Subthreshold Depressive Symptoms Research Articles

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

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

Investigation of risk factors associated with the development of depressive symptoms in healthy subjects exposed to long-term stress: A prospective study of the Japanese Antarctic research expedition wintering party.

Stressors induce depression together with parenting experienced in childhood, personality traits, and sleep. In this study, we investigated factors associated with the development of depression in a long-term stressful environment, namely, the Antarctic Research Expedition wintering party, by comparing 2 groups, the depression and nondepression groups. A self-administered questionnaire was used to survey 91 members of the Japanese Antarctic Research Expedition who spent winters in the Antarctic base. Psychological evaluations of depression, anxiety, and sleep were performed using a questionnaire every 3 months during the participants' stay in Antarctica. The primary endpoint was the occurrence of minor or major depression, as evaluated by the PHQ-9 score. Participants with a PHQ-9 score of 5 or more during their stay in Antarctica were defined as the depression group (25 subjects), and participants with a PHQ score of 4 or less were defined as the nondepression group (43 subjects). Compared with the nondepression group, the depression group had significantly higher scores for predeparture PHQ-9, state and trait anxiety, sleep disturbance, and neuroticism. Multivariable logistic regression analyses showed that higher predeparture scores of subthreshold depressive symptoms and neuroticism were found to be significant predictors of the occurrence of depression during their stay in Antarctica. This study prospectively showed that subthreshold depressive symptoms and neuroticism, which were suggested as risk factors in previous studies, were confirmed to be risk factors for depression. The results of our study are expected to contribute to the understanding of depression in harsh environments.

Mind-Body Medicine in the Treatment of Depression: A Narrative Review of Efficacy, Safety and Mechanisms.

This narrative review examines the efficacy, mechanisms and safety of mind-body medicine (MBM) in the treatment of depression. We reviewed the potential effects of various MBM interventions such as yoga, tai chi, qigong, mindfulness-based interventions and nutrition on clinical and subthreshold depressive symptoms. Current studies indicate a growing interest in the use of MBM for psychiatric disorders, including depression. MBM interventions demonstrate efficacy in reducing depressive symptoms with fewer adverse effects and costs compared to pharmacological treatments. MBM has significant potential to improve mental health outcomes for depression. These interventions encourage self-care and stress management through behavioural, exercise, relaxation and nutritional approaches. While existing data are promising, further, more rigorous studies are required to confirm long-term effectiveness and to determine the role of MBM in comprehensive depression treatment strategies.

A self-help mobile messaging intervention to improve subthreshold depressive symptoms among older adults in a socioeconomically deprived region of Brazil (PRODIGITAL): a pragmatic, two-arm randomised controlled trial

Subthreshold depression is a risk factor for major depression and is associated with increased morbidity and mortality, especially in older adults. There is emerging evidence that digital interventions, including self-help interventions, may reduce depressive symptoms. We aimed to evaluate the effectiveness of a mobile messaging intervention at reducing subthreshold depressive symptoms among older adults in Brazil. PRODIGITAL was a single blind, two-arm, individually randomised controlled trial conducted in 46 primary care clinics in the city of Guarulhos, Brazil. Individuals aged 60+ years were contacted by phone following a randomly ordered list for a screening assessment. Those who presented with anhedonia and/or depressed mood (Patient Health Questionnaire (PHQ)-2≥1), and who subsequently scored between 5 and 9 on the PHQ-9 were invited to participate. The intervention arm received the 'Viva Vida' digital self-help intervention consisting of automated multi-media messages sent via WhatsApp. Forty-eight audio and visual messages based on psychoeducation and behavioural activation were automatically delivered over six weeks. The control arm received a single message containing information about depression. The primary outcome was the difference in mean PHQ-9 scores between treatment arms at the three-month follow-up. All primary analyses were performed according to allocated arm with imputed data. The trial is registered with ReBEC, RBR-6c7ghfd. Participants were recruited between 8 September 2021 and 19 August 2022. Of the 454 participants enrolled, 223 were randomised to the intervention arm, 231 to the control arm. Participants' mean age was 65.3 years (SD 5.0) and 64.0% (n=292) were female. A total of 385 (84.8%) completed the three-month follow-up assessment; no difference in mean PHQ-9 scores between the treatment arms was observed (adjusted difference:-0.61; 95% CI:-1.75, 0.53; p=0.29). These results demonstrate that the Viva Vida digital self-help intervention did not help to improve subthreshold depressive symptoms amongst older adults. Further research is needed to understand why this self-help intervention was not effective in this population, and to explore how it might be adapted to achieve this goal. São Paulo Research Foundation and UK Joint Global Health Trials.

