Inventory Of Depressive Symptomatology Research Articles

Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial

Abstract Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)—both implemented and monitored in an individual, naturalistic setting via a mobile health (m-health) system—for feasibility of trial design and interventions, and to estimate their effects on depressive symptoms in young people with ADHD. Two hundred seven participants aged 14–45 years were randomised to 10-week add-on intervention of either BLT (10,000 lx; daily 30-min sessions) (n = 70), EI (aerobic and muscle-strengthening activities 3 days/ week) (n = 69), or treatment-as-usual (TAU) (n = 68), of whom 165 (80%) were retained (BLT: n = 54; EI: n = 52; TAU: n = 59). Intervention adherence (i.e. ≥ 80% completed sessions) was very low for both BLT (n = 13, 22%) and EI (n = 4, 7%). Usability of the m-health system to conduct interventions was limited as indicated by objective and subjective data. Safety was high and comparable between groups. Changes in depressive symptoms (assessed via observer-blind ratings, Inventory of Depressive Symptomatology) between baseline and end of intervention were small (BLT: −0.124 [95% CI: −2.219, 1.971], EI: −2.646 [95% CI: −4.777, −0.515], TAU: −1.428 [95% CI: −3.381, 0.526]) with no group differences [F(2,153) = 1.45, p = 0.2384]. These findings suggest that the m-health approach did not achieve feasibility of EI and BLT in young people with ADHD. Prior to designing efficacy studies, strategies how to achieve high intervention adherence should be specifically investigated in this patient group. Trial registration ClinicalTrials.gov, NCT03371810, 13 December 2017.

The role of immuno-metabolic depression features in the effects of light therapy in patients with depression and type 2 diabetes mellitus: A randomized controlled trial

ObjectiveImmuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored. MethodsIn secondary analyses, clinical trial data was used from 77 individuals with depression and type 2 diabetes mellitus (T2DM) randomized to four weeks of light therapy or placebo. AES severity and depressive symptom severity were based on the Inventory of Depressive Symptomatology. Biomarkers included 73 metabolites (Nightingale) summarized in three principal components and CRP, IL-6, TNF-α, INF-γ. Linear regression analyses were performed. ResultsLight therapy had no effect on AES severity, inflammatory markers and metabolite principle components versus placebo. None of these baseline features moderated the effects of light therapy on AES severity. Only a principle component reflecting metabolites implicated in glucose homeostasis moderated the effects of light therapy on depressive symptom severity (βinteraction = 0.65, P = 0.001, FDR = 0.003). Changes in AES were not associated with changes in biomarkers. ConclusionFindings do not support the efficacy of light therapy in reducing IMD features in patients with depression and T2DM. We find limited evidence that light therapy is a more beneficial depression treatment among those with more IMD features. Changes in clinical and biological IMD features did not align over four-weeks' time.Trial registration: The Netherlands Trial Register (NTR) NTR4942.

The effects of intranasal oxytocin on the efficacy of psychotherapy for major depressive disorder: a pilot randomized controlled trial.

Although both pharmacotherapy and psychological treatments are considered to be efficacious in the treatment of major depressive disorder (MDD), one third of patients do not respond to treatment and many experience residual symptoms post-treatment. In this double-blind placebo-controlled randomized control trial (RCT), we assessed whether intranasal oxytocin (OT) augments the therapeutic efficacy of psychotherapy for MDD and improves the therapeutic alliance. Twenty-three volunteers (12 female) with MDD underwent 16 sessions of interpersonal therapy. Prior to each session, volunteers self-administered 24 International Units of intranasal OT (n = 12; Syntocinon) or placebo (n = 11). Depressive symptoms were assessed with the Inventory of Depressive Symptomatology at pre- and post-treatment, and at a six month follow-up. Multilevel modeling found a significant effect of OT on the negative slope of depressive symptoms over time (p < 0.05), with medium-large effect sizes at post-treatment (Cohen's d = 0.75) and follow-up (Cohen's d = 0.82). Drug intervention also predicted the intercept when examining the weekly ratings of the therapeutic alliance (p < 0.05), such that volunteers receiving OT, relative to placebo, reported improved therapeutic alliance at session 1. The agreement of goals between therapists and participants, a facet of the therapeutic alliance, mediated the relationship between drug intervention and clinical outcome. In this pilot study, the administration of intranasal OT, relative to placebo, improved the therapeutic alliance at the beginning of therapy and therapeutic efficacy of psychotherapy in persons with MDD. Future RCTs should attempt to replicate these findings in larger samples with different therapeutic modalities (ClinicalTrials.gov: NCT02405715).

