Major Depressive Symptoms Research Articles

Use of passively collected actigraphy data to detect individual depressive symptoms in a clinical subpopulation and a general population.

The presentation of major depressive disorder (MDD) can vary widely due to its heterogeneity, including inter- and intraindividual symptom variability, making MDD difficult to diagnose with standard measures in clinical settings. Prior work has demonstrated that passively collected actigraphy can be used to detect MDD at a disorder level; however, given the heterogeneous nature of MDD, comprising multiple distinct symptoms, it is important to measure the degree to which various MDD symptoms may be captured by such passive data. The current study investigated whether individual depressive symptoms could be detected from passively collected actigraphy data in a (a) clinical subpopulation (i.e., moderate depressive symptoms or greater) and (b) general population. Using data from the National Health and Nutrition Examination Survey, a large nationally representative sample (N = 8,378), we employed a convolutional neural network to determine which depressive symptoms in each population could be detected by wrist-worn, minute-level actigraphy data. Findings indicated a small-moderate correspondence between the predictions and observed outcomes for mood, psychomotor, and suicide items (area under the receiver operating characteristic curve [AUCs] = 0.58-0.61); a moderate-large correspondence for anhedonia (AUC = 0.64); and a large correspondence for fatigue (AUC = 0.74) in the clinical subpopulation (n = 766); and a small-moderate correspondence for sleep, appetite, psychomotor, and suicide items (AUCs = 0.56-0.60) in the general population (n = 8,378). Thus, individual depressive symptoms can be detected in individuals who likely meet the criteria for MDD, suggesting that wrist-worn actigraphy may be suitable for passively assessing these symptoms, providing important clinical implications for the diagnosis and treatment of MDD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Gray matter volume differences based on sex in first-episode drug-naive patients with major depressive disorder and its molecular analysis.

This study analyzed whether gray matter volume (GMV) differences exist between the sexes in patients with major depressive disorder (MDD) and explored the relationships between these differences and neurotransmitter systems. This study enrolled 190 first-episode drug-naive patients with MDD and 293 healthy controls. All participants underwent T1-weighted high-resolution MRI. The interaction between the diagnosis (healthy controls vs. MDD) and sex (male vs. female) regarding GMV alterations was analyzed. The JuSpace toolbox, which covers a wide range of neurotransmitter systems, was used to identify the relationship between MDD-induced and sex-induced GMV alterations and specific receptor/transporter proteins in the brain. Sex-specific GMV differences were observed in the healthy controls but not in MDD patients. Male healthy controls had a larger GMV in the bilateral parahippocampal, lingual, inferior occipital, fusiform, cerebellar subregions, and left inferior temporal than female healthy controls, but several subregions of the thalamus had a larger GMV in female healthy controls than in male healthy controls. Sex-induced GMV alterations were associated with 5-hydroxytryptamine receptor subtype 1a, cannabinoid receptor, and dopamine receptor (P < 0.01, false discovery rate corrected). GMV differences were not detected in the main effect of diagnosis and the interaction of diagnosis and sex. Sex-specific GMV differences are associated with the spatial distribution of serotonin, dopamine, and cannabinoid neurotransmitter receptor systems. Sex-based physiological differences in the GMV may account for male and female susceptibility to and differences in the clinical symptoms of MDD.

Exercise alleviates CUS-induced depressive-like behaviors by modulating paracellular and transcellular permeability of the blood-brain barrier in the prefrontal cortex

BackgroundIncreased blood-brain barrier (BBB) permeability is implicated in the pathophysiology of major depressive disorder (MDD). While aerobic exercise has shown promise in mitigating MDD symptoms by potentially preserving BBB integrity, the detailed mechanisms remain unclear. This study explores these mechanisms to assess aerobic exercise's therapeutic potential for MDD. MethodsMale C57BL/6 J mice were used in this study to investigate the effects of aerobic exercise on CUS-induced BBB permeability and depressive-like behaviors. Chronic unpredictable stress (CUS)-induced MDD mouse models were divided into three groups: Control, CUS, and CUS+Exercise. We monitored body weight, blood S100β levels, and cytokines via ELISA. Claudin-5 and Caveolin-1 (CAV-1) expressions in the medial prefrontal cortex were evaluated using Western blotting and immunofluorescence. BBB permeability was assessed using biocytin-TMR and Alb-Alexa 594 tracers. Transmission electron microscopy was used to observe ultrastructural changes in the BBB directly. Depression-related behaviors were tested through several behavioral assays. ResultsCUS significantly increased CAV-1 expression and Alb-Alexa 594 leakage, suggesting enhanced transcellular BBB permeability. Despite unchanged Claudin-5 levels, its tight junction ultrastructure was altered, leading to increased biocytin-TMR leakage. Aerobic exercise ameliorated these disruptions, reduced inflammatory cytokines, and improved behavioral outcomes in CUS mice. ConclusionDisruptions in both paracellular and transcellular BBB pathways are pivotal in depression development. Aerobic exercise offers potential therapeutic benefits for MDD linked with BBB dysfunction by mitigating stress-induced structural and functional changes.

