Non-depressed Controls Research Articles

Intensity dependence of auditory evoked potentials distinguish participants with unmedicated depression from non-depressed controls.

Depression is a heterogeneous syndrome that impacts an individual's emotional, social, cognitive and bodily functioning. Depression is associated with biases in emotional processing, but alterations in basic sensory processing have received less attention in depression research. Here, we measured event-related potentials (ERPs) in response to changes in the intensity of auditory stimuli and the location of somatosensory stimuli in participants with depression and in non-depressed control participants. We tested whether auditory mismatch negativity, P3a or N1 intensity dependence response or somatosensory mismatch response, P3a, P50 or N80 can dissociate depressed participants and non-depressed controls, and we also analysed the effects of depression medication and age in this sample. N1 intensity dependence response was increased in unmedicated depressed participants relative to non-depressed controls. When age was controlled for in the analysis, the effect of depression was only at a trend level. N1 intensity dependence response correlated with depression severity at the whole sample level. We did not observe any depression-related alterations in auditory mismatch negativity or P3a or somatosensory ERPs. Our results may reflect an association between the N1 intensity dependence response and altered neurotransmitter activity in depression, but this should be confirmed in future studies.

Impact of Depression on Postoperative Medical and Surgical Outcomes in Spine Surgeries: A Systematic Review and Meta-Analysis.

Introduction: The relationship between psychiatric disorders, including depression, and invasive interventions has been a topic of debate in recent literature. While these conditions can impact the quality of life and subjective perceptions of surgical outcomes, the literature lacks consensus regarding the association between depression and objective perioperative medical and surgical complications, especially in the neurosurgical domain. Methods: MEDLINE (PubMed), EMBASE, PsycINFO, and the Cochrane Library were queried in a comprehensive manner from inception until 10 November 2023, with no language restrictions, for citations investigating the association between depression and length of hospitalization, medical and surgical complications, and objective postoperative outcomes including readmission, reoperation, and non-routine discharge in patients undergoing spine surgery. Results: A total of 26 articles were considered in this systematic review. Upon pooled analysis of the primary outcome, statistically significantly higher rates were observed for several complications, including delirium (OR:1.92), deep vein thrombosis (OR:3.72), fever (OR:6.34), hematoma formation (OR:4.7), hypotension (OR:4.32), pulmonary embolism (OR:3.79), neurological injury (OR:6.02), surgical site infection (OR:1.36), urinary retention (OR:4.63), and urinary tract infection (OR:1.72). While readmission (OR:1.35) and reoperation (OR:2.22) rates, as well as non-routine discharge (OR:1.72) rates, were significantly higher in depressed patients, hospitalization length was comparable to non-depressed controls. Conclusions: The results of this review emphasize the significant increase in complications and suboptimal outcomes noted in patients with depression undergoing spinal surgery. Although a direct causal relationship may not be established, addressing psychiatric aspects in patient care is crucial for providing comprehensive medical attention.

Executive function deficits in patients with the first episode of late-life depression before and after SSRI treatment: A pilot fMRI study.

Executive function deficits (EFD) in late-life depression (LLD) has been reported to be associated with antidepressant treatment resistance, increased disability, and poor quality of life. However, the underlying neutral mechanisms of EFD in patients with the first episode of LLD remains unclear. A total of 27 patients with first-episode, drug-naive LLD and 27 non-depressed controls (NC) were recruited for the present research. Participants underwent the Trail Making Test, the 17-item Hamilton depression rating scale (HAMD-17) test, and task-state functional magnetic resonance imaging scans under the neutral Stroop task. LLD patients' executive functions, depressive symptoms, and brain activity were examined again after 6months of antidepressant treatment. Of the 27 LLD patients, 16 cases completed 6-month follow-ups. Patients in the LLD baseline group spent more time on the Trail Making Test A test than those in the NC group (p<0.05). In the presence of an incongruency between the word color and meaning, the accuracy rate of the neutral Stroop task in the LLD baseline group was lower, and the reaction time was greater than that in the NC group, with statistically significant difference (p<0.05). The HAMD-17 score in the LLD follow-up group was significantly lower than that in the LLD baseline group (p<0.05). More activated brain regions were present in the LLD baseline group than in the NC group when performing the neutral Stroop task. Compared with the LLD baseline group, abnormal activation of relevant brains in the cingulate-prefrontal-parietal network of LLD patients still existed in the LLD follow-up group. LLD patients engaged more brain areas than the NC group while performing the neutral Stroop task. Abnormal activation of the cingulate-prefrontal-parietal network could be a contributing factor to EFD in LLD. ChiCTR, ChiCTR2100042370 (Date of registration: 21/01/2021). We didn't enroll enough first-episode, LLD patients, the robustness of the findings need to be confirmed by large sample clinical trials.