Anhedonia and depression severity measures during ketamine administration in treatment-resistant depression.

Anhedonia is a core symptom of depression characterized by a diminished ability to experience pleasure. Currently available treatments for depression often fall short in adequately addressing anhedonia that often presents as a chronic and debilitating symptom. Ketamine is known to possess antianhedonic properties. This post-hoc analysis of a naturalistic observational study of treatment-resistant depression inpatients (n=28) analyzed antianhedonic response patterns measured by Snaith-Hamilton Pleasure Scale and changes in Inventory of Depressive Symptomatology in responders (n=6) and non-responders (n=22) stratified per Montgomery-Åsberg Depression Rating Scale during short-term ketamine treatment. Results show that responders significantly improve in anhedonia over time (p=0.0084) and at the 7th infusion and follow-up (both p<0.05). Non-responders reported significant reduction in anhedonia over time (p=0.0011) and at the 5th, 7th infusion and at the follow-up (all p's<0.05). Non-responders were also observed to improve significantly in self-reported depression at the 7th infusion (p=0.0219) but not at the follow-up. There is no complete overlap between change in depressive symptoms and anhedonia. Therefore, it might be assumed ketamine alleviates anhedonia as an individual symptom domain regardless of formal treatment outcome.

Effectiveness and Safety of Flumazenil Augmentation During Electroconvulsive Therapy.

Benzodiazepines are considered to negatively affect seizure quality and duration during electroconvulsive therapy (ECT). Several researchers have advocated the use of flumazenil, a competitive benzodiazepine receptor antagonist, for patients treated with benzodiazepines during ECT. However, clinical evidence regarding flumazenil use in ECT remains sparse. The aim of this study is to investigate the effects of flumazenil on seizure duration and adverse effects. All patients with depressive disorders, treated with flumazenil during a course of ECT in 2019 in a tertiary hospital, were identified through a retrospective chart review. Seizure duration was recorded before and after flumazenil administration. Effectiveness of ECT was assessed using the Inventory of Depressive Symptomatology and the Bush-Francis Catatonia Rating Scale. Postictal agitation was ascertained by identifying patients who received additional sedatives immediately after ECT or who needed physical restraint. Twenty-six patients were included, receiving a total of 363 treatments, of which 263 were augmented with flumazenil. Flumazenil administration increased electroencephalogram seizure duration on average with 10.5 seconds comparing ECT with or without flumazenil (P = 0.003). In 21.8% of the cases, no increase in seizure duration was observed. Postictal agitation occurred at least once in 34.6% of the patients receiving flumazenil during their course of ECT. Our results show that flumazenil increases seizure duration, albeit with limited clinical implications. Noteworthy, the prevalence of postictal agitation is high. When confronted with short seizures, clinicians should therefore deploy other available techniques to lower seizure threshold before considering flumazenil.

Melancholic features and treatment outcome to selective serotonin reuptake inhibitors in major depressive disorder: A re-analysis of the STAR*D trial

BackgroundMelancholia has been positioned as a qualitatively different form of Major Depressive Disorder (MDD). Some studies have suggested that melancholic MDD patients may show lower remission when receiving treatment with Selective Serotonin Reuptake Inhibitors, but this has not yet been explored in large, representative samples of MDD. MethodsWe used data from the STAR*D, a multisite randomized controlled trial (n = 4041). We defined melancholia status through the BA Melancholia Empirical Index, constructed using items from the Inventory of Depressive Symptomatology (IDSC). The main outcome of interest was symptomatic remission defined as a Quick Inventory of Depressive Symptoms (Clinician version) (QIDS-C) below or equal to 5. Inverse probability weighting was used to control for confounding. Results3827 patients were eligible for this study. Melancholic patients were more likely to be unemployed, never married, to self-report an African American race, and to have a higher depressive severity. The adjusted 4-month probability of remission was 26.9 % (22.0, 45.5) for melancholic and 53.8 % (53.2, 58.5), for nonmelancholic patients. Compared with nonmelancholic, the difference in 4-month probability of remission was −26.9 % (−37.0, −15.6). Results were consistent across sensitivity analyses. LimitationsItems from IDSC were used as a surrogate measure of the BA Melancholia Index, and extrapolation of the results to agents other than citalopram and to psychotic MDD patients requires caution. ConclusionsMelancholic MDD patients showed lower probabilities of remission at 4-months receiving treatment with citalopram. The results of this study show how validly subtyping episodes could contribute to the personalized treatment of depression.

