Depressive Episode Research Articles

Clustering and drivers of symptoms observed at week six after antidepressant treatment in depressed outpatients.

Depressive symptoms remaining after antidepressant treatment increase the risk of relapse and recurrence. We aimed to analyze the distribution and main drivers of remaining symptoms in patients with a major depressive episode. Two independent samples of 8,229 and 5,926 patients from two large naturalistic studies were retrospectively analyzed. DSM-IV criteria for major depressive episodes were assessed during two face-to-face visits with clinicians: before the prescription of a new antidepressant, and after 6weeks of treatment. The Hospital Anxiety and Depression Scale (HADS) was used to assess baseline severity of anxiety and depression. In both samples, two clusters of remaining symptoms were observed. The first cluster encompassed symptoms related to a negative emotional and cognitive bias and was specifically driven by the baseline severity of depression. The second cluster encompassed neurovegetative symptoms and was specifically driven by the baseline severity of anxiety. The baseline anxiety-depressive balance of patients could be considered to adapt the treatment, focusing on emotional and cognitive symptoms with patients with high baseline severity of depression, and neurovegetative symptoms with patients with high baseline anxiety severity.

Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action.

There is an ongoing need to identify novel pharmacological agents for the effective treatment of depression. One emerging candidate, which has demonstrated rapid-acting antidepressant effects in treatment-resistant groups, is nitrous oxide (N2O)-a gas commonly used for sedation and pain management in clinical settings and with a range of pharmacological effects, including antagonism of NMDA glutamate receptors. A growing body of evidence suggests that subanaesthetic doses of N2O (50%) can interfere with the reconsolidation of maladaptive memories in healthy participants and across a range of disorders. Negative biases in memory play a key role in the onset, maintenance, and recurrence of depressive episodes, and the disruption of affective memory reconsolidation is one plausible mechanism through which N2O exerts its therapeutic effects. Understanding N2O's mechanisms of action may facilitate future treatment development in depression. In this narrative review, we introduce the evidence supporting an antidepressant profile of N2O and evaluate its clinical use compared to other treatments. With a focus on the specific memory processes that are thought to be disrupted in depression, we consider the effects of N2O on memory reconsolidation and propose a memory-based mechanism of N2O antidepressant action.

The Link between Nutrition and Bipolar Disorder

Bipolar disorder (BD) is a complex mental health condition characterized by extreme mood swings, including manic and depressive episodes. This study explores the relationship between nutrition and bipolar disorder with the goal of determining how dietary factors may affect how this condition is managed. Recent studies suggest that dietary consumption of specific vitamins, minerals, and fatty acids, including omega-3, vitamin D, and essential minerals, may be important in reducing the symptoms of BD. These nutrients have been linked to better mood stabilization and may increase the efficacy of pharmaceutical treatments, which could improve treatment outcomes and lower patient suicide rates. A review and analysis of the literature is the methodology used in this paper. This study reveals a link between bipolar disorder and nutrition, suggesting that patients with BD can benefit from using omega-3, vitamin D, and specific minerals to treat their illness and lower their risk of suicide or suicidal thoughts. Additionally, the study finds that certain nutrient combinations can reduce side effects and improve BD treatment when taken with medication. Overall, this study highlights how nutrition can improve the quality of life for those with bipolar disorder.

Measuring psychological well-being in a danish pregnancy cohort using the self-reported WHO-5 index

BackgroundReduced well-being and depressive episodes frequently complicate pregnancy and can result in serious adverse outcomes for both mother and infant if left untreated. This study aimed to assess the psychometric validity of the 5-item World Health Organization index (WHO-5), and to evaluate if the WHO-5 index can serve as a proxy for two items of core depressive symptoms from the Major Depression Inventory (MDI), identified as MDI-2. Additionally, the paper aimed to assess well-being and detect risk factors of reduced well-being using the WHO-5 index.MethodsUsing the WHO-5 index, this study analyzed the psychological well-being of a population of 37,129 women in their first trimester of pregnancy. The psychometric validity of the WHO-5 index was evaluated using confirmatory factor analysis and item response theory. Furthermore, cut-off scores of the WHO-5 index previously associated with mental distress, ≤ 50 and ≤ 28, were evaluated in terms of sensitivity, specificity, and positive- and negative predictive values compared to the MDI-2 in a subsample of n = 1001 women.ResultsLower mean score on the WHO-5 index was seen among pregnant women ≤ 25 years old, with lower educational level, who were unemployed, nulliparous, did not understand Danish language, were not cohabitating, were smokers, and women who did not exercise prior to pregnancy. The WHO-5 index was found to be a valid psychometric instrument, however, scores could not be pooled or compared across women who understood Danish and women who did not understand Danish. The sensitivity and specificity of cut-off score of ≤ 50 on the WHO-5 index with a for predicting the presence of one core symptom from the MDI-2 was 0.81 and 0.82, respectively, while the sensitivity and specificity using a cut-off of ≤ 28 was 0.32 and 0.98, respectively.ConclusionsThe WHO-5 index had high degree of acceptability and identified well-known risk factors of mental distress in a pregnant population. The WHO-5 index was found to be a valid psychometric instrument in pregnancy, however, our analysis indicated low predictive value of the investigated cut-off scores on the WHO-5 index in identification of MDI-2 core symptoms.