Psychological outcomes of dementia risk estimation in MCI patients: Results from the PreDADQoL project.

Understanding the impact of biomarker-based dementia risk estimation in people with mild cognitive impairment (MCI) and their care partners is critical for patient care. MCI patients and study partners were counseled on Alzheimer's disease (AD) biomarker and dementia risk was disclosed. Data on mood, quality of life (QoL), and satisfaction with life (SwL) were obtained 1 week and 3 months after disclosure. Seventy-five dyads were enrolled, and two-thirds of the patients opted for biomarker testing. None of the participants experienced clinically relevant depression or anxiety after disclosure. All dyads reported moderate to high QoL and SwL throughout the study. Patients reported more subthreshold depressive symptoms 1 week and lower QoL and SwL 3 months after disclosure. In patients, depression (odds ratio [OR]: 0.76) and anxiety (OR: 0.81) were significant predictors for the decision against biomarker testing. No major psychological harm is to be expected in MCI patients and care partners after dementia risk disclosure. This study is registered in the German clinical trials register (Deutsches Register Klinischer Studien, DRKS): http://www.drks.de/DRKS00011155, DRKS registration number: DRKS00011155, date of registration: 18.08.2017. Patients with mild cognitive impairment (MCI) and study partners were counseled on Alzheimer's disease (AD) biomarker-based dementia risk estimation. About two-thirds of patients opted for biomarker testing and received their dementia risk based on their AD biomarker status. Patients who decided in favor or against CSF biomarker testing differed in psychological features. We did not observe major psychological harm after the dementia risk disclosure. Coping strategies were associated with better subsequent mood and well-being in all participants.

Past body shaming experiences and food and alcohol disturbance in young adults: indirect effects via psychological distress

PurposeThis study investigated the associations between retrospective reports of body image victimization (i.e. body shaming) perpetrated by peers and by parents during childhood or adolescence, and food and alcohol disturbance (FAD) in young adulthood, considering the possible mediating role of psychological distress (i.e. subthreshold symptoms of anxiety and depression).MethodsThe study involved 1624 young adults aged between 18 and 30 (69% women), who completed an online survey.ResultsOur findings revealed that participants who reported more frequent body image victimization episodes during childhood and adolescence exhibited higher levels of psychological distress and, in turn, higher scores of FAD in young adulthood.ConclusionsThis result represents a novel contribution to understanding the psychological correlates of FAD in youths. Limitations and implications are discussed.Level of evidence Level V, descriptive study.

Impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in adults with leukemia.