Suicidal ideation across depressive episodes: 9-year longitudinal cohort study.

Depression is a highly recurrent disorder, with more than 50% of those affected experiencing a subsequent episode. Although there is relatively little stability in symptoms across episodes, some evidence indicates that suicidal ideation may be an exception. However, these findings warrant replication, especially over longer periods and across multiple episodes. To assess the relative stability of suicidal ideation in comparison with other non-core depressive symptoms across episodes. We examined 490 individuals with current major depressive disorder (MDD) at baseline and at least one subsequent episode during 9-year follow-up within the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology (IDS) was used to assess DSM-5 non-core MDD symptoms (fatigue, appetite/weight change, sleep disturbance, psychomotor disturbance, concentration difficulties, worthlessness/guilt, suicidal ideation) at baseline and 2-, 4-, 6- and 9-year follow-up. We examined consistency in symptom presentation (i.e. whether the symptom met the diagnostic threshold, based on a binary categorisation of the IDS) using kappa (κ) and percentage agreement, and stability in symptom severity using Spearman correlation, based on the continuous IDS scores. Out of all non-core depressive symptoms, insomnia appeared the most stable across episodes (r = 0.55-0.69, κ = 0.31-0.47) and weight decrease the least stable (r = 0.03-0.33, κ = 0.06-0.19). For suicidal ideation, correlations across episodes ranged from r = 0.36 to r = 0.55 and consistency ranged from κ = 0.28 to κ = 0.49. Suicidal ideation is moderately stable in recurrent depression over 9 years. Contrary to prior reports, however, it does not exhibit substantially more stability than most other non-core symptoms of depression.

41 Predictors of Cognitive Symptoms Following Adult Civilian Mild Traumatic Brain Injury

Objective:Mild traumatic brain injury (mTBI) is an important public health problem, due to its high incidence and the failure of at least 20% of patients to successfully recover from injury. Cognitive symptoms, in particular, are an important area of research in mTBI, due to their association with return to work and referral to neuropsychological services. Understanding the predictors of cognitive symptoms may help to improve outcomes after mTBI. This study explored female sex, psychological distress, coping style and illness perceptions as potential predictors of cognitive symptoms following adult civilian mTBI.Participants and Methods:Sixty-nine premorbidly healthy adults with mTBI (mean age = 36.7, SD = 14.7, range = 18-60; 15 females) were recruited from trauma wards at two public hospitals in Australia and assessed 6-12 weeks following injury. Cognitive complaint was measured using a comprehensive 30-item scale (CCAMCHI) assessing mTBI-specific symptoms in the domains of processing speed, attention, memory and executive function. Participants additionally completed the following measures: Brief-COPE, Illness Perceptions Questionnaire-Revised, Inventory of Depressive Symptomatology, Beck Anxiety Inventory, and PTSD Checklist for DSM-5. The latter three measures were combined to create an index of psychological distress.Results:Bivariate nonparametric correlational analyses indicated that female sex (r[67] = .26, 95% CI [.14, .55], p = .03) and psychological distress (r[66] = .54, 95% CI [.40, .72], p &lt; .001) were each significantly associated with cognitive symptom reporting following mTBI. Additionally, while none of the three coping style factors were associated with cognitive symptom reporting, seven of the eight dimensions of illness perceptions were associated with symptom reporting (|r| = .25 - .58, p &lt; 0.05). In a linear regression model assessing the combined effects of each variable, female sex, greater psychological distress, and overall negative illness perceptions were each significant independent predictors of increased cognitive complaint (adj. R2 = .47, F[4,63] = 15.59, p &lt; .001).Conclusions:These findings implicate female sex, psychological distress, and illness perceptions as key factors associated with cognitive symptom reporting after mTBI. This research suggests that these factors may be useful in clinical practice when considering early identification of individuals at risk of poor recovery. Specifically, this research implicates females, individuals with high psychological distress, and individuals with negative illness perceptions as important to subgroups to consider for potential intervention after mTBI. Additionally, as psychological distress and illness perceptions are both potentially modifiable, this research suggests that these factors may be useful targets for intervention.

