. Methods: Bidirectional two-sample Mendelian randomization (MR) analysis was performed to confirm the causal link between MDD, AXD and constipation. Genetic instrumental variables for MDD, AXD, and constipation were obtained from publicly available genome-wide association studies (GWASs). In this MR analysis, inverse variance weighting (IVW) was used as the primary analysis method to evaluate the causal effect. Additionally, we employed Cochran's Q test, MR‒Egger intercept and MR-PRESSO analysis to examine heterogeneity and pleiotropy. Moreover, leave-one-out analysis was employed to investigate the stability of the associations. Finally, a reverse analysis of Mendelian randomization was conducted. Results: The results revealed a causal relationship between MDD and an increased risk of constipation (p = 0.0001), whereas AXD (p = 8.52 × 10–1) did not increase the risk of constipation. In the inverse MR analysis, no causal associations were found (constipation to MDD: p = 9.37 × 10–1; constipation to AXD: p = 8.51 × 10–1). Conclusion: This MR study revealed genetic evidence supporting a causal relationship between MDD and constipation. [ABSTRACT FROM AUTHOR]

Background: How cognition is influenced by electroconvulsive treatment (ECT) and major depressive disorder (MDD) is still debated. The development and etiology of neurocognitive impairment in MDD were examined by investigating the cognitive profile following ECT related to the state, scar, and trait perspectives, with the former predicting improvements parallel with depressive symptoms, while the two latter expected persisting impairments. Executive functions (EF) and attention are central to cognition and alterations in these functions could influence other domains like memory. The main aims of the present study were to examine the short and long-term effects of ECT on EF and attention in patients with major depressive disorder by exploiting the rapid antidepressant effect of this treatment. Methods: A case-control longitudinal follow-up design was used to investigate the effects of unilateral brief-pulse ECT on EF and attention in patients with depression (n = 36) compared to untreated healthy controls (n = 16). EF and attention were measured pre-treatment, approximately two weeks, and six months post-treatment. Results: The patient group showed significantly worse performance on most tests compared to healthy controls pre-treatment, and no short- or long-term worsening of EF and attention following ECT was found. Significant improvement was identified in patients' attention, processing speed and inhibition after ECT. Conclusions: The present study showed that there was no cognitive worsening after ECT treatment. An improvement in several of the tests measuring inhibition, attention, and processing speed was parallel to symptom reduction, with the former showing associations to symptom change, suggesting state-related effects from improved mood. Still, the patient group performed significantly worse on most measures both pre-treatment and at the short and long-term follow-ups, indicating prevailing trait or scar effects on cognitive functions and potential lack of practice effects. Clinical trial number: NCT04348825 (14.04.20). [ABSTRACT FROM AUTHOR]

Objective: An alternative metric for evaluating insulin resistance (IR) is the triglyceride glucose-body mass index (TyG-BMI). However, it is yet unclear how TyG-BMI and suicide attempts (SA) are related. The objective of this research was to explore the correlation between the TyG-BMI index and SA in individuals with untreated first-episode (UFE) major depressive disorder (MDD) in Shanxi Province. Methods: This cross-sectional study was conducted from September 2016 to December 2018 in the psychiatric outpatient clinic of Taiyuan General Hospital and included 1718 patients with UFE MDD, with a mean age of 34.9 ± 12.4 years. The relationship between TyG-BMI and SA was assessed using logistic regression modeling. We investigated threshold effects using a two-piecewise linear regression model. Results: Taking into consideration the potential influence of confounding variables, a comprehensive multivariate logistic regression analysis was conducted, which demonstrated the absence of a statistically significant association between the TyG-BMI index and the occurrence of SA, as evidenced by P-values that were all greater than 0.05. On the other hand, the visual analysis of the smoothed plots revealed a U-shaped relationship between the TyG-BMI index and the incidence of SA, with a notable inflection occurring at a TyG-BMI value of around 210. It was observed that the effect sizes flanking the inflection point, accompanied by their 95% confidence intervals, were 0.985 (95% CI: 0.972 to 0.999, P = 0.031) and 1.012 (95% CI: 1.003 to 1.047, P = 0.005), respectively. Conclusions: In UFE MDD patients, a U-shaped link was observed between TyG-BMI and SA, with the minimal SA incidence noted at a TyG-BMI level of 210, signifying that an augmented risk for SA might be connected to both diminished and augmented TyG-BMI levels. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to assess the prevalence and associated factors of major depressive disorder (MDD), generalized anxiety disorder (GAD), and past 12-month suicidal behaviour (PSB) among adolescents in Mozambique. Methods: Data from 3,109 females (aged 15–19 years) and 1,439 males (aged 15–19 years) that participated in the 2022-23 Mozambique Demographic and health Survey were analysed. MDD was assessed with the PHQ-9 and GAD with the GAD-7. Results: Results indicate that among girls the prevalence of PSB was 4.3% (attempt 1.0%, plan 1.9% and/or ideation 3.6%) and among boys 2.5% (attempt 0.3%, plan 0.7% and/or ideation 2.4%). Among girls and boys, the prevalence of MDD (≥ 8 scores) was 15.5% and 3.7%, respectively, and the prevalence of GAD (≥ 5 scores) was 25.0% and 10.3%, respectively. In adjusted logistic regression analysis, among girls, GAD was positively and solid fuel use was negatively associated with PSB, while among boys MDD and urban residence were positively associated with PSB. Among female adolescents, currently being pregnant and "big problem to get money for medical treatment" increased the odds of MDD. While among male adolescents, urban residence, having a genital sore or ulcer, has living children, and early sexual debut were positively associated with MDD. Urban residence, current alcohol use, and early sexual debut were positively associated with GAD in male adolescents, while poorer wealth status, being pregnant, and having a "big problem to get money for medical treatment" were positively associated with GAD in female adolescents. Conclusion: About 3% of participants had PSB, among girls one in five had MDD or GAD and among boys more than 5% had MDD or GAD. Public health interventions can be guided by several associated factors that have been identified. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods: We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients' blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results: The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion: TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear. Methods: This study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery. Results: Multivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes. Conclusion: Thus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study. [ABSTRACT FROM AUTHOR]

Introduction: Gender- and age-specific research on medications is essential for personalizing treatment plans, optimizing dosing, minimizing adverse effects and improving outcomes. Women are twice as likely to be diagnosed with major depressive disorder (MDD), and it is commonly reported during their reproductive years. This post-hoc pooled analysis evaluated the efficacy of sertraline (one of the most studied medications in women) in women of reproductive age (18–44 years). Methods: Data was pooled from nine clinical trials of sertraline that included 1832 subjects with MDD. The analysis set included 1097 women, 651 of those were of reproductive age. Sertraline was compared with placebo for changes in total HAM-D17 and CGI scores measured over time through MMRM analysis. The change from baseline to the end of study (-week 8) was assessed using ANCOVA. Results: The changes from baseline in total HAM-D17 and CGI scores were significantly higher for sertraline than for placebo at the end of 8 weeks for all women (LS Mean difference, 95% CI: -1.81(-3.01,-0.62), P = 0.0029; -0.38(-0.55,-0.20), P < 0.0001, respectively). For women of reproductive age these changes (LS Mean difference, 95% CI: -2.08(-3.52,-0.64), P = 0.0047; -0.44(-0.66,-0.22), P < 0.0001, respectively), were significant from week 2 (HAM-D17) and week 1 (CGI) till the end of study. Limitations: Only sertraline and placebo arms were included in the analysis. The dosing varied between studies, and the effect of dose was not addressed. Conclusions: Sertraline is an effective option for treatment of MDD in women, including those in the childbearing age. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is a common mental disease that significantly impact the daily lives of those affected. Acupuncture has shown promising therapeutic effects in the treatment of MDD, but its underlying mechanisms remain unclear. This study aims to evaluate the influence of acupuncture on the brain function of patients with MDD and it's therapeutic effects on MDD. Methods: This study plans to recruit 112 participants, who will be randomly allocated to either the acupuncture group or the sham acupuncture group in a 1:1 ratio. Both groups will undergo 8 weeks of treatment, consisting of three sessions per week, with each session lasting for 30 min. A follow-up period of 3 months will be conducted after the treatment. Assessments will be conducted at weeks 0, 8, 12, 16, and 20 in this study. The primary outcome measure will be functional near-infrared spectroscopy (fNIRS) brain imaging, while secondary outcome measures will include Beck Depression Inventory II (BDI-II), Self-Rating Anxiety Scale (SAS), 36-Item Short Form Survey Instrument (SF-36), Traditional Chinese Medicine (TCM) syndrome score scale, and symptom elimination rate. Discussion: While acupuncture has been confirmed to have a certain degree of therapeutic efficacy in the treatment of MDD, research on the mechanisms underlying acupuncture's treatment of MDD remains limited, particularly with regards to its impact on the brain function of individuals with MDD. This study aims to explore both the clinical effectiveness and treatment mechanisms of acupuncture for MDD, with a specific focus on its influence on brain function. This research endeavors to provide new insights into the potential of acupuncture as a therapeutic approach for the treatment of MDD in the future. Trial Registration: www.chictr.org.cn, ID: ChiCTR2300076292. Registered on 28 September 2023. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). Methods: We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center's cohort. Results: We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. Conclusions: Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment (CM) is closely linked to internet addiction (IA), especially in adolescents with Major Depressive Disorder (MDD). Previous studies have shown that adolescents who experience CM are more likely to develop IA and other psychological problems. This study aims to explore the complex relationship between CM and IA through network analysis, particularly identifying the core symptoms and bridge symptoms to better understand the development of IA in these adolescents. Methods: A cross-sectional study was conducted in seven hospitals in Anhui Province, China, involving 332 adolescents diagnosed with MDD using DSM-5 criteria. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Internet Addiction Test (IAT) were used to assess CM and IA symptoms, respectively. Gender-based network analysis was also performed. Results: Network analysis constructed a CM-IA network and identified core and bridge symptoms. "Depress/moody/nervous being offline", "Request an extension for longer time", "Sleep loss due to late-night logins", and "emotional abuse" emerged as central symptoms within the CM-IA network. Additionally, "emotional abuse", "sexual abuse", and "complaints about online time" were identified as key bridge symptoms linking CM and IA. These symptoms demonstrated significant connectivity, underscoring their critical role in linking CM and IA. Conclusion: The findings highlight the complex relationship between CM and IA in adolescents with MDD. Specific symptoms, such as emotional abuse and online-related symptoms, play important roles in understanding and intervening in adolescent IA. Future interventions should target these core and bridge symptoms for more effective prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE). Method: In a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall's W test. Results: A significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p < 0.001) as well as in HAM-A scores, from severe to moderate-severe anxiety through the four visits (p < 0.001). Furthermore, only one case was reported as a serious side effect. Nausea and insomnia were the most predominant side effects reported among the studied population. Conclusion: Vortioxetine was found effective and safe among patients with MDD and comorbid GAD. [ABSTRACT FROM AUTHOR]

Background: Empathy is an important factor in the doctor-patient relationship, but mental illness is more difficult to understand than other diseases. Besides traditional skills, virtual reality (VR) has been identified as a promising tool in empathy education. This study aimed to investigate the ability of empathy enhancement, the feasibility of depression education, and the changes in thoughts and attitudes in medical students through a single VR experience. Methods: We recruited medical students and randomly assigned them to two groups based on their completed Interpersonal Response Index scores. Two sets of VR systems were provided; the intervention group experienced the daily life of the depressed medical student, while the control group experienced the general medical student scenario. The improvement of empathy