Major Depressive Disorder Research Articles

Gender differences in the prevalence and clinical correlates of suicide attempts in young first-episode drug-naïve major depressive disorder patients with thyroid dysfunction

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.

Neural response to errors among mothers with a history of recurrent depression and their adolescent daughters.

Depression is transmitted within families, but the mechanisms involved in such transmission are not clearly defined. A potential marker of familial risk is the neural response to errors, which may play a role in depression symptoms and is known to be partially heritable. Here, 97 mother-daughter dyads completed a Flanker task while electroencephalography markers of error monitoring were recorded: the error-related negativity (ERN) and response-locked delta and theta power. We assessed whether these measures of neural response to errors 1) were associated with history of recurrent major depressive disorder (MDD) and current depression symptoms among mothers, 2) were correlated among mother-daughter dyads, and 3) were associated with maternal history of recurrent MDD and maternal symptoms of depression among daughters. A history of recurrent MDD was associated with blunted delta and increased theta among mothers. Across mothers, delta and theta were negatively and positively associated, respectively, with current depression symptoms. Mothers' and daughters' ERN were positively correlated. Finally, current maternal depression symptoms were negatively associated with delta power in daughters. These results suggest that neural responses to errors may be implicated in the intergenerational transmission of depression. These results also support the relevance of delta oscillations to understanding pathways to depression.

Headaches and adolescents: why so many failures in their management

The management of headaches in children and adolescents is still a challenge, with patients experiencing pain for years and polypharmacy. We reviewed the medical history of 31 patients referred to our pain clinic for chronic headaches between April 2023 and April 2024. There were more female than male patients (73%). Patients have been reporting headaches for 52 ± 44 months on average. Twenty-nine patients (94%) were experiencing different types of pain besides headaches. The most common medication prescribed in this group of patients was topiramate (70%), followed by tricyclic antidepressants (35%) and triptans (21%). Patients had been prescribed and tried, on average, 4.5 ± 2 (range 1–10) different medications to manage headaches and concomitant psychiatric disorders. Twenty-two patients (71%) had been diagnosed with a psychiatric disorder, including depression, anxiety, and PTSD, and 16% had a history of attempted suicide/self-harm. Fourteen of them (45%) had been prescribed antidepressants or benzodiazepines. They had been prescribed, on average, 2 ± 1 (range 1–4) psychiatric stabilizer medications. We agreed with the referral diagnosis in 39% of the patients. We attributed the headaches to more complex chronic pain conditions, including fibromyalgia (15%) and AMPS (15%), autism with sensory integration problems (9%), and major depression (9%). Patients had seen an average of 3 ± 1 (range 1–5) different specialists; none consulted a pain specialist. Patients underwent between 0 (12%) and four tests (6%), including MRI (52%) and CT of the brain (8%). These neuroimaging studies did not demonstrate any brain pathology. We prescribed new medications and treatments, including nerve blocks, in 19 (61%) patients. In 47% of the cases, patients reported improved headaches, while 22% did not feel our recommendations were effective. Twenty-one percent of patients never came back to the clinic for a follow-up. Significant catastrophizing was present in 57% of the patients; 52% of patients had mild to severe anxiety, and 57% had symptoms of depressive disorder. Conclusions: Headaches are often the manifestation of more complex pain syndromes that require a more holistic approach, different from conventional pharmacological management.What is Known:• Headache is one of the most disabling diseases.• Prevalence of headaches in hildrens and adolescents can be as high as 58%.What is New:• Conventional pharmacological management often fails to help young patients.• A relationship between chronic headaches and psychopathology should be investigated in these young patients.

Efficacy of the "7mind"-app as intervention to prevent postpartum depression in a low-risk sample group.