Expression of ANK3 moderates the association between childhood trauma and affective traits in severe mental disorders

Exposure to early life trauma increases the risk of psychopathology later in life. Here we investigated if ANK3 mRNA levels influence the relationship between childhood trauma experiences and clinical characteristics in mental disorders. A sample of 174 patients with bipolar disorder and 291 patients with schizophrenia spectrum disorder were included. Patients were diagnosed using the Structured Clinical Interview for DSM-IV, and childhood trauma was assessed using the childhood trauma questionnaire. Age at illness onset and number of psychotic and affective episodes were assessed from interview and medical records. Current depressive symptoms were measured using the calgary depression scale for schizophrenia and the inventory for depressive symptomatology. ANK3 expression was analyzed in whole blood using the Illumina HumanHT-12 v4 Expression BeadChip. Analyses were carried out with the Process adjusted for confounders. Within the total sample, patients with both high ANK3 expression and with the most severe childhood sexual abuse had more manic/hypomanic episodes and an earlier age at onset of the first episode. ANK3 mRNA levels also moderated the relationship between emotional neglect and manic/hypomanic episodes. Our results suggest that ANK3 expression levels moderate the association between specific types of childhood trauma and affective traits in mental disorders.

Metabolomics signatures of depression: the role of symptom profiles

Depression shows a metabolomic signature overlapping with that of cardiometabolic conditions. Whether this signature is linked to specific depression profiles remains undetermined. Previous research suggested that metabolic alterations cluster more consistently with depressive symptoms of the atypical spectrum related to energy alterations, such as hyperphagia, weight gain, hypersomnia, fatigue and leaden paralysis. We characterized the metabolomic signature of an “atypical/energy-related” symptom (AES) profile and evaluated its specificity and consistency. Fifty-one metabolites measured using the Nightingale platform in 2876 participants from the Netherlands Study of Depression and Anxiety were analyzed. An ‘AES profile’ score was based on five items of the Inventory of Depressive Symptomatology (IDS) questionnaire. The AES profile was significantly associated with 31 metabolites including higher glycoprotein acetyls (β = 0.13, p = 1.35*10-12), isoleucine (β = 0.13, p = 1.45*10-10), very-low-density lipoproteins cholesterol (β = 0.11, p = 6.19*10-9) and saturated fatty acid levels (β = 0.09, p = 3.68*10-10), and lower high-density lipoproteins cholesterol (β = −0.07, p = 1.14*10-4). The metabolites were not significantly associated with a summary score of all other IDS items not included in the AES profile. Twenty-five AES-metabolites associations were internally replicated using data from the same subjects (N = 2015) collected at 6-year follow-up. We identified a specific metabolomic signature—commonly linked to cardiometabolic disorders—associated with a depression profile characterized by atypical, energy-related symptoms. The specific clustering of a metabolomic signature with a clinical profile identifies a more homogenous subgroup of depressed patients at higher cardiometabolic risk, and may represent a valuable target for interventions aiming at reducing depression’s detrimental impact on health.

0102 Are there associations between intraindividual variability in sleep and mental health among adolescents reporting alcohol use?