Patients not only experience symptoms caused by cancer but also suffer from the accompanying psychological pain. Therefore, these patients do not have high quality of life. According to the World Health Organization, the incidence of leukemia in China in 2020 was 5.1/100000, the mortality rate was 3.3/100000, and the prevalence rate was 16.7/100000. Therefore, it is important to examine the influence of comorbid subthreshold depressive symptoms on leukemia patients. To determine the impact of comorbid subthreshold depressive symptoms on cancer-related fatigue and complications in leukemia patients, thereby providing a basis for early diagnosis and treatment in clinical practice. A questionnaire survey was conducted among leukemia patients admitted to a tertiary hospital in Xi'an, Shaanxi Province, China, from August 2022 to December 2023. Patients with a score > 16 on the Chinese Classification of Mental Disorders (CCMD-3) and a Hamilton Depression Rating Scale score of 8-17 were classified as the subthreshold depressive group (n = 95), while 100 leukemia patients admitted during the same period were classified as the control group. Data were collected using Epidata 3.1 software, and comparisons were made between the two groups regarding general clinical data, the Piper Fatigue Scale (PFS), the Pittsburgh Sleep Quality Index (PSQI), the Numeric Rating Scale for pain assessment, laboratory indicators, and the occurrence of complications. In this survey, 120 leukemia patients with depression were preliminarily screened, 95 patients with subthreshold depression were ultimately selected as the subthreshold depression group, and 100 leukemia patients admitted during the same period were enrolled as the normal group. Comparison of basic clinical data between the two groups revealed no significant differences in age, sex, body mass index, cognitive function, or comorbidity with other chronic diseases. However, there were statistically significant differences in the use of radiotherapy and regular exercise between the two groups (P < 0.05). Comparisons of scales and laboratory indicators revealed no significant differences in albumin or PSQI scores between the two groups, but there were statistically significant differences in pain scores, PSQI scores, PFS scores, hemoglobin levels, and C-reactive protein levels (P < 0.05). Spearman's correlation analysis indicated that cancer-related fatigue was correlated with age, hemoglobin levels, C-reactive protein levels, pain, and regular exercise among leukemia patients with subthreshold depression. Multivariate regression analysis revealed that advanced age, combined radiotherapy, pain, and low hemoglobin levels were risk factors for cancer-related fatigue in leukemia patients with comorbid subthreshold depression, while regular exercise was a protective factor against cancer-related fatigue. Follow-up comparisons revealed a significantly lower overall incidence of complications in the control group (4%) than in the depressive group (24.21%; P < 0.001). Leukemia patients with comorbid subthreshold depressive symptoms experience more severe cancer-related fatigue and a higher incidence of complications. These findings may be related to advanced age, combined radiotherapy, pain, and low hemoglobin levels, while regular exercise may effectively alleviate symptoms.

Effect of elevated depressive symptoms during adolescence on health-related quality of life in young adulthood-a six-year cohort study with repeated exposure measurements.

Depression is a major contributor of young people's burden of disease. In this study we aim to estimate the effect of elevated depressive symptoms on physical health-related quality of life. We used self-reported information from the prospective BELLA cohort study, which included adolescents selected from the general population in Germany. The baseline assessment (2003-2006) and the 1-, 2-, and 6-year follow-up waves provide the data basis. The baseline study population consisted of 1,460 adolescents between the ages of 12 and 17 who, according to their caregivers, did not suffer from depression. The primary outcome, as measured by the physical component score (PCS) of the SF-36 at a 6-year follow-up (range: 0-100), is physical health-related quality of life. The exposure of interest is depressive symptoms, as measured by the Center for Epidemiological Studies Depression Scale for Children (CES-DC) at baseline, 1-year follow-up and 2-year follow-ups (range: 0-60). We dichotomized the exposure into subthreshold (≤15) and elevated depressive symptoms (>15). For the main analyses we considered a cumulative index for elevated depressive symptoms across the three time points (range: 0-3). Considered confounders are sex, age, socioeconomic status, migrant background, social support, anxiety symptoms, physical activity, chronic diseases, and sleeping problems. We used multiple imputation to account for missing values. Within each imputed dataset, we applied inverse probability weighting (IPW) to estimate the effect of the cumulative index for elevated depressive symptoms at baseline, 1- and 2-year follow-up on physical health-related quality of life at 6-year follow-up. We derived 95% confidence intervals by bootstrapping. After adjusting with IPW, the effect of the cumulative index per one unit increase of elevated depressive symptoms on the physical component score was -1.71 (95% CI: -3.51 to -0.04). The adjusted effect estimates of single exposure of elevated depressive symptoms on physical health-related quality of life were -0.83 (95% CI: -3.69 to 1.87) at baseline, -2.96 (95% CI: -4.94 to -0.52) at 1-year follow-up and -1.32 (95% CI: -3.85 to 1.15) at 2-year follow-up. Findings suggest that elevated depressive symptoms during adolescence decrease physical health-related quality of life in young adulthood.