Postpartum depression (PPD) is a severe complication in the postpartum period and equals a major depression occurring in the first weeks after delivery. During the COVID-19 pandemic, an increased incidence of PPD was observed. For this reason, we conducted an intervention study to test the effectiveness of the "7mind"-app, an app-based mindfulness training program, in the prevention of PPD. For this purpose, 145 women who gave birth between March and September 2021 were observed up to six months postpartum, with 80 women using the "7mind"-app. The BSF (Berlin Mood Questionnaire) and the EPDS (Edinburgh Postnatal Depression Scale) were used to measure depressive symptoms at different time points and were supplemented by questionnaires regarding COVID-related anxieties. The BSF showed a significant improvement over time in the categories "anxiety" (p < .001) and "fatigue" (p < .001). Regarding the EPDS, there were no significant differences between the intervention and control groups. With a mean EPDS of 7.6 prepartum and 7.4 postpartum, our sample group can be classified as a low-risk collective. Furthermore, there were no significant differences between the control and intervention groups with regard to COVID-19-related anxiety. However, a comparison of the correlation analysis of COVID-19-related fears over time showed a clear advantage of the intervention. In particular, fear of the consequences of maternal COVID-19 infection increased significantly in the control group over time (r = 0.98, p = 0.040), while there was no significant change in the intervention group (r = -0.39, p = 0.218). In conclusion, the intervention with the app "7mind" seems to lead to a clear benefit in the prevention of general anxiety and COVID-19-related anxieties, but needs further research to represent a valid intervention for the prevention of PPD.

Aberrant network topological structure of sensorimotor superficial white-matter system in major depressive disorder.

White-matter tracts play a pivotal role in transmitting sensory and motor information, facilitating interhemispheric communication and integrating different brain regions. Meanwhile, sensorimotor disturbance is a common symptom in patients with major depressive disorder (MDD). However, the role of aberrant sensorimotor white-matter system in MDD remains largely unknown. Herein, we investigated the topological structure alterations of white-matter morphological brain networks in 233 MDD patients versus 257 matched healthy controls (HCs) from the DIRECT consortium. White-matter networks were derived from magnetic resonance imaging (MRI) data by combining voxel-based morphometry (VBM) and three-dimensional discrete wavelet transform (3D-DWT) approaches. Support vector machine (SVM) analysis was performed to discriminate MDD patients from HCs. The results indicated that the network topological changes in node degree, node efficiency, and node betweenness were mainly located in the sensorimotor superficial white-matter system in MDD. Using network nodal topological properties as classification features, the SVM model could effectively distinguish MDD patients from HCs. These findings provide new evidence to highlight the importance of the sensorimotor system in brain mechanisms underlying MDD from a new perspective of white-matter morphological network.

Proteomics analysis in rats reveals convergent mechanisms between major depressive disorder and dietary zinc deficiency

Abstract Background Preclinical and clinical studies have shown that dietary zinc deficiency can lead to symptoms similar to those observed in major depressive disorder (MDD). However, the underlying molecular mechanisms remain unclear. To investigate these mechanisms, we examined proteomic changes in the prefrontal cortex (PFC) and hippocampus (HP) of rats, two critical brain regions implicated in the pathophysiology of depression. Methods Rats were fed diets either adequate in zinc (ZnA, 50 mg Zn/kg) or deficient in zinc (ZnD, &lt;3 mg/kg) for four weeks. High-throughput proteomic analysis was used to detect changes in protein expression, supplemented by enzyme activity assay for mitochondrial complexes I and IV, examining their functional impacts. Results ZnD led to significant alterations in protein expression related to zinc transport and mitochondrial function. Proteomic analysis revealed changes in zinc transporter family members such as Slc30a1 (6.64 log2FC), Slc30a3 (-2.32 log2FC), Slc30a4 (2.87 log2FC), Slc30a5 (5.90 log2FC), Slc30a6 (1.50 log2FC), and Slc30a7 (2.17 log2FC) in the PFC, and Slc30a3 (-1.02 log2FC), Slc30a5 (-1.04 log2FC), and Slc30a7 (1.08 log2FC) in the HP of rats subjected to ZnD. Furthermore, ZnD significantly affected essential mitochondrial activity proteins, including Atp5pb (3.25 log2FC), Cox2 (2.28 log2FC), Atp5me (2.04 log2FC), Cyc1 (2.30 log2FC), Cox4i1 (1.23 log2FC), Cox7c (1.63 log2FC), and Cisd1 (1.55 log2FC), with a pronounced decrease in complex I activity in the PFC. Conclusions Our study demonstrates that ZnD leads to significant proteomic changes in the PFC and HP of rats. Specifically, ZnD alters the expression of zinc transporter proteins and proteins critical for mitochondrial function. The significant decrease in complex I activity in the PFC further underscores the impact of ZnD on mitochondrial function. These results highlight the molecular mechanisms by which ZnD can influence brain function and contribute to symptoms similar to those observed in depression.