was assessed using the Jefferson Scale of Empathy-Health Professional Students (JSE-HPS), and the change of attitude was assessed through the Implicit Association Test. In addition, other questionnaires were used to evaluate the user experience of this VR system, and correlation analysis was conducted to examine the association between the use of VR and changes in the JSE and IAT scores. Results: A total of 59 medical students were enrolled in this study. The intervention group showed a significant increase in the perspective-taking (pre: mean 5.817, SD 0.536; post: mean 5.947, SD 0.620; P =.03) and compassionate care (pre: mean 5.546, SD 0.581; post: mean 5.721, SD 0.629; P =.01) domains of the JSE score and a significant decrease in the standing in the patient's shoes (SP) domain (pre: mean 3.583, SD 1.253; post: mean 2.967, SD 1.252; P =.002). The Pearson correlation analysis found a significant positive correlation between the JSE score with immersion aspect (r =.308, P =.049) and presence aspect (r =.415, P =.01), and we also found a significant negative correlation between the IAT score and presence aspect (r=-.333, P =.04). Conclusions: This study is the first randomized case-control study to investigate the effect of two different versions of VR on empathy development toward depression for medical students. Although the single VR experience was unable to induce a great improvement in empathy or attitude, the VR system could help medical students enhance their understanding of depressive disorders. Trial registration: This trial was retrospectively registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) (21/03/2024, ACTRN12624000297527). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386683&isReview=true. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated that breakfast skipping and gut microbiome dysbiosis are associated with a higher risk of major depressive disorder (MDD). However, it remains unknown whether the alteration of gut microbes is implicated in the associations between breakfast skipping and MDD. Methods: Leveraging genome-wide association studies (GWAS) on breakfast skipping, gut microbes, and MDD, we conducted a two-step Mendelian randomization (MR) study to determine the causal associations between breakfast skipping (N = 193,860) and MDD (N = 1,815,091), and evaluate the role of gut microbes (N = 18,340). Genetic variants with a P-value less than 5E-08 were selected as instrumental variables (IVs). The false discovery rate (FDR) method was employed to correct the P-values for multiple tests in gut microbes. Results: Breakfast skipping was associated with an increased risk of MDD (odds ratio [OR] = 1.36, 95%CI = 1.12–1.65, P = 0.002), but no effect of MDD on breakfast skipping was observed (β per doubling odds of MDD =-0.001, 95%CI=-0.024 to 0.023, P = 0.957). After adjusting for multiple comparisons, the MR analysis provided little evidence for an association between breakfast skipping and the abundance of any gut microbes (PFDR>0.05). Among the 21 gut microbes with IVs available, only the abundance of Class Actinobacteria was causally associated with a reduced risk of MDD (OR = 0.85, 95%CI = 0.75–0.97, PFDR=0.015). Conclusions: Our findings demonstrated that breakfast skipping was associated with an increased risk of MDD, but provided little evidence supporting the role of the abundance of gut microbes in it. Further efforts with a large sample size are warranted to clarify the findings. [ABSTRACT FROM AUTHOR]

Background: The study aimed to explore the influence of gender on the prevalence of various somatic symptoms and their associations with suicidal ideation (SI) among patients with major depressive disorder (MDD). Methods: We recruited 3,275 patients with MDD from the National Survey on Symptomatology of Depression (NSSD), among whom 1,745 patients had SI. The clinical characteristics and the prevalence of somatic symptoms across 20 dimensions in MDD patients with SI were compared between male and female patients. Spearman correlation analysis and logistic regression analysis were used to explore the relationship between somatic symptoms and SI. Results: In patients with SI, 32.2% of female participants attributed the onset of MDD to physical concerns, whereas 27% of male patients held a similar perspective (P = 0.032). Female patients exhibited a higher prevalence of early insomnia (64.6% vs. 70.2%) and a lower prevalence of hypersomnia (17.2% vs. 12.9%) and urinary system symptoms (25.0% vs. 17.8%). Logistic regression analysis indicated that female patients displayed a broader range of somatic symptoms identified as risk factors for SI, including increased appetite, respiratory symptoms, circulatory system symptoms, limb pain, and various others. Conclusion: This study