Effect of virtual reality-based biofeedback for depressive and anxiety symptoms: Randomized controlled study

BackgroundThe use of virtual reality (VR)-based biofeedback (BF), a relatively new intervention, is a non-pharmacological treatment of depressive and anxiety symptoms. However, studies on VR-based BF are lacking and inconclusive. MethodsA total of 131 adults were recruited from the community. Participants who scored ≥10 on the Patient Health Questionnaire-9 (PHQ-9) or ≥9 on the Panic Disorder Severity Scale (PDSS) were included in the group with depressive or anxiety symptoms (DAS group), and others as the healthy control group (HC group). Participants from the DAS group were randomly assigned to VR-based or conventional BF intervention. All individuals visited at three times (weeks 0, 2, and 4), and completed the Montgomery-Asberg Depression Rating Scale (MADRS), the State-Trait Anxiety Inventory (STAI), and a visual analog scale (VAS) before and after the intervention, and PHQ-9 at the beginning and final visit. ResultsThe analysis included a total of 118 participants (DAS/VR: 40, DAS/BF: 38, HC/VR: 40). There was no significant difference in demographic variables among the three groups. After the intervention, the DAS/VR group exhibited significant decreases in MADRS (70.0 %), PHQ-9 (64.1 %), STAI (29.5 %), and VAS (61.7 %) scores compared to the baseline (p <0.001). There were no significant differences between the effects of VR-based BF and conventional BF with a therapist. The HC group also showed significant decreases in the measures of depression and anxiety after receiving VR-based BF. ConclusionVR-based BF was effective in reducing depressive and anxiety symptoms, even for subthreshold depression and anxiety symptoms in the HC group.

A Preliminary Study of Brain Developmental Features of Bipolar Disorder Familial Risk and Subthreshold Symptoms

BackgroundRisk for bipolar disorder (BD) is increased among individuals with a family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remain unknown. MethodsThis longitudinal cohort study examined the brain gray matter volume (GMV) developmental features of familial and symptomatic risks for BD and their associations with participants’ global function levels. We recruited unaffected BD offspring with (n = 26, 14 female, mean ± SD age = 14.9 ± 2.9 years) or without (n = 35, 19 female, age = 15.3 ± 2.7 years) subthreshold manic or depressive symptoms and unaffected non-BD offspring with (n = 49, 30 female, age = 14.5 ± 2.2 years) or without (n = 68, 37 female, age = 15.0 ± 2.3 years) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63 ± 1.63 years. ResultsAt baseline, we found significant interactive effects of familial risk and subthreshold symptoms that indicated that the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and nonsymptomatic) displayed a more accelerated GMV decrease than BD nonoffspring in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and nonoffspring) displayed a slower GMV decrease than nonsymptomatic participants in the ventromedial prefrontal cortex. Larger GMV at baseline and accelerated GMV decrease during follow-up prospectively and longitudinally predicted positive global function changes. All results survived multiple testing correction. ConclusionsThese findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.