Differences in bacterial taxa between treatment-naive patients with major depressive disorder and non-affected controls may be related to a proinflammatory profile

BackgroundMajor depressive disorder (MDD) is characterized by sadness and anhedonia, but also physical symptoms such as changes in appetite and weight. Gut microbiota has been hypothesized to be involved in MDD through gut-brain axis signaling. Moreover, antidepressants display antibacterial properties in the gastrointestinal tract. The aim of this study was to compare the gut microbiota and systemic inflammatory profile of young patients with MDD before and after initiation of antidepressant treatment and/or psychotherapy in comparison with a non-depressed control group (nonMDD).MethodsFecal and blood samples were collected at baseline and at follow-up after four and twelve weeks, respectively. Patients started treatment immediately after collection of the baseline samples. The gut microbiota was characterized by 16 S rRNA gene sequencing targeting the hypervariable V4 region. Plasma levels of 49 unique immune markers were assessed using Mesoscale.ResultsIn total, 27 MDD patients and 32 nonMDD controls were included in the study. The gut microbiota in the baseline samples of MDD versus nonMDD participants did not differ regarding α- or β-diversity. However, there was a higher relative abundance of the genera Ruminococcus gnavus group, and a lower relative abundance of the genera Desulfovibrio, Tyzzerella, Megamonas, Olsenella, Gordonibacter, Allisonella and Rothia in the MDD group compared to the nonMDD group. In the MDD group, there was an increase in the genera Rothia, Desulfovibrio, Gordinobacteer and Lactobacillus, while genera belonging to the Firmicutes phylum were found depleted at twelve weeks follow-up compared to baseline. In the MDD group, IL-7, IL-8 and IL-17b levels were elevated compared to the nonMDD group at baseline. Furthermore, MDI score in the MDD group was found to correlate with Bray-Curtis dissimilarity at baseline, and several inflammatory markers at both baseline and after initiation of antidepressant treatment.ConclusionSeveral bacterial taxa differed between the MDD group and the nonMDD group at baseline and changed in relative abundance during antidepressant treatment and/or psychotherapy. The MDD group was furthermore found to have a pro-inflammatory profile compared to the nonMDD group at baseline. Further studies are required to investigate the gut microbiota and pro-inflammatory profile of patients with MDD.

Correspondence between the Simple Physical Activity Questionnaire (SIMPAQ) and accelerometer-based physical activity in inpatients treated for major depressive disorders in comparison to non-depressed controls.

Major depressive disorders (MDD) are a leading health concern worldwide. While first line medication treatments may fall short of desired therapeutic outcomes, physical activity (PA) interventions appear to be a promising and cost-effective add-on to improve symptoms of depression. This study aimed to address challenges in the assessment of PA in inpatients treated for MDD by examining the correspondence of self-reported and accelerometer-based PA. In 178 inpatients treated for MDD (mean age: M = 41.11 years, SD = 12.84; 45.5% female) and 97 non-depressed controls (mean age: M = 35.24 years, SD = 13.40; 36.1% female), we assessed self-reported PA via the Simple Physical Activity Questionnaire (SIMPAQ) for one week, followed by a week where PA was monitored using an accelerometer device (Actigraph wGT3x-BT). Additionally, we examined correlations between PA levels assessed with the SIMPAQ and exercise determinants in both groups. Descriptively, inpatients treated for MDD showed lower levels of light PA on accelerometer-based measures, whereas they self-reported increased levels of certain types of PA on the SIMPAQ. More importantly, there was only a small degree of correspondence between self-reported and actigraphy-based PA levels in both in patients (r = 0.15, p < 0.05) and controls (r = 0.03, ns). Only few significant correlations were found for self-reported PA (SIMPAQ subscores) and perceived fitness, whereas self-reported PA and estimated VO2max were unrelated. Furthermore, only weak (and mostly statistically non-significant) correlations were found between exercise determinants and SIMPAQ-based exercise behavior in both populations. Our findings emphasize the intricate challenges in the assessment of PA, not only in inpatients treated for MDD, but also in non-depressed controls. Our findings also underline the necessity for a diversified data assessment. Further efforts are needed to refine and improve PA questionnaires for a more accurate data assessment in psychiatric patients and healthy controls.