Abstract Introduction Considering the increasing number of studies that report on ecological momentary assessment by uses of sleep diary and actigraphy, it may also be valuable to consider the relationship between fluctuations that exists in sleep measures on adolescent health outcomes. Above the impact of mean sleep measures, intraindividual variability (IIV) in sleep provides information on the degree to which daily variations or fluctuations in sleep/wake patterns are occurring and may prompt important cues to adolescents’ health outcome. The present study examined the objective IIV in sleep and its relationship to their sleep and mental health outcomes among adolescents with history of alcohol use. Methods The study analyzed 8 days of wrist actigraphy data from 72 high school students reporting prior alcohol use (58.3% female; mean age 17.0 years). Bayesian variability method using varian (R package) was performed to calculate IIV in total sleep time (TST), time in bed (TIB), midpoint sleep, bedtime, and risetime. Participants also completed Pittsburgh Sleep Quality Index (PSQI), Cleveland Adolescent Sleepiness Questionnaire (CASQ), Inventory of Depressive Symptomatology (IDS-SR-30), Chapman’s Inventories – Social Anhedonia (CHAPSAS), and Rutgers Alcohol Problem Index (RAPI). Multiple linear regression models were adjusted for biological sex, age, and the sum of alcohol drinks in the past 3 months. Results Participants reported average of 18.52 (SD=23.10) total drinks consumed over the past 3 months. IIV in TST, TIB, and risetime were associated with lower sleep quality (B=3.04, 95% CI, 0.02, 7.39, p&amp;lt; 0.05 for IIV in TST; B=2.87, 95% CI, 0.39, 5.88, p&amp;lt; 0.05 for IIV in TIB; and B=2.74, 95% CI, 0.57, 6.19, p&amp;lt; 0.05 for IIV in risetime, respectively). There was no statistically significant association between IIV of sleep measures and excessive daytime sleepiness or mental health outcomes such as social anhedonia, depressive symptoms, and problematic alcohol use. Conclusion Greater fluctuation in TST, TIB, and risetime were negatively associated with overall sleep quality. Our findings add to a growing body of research on IIV in sleep/wake patterns and clinical implications. Future studies should explore the prospective relationship between variability in sleep and other various health outcomes. Support (if any) NIH/NIAAA R01AA025626 (Hasler); Sleep Research Society Foundation Mentor-Mentee Award (Kwon)

Glucocorticoid Receptor (GR) antagonism as disease-modifying treatment for MDD with childhood trauma: protocol of the RESET-medication randomized controlled trial

BackgroundMajor depressive disorder (MDD) is a heterogeneous psychiatric disorder. Childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18) is one of the largest and most consistent risk factors for development and poor course of MDD. Overactivity of the HPA-axis and the stress hormone cortisol is thought to play a role in the vulnerability for MDD following exposure to CT. Rodent experiments showed that antagonism of the glucocorticoid receptor (GR) at adult age reversed the effects of early life stress. Similarly, we aim to target MDD in individuals with CT exposure using the GR antagonist mifepristone.MethodsThe RESET-medication study is a placebo-controlled double-blind randomized controlled trial (RCT) which aims to include 158 adults with MDD and CT. Participants will be randomized (1:1) to a 7-day treatment arm of mifepristone (1200 mg/day) or a control arm (placebo). Participants are allowed to receive usual care for MDD including antidepressants. Measurements include three face-to-face meetings at baseline (T0), day 8 (T1), week 6 (T2), and two online follow-up meetings at 12 weeks (T3) and 6 months (T4). A subgroup of participants (N = 80) are included in a fMRI sub-study (T0, T2). The main study outcome will be depressive symptom severity as measured with the Inventory of Depressive Symptomatology—Self Rated (IDS-SR) at T2. Secondary outcomes include, among others, depressive symptom severity at other time points, disability, anxiety, sleep and subjective stress. To address underlying mechanisms mifepristone plasma levels, cortisol, inflammation, epigenetic regulation and fMRI measurements are obtained.DiscussionThe RESET-medication study will provide clinical evidence whether GR antagonism is a disease-modifying treatment for MDD in individuals exposed to CT. If effective, this hypothesis-driven approach may extend to other psychiatric disorders where CT plays an important role.Trial registrationThe trial protocol has been registered 01–02-2022 on ClinicalTrials.gov with ID “NCT05217758”.

A network analysis of depressive symptoms and metabolomics

Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models. We used data from the Netherlands Study of Depression and Anxiety (N = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later. The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave. The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.