Effects of a single subanesthetic dose of esketamine on postoperative subthreshold depressive symptoms in patients undergoing unilateral modified radical mastectomy: a randomised, controlled, double-blind trial

BackgroundBreast cancer is the most common malignant tumor in females worldwide. During disease development, breast cancer patients suffer anxious and depressed, which may lead to worse quality of life or even higher mortality. Esketamine has been regarded as an antidepressant in breast cancer patients with mild or moderate depression. Here, we wonder whether the administration of esketamine could reduce the postoperative depressive symptom score of breast cancer patients who have no preoperative depression.MethodsA total of 64 patients treated with unilateral modified radical mastectomy were randomly divided into an experimental group (esketamine group, Group E) and a control group (Group C), with 32 cases in each one. After anesthesia induction, Group C received 0.2 ml/kg of normal saline intravenously and Group E was administered 0.2 mg/kg intravenous esketamine. The primary outcome was the Patient Health Questionnaire-9 (PHQ-9) scores. The secondary outcomes included the Visual Analogue Scale (VAS) scores for pain, inflammatory markers, perioperative-related indicators, and the incidence of postoperative delirium, nausea and vomiting.ResultsThe PHQ-9 score on postoperative day (POD) 1 in Group E declined from the preoperative level, while the score in Group C was higher than before, and the former was far lower than the latter (P = 0.047). There is no statistically significant difference in PHQ-9 scores between Group E and Group C on POD 3, 7, and 30. Moreover, the postoperative leukocyte level of Group E was higher than that of Group C, and the difference was statistically significant (P = 0.030).ConclusionsA single subanesthetic dose of esketamine can result in lower postoperative score on subthreshold depressive symptoms compared to the Group C on POD 1, without increasing the occurrence of postoperative adverse reactions.Trial registrationRegistration number: Chinese Clinical Trial Registry ChiCTR2200057028. Date of registration: 26/02/2022.

Research on adults with subthreshold depression after aerobic exercise: a resting-state fMRI study based on regional homogeneity (ReHo).

Subthreshold depression (StD)/subsyndromal depression refers to a threatening precursor to depression. Aerobic exercise is a promising self-supportive adjunctive intervention and an effective measure for StD. Our study utilizes regional homogeneity (ReHo) to investigate the impact of aerobic exercise on resting-state brain function. A total of 78 subjects, aged between 18 and 48 years, (StD group, n = 44; healthy control (HC) group, n = 34) engaged in moderate-intensity aerobic exercise 3-4 times per week for 8 weeks. Resting-state brain function and structural images were acquired before and after the exercise intervention. The ReHo method was employed to analyze abnormal changes in regional brain function, and a correlation analysis was performed using the Patient Health Questionnaire-9 (PHQ-9) and Self-Rating Anxiety Scale (SAS) scores. The principal observation reveals synchronous abnormalities in the right anterior cingulate gyrus of the brain in StD subjects compared to HCs at baseline, with these differences dissipating after the implementation of aerobic exercise. After completing the aerobic exercise program, the StD group exhibited a difference in the right middle cingulate gyrus, while the left supplementary motor area (SMA) was altered in the HC group. Disparities in neural synchronization are evident between HCs and StD subjects, and the implementation of aerobic exercise intervention can effectively mitigate these distinctions, leading to a significant reduction in depressive symptoms among StD subjects. The primary mechanism of StD symptoms may involve the inhibition of the anterior cingulate gyrus, while the effects of aerobic exercise may be related to the modulation of neural synchronization of emotional reflexes. The discovery of these fMRI evidence findings may offer novel strategies for early detection and intervention in cases of StD.

Strength training has antidepressant effects in people with depression or depressive symptoms but no other severe diseases: A systematic review with meta-analysis

Depression and subthreshold depressive symptoms reduce quality of life and function and treatment does not work effectively in one-third of patients. Exercise can reduce depressive symptoms, but more information is required regarding strength training (ST). The objective of the present meta-analysis was to summarize and estimate the efficacy of ST in people with a diagnosis of depression or subthreshold depressive symptoms and no other severe disease. We also aimed to explore the variables that could influence the antidepressant effects. PubMed, Embase, Web of Science, PsyINFO, CINAHL, and SPORTDiscus were searched from inception to August 2022. The overall effect antidepressant of training was moderate (SMD = −0.51, 95 % CI −0.72 to −0.30, p < 0.001). The meta-regression demonstrated preliminary evidence that the variables: duration of the intervention in weeks, weekly frequency of the intervention, number of sets, and number of repetitions can influence the antidepressant effects. However, these variables had a small role in the variation of the effect.