A randomized controlled trial of a self-guided mobile app targeting repetitive negative thought to prevent depression in university students: study protocol of the Nurture-U Reducing Worry prevention trial

BackgroundTackling poor mental health in university students has been identified as a priority in higher education. However, there are few evidence-based prevention initiatives designed for students. Repetitive Negative Thought (RNT, e.g. worry, rumination) is elevated in university students and is a well-established vulnerability factor for anxiety and depression. Furthermore, there are now evidence-based cognitive-behavioural interventions to tackle RNT. A mobile self-help cognitive-behavioural app targeting RNT, adapted for students may therefore be an effective, scalable, and acceptable way to improve prevention in students.MethodsAn online single blind, two-arm parallel-group Randomised Controlled Trial (RCT) to examine the incidence of major depression and symptoms of anxiety and depression across 12 months in university students aged over 16 who screen into the study with self-reported high levels of worry and/or rumination and no current diagnosis of major depression. Eligible participants will be randomised to the active intervention arm (usual practice plus using a self-guided mobile app targeting RNT) or to the control arm (usual practice). In total, 648 participants aged over 16, with no current major depression, bipolar disorder or psychosis will be recruited from UK universities. Assessments will take place at baseline (pre-randomisation), 3 months and 12 months post- randomisation. Primary endpoint and outcome is incidence of major depression as determined by self-reported diagnostic criteria at 12-month follow-up. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and academic outcomes are secondary outcomes. Compliance, adverse events, and potentially mediating variables will be carefully monitored.DiscussionThe trial aims to provide a better understanding of the causal role of tackling RNT (worry, rumination) using a self-help mobile app with respect to preventing depression in university students. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective mobile-health public health strategies for preventing common mental health problems.Trial registrationhttps://www.isrctn.com/ISRCTN86795807 Date of registration: 27 October 2022

Hypomanic symptoms in major depressive disorder: Prognostic impact and treatment issues

BackgroundMixed depression (MXD), defined as (hypo)manic symptoms occurring within major depressive episodes, is common in both bipolar and unipolar disorders, but its prognostic and treatment implications remain unclear. This study aimed to examine the relationship between hypomanic symptoms, treatment response and remission of suicidal thoughts. MethodsWe analyzed 1243 adults with major depressive disorder (MDD), recruited for a naturalistic study on treatment-resistant depression. Data were gathered cross-sectionally and retrospectively through structured interviews and clinical rating scales including the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS); statistical analyses were performed using univariate and multivariate methods. ResultsHypomanic symptoms were present in 651 patients (45 %), while 307 patients (25 %) responded to treatment. Both treatment responders (p < 0.0001) and those who achieved remission from suicide ideation (p = 0.0085) showed lower hypomanic (YMRS) scores. Multivariate analysis showed that hypomanic symptoms were negatively linked to treatment response (O.R. 0.71–0.87), while bipolar spectrum markers such as age at illness onset (O.R. 1.00–1.03) and MDD recurrence (O.R. 0.47–0.89) predicted remission from suicidal thoughts. Medications commonly used to treat bipolar disorder showed some benefits, with dopamine/serotonin antagonists improving suicide ideation (p < 0.0001) and mood stabilizers being associated with reduced hypomanic symptoms (p = 0.0003). LimitationsThe study lacked prospective clinical assessments and treatment randomization. ConclusionHypomanic symptoms are common in unipolar depression; their assessment is essential to identify challenging-to-treat cases and select the best pharmacological options.