Altered tRNA expression profile associated with codon-specific proteomic changes in the suicide brain.

Suicide is a major public health concern, and the number of deaths by suicide has been increasing in recent years in the US. There are various biological risk factors for suicide, but causal molecular mechanisms remain unknown, suggesting that investigation of novel mechanisms and integrative approaches are necessary. Transfer (t)RNAs and their modifications, including cytosine methylation (m5C), have received little attention regarding their role in normal or diseased brain function, though they are dynamic mediators of protein synthesis. tRNA regulation is highly interconnected with proteomic and metabolomic outcomes, suggesting that investigating these multiple levels of molecular regulation together may elucidate more information on neural function and suicide risk. In the current study, we used an integrative 'omics' approach to probe tRNA dysregulation, including tRNA expression and tRNA m5C, proteomics, and amino acid metabolomics in prefrontal cortex from 98 subjects who died by suicide during an episode of major depressive disorder (MDD) and neurotypical controls. While no changes were detected in amino acid content, results showed increased tRNAGlyGCC expression in the suicide brain that is not driven by changes in m5C. Proteomics revealed increased expression of proteins with high glycine codon GGC content, demonstrating a strong association between isoacceptor-specific tRNA expression and proteomic outcomes in the suicide brain, which is in line with previous work linking tRNAGly with alterations in glycine-rich proteins in a translational rodent model of depression. Further, we confirmed using a rodent model that tRNAGlyGCC overexpression was sufficient to increase the expression of proteins with high glycine codon GGC content that were upregulated in the suicide brain. By characterizing the effects of MDD-suicide in human PFC tissue, we now begin to elucidate a novel molecular signature with downstream consequences for psychiatric outcomes.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD). We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis. Based on individual genotypes from case-control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses. Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case-case GWAS and that of case-control BPD. We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Intravenous trazodone for the treatment of psychomotor agitation and associated symptoms in major depressive disorder patients experiencing a depressive episode with mixed features.

Psychomotor agitation is a challenging symptom of major depressive disorder with mixed features (MDD-MF), often worsening outcomes and complicating treatment. This retrospective study assessed the efficacy and tolerability of intravenous trazodone in 97 hospitalized patients with MDE-MF. Symptom severity was evaluated using montgomery asberg depression rating Scale (MADRS), young mania rating scale, hamilton anxiety rating scale, GAD-7, and clinical global impression scale-severity of illness (CGI-S) scales, with significant reductions in agitation, anxiety, and irritability observed early during treatment. Correlation analyses revealed significant negative associations between intravenous (IV) trazodone dosage and improvements in MADRS (r = -0.23; P < 0.05), item 5 of GAD-7 (r = -0.27; P < 0.001), and CGI-S scores (r = -0.22; P < 0.05). Therapy duration also correlated negatively with improvements in GAD-7 item 5 (r = -0.29; P < 0.001) and CGI-S (r = -0.27; P < 0.001), indicating diminishing returns with prolonged treatment. Regression analyses showed that therapy duration, but not dosage, significantly influenced improvements in GAD-7 item 5 and CGI-S. Trazodone was well-tolerated, with only mild side effects in 11.3% of patients. These findings suggest that IV trazodone effectively reduces agitation and related symptoms in MDD-MF, particularly in the early treatment phase, emphasizing the importance of optimizing treatment duration. Future studies should investigate individualized dosing strategies and explore long-term outcomes in this population.