Impact of lipodystrophy on health-related quality of life: the QuaLip study

BackgroundLipodystrophy is a rare disease characterized by loss of adipose tissue. Natural history studies have demonstrated significant burden of disease; however, there is limited data on the impact of lipodystrophy on quality of life (QoL) and psychoemotional well-being. The QuaLip study is a prospective observational real-world study that aims to determine the impact of lipodystrophy on QoL and psychoemotional well-being and explore subjective burden of the disease. Sixty-seven adult patients and eight pediatric patients with lipodystrophy were included. Patients were followed up for 24 months and assessments were repeated every three months. Patients were examined by licensed psychiatrists at baseline, and at year 1 and year 2 visits.ResultsEighteen (27.69%) of 65 adult patients (two subjects refused psychiatric assessment) were diagnosed with a psychiatric disorder (e.g., depressive episodes, mixed anxiety and depressive disorder, anxiety disorder, adjustment disorder, recurrent depression, panic disorder, generalized anxiety disorder, unspecified mood disorder, nonorganic sleep disorder, post-traumatic stress disorder, depressive episode comorbidity, social phobia and obsessive–compulsive disorder comorbidity). Lipodystrophy disease and QoL questionnaires revealed a significant disease burden over the study period. More than one-third of patients reported depression symptoms on the Beck Depression Inventory and more than one-fourth of the patients reported significant hunger throughout the study period. Physical appearance, fatigue, and pain contributed to the disease burden. QoL scores were lower in patients with psychiatric disease and in those with poor metabolic control. Attention deficit hyperactivity disorder, depressive disorder, sub-threshold depressive symptoms, obsessive–compulsive disorder, appetite problems, and issues with physical appearance were identified in selected pediatric subjects.ConclusionsLipodystrophy has a significant impact on QoL and psychoemotional well-being. Psychiatric disorders seem to be underdiagnosed among patients with lipodystrophy.

Longitudinal Clusters of Long-Term Trajectories in Patients with Early-Onset Chronic Depression: 2 Years of Naturalistic Follow-Up after Extensive Psychological Treatment

Introduction: In clinical trials, mostly group-level treatment effects of repeated cross-sectional measures are analyzed. However, substantial heterogeneity regarding individual symptom profiles and the variability of treatment effects are often neglected, especially over the long-term course. To provide effective personalized treatments, investigations of these characteristics are urgently needed. Methods: Depression severity ratings over 104 weeks of follow-up after year-long treatment with the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) or Supportive Psychotherapy (SP) were analyzed. Longitudinal cluster analysis and multinomial logistic regression analysis were conducted to investigate intraindividual trajectories from one of the largest psychotherapy trials in early-onset chronic depression. Results: Two-year post-study-treatment trajectories of N = 188 patients with early-onset chronic depression were grouped into four prototypical clusters. Overall, 16.0% of patients remitted (cluster 1) and most of them did not receive any treatment during the 2-year follow-up. However, 84.0% of patients continued to experience subthreshold (37.2% cluster 2) or major depressive symptoms (46.8% clusters 3–4) and spent on average more than half of the follow-up in pharmacological and psychological treatment. Hierarchical regression analysis indicated that previous study treatment with CBASP or SP did not significantly predict cluster allocation, while baseline variables accounted for a large proportion of explained variance (R² _N = 0.64). Conclusion: While some patients experienced stable remission over 2 years of follow-up, the majority of patients experienced subthreshold or major depressive symptoms regardless of former study treatment with CBASP or SP. This calls for a long-term perspective implementing staging and innovative treatment approaches such as the sequential model or modular psychotherapy.