Electric Field, Ictal Theta Power, and Clinical Outcomes in Electroconvulsive Therapy

BackgroundElectroconvulsive therapy (ECT) is efficacious for treatment-resistant depression. Treatment-induced cognitive impairment can adversely impact functional outcomes. Our pilot study linked the electric field to ictal theta power from a single suprathreshold treatment and linked ictal theta power to changes in phonemic fluency. In this study, we set out to replicate our findings and expand upon the utility of ictal theta power as a potential cognitive biomarker. MethodsTwenty-seven participants (18 female and 9 male) received right unilateral ECT for treatment-resistant depression. Pre-ECT magnetic resonance imaging and finite element modeling determined the 90th percentile maximum electric field in the brain. Two-lead electroencephalographs were digitally captured across the ECT course, with the earliest suprathreshold treatment used to determine power spectral density. Clinical and cognitive outcomes were assessed pre-, mid-, and post-ECT. We assessed the relationship between the electric field in the brain, ictal theta power, clinical outcome (Inventory of Depressive Symptomatology), and cognitive outcomes (phonemic and semantic fluency) with linear models. ResultsIctal theta power in the Fp1 and Fp2 channels was associated with the electric field, antidepressant outcome, and phonemic and semantic fluency. The relationship between ictal theta power and phonemic fluency was strengthened in the longitudinal analysis. The electric field in the brain was directly associated with phonemic and semantic fluency but not with antidepressant outcome. ConclusionsIctal theta power is a potential cognitive biomarker early on in the ECT course to help guide parameter changes. Larger studies are needed to further assess ictal theta power’s role in predicting mood outcome and changes with ECT parameters.

FMRI study of implicit emotional face processing in patients with MDD with melancholic subtype.

The accurate perception of facial expressions plays a vital role in daily life, allowing us to select appropriate responses in social situations. Understanding the neuronal basis of altered emotional face processing in patients with major depressive disorder (MDD) may lead to the appropriate choice of individual interventions to help patients maintain social functioning during depressive episodes. Inconsistencies in neuroimaging studies of emotional face processing are caused by heterogeneity in neurovegetative symptoms of depressive subtypes. The aim of this study was to investigate brain activation differences during implicit perception of faces with negative and positive emotions between healthy participants and patients with melancholic subtype of MDD. The neurobiological correlates of sex differences of MDD patients were also examined. Thirty patients diagnosed with MDD and 21 healthy volunteers were studied using fMRI while performing an emotional face perception task. Comparing general face activation irrespective of emotional content, the intensity of BOLD signal was significantly decreased in the left thalamus, right supramarginal gyrus, right and left superior frontal gyrus, right middle frontal gyrus, and left fusiform gyrus in patients with melancholic depression compared to healthy participants. We observed only limited mood-congruence in response to faces of differing emotional valence. Brain activation in the middle temporal gyrus was significantly increased in response to fearful faces in comparison to happy faces in MDD patients. Elevated activation was observed in the right cingulate for happy and fearful faces, in precuneus for happy faces, and left posterior cingulate cortex for all faces in depressed women compared to men. The Inventory for Depressive Symptomatology (IDS) score was inversely correlated with activation in the left subgenual gyrus/left rectal gyrus for sad, neutral, and fearful faces in women in the MDD group. Patients with melancholic features performed similarly to controls during implicit emotional processing but showed reduced activation. This finding suggests that melancholic patients compensate for reduced brain activation when interpreting emotional content in order to perform similarly to controls. Overall, frontal hypoactivation in response to implicit emotional stimuli appeared to be the most robust feature of melancholic depression.

Nicotine use and non-pathological alcohol use and their relationship to affective symptoms and sleep disturbances in bipolar disorder