Endometriosis and risk of depression among oral contraceptive users: a pooled analysis of cohort studies from 13 countries.

Does endometriosis affect the mental health of women using oral contraceptives? Among oral contraceptive users, women with endometriosis have a higher risk of depression compared to those without endometriosis, although the absolute risk increase is small. Previous studies have suggested a potential link between endometriosis and mental health issues, but the impact of endometriosis on depression among oral contraceptive users remains unclear. A secondary pooled cohort study utilizing data from two longitudinal patient-centric studies (INAS-VIPOS and PRO-E2) was conducted across 11 European countries, Colombia and Australia. The study included 93541 women newly prescribed oral contraceptives, with or without endometriosis, and without a self-reported history of depression. Participant's mental health was captured using self-administered questionnaires at baseline and every 6-12 months thereafter, asking about any newly occurred episodes of depression. Incidence rates (IRs) of self-reported depression were calculated per 10000 woman-years. Absolute risk difference (ARD) and number needed to harm (NNH) were calculated with 95% CIs. The association between endometriosis and self-reported depression was estimated through crude and adjusted hazard ratios (HRs) with 95% CI, using stabilized inverse probability of treatment weighting (IPTW). Of the included 93541 women, 21090 had endometriosis (49541 woman-years) and 72451 had no endometriosis (137137 woman-years.) Of those with endometriosis, 308 (1.5%) reported an episode of depression (IR: 62.2/10000, 95% CI: 55.4-69.5) compared to 535 (0.7%) of women without endometriosis (IR 39.0/10000, 95% CI: 35.8-42.5). The ARD and NNH were 23.2 per 10000 (95% CI: 15.2-30.9) and 431 (95% CI: 323.7-657.0) respectively. The HR of depression in women with endometriosis was 1.85 (95% CI: 1.60-2.13) using stabilized IPTW to control for age, BMI, smoking, education, and age at menarche. Subgroup and sensitivity analyses showed similar results. While efforts were made to control for confounding factors, residual confounding may still exist. Additionally, the results can only be generalized to users of oral contraceptives. These results highlight the importance of considering the mental health implications of endometriosis among women using oral contraceptives. Further research is needed to explore additional contributing factors and potential interventions. No funding was received for this study. No competing interests apply for this research. N/A.

Is Artificial Intelligence the Next Co-Pilot for Primary Care in Diagnosing and Recommending Treatments for Depression?

Depression poses significant challenges to global healthcare systems and impacts the quality of life of individuals and their family members. Recent advancements in artificial intelligence (AI) have had a transformative impact on the diagnosis and treatment of depression. These innovations have the potential to significantly enhance clinical decision-making processes and improve patient outcomes in healthcare settings. AI-powered tools can analyze extensive patient data—including medical records, genetic information, and behavioral patterns—to identify early warning signs of depression, thereby enhancing diagnostic accuracy. By recognizing subtle indicators that traditional assessments may overlook, these tools enable healthcare providers to make timely and precise diagnostic decisions that are crucial in preventing the onset or escalation of depressive episodes. In terms of treatment, AI algorithms can assist in personalizing therapeutic interventions by predicting the effectiveness of various approaches for individual patients based on their unique characteristics and medical history. This includes recommending tailored treatment plans that consider the patient’s specific symptoms. Such personalized strategies aim to optimize therapeutic outcomes and improve the overall efficiency of healthcare. This theoretical review uniquely synthesizes current evidence on AI applications in primary care depression management, offering a comprehensive analysis of both diagnostic and treatment personalization capabilities. Alongside these advancements, we also address the conflicting findings in the field and the presence of biases that necessitate important limitations.

Substance use and psychiatric outcomes following substance use disorder treatment: An 18-month prospective cohort study in Chile.