Differential gene expression analysis in individuals with depression in Alzheimer’s disease using RNAseq

AbstractBackgroundDepression in individuals with Alzheimer’s disease (AD) is common, distressing, difficult to treat, may increase carer burden and is inadequately understood. It occurs more frequently in AD than in older adults without dementia. The underlying biology remains obscure.We aimed to identify patterns of differential gene expression in individuals with depression in AD compared to individuals with AD but no history of depressive illness.MethodWe used data from the Religious Orders Study and the Memory and Aging Project: the ROSMAP cohort. Individuals with other disorders which could have caused cognitive impairment e.g. Parkinson’s disease(n = 122) or clinically significant head trauma (n = 234) were excluded, and those with bipolar disorder(n = 13). Those with neuropathological or consensus clinical evidence of a dementia other than Alzheimer’s disease were also excluded (n = 116).Depression caseness was defined as a highly probable/probable clinical diagnosis of depression made by the assessing clinician at a study visit or a CESD score of &gt;7 at a study visit. Individuals with treated depression (n = 301) who were taking antidepressants but never met depression caseness criteria and 380 individuals with subthreshold depressive symptoms on the CESD but a clinical assessment that depression was “not present” were also excluded.RNAseq data was available from the DLPFC and posterior cingulate. The posterior cingulate analysis is ongoing. Fastq files were quality controlled using fastqc and Picard following HISAT2 alignment to GRCh38. After exclusion of files which failed QC fastq files were aligned to the GRCh38 transcriptome using Salmon. Files with low transcriptome alignment (&lt;28%) were also excluded. Differential gene expression analysis was carried out in Rstudio using DEseq2.ResultAfter exclusions and QC, data was available for 15 individuals with depression &amp; AD and 25 individuals with AD but no depression for the DLPFC. Age, RIN, sex and Braak stage were included in the analysis model. After adjustment of the p value for multiple comparison 64 genes were differentially expressed in depression including Fbox proteins, nucleosome assembly proteins and voltage‐gated channel proteins. KEGG pathway analysis is underwayConclusionWe have identified genes differentially expressed in depression in AD which may allow better understanding of this condition.

Impact of painful physical symptoms on first-episode major depressive disorder in adults with subthreshold depressive symptoms: A prospective cohort study

ObjectiveTo investigate the impact of baseline painful physical symptoms (PPS) on subsequent first-episode major depressive disorder (MDD) in adults with subthreshold depressive symptoms, including subgroup analyses to assess whether the associations differ in individuals with and without physical diseases. MethodsA total of 2343 adults with subthreshold depressive symptoms were recruited at 34 primary health care centers. PPS were measured at baseline. First-episode MDD during follow-up was diagnosed by professional psychiatrists using the Mini-International Neuropsychiatric Interview. ResultsBaseline PPS showed independent impacts on first-episode MDD in adults with subthreshold depressive symptoms without physical diseases, but not in those with physical diseases. A non-linear association (P < 0.001) was observed between PPS burden and the risk of first-episode MDD. The HRs for first-episode MDD exhibited a rapidly increasing trend between PPS burden scores of 10–16, and maintained consistently high when scores exceeded 16. The analyses for specific PPS revealed that headache, neck pain, and heart or chest pain were independently associated with first-episode MDD in participants without physical diseases, the HRs were 1.57 (1.15–2.36), 1.53 (1.02–2.30), and 1.69 (1.14–2.50), respectively. Further network analysis demonstrated that heart or chest pain serves as a bridge symptom among the seven specific PPS and first-episode MDD in those without physical diseases. ConclusionPPS burden and heart or chest pain may be significant indicators for first-episode MDD in adults with subthreshold depressive symptoms without physical diseases. Future studies should investigate whether interventions targeting PPS can prevent episode MDD in this subthreshold population.