unveils gender-specific patterns in somatic symptoms among MDD patients with SI, highlighting the clinical significance of these symptoms in diagnosis and intervention. Understanding how physical concerns contribute to MDD, especially among females, underscores the need for tailored clinical approaches. Recognizing and addressing these symptoms could guide more effective suicide prevention strategies and enhance MDD management in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is one of the most common psychiatric disorders worldwide. Hypericumperforatum (HP) is a traditional herb that has been shown to have antidepressant effects, but its mechanism is unclear. This study aims to identify the molecular targets of HP for the treatment of MDD. Methods: We performed differential analysis and weighted gene co-expression network analysis (WGCNA) with blood mRNA expression cohort of MDD and healthy control to identify DEGs and significant module genes (gene list 1). Three databases, CTD, DisGeNET, and GeneCards, were used to retrieve MDD-related gene intersections to obtain MDD-predicted targets (gene list 2). The validated targets were retrieved from the TCMSP database (gene list 3). Based on these three gene lists, 13 key pathways were identified. The PPI network was constructed by extracting the intersection of genes and HP-validated targets on all key pathways. Key therapeutic targets were obtained using MCODE and machine learning (LASSO, SVM-RFE). Clinical diagnostic assessments (Nomogram, Correlation, Intergroup expression), and gene set enrichment analysis (GSEA) were performed for the key targets. In addition, immune cell analysis was performed on the blood mRNA expression cohort of MDD to explore the association between the key targets and immune cells. Finally, molecular docking prediction was performed for the targets of HP active ingredients on MDD. Results: Differential expression analysis and WGCNA module analysis yielded 933 potential targets for MDD. Three disease databases were intersected with 982 MDD-predicted targets. The TCMSP retrieved 275 valid targets for HP. Separate enrichment analysis intersected 13 key pathways. Five key targets (AKT1, MAPK1, MYC, EGF, HSP90AA1) were finally screened based on all enriched genes and HP valid targets. Combined with the signaling pathway and immune cell analysis suggested the effect of peripheral immunity on MDD and the important role of neutrophils in immune inflammation. Finally, the binding of HP active ingredients (quercetin, kaempferol, and luteolin) and all 5 key targets were predicted based on molecular docking. Conclusions: The active constituents of Hypericumperforatum can act on MDD and key targets and pathways of this action were identified. [ABSTRACT FROM AUTHOR]

Background: Depression is a leading cause of disability worldwide, and treatments could be more effective. Identifying methods to improve treatment success has the potential to reduce disease burden dramatically. Preparing or "priming" someone to respond more effectively to psychotherapy (e.g., cognitive behavioral therapy [CBT]) by preceding sessions with aerobic exercise, a powerful neurobiological activator, could enhance the success of the subsequently performed therapy. However, the success of this priming approach for increasing engagement of working mechanisms of psychotherapy (e.g., increased working alliance and behavioral activation) has yet to be formally tested. Methods: The CBT + trial will be a parallel-arm randomized controlled trial that will recruit 40 adult participants with DSM-5 diagnosed depression (verified with clinical interview) via referrals, mass emails, local flyers, and social media posts. Participants will be randomized to an ActiveCBT or CalmCBT condition. The ActiveCBT group will receive an 8-week CBT intervention primed with 30 min of moderate-intensity aerobic exercise (cycling on a stationary bike at a 13 rating of perceived exertion). The CalmCBT group will receive the same 8-week CBT intervention while resting for 30 min before CBT (i.e., cycling vs no cycling is the only difference). The primary outcome measures will be mean working alliance (assessed with the client version of the Working Alliance Inventory—Short Revised) and mean behavioral activation (self-reported Behavioral Activation for Depression Scale) recorded at each of the 8 therapy sessions. Secondary outcomes include evaluation of state anhedonia and serum brain-derived neurotrophic factor before the active/calm conditions, between the condition and therapy, and after the therapy. Additional exploratory analyses will evaluate group differences in algorithm-generated ratings of therapist-participant interactions via the Lyssn platform. Discussion: The novel approach of priming CBT with moderate-intensity aerobic exercise evaluated in a randomized controlled trial (CBT + trial) has the potential to demonstrate the usefulness of exercise as an augmentation strategy that improves working mechanisms of therapy and overall treatment outcomes for adults with depression. Trial registration: ClinicalTrials.gov NCT06001346. Registered on August 21, 2023. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. Methodology: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. Results: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. Conclusions: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder, or depression, has been extensively linked to dysregulated HPA axis function, chronic inflammation and cardiovascular diseases. While the former two have been studied in depth, the mechanistic connection between depression and cardiovascular disease is unclear. As major mediators of vascular homeostasis, vascular pathology and immune activity, endothelial cells represent an important player connecting the diseases. Exaggerated inflammation and glucocorticoid function are important topics to explore in the endothelial response to MDD. Glucocorticoid resistance in several cell types strongly promotes inflammatory signaling and results in worsened severity in many diseases. However, endothelial health and inflammation in chronic stress and depression are rarely considered from the perspective of glucocorticoid signaling and resistance. In this review, we aim to discuss (1) endothelial dysfunction in depression, (2) inflammation in depression, (3) general glucocorticoid resistance in depression and (4) endothelial glucocorticoid resistance in depression co-morbid inflammatory diseases. We will first describe vascular pathology, inflammation and glucocorticoid resistance separately in depression and then describe their potential interactions with one another in depression-relevant diseases. Lastly, we will hypothesize potential mechanisms by which glucocorticoid resistance in endothelial cells may contribute to vascular disease states in depressed people. Overall, endothelial-glucocorticoid signaling may play an important role in connecting depression and vascular pathology and warrants further study. [ABSTRACT FROM AUTHOR]

Background : Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. Methods: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 μm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. Results: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. Conclusions: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network. [ABSTRACT FROM AUTHOR]

Aim: In line with the publication of clinical information related to the therapeutic process of repetitive transcranial magnetic stimulation (rTMS) and the updating of relevant treatment guidelines, the present meta-analysis study was designed and conducted to determine the effect of repetitive transcranial magnetic stimulation (rTMS) on the Hamilton Depression Rating Scale-17 (HDRS-17) criterion in patients with major depressive disorder (MDD) without psychotic features. Methods: In this study, a systematic search was conducted in electronic databases such as PubMed [Medline], Scopus, Web of Science, Embase, Ovid, Cochrane Library, and ClinicalTrials. gov using relevant keywords. The search period in this study was from January 2000 to January 2022, which was updated until May 2023. Randomized controlled trials (RCTs) that determined the effect of repetitive transcranial magnetic stimulation (rTMS) on the Hamilton Depression Rating Scale-17 (HDRS-17) criterion in patients with major depressive disorder (MDD) without psychotic features were included in the analysis. The quality of the included RCTs was assessed using the Cochrane Risk of Bias checklist. Statistical analyses were performed using STATA (Version 16) and RevMan (Version 5). Results: Following the combination of results from 16 clinical trial studies in the present meta-analysis, it was found that the mean Hamilton Depression Rating Scale-17 (HDRS-17) in patients with major depressive disorder (MDD) decreases by an average of 1.46 units (SMD: -1.46; % 95 CI: -1.65, -1.27, I square: 45.74%; P heterogeneity: 0.56). Subgroup analysis results indicated that the standardized mean difference of Hamilton Depression Rating Scale-17 (HDRS-17) varied based on the number of treatment sessions: patients receiving 10 or fewer repetitive transcranial magnetic stimulation (rTMS) sessions showed a mean Hamilton Depression Rating Scale-17 (HDRS-17) reduction of 2.60 units (SMD: -2.60; % 95 CI: -2.86, -2.33, I square: 55.12%; P heterogeneity: 0.55), while those receiving 11 to 20 sessions showed a mean Hamilton Depression Rating Scale-17 (HDRS-17) reduction of 0.28 units (SMD: -0.28; % 95 CI: -0.65, -0.09, I square: 39.91%; P heterogeneity: 0.89). Conclusion: In conclusion, our meta-analysis demonstrates the efficacy of repetitive transcranial magnetic stimulation (rTMS) in reducing depressive symptoms in major depressive disorder (MDD) patients. The complex results of subgroup analysis revealed insight on the possible benefits of a more focused strategy with fewer sessions, as well as the impact of treatment session frequency. These findings add to our understanding of repetitive transcranial magnetic stimulation (rTMS) as a therapeutic intervention for the treatment of major depressive illnesses. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. Methods: In total, 601 patients (aged 12–18) with MDD were recruited. The Patient Health Questionnaire – 9 items (PHQ – 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. Results: The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p < 0.05). Conclusions: PRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) poses a significant global health burden with available treatments limited by inconsistent efficacy and notable side effects. Classic psychedelics, including lysergic acid diethylamide (LSD), have garnered attention for their potential in treating psychiatric disorders. Microdosing, the repeated consumption of sub-hallucinogenic doses of psychedelics, has emerged as a self-treatment approach for depression within lay communities. Building upon preliminary evidence and the successful completion of an open-label pilot trial of microdosing LSD for depression (LSDDEP1), this protocol outlines a phase 2b randomised controlled trial (LSDDEP2). The main objective of LSDDEP2 is to assess the modification of depressive symptoms, measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), following a regimen of LSD microdoses versus placebo. Methods: This is a randomised, double-dummy, triple-blind, active placebo-controlled, parallel groups trial of LSD microdosing in patients meeting DSM-5 criteria for major depressive disorder. Participants will undergo an 8-week LSD microdosing regimen using the titratable MB-22001 formulation taking two doses a week. All doses will be self-administered at home and will be titratable from 4 to 20 μg based on subjective perception and tolerability. In addition to depression symptoms, outcome will include psychiatric and personality inventories, sleep and activity tracking, electroencephalography (EEG), blood biomarkers, semi-structured interviews, and safety (e.g. adverse event, laboratory exam) measures. Discussion: This study will be the first randomised controlled trial to administer controlled microdoses of LSD for treatment of MDD in participants' naturalistic environment. The measures included are designed to assess the drug's safety, mechanism, and treatment efficacy over placebo in this population. The results of this study will be important for assessing the viability of psychedelic microdosing as an additional treatment option and for informing the direction of future clinical trials. Trial registration: ANZCTR, ACTRN12624000128594. Prospectively Registered on 13 February 2024. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a disabling mental illness that can affect all aspects of daily life and is a leading cause of healthcare resource utilisation (HCRU). Aims: We aimed to characterise patients with MDD with moderate-to-high-suicide-intent, compare their HCRU to patients with MDD without moderate-to-high-suicide-intent, and better understand their patient pathways. Methods: This retrospective cohort study used data collected from primary care electronic health records from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics, Mental Health Services Data Set, and Office for National Statistics in England. Adults diagnosed with ≥ 1 MDD diagnosis between 04/2007 and 11/2015 were categorised by suicide intent. Results: 307,476 patients with MDD were included (294,259 patients without moderate-to-high-suicide-intent and 13,217 with moderate-to-high-suicide-intent). Patients with MDD with moderate-to-high-suicide-intent were younger on average (39.0 vs. 44.8 years) and included a lower percentage of females (58% vs. 65%) compared to patients without moderate-to-high-suicide-intent. HCRU was greater among patients with moderate-to-high-suicide-intent than patients without moderate-to-high-suicide-intent during the first follow-up year for general practitioner consultations (38.5 vs. 29.4), psychiatric outpatient visits (1.5 vs. 0.1), psychiatrist visits (3.6 vs. 0.3), emergency visits (1.5 vs. 0.3), and hospitalisations (86% vs. 26%). Overall, 56% of patients with moderate-to-high-suicide-intent had an antidepressant prescription within 30 days from the initial moderate-to-high-suicide-intent. Conclusions: Patients with MDD and moderate-to-high-suicide-intent were younger, included more males and incurred greater HCRU than those without moderate-to-high-suicide-intent. These results suggest a greater need for effective medical care and appropriate treatments for patients with moderate-to-high-suicide-intent, which could help reduce associated symptoms, mortality, and HCRU. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are two high-prevalent conditions where the Endocannabinoid system (ECS) is believed to play an important role. The ECS regulates how different neurotransmitters interact in both disorders, which is crucial for controlling emotions and responses to stress and reward stimuli. Measuring peripheral endocannabinoids (eCBs) in human serum and plasma can help overcome the limitations of detecting endocannabinoid levels in the brain. This systematic review aims to identify levels of peripheral eCBs in patients with MDD and/or AUD and find eCBs to use as diagnostic, prognostic biomarkers, and potential therapeutic targets. Methods: We conducted a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines from the earliest manuscript until October 22, 2023, in three electronic databases. We included studies of human adults who had a current diagnosis of AUD and/or MDD and evaluated plasma or serum endocannabinoids. We carefully considered known variables that may affect endocannabinoid levels. Results: We included 17 articles in this systematic review, which measured peripheral eCBs in 170 AUD and 359 MDD patients. Stressors increase peripheral 2-arachidonyl-glycerol (2-AG) concentrations, and 2-AG may be a particular feature of depression severity and chronicity. Anxiety symptoms are negatively correlated with anandamide (AEA) concentrations, and AEA significantly increases during early abstinence in AUD. Studies suggest a negative correlation between Oleoylethanolamide (OEA) and length of abstinence in AUD patients. They also show a significant negative correlation between peripheral levels of AEA and OEA and fatty acid amide hydrolase (FAAH) activity. Eicosapentaenoylethanolamide (EPEA) is correlated to clinical remission rates in depression. Included studies show known variables such as gender, chronicity, symptom severity, comorbid psychiatric symptoms, length of abstinence in the case of AUD, and stress-inducibility that can affect peripheral eCBs. Conclusions: This systematic review highlights the important role that the ECS plays in MDD and AUD. Peripheral eCBs appear to be useful biomarkers for these disorders, and further research may identify potential therapeutic targets. Using accessible biological samples such as blood in well-designed clinical studies is crucial to develop novel therapies for these disorders. [ABSTRACT FROM AUTHOR]

Background: Bipolar depression (BPD) is often misdiagnosed as a major depressive disorder (MDD) in clinical practice, which may be attributed to a lack of robust biomarkers indicative of differentiated diagnosis. This study analysed the differences in various hormones and inflammatory markers to explore peripheral biomarkers that differentiate BPD from MDD patients. Methods: A total of 2,048 BPD and MDD patients were included. A panel of blood tests was performed to determine the levels of sex hormones, stress hormones, and immune-related indicators. Propensity score matching (PSM) was used to control for the effect of potential confounders between two groups and further a receiver operating characteristic (ROC) curve was used to analyse the potential biomarkers for differentiating BPD from MDD. Results: Compared to patients with MDD, patients with BPD expressed a longer duration of illness, more hospitalisations within five years, and an earlier age of onset, along with fewer comorbid psychotic symptoms. In terms of biochemical parameters, MDD patients presented higher IgA and IgM levels, while BPD patients featured more elevated neutrophil and monocyte counts. ROC analysis suggested that combined biological indicators and clinical features could moderately distinguish between BPD and MDD. In addition, different biological features exist in BPD and MDD patients of different ages and sexes. Conclusions: Differential peripheral biological parameters were observed between BPD and MDD, which may be age-sex specific, and a combined diagnostic model that integrates clinical characteristics and biochemical indicators has a moderate accuracy in distinguishing BPD from MDD. [ABSTRACT FROM AUTHOR]

Background: The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups. Methods: In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion. Results: A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG). Conclusions: The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD. [ABSTRACT FROM AUTHOR]