RNA Editing Signatures Powered by Artificial Intelligence: A New Frontier in Differentiating Schizophrenia, Bipolar, and Schizoaffective Disorders

Mental health disorders are devastating illnesses, often misdiagnosed due to overlapping clinical symptoms. Among these conditions, bipolar disorder, schizophrenia, and schizoaffective disorder are particularly difficult to distinguish, as they share alternating positive and negative mood symptoms. Accurate and timely diagnosis of these diseases is crucial to ensure effective treatment and to tailor therapeutic management to each individual patient. In this context, it is essential to move beyond standard clinical assessment and employ innovative approaches to identify new biomarkers that can be reliably quantified. We previously identified a panel of RNA editing biomarkers capable of differentiating healthy controls from depressed patients and, among depressed patients, those with major depressive disorder and those with bipolar disorder. In this study, we integrated Adenosine-to-Inosine RNA editing blood biomarkers with clinical data through machine learning algorithms to establish specific signatures for bipolar disorder and schizophrenia spectrum disorders. This groundbreaking study paves the way for the application of RNA editing in other psychiatric disorders, such as schizophrenia and schizoaffective disorder. It represents a first proof-of-concept and provides compelling evidence for the establishment of an RNA editing signature for the diagnosis of these psychiatric conditions.

Age at onset as an index of genetic heterogeneity in major psychiatric and substance use disorders.

Robust clinical indices of etiologic heterogeneity for psychiatric disorders are rare. We investigate whether age at onset (AAO) reflects genetic heterogeneity, utilizing Genetic Risk Ratios (GRR) derived from Family Genetic Risk Scores (FGRS). We examined, in individuals born in Sweden 1940-2003, whether AAO for five primary disorders -- drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), and schizophrenia (SZ)-- was associated with varying levels of GRRs with a range of informative secondary disorders and traits. Our disorders displayed a varying pattern of change of GRRs with increasing AAO. At one end was SZ, where all GRRs rose with increasing AAO meaning that SZ became increasing genetically heterogeneous with later AAO. The most balanced disorder was AUD where, with increasing AAO, GRRs rose for AD, BD, and MD and declined for DUD, CB, and ADHD. That is, at young AAO, AUD had high levels of genetic risk for other externalizing disorders while at older AAO, high genetic risk for internalizing disorders were more prominent. MD was at the continuum's other end where all GRRs, except for AD, decreased with higher AAO, meaning that MD became increasingly genetically homogeneous with later AAO. Genetic heterogeneity was robustly associated with AAO across our five primary disorders with substantial inter-disorder differences in the observed patterns. In particular, young AAO was associated with maximal genetic homogeneity for SZ and DUD while older AAO had greater genetic homogeneity for MD with AUD falling in between.

The Docking and Dynamics Simulation of Natural Compounds from Abrus precatorius L. for Investigating the Possibility of GluR3 Inhibition to Treat Depression

Background The rising incidence of Major Depressive Disorder (MDD), in conjunction with the inadequate effectiveness and resistance observed in existing therapeutic approaches, emphasizes the urgent need to investigate novel therapeutics that provide enhanced efficacy with reduced adverse effects. Abrus precatorius L., an herb that is readily available and frequently utilized in traditional medicine, is frequently prescribed to patients suffering from neurological disorders. Purpose The goal of this study is to discover novel active compounds from the A. precatorius plant that can specifically target the GluR3 receptor using in silico techniques, to develop a safe and efficient treatment for MDD. Methods Homology modeling, molecular docking, molecular dynamics simulation, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis were employed in this investigation to screen compounds derived from A. precatorius. Their potential to inhibit α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activity, specifically glutamate receptor 3 (GluR3), which is associated with MDD, was the objective of this study. Results Among 31 compounds derived from A. precatorius, 15 successfully cleared the ADMET filter criteria. Subsequently, the best homology model of GluR3 was constructed using Phyre2. This facilitated an investigation into the intramolecular interactions exhibited by the filtered compounds. Notably, the four compounds with the most pronounced binding affinities are identified by their PubChem compound IDs (CIDs): 160511, 44257585, 1983, and 145857. The binding affinity and internal molecular interactions of the top-ranking compound, PubChem CID 160511, were subjected to further validation through MD simulations, affirming its sustained stability in binding. Conclusion CIDs: The compound 160511 cleared ADMET analysis with no notable side effects and high binding affinity and stability, making it a potential drug candidate for MDD. To ascertain the precise efficacy of medications, additional in vitro, in vivo, and clinical studies are required.