Hypocretin-1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model.

Cognitive dysfunction is not only a common symptom of major depressive disorder, but also a more common residual symptom after antidepressant treatment and a risk factor for chronic and recurrent disease. The disruption of hypocretin regulation is known to be associated with depression, however, their exact correlation is remains to be elucidated. Hypocretin-1 levels are increased in the plasma and hypothalamus from chronic unpredictable mild stress (CUMS) model mice. Excessive hypocretin-1 conducted with hypocretin receptor 1 (HCRTR1) reduced lactate production and brain-derived neurotrophic factor (BDNF) expression by hypoxia-inducible factor-1α (HIF-1α), thus impairing adult hippocampal neuroplasticity, and cognitive impairment in CUMS model. Subsequently, it is found that HCRTR1 antagonists can reverse these changes. The direct effect of hypocretin-1 on hippocampal lactate production and cognitive behavior is further confirmed by intraventricular injection of hypocretin-1 and microPET-CT in rats. In addition, these mechanisms are further validated in astrocytes and neurons in vitro. Moreover, these phenotypes and changes in molecules of lactate transport pathway can be duplicated by specifically knockdown of HCRTR1 in hippocampal astrocytes. In summary, the results provide molecular and functional insights for involvement of hypocretin-1-HCRTR1 in altered cognitive function in depression.

Structural alterations in a rumination-related network in patients with major depressive disorder

Rumination is a common symptom in major depressive disorder (MDD). Previous work has connected individual differences in rumination to structural properties in various brain regions. Some of these, such as the dorsolateral prefrontal cortex (dlPFC), have also been highlighted as being altered in MDD, suggesting a connection between structural changes and ruminative symptoms. Although informative, such localised relations have limitations in the context of a network view of the brain. To further investigate rumination-related structural changes in depression, and to situate these within potential functional networks, we acquired T1-weighted structural MRI data from patients with MDD (n=32) and controls (n=69). Rumination was measured with the Rumination Response Scale. Surface-based, whole-brain analysis of cortical grey-matter identified group differences in the dlPFC that were, however, not related to rumination. Instead, rumination was correlated with grey-matter properties in the right precuneus. Using normative functional connectivity analysis on an independent sample (n = 100), we show these two regions to be interconnected. Further developing a network-based perspective, it was shown that the rumination-related precuneus region is connected with networks associated with processes such as executive function, autobiographical memory, and visual perception. Notably, these processes have been connected to rumination. These results suggest that rumination in depression may be linked to focal structural changes. The effects of these focal changes on rumination may then be connected to their influence on distributed functional networks.

Depressive self-focus bias following failure: an eye-tracking study among individuals with clinical depression.

Depression is often characterized by a persistent sense of failure. Cognitive theories of depression suggest that depressed individuals may exhibit a maladaptive cognitive style, characterized by increased self-focus following personal failure. The validity of this proposition, however, is yet to be fully examined. This study aimed to identify the relation between symptoms in major depressive disorder and increased self-focus in failure situations. This clinical study involved a cohort of 30 patients diagnosed with and treated for depression. We used an eye-tracking paradigm to observe and analyze gaze direction - indicative of either self-focus or self-avoidance - after remembering a significant failure event. Contrary to the maladaptive cognitive style hypothesis, a majority of the depressed participants demonstrated an inclination towards self-avoidance following failure. Nevertheless, approximately 30% of the patient group - those with the highest scores of guilt, punishment, and self-blame - displayed a self-focused attentional bias post-failure. The presence of a maladaptive self-focusing style may be confined to severely depressed patients with high levels of guilt, punishment, and self-blame. These findings could have substantial clinical implications, as attention bias modification interventions could be particularly beneficial for this subgroup of patients.