Evidence from high-income countries has linked duration and compliance with treatment for substance use disorders (SUDs) with reductions in substance use and improvements in mental health. Generalizing these findings to other regions like South America, where opioid and injection drug use is uncommon, is not straightforward. We examined if length of time in treatment and compliance with treatment reduced subsequent substance use and presence of psychiatric comorbidities. Prospective cohort analysis (3 assessments, 18 months) using inverse probability weighting to account for confounding and loss to follow-up. Outpatient/inpatient programs in Región Metropolitana, Chile. Individuals initiating publicly funded treatment (n = 399). Exposures included length of time in (0-3, 4-7, 8 + months, currently in) and compliance with treatment (not completed, completed, currently in) measured in the intermediate assessment (12 months). Primary outcomes were past-month use of primary substance (most problematic) and current psychiatric comorbidities (major depressive episode, panic, anxiety or post-traumatic stress disorders) measured 6months later (18 months). Secondary outcomes included past month use of alcohol, cannabis, cocaine powder and cocaine paste. 18.3% [95% confidence interval (CI) = 14.7%-22.6%] of individuals participated for 3 or fewer months in treatment and 50.1% (95% CI = 45.2%-55.1%) did not complete their treatment plan at 12 months. Participating for 8 + months in treatment was associated with lower risk of past month use of primary substance at 18 months [vs. 0-3 months, risk ratio (RR) = 0.62, 95% CI = 0.38-1.00] and completion of treatment (vs. not completed, RR = 0.49, 95% CI = 0.30-0.80). Neither participating 8 + months (vs. 0-3 months, RR = 0.83, 95% CI = 0.57-1.22) nor treatment completion (vs. not completed, RR = 1.02, 95% CI = 0.72-1.46) were associated with lower risk of psychiatric comorbidity at 18 months. Longer time in treatment and compliance with treatment for substance use disorders in Chile appears to be associated with lower risk of substance use but not current comorbid psychiatric conditions 18 months after treatment initiation.

Reconsidering remission in recurrent late-life depression: clinical presentation and phenotypic predictors of relapse following successful antidepressant treatment.

Late-life depression (LLD) is characterized by repeated recurrent depressive episodes even with maintenance treatment. It is unclear what clinical and cognitive phenotypic characteristics present during remission predict future recurrence. Participants (135 with remitted LLD and 69 comparison subjects across three institutions) completed baseline phenotyping, including psychiatric, medical, and social history, psychiatric symptom and personality trait assessment, and neuropsychological testing. Participants were clinically assessed every two months for two years while receiving standard antidepressant treatment. Analyses examined group differences in phenotypic measure using general linear models. Concurrent associations between phenotypic measures and diagnostic groups were examined using LASSO logistic regression. Sixty (44%) LLD participants experienced a relapse over the two-year period. Numerous phenotypic measures across all domains differed between remitted LLD and comparison participants. Only residual depressive symptom severity, rumination, medical comorbidity, and executive dysfunction significantly predicted LLD classification. Fewer measures differed between relapsing and sustained remission LLD subgroups, with the relapsing group exhibiting greater antidepressant treatment intensity, greater fatigue, rumination, and disability, higher systolic blood pressure, greater life stress and lower instrumental social support. Relapsing group classification was informed by antidepressant treatment intensity, lower instrumental social support, and greater life stress. A wide range of phenotypic factors differed between remitted LLD and comparison groups. Fewer measures differed between relapsing and sustained remission LLD subgroups, with less social support and greater stress informing vulnerability to subsequent relapse. This research suggests potential targets for relapse prevention and emphasizes the need for clinically translatable relapse biomarkers to inform care.

Prevalence, correlates and comorbidity of irritability in adults with major depressive episode in the U.S. population (2012-2013).

Irritability has been documented in major depressive episodes (MDE) in children and adolescents. However, the prevalence of irritability in MDE and its clinical correlates remain unknown in adults. We showed associations between the prevalence of irritability and its sociodemographic characteristics in a representative U.S. sample, along with the associations between irritability and other psychiatric disorders and its relationship with health-related quality of life. This cross-sectional study utilized a large national sample (n=36,309) from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Face-to-face interviews were conducted to collect sociodemographic characteristics, structured diagnoses, and self-reported irritability. The irritable MDE group (n=4988) was compared to the non-irritable MDE group (n=3065). The lifetime prevalence of irritability in MDE was estimated at 61.3%. Participants with irritable MDE were significantly more likely to report a lifetime history of psychiatric disorders (aOR=1.96) than those with non-irritable MDE. Irritable MDE was also positively associated with severe MDE (aOR=2.12). Participants with irritable MDE were more likely to report a lifetime history of suicide attempts (aOR=1.15), substance use disorders (aOR=1.54), mood disorders (aOR=1.93), and anxiety disorders (aOR=1.67). Participants with irritable MDE had lower levels of health-related quality of life than those with non-irritable MDE. The majority of adults with MDE exhibits irritability. Irritability is associated with severe characteristics and comorbidities, leading to a higher burden of depression. This study demonstrates a strong association between irritable MDE and psychiatric comorbidities, as well as a substantial burden of depression and related conditions. As a cross-sectional study using a representative sample of the U.S. population with highly reliable psychiatric diagnoses, our results are generalizable. Practitioners managing MDE should identify and treat these comorbidities.