Childhood sexual abuse and lifetime depressive symptoms: the importance of type and timing of childhood emotional maltreatment

Abstract Background Childhood sexual abuse (CSA) and emotional maltreatment are salient risk factors for the development of major depressive disorder (MDD) in women. However, the type- and timing-specific effects of emotional maltreatment experienced during adolescence on future depressive symptomatology in women with CSA have not been explored. The goal of this study was to fill this gap. Methods In total, 203 women (ages 20–32) with current depressive symptoms and CSA (MDD/CSA), remitted depressive symptoms and CSA (rMDD/CSA), and current depressive symptoms without CSA (MDD/no CSA) were recruited from the community and completed self-report measures. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II) and a detailed maltreatment history was collected using the Maltreatment and Abuse Chronology of Exposure (MACE). Differences in maltreatment exposure characteristics, including multiplicity and severity of maltreatment, as well as the chronologies of emotional maltreatment subtypes were compared among groups. A random forest machine-learning algorithm was utilized to assess the impact of exposure to emotional maltreatment subtypes at specific ages on current depressive symptoms. Results MDD/CSA women reported greater prevalence and severity of emotional maltreatment relative to rMDD/CSA and MDD/no CSA women [F(2,196) = 9.33, p &lt; 0.001], specifically from ages 12 to 18. The strongest predictor of current depressive symptoms was parental verbal abuse at age 18 for both MDD/CSA women (variable importance [VI] = 1.08, p = 0.006) and MDD/no CSA women (VI = 0.68, p = 0.004). Conclusions Targeting emotional maltreatment during late adolescence might prove beneficial for future intervention efforts for MDD following CSA.

A Cross-sectional Study on Utilization of Herbal Medications for Anxiety in the Lebanese Population: Usage Patterns and Implications for Harmonizing Mental Health

Background Anxiety is a highly prevalent mental health issue worldwide, but it is also notably prevalent in Lebanon, where herbal medications and plants are commonly used as complementary or alternative treatments to manage anxiety. Lebanese citizens have undergone various disasters, starting with the economic crisis in 2019, the Beirut port explosion in 2020, and the COVID-19 pandemic, which led to several mental disorders such as anxiety, unipolar depression, and insomnia. Objective This study aimed to measure the prevalence and patterns of herbal medications and plant usage for anxiety among the Lebanese population, as well as to explore the factors influencing the decision to use herbal remedies, patient perspectives, and potential implications for mental health support. Methods A cross-sectional study was conducted to assess the prevalence of anxiety and the usage of herbal medications and plants among 501 Lebanese outpatients (General Population) aged 20 years and older at Lebanese community pharmacies within Beirut, Mount Lebanon, South, North, Beqaa. Data was collected through personal face-to-face and online structured interviews and surveys, capturing information on herbal medications and plants usage, sources of recommendations, patient perspectives, and perceived efficacy and safety of herbal medications and plants for anxiety. Results The study revealed that anxiety was a prevalent medical condition among Lebanese outpatients, with more than 50% reporting anxiety through various symptoms. Furthermore, 27.34% of Lebanese patients had consumed herbal medications, with a notable proportion advising others to use herbal remedies for anxiety. The sources of recommendations for herbal medication usage included mass media, pharmacists, and personal reading/internet. Additionally, a considerable percentage of patients expressed beliefs in the effectiveness and safety of herbal remedies for anxiety while also indicating a lack of awareness regarding potential side effects. Conclusion The findings of this study underscore the need for increased awareness, education, and regulatory oversight in Lebanese pharmacists regarding anxiety management using herbal medications and plant-based treatments. This includes public education campaigns, healthcare provider training, and regulatory oversight. Prioritizing patient counseling and further research is essential to assess the efficacy and safety of these treatments within the Lebanese context. This integrative approach, blending traditional practices with evidence-based mental health care, could drive policy changes and improve mental health outcomes in Lebanon.