Standardized weighted low-resolution electromagnetic tomography study of the amygdala activity in patients with comorbid major depressive disorder and anxiety symptoms

Major depressive disorder (MDD) often coexists with anxiety disorders or symptoms, as identified by previous functional magnetic resonance imaging (fMRI) studies. These studies have found abnormal amplitudes of low-frequency fluctuations (ALFF) in the amygdala, which serve as traits and state markers of MDD. This study used standardized weighted low-resolution electromagnetic tomography (swLORETA) technology to explore amygdala markers in patients with comorbid MDD and anxiety. Participants included patients with MDD comorbid with anxiety symptoms (MDD group) and healthy controls (HC group) who completed the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). EEG data collected under resting state, happiness recall, and depressive recall tasks were converted into current-source density (CSD) values using swLORETA to assess amygdala activation. The results indicated higher beta2, beta3, and high beta levels in both the left and right amygdalae during the resting state in the MDD group than in the HC group. Similarly, elevated levels of beta2, beta3, and high beta were observed in the left and right amygdalae of the MDD group during happiness and depressive recall tasks. These findings support the presence of hyperactivity in the amygdala under resting state and emotional tasks in patients with comorbid MDD and anxiety symptoms.

Inflammation in Older Poles with Localized and Widespread Chronic Pain—Results from a Population-Based PolSenior Study

Background: Inflammation leads to a decrease in the excitation threshold and the sensitization of peripheral nociceptors. However, little is known about the effect of inflammation on the sensing of regional (CRegP) and widespread chronic pain (CWP) in older adults. This analysis aimed to characterize the prevalence and associates of both types of chronic pain in a population-based cohort. Methods: Our analysis was based on the Polish nationwide PolSenior study database. We excluded participants with moderate-to-severe dementia. Respondents answered questions concerning the occurrence of pain in 10 regions. CWP was defined as chronic pain present in the axial region (neck, upper back, lower back) and any part of both the lower (lower leg, hip, knee, foot) and upper (shoulder, hand) extremities. Inflammatory status was divided into three subgroups: no inflammation (CRP &lt; 3 mg/dL), mild inflammation (CPR 3–10 mg/dL and IL-6 &lt; 10 ng/mL), and significant inflammation (CRP ≥ 10 mg/dL or IL-6 ≥ 10 ng/mL). Results: CRegP was more frequent (33.9%) than CWP (8.8%). The occurrence of CWP was more frequent in subgroups with significant inflammation than in both subgroups with mild or no inflammation (11.4% vs. both 8.4%). Women (OR 3.67; 95% CI: 2.58–5.21) and subjects with major depression symptoms were more likely to experience CWP (OR 2.85; 95% CI: 1.68–4.82), while, malnourished participants were more likely to report CRegP (OR 2.00; 95% CI: 1.52–2.62). Conclusions: Significant inflammation is associated with increased occurrence of CWP in older adults. Female sex and major depression are the most significant associates of CWP, while malnutrition is the most significant associate of CRegP.

Dissecting the association between long COVID and depressive symptoms in a nationally representative population from France

ObjectiveDepressive symptoms may overlap with those of long COVID. This cross-sectional study aims to compare the prevalence of depressive symptoms among individuals infected with SARS-CoV-2 with versus without long COVID and to explore specific associations with each of the nine core symptoms of major depression. MethodsData regarding age, gender, SARS-CoV-2 infections, current symptoms, their date of onset, impact on daily functioning, and consideration of alternative diagnoses were collected through phone interviews between September and December 2022 in a nationally representative sample of adults aged ≥18. Data on chronic health conditions and depressive symptoms (PHQ-9) were collected online in infected participants with or without long COVID, according to the WHO definition of the post-COVID-19 condition. ResultsAmong 1247 participants (mean age (SD): 48.3 (14.3) years, 53.3 % of women), 12.8 % had long COVID and 87.2 % experienced SARS-CoV-2 infection at least 3 months prior to the survey without long COVID. Participant with long COVID were four-fold more likely to have a PHQ-9 score ≥ 10 than those without (44.0 % versus 11.1 %). Three symptoms out of nine were independently associated with long COVID: little interest or pleasure (aOR [95 % CI]: 2.01 [1.03–3.92]), feeling tired or having little energy (1.92 [1.10–3.33]), and poor attention/concentration (2.02 [1.03–3.96]). ConclusionClinicians should screen patients with long COVID for major depression but associations with specific depressive symptoms suggest some clinical overlap. Future studies should consider the course of each depressive symptom separately and focus on those less prone to overlap with symptoms of long COVID.