BackgroundThe use of alcohol and nicotine can negatively impact the course of bipolar disorder (BD), but there is limited knowledge about how symptoms and sleep disturbances are related to concurrent nicotine use and non-pathological use of alcohol. MethodsWe investigated how nicotine use and non-pathological use of alcohol relates to affective symptoms and sleep disturbances in 453 participants with BD without substance use disorders. Manic symptoms were assessed with the Young Mania Rating Scale, and depressive symptoms with The Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C). Sleep-related questions from IDS-C were used to create proxy variables for sleep disturbances, including Insomnia and Hypersomnia. Multinomial regression analysis was conducted to investigate the associations between nicotine use and sleep disturbances, controlling for possible confounders such as current use of illicit drugs and psychopharmacological treatment. ResultsDepressive and manic symptoms were not associated with the concurrent level of alcohol or nicotine use. Individuals with medium and high levels of daily nicotine use had higher risk of insomnia than those without. Non-pathological alcohol use was not associated with sleep disturbances. LimitationsSleep disturbances were based on items from the IDS-C questionnaire. ConclusionWe found an elevated risk for insomnia in individuals with BD and medium or high levels of daily nicotine use. We found no association between the level of affective symptoms and the level of use of alcohol or nicotine. The direction of the relationship between nicotine use and insomnia needs clarification, as it is highly relevant for treatment planning.

Early detection of depression using a conversational AI bot: A non-clinical trial.

Artificial intelligence (AI) has gained momentum in behavioural health interventions in recent years. However, a limited number of studies use or apply such methodologies in the early detection of depression. A large population needing psychological-intervention is left unidentified due to barriers such as cost, location, stigma and a global shortage of health workers. Therefore, it is essential to develop a mass screening integrative approach that can identify people with depression at its early stage to avoid a potential crisis. This study aims to understand the feasibility and efficacy of using AI-enabled chatbots in the early detection of depression. We use Dialogflow as a conversation interface to build a Depression Analysisn (DEPRA) chatbot. A structured and authoritative early detection depression interview guide, which contains 27 questions combining the structured interview guide for the Hamilton Depression Scale (SIGH-D) and the inventory of depressive symptomatology (IDS-C), underpins the design of the conversation flow. To attain better accuracy and a wide variety of responses, we train Dialogflow with the utterances collected from a focus group of 10 people. The occupation of the focus group members included academics and HDR candidates who are conscious, vigilant and have a clear understanding of the questions. In addition, DEPRA is integrated with a social media platform to provide practical access to all the participants. For the non-clinical trial, we recruited 50 participants aged between 18 and 80 from across Australia. To evaluate the practicability and performance of DEPRA, we also asked participants to submit a user satisfaction survey at the end of the conversation. A sample of 50 participants, with an average age of 34.7 years, completed this non-clinical trial. More than half of the participants (54%) are male and the major ethnicities are Asian (63%), Middle Eastern (25%), and others 12%. The first group comprises professional academic staff and HDR candidates, the second and third groups comprise relatives, friends, and volunteers who were recruited via social media promotions. DEPRA uses two scientific scoring systems, QIDS-SR and IDS-SR to verify the results of early depression detection. As the results indicate, both scoring systems return a similar outcome with slight variations for different depression levels. According to IDS-SR, 30% of participants were healthy, 14% mild, 22% moderate, 14% severe, and 20% very severe. QIDS-SR suggests 32% were healthy, 18% mild, 10% moderate, 18% severe, and 22% very severe. Furthermore, the overall satisfaction rate of using DEPRA was 79% indicating that the participants had a high rate of user satisfaction and engagement. DEPRA shows promises as a feasible option for developing a mass screening integrated approach for early detection of depression. Although the chatbot is not intended to replace the functionality of mental health professionals, it does show promise as a means of assisting with automation and concealed communication with verified scoring systems.

Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial

IntroductionAs the role of (neuro)inflammation in depression pathophysiology is emerging, augmentation of antidepressant treatments with anti-inflammatory drugs have shown beneficial results, but not consistently across all studies. Inconsistencies may be due to depression biological and clinical heterogeneity. Immuno-Metabolic Depression (IMD) has been put forward as a form of depression characterized by the clustering of low-grade inflammation, metabolic dysregulations and atypical, energy-related symptoms (overeating, weight gain, hypersomnia, fatigue and leaden paralysis). IMD features are present in ∼30% of patients with Major Depressive Disorder (MDD). By selecting these specific patients, directly targeting inflammation may reduce depressive symptoms. Methodsand analysis INFLAMED is a double-blind randomized controlled trial. 140 MDD patients with IMD characteristics (MDD with Inventory of Depressive Symptomatology (IDS) ≥ 26, IDS atypical, energy related symptoms ≥6, C-Reactive Protein (CRP) > 1 mg/L) will receive either 400 mg celecoxib per day or matching placebo for a period of 12 weeks. Biological, physical and interview data will be collected after 2, 6 and 12 weeks of starting the intervention. Questionnaires will be sent out bi-weekly during the study period. The main study outcome is the IDS (30-item self-report) total score during 12-week follow-up. Secondary study outcomes include response, remission, adverse side effects, symptom profiles (atypical, energy-related symptoms), fatigue, food craving, sleep, anxiety symptoms, functioning, pain, and optionally, microbiome composition. Explorative analyses will be performed on the role of CRP, IL-6, TNF-α, cholesterol, triglycerides, glucose, BMI, waist and hip circumference. Ethics and disseminationThis protocol has been approved by the Medical Ethics Review Board of the Amsterdam UMC, location VUmc (2022.0015) on 2-6-2022, as well as by the competent authority in The Netherlands: CCMO, on 3-8-2022. Registration detailsTrail registration numbers NCT05415397, EudraCT 2021-003850-21

The association between adiposity and atypical energy-related symptoms of depression: A role for metabolic dysregulations

BackgroundAdiposity has been shown to be linked with atypical energy-related symptoms (AES) of depression. We used genomics to separate the effect of adiposity from that of metabolic dysregulations to examine whether the link between obesity and AES is dependent on the presence of metabolic dysregulations. MethodData were from NEO (n = 5734 individuals) and NESDA (n = 2238 individuals) cohorts, in which the Inventory of Depressive Symptomatology (IDS-SR30) was assessed. AES profile was based on four symptoms: increased appetite, increased weight, low energy level, and leaden paralysis. We estimated associations between AES and two genetic risk scores (GRS) indexing increasing total body fat with (metabolically unhealthy adiposity, GRS-MUA) and without (metabolically healthy adiposity, GRS-MHA) metabolic dysregulations. ResultsWe validated that both GRS-MUA and GRS-MHA were associated with higher total body fat in NEO study, but divergently associated with biomarkers of metabolic health (e.g., fasting glucose and HDL-cholesterol) in both cohorts. In the pooled results, per standard deviation, GRS-MUA was specifically associated with a higher AES score (β = 0.03, 95%CI: 0.01; 0.05), while there was no association between GRS-MHA and AES (β = −0.01, 95%CI: −0.03; 0.01). ConclusionThese results suggest that the established link between adiposity and AES profile emerges in the presence of metabolic dysregulations, which may represent the connecting substrate between the two conditions.

Repeated intravenous esketamine treatment in patients with ECT-resistant major depressive disorder

Ketamine is an anesthetic that appears to be an effective and rapidly acting pharmacological treatment in patients with Treatment-Resistant Depression (TRD). However, the definition of TRD varies greatly between published studies, and studies often did not include patients resistant to electroconvulsive therapy (ECT). We performed a chart study of 24 ECT-resistant TRD patients who received an open-label course of six esketamine infusions (0.5 mg/kg) over two weeks in the Leiden University Medical Center, Leiden, the Netherlands. Effectiveness was assessed with the Montgomery Åsberg Depression Rating Scale (MADRS) and the Inventory of Depressive Symptomatology (IDS-SR) up to four weeks after the last administration. Results : 23 (95.8%) patients (aged 48.7 ± 14.4 years, 79.2% female), completed the course. During treatment, eight patients (33.3%) achieved response (MADRS decrease ≥50%), five (20.8%) achieved remission (MADRS ≤10), and fourteen (58.3%) achieved a minimal clinically important difference (MADRS decrease >3 points). Relapse before or at follow-up occurred in 12.5%, 20% and 35.7% of these patients, respectively. An average decrease in MADRS scores of 9 points, and IDS-SR scores of 20 points, was observed. This retrospective chart review permitted us only to use routinely collected open label and unblinded data. On average, intravenous esketamine demonstrated moderate to clinically meaningful effectiveness in this highly therapy resistant TRD patient population. However, results varied substantially between patients, from clinical deterioration to rapid remission. Despite the relatively lower remission rate compared with published data, a minimal clinically important difference was observed in over half of the patients.