Approximating the semantic space: word embedding techniques in psychiatric speech analysis

Large language models provide high-dimensional representations (embeddings) of word meaning, which allow quantifying changes in the geometry of the semantic space in mental disorders. A pattern of a more condensed (‘shrinking’) semantic space marked by an increase in mean semantic similarity between words has been recently documented in psychosis across several languages. We aimed to explore this pattern further in picture descriptions provided by a transdiagnostic German sample of patients with schizophrenia spectrum disorders (SSD) (n = 42), major depression (MDD, n = 43), and healthy controls (n = 44). Compared to controls, both clinical groups showed more restricted dynamic navigational patterns as captured by the time series of semantic distances crossed, while also showing differential patterns in the total distances and trajectories navigated. These findings demonstrate alterations centred on the dynamics of the flow of meaning across the semantic space in SSD and MDD, preserving previous indications towards a shrinking semantic space in both cases.

Lived experiences of mothers: A longitudinal study of impacts and adjustment following adolescent psychiatric hospitalization for suicide attempts or other reasons.

Parents play crucial roles in monitoring and supporting youth who have been hospitalized after suicide attempts, but their adjustment in the period following hospitalization has been understudied. This study assessed the adjustment and impacts on mothers during the year following hospitalization. Participants included 135 mothers of suicidal adolescents and 117 mothers of adolescents hospitalized for other reasons. The Structured Clinical Interview for DSM (SCID) and the Child and Adolescent Impact Assessment were used to assess psychiatric diagnoses of Major Depressive Disorder [MDD], Generalized Anxiety Disorder [GAD], and Post-Traumatic Stress Disorder [PTSD], and impacts on caregivers at one, three, six, and 12 months after hospitalization. Higher rates of MDD, GAD, and PTSD, and greater impacts were evidenced closer in time to the hospitalization. There were few overall differences between mothers of youth with and without suicidal behavior. However, family history of suicidal behavior was related to higher rates of MDD and PTSD, and greater severity of youth suicidal thoughts and behavior over the follow-up was related to greater impact upon mothers of suicidal youth. This study highlights the mental health struggles of mothers of suicidal and other hospitalized youth and underscores the importance of support for caregivers.

"Caminando y socializando con Happy Older Latinos are Active (HOLA)": Results of a randomized clinical trial to promote health and prevent depression and anxiety in older Latinos.

This study sought to evaluate the feasibility, acceptability, and preliminary efficacy of the Happy Older Latinos are Active (HOLA) health promotion intervention in a group of older Latinos who were at risk for developing major depressive disorder or generalized anxiety disorder. Sixty older Latinos age 60+ with subthreshold depression or anxiety were randomized to receive either HOLA (n = 30) or enhanced psychoeducation through fotonovela control (n = 30). The primary outcomes of interest were feasibility, acceptability, and reduction in depression and anxiety symptom severity. Outcome measures were administered at baseline and at the end of the intervention. Within a year, the enrollment target was met with < 5% of eligible participants refusing randomization. The randomization scheme produced equal numbers of participants randomized to each condition. Four participants (6.7%; HOLA = 1; control = 3) were lost to follow-up, 69% of the HOLA sessions were attended, and participants reported high satisfaction with the intervention. Finally, compared with control, a significant proportion of participants in HOLA experienced a clinically significant reduction in their anxiety symptoms (60% vs. 26.7%). Findings highlight the feasibility, acceptability, and significant impact the HOLA intervention can have in reducing psychological distress because it is responsive, respectful, and specific to the needs of older Latinos. Furthermore, using a community health worker to deliver a health promotion intervention to prevent common mental disorders in older Latinos is an innovative approach for reducing disease burden in a population living with high disparities in accessing and engaging in mental health services. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Service coverage for major depressive disorder: estimated rates of minimally adequate treatment for 204 countries and territories in 2021