Driving Under the Influence of Alcohol in People With Major Depressive Episodes and Alcohol Use Disorder.

Alcohol use disorder (AUD) and depression are the most commonly reported psychiatric comorbid conditions. We examined trends in the past-year prevalence of driving under the influence of alcohol (DUIA) among people with major depressive episodes (MDE), AUD, or both in the United States. We analyzed 543,573 individuals aged 18 years or older from the 2005 to 2019 National Surveys on Drug Use and Health (NSDUH). Multivariate logistic regression models were applied to examine the adjusted past-year prevalence of DUIA. To assess trends in DUIA over time, average annual percent change (AAPC) was calculated. From 2005 to 2019, DUIA prevalence among US adults with MDE declined significantly from 18.1% to 9.4% (AAPC = -4.9). Decreasing trends in DUIA were also observed among those with AUD (from 55.4% to 37.8%, AAPC = -3.0) and among those with co-occurring MDE and AUD (from 58.3% to 38.8%, AAPC = -3.1). Compared to those with no MDE or AUD, individuals with AUD and those with co-occurring MDE and AUD had significantly lower AAPCs across all examined sociodemographic subgroups except Non-Hispanic Other and those without a high school diploma. From 2005 to 2019, DUIA prevalence declined significantly with varying rates of decrease across different diagnostic and sociodemographic groups. Focused public health efforts are needed to engage high-risk groups that have shown a tendency toward less expedient reductions in DUIA.

Machine learning-based prediction of illness course in major depression: The relevance of risk factors.

Major depressive disorder (MDD) comes along with an increased risk of recurrence and poor course of illness. Machine learning has recently shown promise in the prediction of mental illness, yet models aiming to predict MDD course are still rare and do not quantify the predictive value of established MDD recurrence risk factors. We analyzed N = 571 MDD patients from the Marburg-Münster Affective Disorder Cohort Study (MACS). Using random forest classifiers, we predicted i) recurrence of depressive episodes and ii) MDD disease trajectories, within a 2-year interval. Trajectories were identified through latent profile analysis, using a discovery and an internal validation sample. Three distinct models were implemented for predictions: two incorporating only literature-derived MDD recurrence risk factors, and a third incorporating a broader set of explorative features. Basing predictions on only seven recurrence risk factors, MDD recurrence could be predicted with a balanced accuracy (BACC) of 62.83 % and MDD trajectories were predicted with highest performance achieved for a remitted (BACC = 64.23 %) and a severe MDD trajectory (BACC = 63.17 %). Risk factors included childhood maltreatment, previous depressive episodes, residual symptoms, comorbid anxiety, age of onset, depression severity, and neuroticism. Including a broader feature set only yielded in minor increase of predictive performance. Lacking external validation, generalizability to other samples remains uncertain. MDD recurrence and disease trajectories can be predicted based on literature-derived recurrence risk factors. Model performance must increase to be of use in clinical practice which could be achieved by including multimodal risk factors.

Hair-Related Dysmorphic Disorder in a Patient with Bipolar Disorder

Introduction: Hair-related Body Dysmorphic Disorder (BDD) is a psychiatric condition characterized by an obsessive concern with perceived hair defects. It often leads to compulsive behaviors such as excessive mirror checking and avoidance of social interactions, significantly impacting self-esteem and quality of life. While Hair-related BDD frequently coexists with depression and anxiety, its association with bipolar disorder remains underexplored. This study presents a case highlighting this unique comorbidity. Case Report: A 66-year-old female patient initially presented in 2011 with telogen effluvium and experienced recurrent episodes of hair loss until 2021. Although her hair appeared normal during physical examinations, she developed heightened emotional distress and social withdrawal, particularly during depressive episodes. In 2023, she was diagnosed with bipolar disorder following an intense depressive phase, and in 2024, hair-related BDD was identified. Treatment with psychiatric medications, including an antidepressant for BDD, resulted in significant improvement in her symptoms.

Synaptic protein expression in bipolar disorder patient-derived neurons implicates PSD-95 as a marker of lithium response.