Dietary counseling plus omega-3 supplementation in the treatment of generalized anxiety disorder: results of a randomized wait-list controlled pilot trial (the ‘EASe-GAD Trial’)

ABSTRACT Objectives Clinical evidence suggests that nutrition interventions can significantly improve symptoms of major depressive disorder; however, the effect on clinical anxiety symptoms in individuals with anxiety disorders has not been studied. The primary objective of the present study was to assess the feasibility and acceptability of a nutrition intervention. The secondary objectives included assessing changes in anxiety symptom severity, diet quality, self-efficacy, mindful eating, quality of life, and biomarkers. Methods This study was a randomized, wait-list controlled pilot trial delivering a 12-week, biweekly dietary counseling intervention and omega-3 supplementation to 50 adult women with generalized anxiety disorder. Questionnaires and blood work were completed at baseline, after the waiting period, and after the intervention. Results 443 individuals expressed interest within eight months; 50 met the criteria for enrollment. The mean number of sessions attended was 6.4. Final questionnaires were completed by 46 participants. Eighty-four percent of participants strongly agreed with the statement ‘My experience during this study was positive’. The mean anxiety symptom severity score in the intervention group was 26.2 (95% CI 22.94–29.48) at baseline and 11.0 (95% CI 8.05–13.87) at week 12. The mean diet quality score was 7.2 (95% CI 6.32–8.10) and 10.5 (95% CI 9.55–11.49) at baseline and week 12, respectively. Among the waitlist participants, the mean baseline anxiety score was 29.3 (95% CI 24.73–33.91) and 26.8 (95% CI 22.09–31.56) at week 12. Discussion This study was feasible and acceptable. Participation in the intervention was associated with a decrease in anxiety symptoms. These findings lay the foundation for large-scale studies. Trial registration: ClinicalTrials.gov NCT05573672.

A network analysis of eating disorder, PTSD, major depression, state-trait anxiety, and quality of life measures in eating disorder patients treated in residential care.

The network approach in the eating disorder (ED) field has confirmed important links between EDs and posttraumatic stress disorder (PTSD) symptoms. However, studies including comorbid symptoms are scarce, which limits our understanding of potentially important connections. We hypothesised that anxiety, depression and poor quality of life (QOL) would provide a more complete picture of central, maintaining factors. Network analysis using R was performed in 2178 adult ED patients (91% female) admitted to residential treatment. Assessments included the ED Examination Questionnaire (EDEQ), the Eating Disorders Inventory (EDI-2), the PTSD Checklist for DSM-5 (PTSD clusters (PCL-5)), the Patient Health Questionnaire (PHQ-9), the Spielberger State-Trait Anxiety Scale (STAI), and the ED QOL Scale (EDQOL), which measure symptoms of EDs, PTSD, major depression, state-trait anxiety, and QOL, respectively. EDI-2 ineffectiveness showed the highest centrality (expected influence) followed by EDI-2 interoceptive awareness, STAI state anxiety, EDEQ shape concern, EDQOL psychological subscale, and PTSD cluster D (hyperarousal) symptoms. Eating Disorder Quality of Life psychological and physical-cognitive subscales and PHQ-9 major depressive, STAI state anxiety and PCL-5 PTSD cluster E (negative alterations in mood and cognition) symptoms showed the highest bridge expected influence, suggesting their interactive role in maintaining ED-PTSD comorbidity. This is the first network analysis of the interaction between ED and PTSD symptoms to include the comorbid measures of depression, anxiety, and QOL in a large clinical sample of ED patients. Our results indicate that several symptom clusters are likely to maintain ED-PTSD comorbidity and may be important targets of integrated treatment.

Correlating plasma protein profiles with symptomatology and treatment response in acute phase and early remission of major depressive disorder.

This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode. In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-Åsberg Depression Rating Scale (MADRS). Plasma protein analysis was conducted at the onset of acute depression and 6 weeks into treatment. Analytical methods comprised of Linear Models for Microarray Data (LIMMA), Weighted Correlation Network Analysis (WGCNA), Generalized Linear Models, Random Forests, and The Database for Annotation, Visualization and Integrated Discovery (DAVID). Five distinct plasma protein modules were identified, correlating with specific biological processes, and uniquely associated with symptom presentation, the disorder's trajectory, and treatment response. A module rich in proteins related to adaptive immunity was correlated with the manifestation of somatic syndrome, treatment response, and inversely associated with achieving remission. A module associated with cell adhesion was linked to affective symptoms and avolition, and played a role in the initial episodes and treatment response. Another module, characterized by proteins involved in blood coagulation and lipid transport, exhibited negative correlations with a variety of MDD symptoms and was predominantly associated with the manifestation of psychotic symptoms. This research points to a complex interplay between the plasma proteome and MDD's clinical presentation, suggesting that somatic, affective, and psychotic symptoms may represent distinct endophenotypic manifestations of MDD. These insights hold potential for advancing targeted therapeutic strategies and diagnostic tools. The study's limited sample size and its naturalistic design, encompassing diverse treatment modalities, present methodological constraints. Furthermore, the analysis focused on peripheral blood proteins, with potential implications for interpretability.