Access to effective treatment for major depressive disorder remains limited and difficult to track across place and time. We analysed the available data on minimally adequate treatment (MAT) for major depressive disorder globally with the aim of providing a useful metric against which to monitor national responses to the growing public health burden imposed by major depressive disorder. MAT was defined as pharmacotherapy (1 month of medication, plus four visits to a medical doctor) or psychotherapy (eight visits with any professional). From existing reviews, we identified mental health surveys that assessed major depressive disorder within the general population as well as health service uptake by individuals with major depressive disorder. Data by ethnicity were not available. Estimates of MAT, antidepressant use, or use of any mental health service were extracted. The latter two estimates were adjusted to reflect likely MAT rates via a network meta-analysis. Adjusted MAT estimates were analysed via a Bayesian meta-regression using the Disease Modelling Meta-Regression (DisMod-MR 2.1) tool. This analysis estimated MAT coverage among people with major depressive disorder by age, sex, location, and year. Final MAT estimates were standardised by age and sex against the existing age and sex distribution of people with major depressive disorder globally. People with lived experience were involved in the design, preparation, interpretation, and writing of this manuscript. The analysed dataset included 145 estimates from 32 studies, covering 31 countries, 14 regions, and six super-regions. The proportion of people with major depressive disorder receiving MAT globally in 2021 was 9·1% (95% uncertainty interval 7·2-11·6), with 10·2% (8·2-13·1) of females and 7·2% (5·7-9·3) of males with major depressive disorder receiving MAT. MAT coverage was highest in high-income locations (27·0% [21·7-34·4]), with Australasia having the highest rate (29·2% [21·4-40·8]). MAT coverage was lowest in sub-Saharan Africa (2·0% [1·5-2·6]), within which western sub-Saharan Africa (1·8% [1·4-2·5]) had the lowest coverage. Seven countries (Australia, Belgium, Canada, Germany, the Netherlands, South Korea, and Sweden) were estimated to have MAT coverage exceeding 30%, while 90 countries were estimated to have coverage lower than 5%. Despite many gaps in the available data, estimates show that, globally, most individuals with major depressive disorder do not receive MAT. Services must improve to reach a global coverage that better meets the mental health needs of those with major depressive disorder. Urgent attention should be given to the scale-up of effective intervention strategies, especially in low-income and middle-income countries, as well as further research into better quality treatment options for major depressive disorder. We present a means by which the MAT gap for major depressive disorder can be quantified, to monitor and inform action by governments and international partners. Queensland Health and the Bill & Melinda Gates Foundation.

Mood, Activity, and Instability in Bipolar Disorder and Unipolar Disorder-An Exploratory Post Hoc Study Using Digital Data.

Mood, activity, and instability in symptomatology hold significant roles in bipolar disorder (BD) and unipolar disorder (UD). The objectives were to examine disparities in these symptoms among patients with BD and UD. Data from two studies including patients with BD and UD, respectively, were combined for exploratory analyses. Patients provided daily smartphone-based evaluations of mood and activity/energy for a 6-month period. A total of 47 patients with BD and 59 patients with UD were included in the analyses. The dataset contains more than 13,000 patient-reported evaluations of mood and activity. Daily mood and activity instability measures were calculated using the root squared successive difference method. In linear mixed effect regression models adjusted for age, sex, and work status, there were statistically significant lower levels of activity in patients with BD as compared with patients with UD overall, during euthymic states and during depressive states (B: -0.61, 95% CI: -0.98; -0.24, p = 0.001). There were no statistically significant differences in mood instability and activity instability between patients with BD and patients with UD overall, during euthymic states and during depressive states, when accounting for multiple testing (p > 0.012). Analyses were exploratory and post hoc. Findings should be interpreted with caution. The sample size was modest. Patients with BD presented with lower level of activity as compared with patients with UD. There were no differences in mood and activity instability between these groups. Future studies including larger sample sizes should investigate differences between BD and UD. ClinicalTrials.gov identifier: NCT03033420.

The Gut Microbiota and Major Depressive Disorder: Current Understanding and Novel Therapeutic Strategies.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.