Depressive symptoms and anger and aggression in Russian adolescents

Research among adolescents exploring the association between depressive symptoms and aggression has produced inconsistent findings. This study investigated the prevalence of clinically significant (current major depressive episode) and subthreshold depressive symptoms in a general population sample of adolescents from Northern Russia and explored their association with aggression and anger, while controlling for comorbid mental health problems. The sample consisted of 2600 participants, aged 13–17 years (59.5% female; 95.7% ethnic Russian). Symptoms of a current major depressive episode, types of anger and aggression (anger rumination, trait anger, physical, verbal and social aggression) and comorbid problems (posttraumatic stress, alcohol use, anxiety, and hyperactivity/impulsivity) were assessed by means of self-reports. The prevalence of a clinically significant depressive episode in the past month was 3.5%, while for subthreshold depression it was 21.6%. All anger and aggression variables, as well as comorbid problems increased together with increasing levels of depression. The association between overt aggressive behavior and depression was primarily explained by comorbid mental health problems, whereas anger rumination and social aggression had more direct associations with depression, independent of comorbidity. Among adolescents with depression, boys reported higher levels of social and verbal aggression and of anger rumination than girls. The results of this study suggest that interventions aiming to reduce aggressive behavior in adolescents should consider depression and its comorbid conditions.

The effect of subthreshold depressive symptoms on cognitive functions and peripheral biomarkers in bipolar disorder

Objective A global approach to factors responsible for functional impairment in patients with BD is necessary. Method Ninety-three euthymic patients with BD [49 patients with SD (subthreshold depression) and 44 patients without SD] and 48 healthy controls were invited for evaluation of demographic, clinical, and cognitive characteristics. To define SD, the lower limit was HDRS ≥4 points and the upper limit was HDRS <9 points. Stroop test, California verbal learning test, digit-span test, controlled word association test, and clock drawing test were performed. Serum BDNF levels were measured. Additionally in the BD group; blood drug (lithium, valproic acid), leukocyte, C-reactive protein (CRP), TSH, and vitamin B12 levels were measured. Results We found no difference between serum BDNF levels of BD (n = 93) and controls. The cognitive performances of the BD group were worse than the control group (p < 0.001). Attention, working memory, and stroop performance of patients with SD were worse than patients without SD (p < 0.05). Verbal fluency, stroop test, and planning performance decreased as serum CRP level increased in patients with BD (p < 0.05). Conclusions Although the patient group with SD was in euthymia, their cognitive performance was worse than the group without SD. Poor cognitive performance in BD was associated with serum CRP levels.

Prediction of depression onset risk among middle-aged and elderly adults using machine learning and Canadian Longitudinal Study on Aging cohort

BackgroundEarly identification of the middle-aged and elderly people with high risk of developing depression disorder in the future and the full characterization of the associated risk factors are crucial for early interventions to prevent depression among the aging population. MethodsCanadian Longitudinal Study on Aging (CLSA) has collected comprehensive information, including psychological scales and other non-psychological measures, i.e., socioeconomic, environmental, health, lifestyle, cognitive function, personality, about its participants (30,097 subjects aged from 45 to 85) at baseline phase in 2012–2015. We applied machine learning models for the prediction of these participants' risk of depression onset approximately three years later using information collected at baseline phase. ResultsIndividual-level risk for future depression onset among CLSA participants can be accurately predicted, with an area under receiver operating characteristic curve (AUC) 0.791 ± 0.016, using all baseline information. We also found the 10-item Center for Epidemiological Studies Depression Scale coupled with age and sex information could achieve similar performance (AUC 0.764 ± 0.016). Furthermore, we identified existing subthreshold depression symptoms, emotional instability, low levels of life satisfaction, perceived health, and social support, and nutrition risk as the most important predictors for depression onset independent from psychological scales. LimitationsDepression was based on self-reported doctor diagnosis and depression screening tool. ConclusionsThe identified risk factors will further improve our understanding of the depression onset among middle-aged and elderly population and the early identification of high-risk subjects is the first step for successful early interventions.