Major depression symptom severity associations with willingness to exert effort and patch foraging strategy.

Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When selecting goals, people maximize 'expected value' by selecting actions that maximize potential reward while minimizing associated costs, including effort 'costs' and the opportunity cost of time. In MDD, differential weighing of costs and benefits are theorized mechanisms underlying changes in goal-directed cognition and may contribute to symptom heterogeneity. We used the Effort Foraging Task to quantify cognitive and physical effort costs, and patch leaving thresholds in low effort conditions (reflecting perceived opportunity cost of time) and investigated their shared versus distinct relationships to clinical features in participants with MDD (N=52, 43 in-episode) and comparisons (N=27). Contrary to our predictions, none of the decision-making measures differed with MDD diagnosis. However, each of the measures were related to symptom severity, over and above effects of ability (i.e., performance). Greater anxiety symptoms were selectively associated with lower cognitive effort cost (i.e. greater willingness to exert effort). Anhedonia and behavioral apathy were associated with increased physical effort costs. Finally, greater overall depression was related to decreased patch leaving thresholds. Markers of effort-based decision-making may inform understanding of MDD heterogeneity. Increased willingness to exert cognitive effort may contribute to anxiety symptoms such as worry. Decreased leaving thresholds associations with symptom severity is consistent with reward rate-based accounts of reduced vigor in MDD. Future research should address subtypes of depression with or without anxiety, which may relate differentially to cognitive effort decisions.

Connecting the dots: Network structures of internalizing and functional symptoms in a population-based cohort

ObjectiveComorbidities between internalizing disorders (IDs) and functional disorders (FDs) are well-documented, indicating shared pathways. However, their symptom-level relationships have been largely unexplored. This exploratory study employs a network approach to investigate symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS) to identify bridge symptoms explaining comorbidity between the two domains. MethodsWe used cross-sectional data on 72,919 adult subjects from the Lifelines Cohort Study, a Dutch general population sample. A total of 38 symptoms representing diagnostic criteria of IDs and FDs were assessed with validated questionnaires. Network models were estimated using eLasso, based on the Ising model, to identify bridge symptoms. The Network Comparison Test (NCT) was used to test whether there were differences in network structure and strength across sex and age. ResultsSymptoms were moderately connected, with a network density of 52.7%. ID and FD symptoms clustered in their respective domains, but were connected through the bridge symptoms, fatigue, difficulty concentrating, trouble sleeping, and unrefreshing sleep. Fatigue and difficulty concentrating had the most connections, associated with 86.6% and 78.9% of the other symptoms, respectively. NCTs indicated no differences in network connectivity between females versus males or younger versus older adults (>50 years). ConclusionsID and FD symptoms are moderately interconnected. Bridge symptoms displaying strong connections to multiple disorders may play a central role in the mechanisms underpinning the comorbidity between IDs and FDs.

The effect of repetitive transcranial magnetic stimulation on the Hamilton Depression Rating Scale-17 criterion in patients with major depressive disorder without psychotic features: a systematic review and meta-analysis of intervention studies

AimIn 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.MethodsIn 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).ResultsFollowing 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).ConclusionIn 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.

Screening for depression in patients with epilepsy: same questions but different meaning to different patients.