Natural products that alleviate depression: The putative role of autophagy.

Major depressive disorder (MDD) is a common mental disorder that severely disrupts psychosocial function and decreases the quality of life. Although the pathophysiological mechanism underlying MDD is complex and remains unclear, emerging evidence suggests that autophagy dysfunction plays a role in MDD occurrence and progression. Natural products serve as a major source of drug discovery and exert tremendous potential in developing antidepressants. Recently published reports are paying more attention on the autophagy regulatory effect of antidepressant natural products. In this review, we comprehensively discuss the abnormal changes occurred in multiple autophagy stages in MDD patients, and animal and cell models of depression. Importantly, we emphasize the regulatory mechanism of antidepressant natural products on disturbed autophagy, including monomeric compounds, bioactive components, crude extracts, and traditional Chinese medicine formulae. Our comprehensive review suggests that enhancing autophagy might be a novel approach for MDD treatment, and natural products restore autophagy homeostasis to facilitate the renovation of mitochondria, impede neuroinflammation, and enhance neuroplasticity, thereby alleviating depression.

Abnormal ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium

BackgroundThe assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment. MethodsThis study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample t-test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity. ResultsCompared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score. ConclusionOur findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide.

Psychological interventions to prevent the onset of major depression in adults: a systematic review and individual participant data meta-analysis

Psychological interventions are increasingly discussed as a method to prevent major depressive disorder (MDD) in adults who already experience subthreshold depressive symptoms. In this individual participant data meta-analysis, we quantify the effect of preventive interventions against control on MDD onset in this population, and explore effect modifiers. In this systematic review and individual participant data meta-analysis, we screened full-texts of eligible studies within the Metapsy research domain for articles on psychological interventions for depression, from database inception to May 1, 2023, published in English, German, Spanish, and Dutch. We included individual participant data of randomised trials comparing psychological interventions with a control group regarding their effects on MDD onset in adults with subthreshold depressive symptoms but no MDD at baseline, confirmed by standardised diagnostic interviews. Risk of bias was assessed using the RoB 2 tool. Effect on the onset of MDD (the primary outcome) and moderators were analysed using one-stage individual participant data meta-analysis. Survival analyses were conducted to examine effects on time to MDD onset within 12 months. We involved people with related lived experience in the study design and implementation. This study is registered with PROSPERO, CRD42017058585. 30 of 42 eligible randomised controlled trials with 7201 participants (2227 [30·9%] male, 4957 [68·9%] female, and 17 [0·2%] preferred not to report their sex) were included in our analysis (3697 participants had intervention and 3504 participants had control). The mean age of participants was 49·9 years (SD 19·2). Of the 3152 participants with reported ethnicity, 1608 (51·0%) were White. Five studies received a high risk of bias rating. Psychological interventions were associated with significantly reduced MDD incidence at post-treatment (incidence rate ratio [IRR] 0·57 [95% CI 0·35-0·93]; τ2=0·29; 18 studies), within 6 months (0·58 [0·39-0·88]; τ2=0·11; 18 studies), and within 12 months (0·67 [0·51-0·88]; τ2=0·05; 19 studies). No significant effect was observed at 24 months (IRR 1·16 [95% CI 0·66-2·03]; τ2=0·10; six studies). Preventive effects were stronger for individuals who had not previously had psychotherapy (IRR 0·39 [95% CI 0·25-0·62]) compared with those who had received psychotherapy before (0·92 [0·61-1·36]; p=0·029; seven studies). Although no overall linear association was identified, higher baseline depressive (Patient Health Questionnaire-9) and anxiety symptom (Generalized Anxiety Disorder-7) scores were associated with greater reductions in MDD onset risk. On the study level, delivery type appeared to moderate outcomes, with conference telephone calls being more effective than delivery via face-to-face, internet-based, and other formats (p=0·002), albeit based on only two studies of conference telephone calls with four comparisons. Other factors (eg, age) showed no significant differential effects. Our findings show the effectiveness of preventive psychological interventions for subthreshold depressive symptoms. Tailoring interventions to consider participant-level and study-level factors could help to increase the impact of such interventions on a population level. None.