Bipolar disorder (BD) is a severe mental illness characterized by recurrent episodes of depression and mania. Lithium is the gold standard pharmacotherapy for BD, but outcomes are variable, and the relevant therapeutic mechanisms underlying successful treatment response remain uncertain. To identify synaptic markers of BD and lithium response, we measured the effects of lithium on induced pluripotent stem cell-derived neurons from BD patients and controls. We determined that baseline expression of synapsin I (SYN1) and PSD-95 is reduced in BD neurons compared to controls. In control neurons, lithium treatment had modest, transient effects increasing SYN1 and PSD-95 expression. In BD neurons, lithium increased SYN1 expression regardless of lithium response history. However, lithium only increased PSD-95 expression selectively in neurons from lithium-responders and not in neurons from lithium non-responders, leading to group differences in the colocalization of SYN1 and PSD-95. In conclusion, this preliminary work indicates synaptic protein markers are associated with BD pathology and correction of post-synaptic protein expression may be an important mechanism underlying lithium response.

Biased attention allocation in major depressive disorder: A replication and exploration of the potential effects of depression history.

Increased attention allocation to negative-valenced information and decreased attention allocation to positive-valenced information have been implicated in the etiology and maintenance of depression. The Matrix task, a free-viewing eye-tracking attention assessment task, has shown corroborating results, coupled with adequate reliability. Yet, replication efforts are still needed. Therefore, we replicated a previously published study in depression, using the same task and attention measures. We also explored the potential added effect of depression history on attention allocation. Participants diagnosed with major depressive disorder (n = 65) and a matched control group of healthy participants (n = 37) freely viewed 60 different face matrices, each presented for six seconds and comprised of eight sad and eight happy faces. Attention allocation to corresponding areas of interest (AOIs) was compared, and the internal consistency of attention allocation measures was assessed. We then compared the attention allocation of participants amidst their first episode (n = 33) to that of participants with a recurrent depressive episode (n = 32). A significant group-by-stimulus type (happy vs. sad faces) interaction emerged for total dwell time, replicating the findings of the original study. Groups differed on attention allocation to both the sad and happy faces. No findings emerged for first fixation measures. Internal consistency of the total dwell time measure was high. Depression history had no effect on attention allocation. Due to ethical constraints (delay of treatment), test-retest reliability was not assessed. The Matrix task provides a reliable and replicable measure of attention allocation in MDD, showing no effects for depression history.

Altered topology in cortical morphometric similarity network in recurrent major depressive disorder

BackgroundRecurrent major depressive disorder (RDD) is increasingly understood to be associated with a 'disconnection' within the brain areas. But, the true understanding of cortical connectivities remains challenging. Morphometric similarity network (MSN) with multi-modal magnetic resonance imaging (MRI) could provide more information about cortical micro-architecture changes in individuals with RDD. MethodsHere, we integrated multi-modal features from T1-weighted imaging, diffusion tensor imaging (DTI), and inhomogeneous magnetization transfer imaging (ihMT) to construct MSN. We used graph theory to calculate topological changes in MSN and explore their relationship with the severity and recurrence. The topological properties of 42 RDD patients were compared with 56 age, sex, and education-matched healthy controls. ResultsRDD subjects showed significantly decreased global efficiency, increased characteristic path length, reduced nodal efficiencies in the parietal lobe, subcortical area, and temporal lobe, increased betweenness centrality in the left supplementary motor area (SMA), decreased intra-modular connections in the parietal module and decreased inter-modular connections between the parietal and prefrontal modules. Notably, the global efficiency, characteristic path length, local efficiency of the right superior parietal gyrus, and inter-modular connections between the parietal and prefrontal modules were significantly associated with the number of depressive episodes. The betweenness centrality in SMA and the intra-modular connections in the parietal module showed a positive relationship with 17-item Hamilton Rating Scale for Depression (HAMD) scores. ConclusionsThe altered topology of MSN may serve as potential underlying pathological mechanisms of RDD. The impaired information integration of the network, particularly the disconnection within the fronto-parietal network, may be associated with the recurrence of depression. The SMA and the fronto-parietal network may be related to the severity of depression.

Evidence for a causal link between lipoprotein (a) and mental disorders: A retrospective and Mendelian randomization study.