Patient-reported outcome measures (PROMs) such as the Neurological Disorders Depression Inventory in Epilepsy (NDDI-E), a 6-item epilepsy-specific PROM, is used to screen for major depressive disorder symptoms for patients with epilepsy (PWE). The validity and interpretation of PROMs can be affected by differential item functioning (DIF), which occurs when subgroups of patients with the same underlying health status respond to and interpret questions about their health status differently. This study aims to determine whether NDDI-E items exhibit DIF and to identify subgroups of PWE that exhibit DIF in NDDI-E items. Data were from the Calgary Comprehensive Epilepsy Program database, a clinical registry of adult PWE in Calgary, Canada. A tree-based partial credit model based on recursive partitioning (PCTree) was used to identify subgroups that exhibit DIF on NDDI-E items using patients' characteristics as covariates. Differences in the identified subgroups were characterized using multinomial logistic regression. Of the 1,576 patients in this cohort, 806 (51.1%) were female, and the median age was 38.0 years. PCTree identified four patient subgroups defined by employment status, age, and sex. Subgroup 1 were unemployed patients ≤ 26 years old, subgroup 2 were unemployed patients > 26 years, subgroup 3 were employed females, while subgroup 4 were employed male patients. The subgroups exhibited significant differences on education level, comorbidity index scores, marital status, type of epilepsy, and driving status. PWE differed in their interpretation and responses to questions about their depression symptoms, and these differences were a function of sociodemographic and clinical characteristics.

Depressive symptoms during the transition to adolescence: Left hippocampal volume as a marker of social context sensitivity

The transition to adolescence is a critical period for mental health development. Socio-experiential environments play an important role in the emergence of depressive symptoms with some adolescents showing more sensitivity to social contexts than others. Drawing on recent developmental neuroscience advances, we examined whether hippocampal volume amplifies social context effects in the transition to adolescence. We analyzed 2-y longitudinal data from the Adolescent Brain Cognitive Development (ABCD®) study in a diverse sample of 11,832 youth (mean age: 9.914 y; range: 8.917 to 11.083 y; 47.8% girls) from 21 sites across the United States. Socio-experiential environments (i.e., family conflict, primary caregiver's depressive symptoms, parental warmth, peer victimization, and prosocial school environment), hippocampal volume, and a wide range of demographic characteristics were measured at baseline. Youth's symptoms of major depressive disorder were assessed at both baseline and 2 y later. Multilevel mixed-effects linear regression analyses showed that negative social environments (i.e., family conflict, primary caregiver's depressive symptoms, and peer victimization) and the absence of positive social environments (i.e., parental warmth and prosocial school environment) predicted greater increases in youth's depressive symptoms over 2 y. Importantly, left hippocampal volume amplified social context effects such that youth with larger left hippocampal volume experienced greater increases in depressive symptoms in more negative and less positive social environments. Consistent with brain-environment interaction models of mental health, these findings underscore the importance of families, peers, and schools in the development of depression during the transition to adolescence and show how neural structure amplifies social context sensitivity.

A Dose-Finding, Biomarker Validation, and Effectiveness Study of Transcranial Magnetic Stimulation for Adolescents With Depression

Research and clinical application of transcranial magnetic stimulation (TMS) for adolescents with major depressive disorder (MDD) has advanced slowly. Significant gaps persist in our understanding of optimized, age-specific protocols and dosing strategies. This study aimed to compare the clinical effects of 1 Hz versus 10 Hz TMS regimens and examine a biomarker-informed treatment approach with glutamatergic intracortical facilitation (ICF). Participants with moderate-to-severe symptoms of MDD were randomized to 30 sessions of left prefrontal 1 Hz or 10 Hz TMS, stratified by baseline ICF measures. The primary clinical outcome measure was the Children's Depression Rating Scale, Revised (CDRS-R). The CDRS-R and ICF biomarker were collected weekly. Forty-one participants received either 1 Hz (n = 22) or 10 Hz (n = 19) TMS treatments. CDRS-R scores improved compared to baseline in both 1 Hz and 10 Hz groups. For participants with low ICF at baseline, the overall least squares means of CDRS-R scores over the 6-week trial showed that depressive symptom severity was lower for the group treated with 1 Hz TMS than for those who received 10 Hz TMS. There were no significant changes in weekly ICF measurements across the 6 weeks of TMS treatment. Low ICF may reflect optimal glutamatergic N-methyl-d-aspartate (NMDA) receptor activity that facilitates the therapeutic effect of 1 Hz TMS through long-term depression-like mechanisms on synaptic plasticity. The stability of ICF suggests that it is a tonic, trait-like measure of NMDA receptor-mediated neurotransmission, with potential utility to inform parameter selection for therapeutic TMS in adolescents with MDD.