Lipoprotein (a) [Lp(a)] is a biomarker of atherosclerotic cardiovascular disease, but its role in mental disorders is controversial. Our study aimed to explore the causality between Lp(a) levels and mental disorders by combining retrospective and Mendelian randomization (MR) studies. All genome-wide association study datasets used in the MR study were obtained from UK Biobank, FinnGen, and the Psychiatric Genomics Consortium. The matched case-control study were based on electronic health records from the Second Affiliated Hospital of Nanchang University and NHANES III cohort. In the MR analysis, Lp(a) had a positive causal effect on the longest period of depression [1.05 (1.02-1.08), P = 0.0001], the number of depressive episodes [1.03 (1.01-1.06), P = 0.009] and a weak negative effect on memory loss [0.84 (0.72-0.99), P = 0.039]. Meanwhile, bipolar and major depressive disorder status was causally associated with significantly lower Lp(a) levels [0.96 (0.93-0.98), P = 0.003]. Retrospective study revealed low Lp(a) levels were associated with a significantly higher risk of depression (n = 670) [1.273 (1.007, 1.609), P = 0.044], anxiety (n = 1284) [1.231 (1.041, 1.456), P = 0.015] and major depression (n = 538) [1.364 (1.012,1.841), P = 0.042]. This study found there is a causal relationship between the number and longest period of depressive episodes or memory loss and Lp(a), while bipolar disorder and major depressive disorder were associated with a significant causal effect on reduced Lp(a) levels. Future studies should focus on whether a sustained decrease in Lp(a) levels could cause the development of mental disorders, and which target value is suitable for clinical practice.

Investigating amygdala nuclei volumes in military personnel with post-traumatic stress disorder, major depressive disorder, and adjustment disorder: A retrospective cross-sectional study using clinical routine data.

Post-traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and Adjustment Disorder (AdjD) are highly prevalent among military personnel, often presenting diagnostic challenges due to overlapping symptoms and reliance on self-reporting. The amygdala, particularly the basolateral complex involved in fear-related memory formation and extinction recall, plays a crucial role in emotional processing. Abnormalities in these amygdala nuclei are implicated in PTSD and may distinguish it from other disorders like MDD and AdjD, where these mechanisms are less central. Investigating structural differences in specific amygdala nuclei could enhance diagnostic precision and inform targeted interventions. This study aimed to explore volumetric differences in amygdala nuclei among patients with PTSD, MDD, comorbid PTSD and MDD (PTSD+MDD), and AdjD using routine clinical MRI data. We hypothesized that patients with PTSD would exhibit distinct amygdala nuclei volumes compared to those with MDD or AdjD. Additionally, we examined the influence of symptom duration, prior medication, and psychotherapeutic experience on amygdala volumes. We conducted a retrospective cross-sectional study with 185 military personnel (162 men, 23 women) diagnosed with PTSD (n = 50), MDD (n = 70), PTSD+MDD (n = 38), and AdjD (n = 27). High-resolution T1-weighted MRI scans were obtained using a 3T Siemens Skyra scanner. Amygdala subfields were automatically segmented and volumetrized using FreeSurfer software. Analysis of covariance (ANCOVA) models compared amygdala nuclei volumes across diagnostic groups, controlling for estimated total intracranial volume (eTIV), age, and gender. Exploratory analyses included symptom duration, medication use, and prior psychotherapy as additional covariates. Sensitivity analyses further examined the impact of depressive episode type (first vs. recurrent), severity (mild, moderate, severe), and AdjD symptom duration. The main analyses revealed no significant differences in the volumes of the basolateral and medial amygdala nuclei among the PTSD, MDD, PTSD+MDD, and AdjD groups. Exploratory analyses did not identify significant associations between amygdala volumes and symptom duration, medication use, or prior psychotherapy. Sensitivity analyses also showed no significant volumetric differences related to depressive episode type, severity, or AdjD symptom duration. Our findings suggest that, within this military population, amygdala nuclei volumes measured using routine clinical MRI data do not significantly differ among patients with PTSD, MDD, PTSD+MDD, and AdjD. This indicates that structural amygdala volumetry alone may not suffice to distinguish between these stress-related disorders in clinical settings. The study highlights the complexity of diagnosing overlapping mental health conditions and underscores the need for comprehensive approaches that integrate neuroimaging with clinical assessments. Future research should include healthy control groups, consider additional brain regions and functional connectivity, and employ longitudinal designs to better understand the temporal dynamics of amygdala changes and their relation to symptomatology.