Serum Levels of the Steroid Hormone Dehydroepiandrosterone Are Associated with Psychological Trauma and Lymphocyte Telomere Integrity in Women Suffering from Depression.

Emerging studies highlight the telomere system as an aging mechanism underlying the association between exposure to psychological trauma and the development of a wide range of physical and mental disorders, including major depressive disorder (MDD). Here, we investigated associations of circulating levels of the steroid hormone dehydroepiandrosterone (DHEA) with immune cell telomere length (TL) in the context of lifetime trauma exposure and MDD. Lifetime traumatic events (trauma load) were assessed using the Essener Trauma Inventory in n = 22 postmenopausal female inpatients with MDD and n = 22 non-depressed controls. All women completed the Beck's Depression Inventory II to assess the severity of current depressive symptoms. DHEA concentration in serum was measured by immunoassay, and TL was quantified in kilobase units using quantitative fluorescent in situ hybridization in total peripheral blood mononuclear cells (PBMC) and in selected T-cell subpopulations isolated by FACS separation. Higher trauma load was significantly associated with lower DHEA concentration, which in turn was linked to more depression-related fatigue. Furthermore, DHEA concentration was positively and significantly associated with TL in memory CD4+ T cells as well as in naïve and memory CD8+ T cells, but not in naïve CD4+ T cells and total PBMC. Mediational analysis suggested that DHEA concentration is a mediator in the relationship between trauma load and memory CD8+ T-cell TL. The current findings suggest a potential role of DHEA as a biological resilience factor that may exert beneficial effects on telomere integrity, especially in conditions related to distress.

Optomyography-based sensing of facial expression derived arousal and valence in adults with depression.

Continuous assessment of affective behaviors could improve the diagnosis, assessment and monitoring of chronic mental health and neurological conditions such as depression. However, there are no technologies well suited to this, limiting potential clinical applications. To test if we could replicate previous evidence of hypo reactivity to emotional salient material using an entirely new sensing technique called optomyography which is well suited to remote monitoring. Thirty-eight depressed and 37 controls (≥18, ≤40 years) who met a research diagnosis of depression and an age-matched non-depressed control group. Changes in facial muscle activity over the brow (corrugator supercilli) and cheek (zygomaticus major) were measured whilst volunteers watched videos varying in emotional salience. Across all participants, videos rated as subjectively positive were associated with activation of muscles in the cheek relative to videos rated as neutral or negative. Videos rated as subjectively negative were associated with brow activation relative to videos judged as neutral or positive. Self-reported arousal was associated with a step increase in facial muscle activation across the brow and cheek. Group differences were significantly reduced activation in facial muscles during videos considered subjectively negative or rated as high arousal in depressed volunteers compared with controls. We demonstrate for the first time that it is possible to detect facial expression hypo-reactivity in adults with depression in response to emotional content using glasses-based optomyography sensing. It is hoped these results may encourage the use of optomyography-based sensing to track facial expressions in the real-world, outside of a specialized testing environment.

Cardiorespiratory fitness and cardiovascular risk among in-patients with depression compared to healthy controls.

Compared to the general population, individuals with depression have an increased risk for cardiovascular diseases. Nevertheless, little is known so far whether cardiorespiratory fitness (CRF) moderates this relationship. Therefore, we examined whether common physiological cardiovascular risk factors differ between patients with depression and healthy (non-depressed) controls, whether patients and controls differ in CRF, and whether higher CRF is associated with a lower cardiovascular risk in both patients and healthy controls. Additionally, we examined whether within the patient sample, cardiovascular risk factors differ between patients with mild, moderate and severe depression, and whether the relationship between symptom severity and cardiovascular risk is moderated by patients' CRF levels. Data from a multi-centric, two-arm randomized controlled trial (RCT) was analyzed, including 210 patients (F32, single episode: n = 72, F33, recurrent major depression: n = 135, F31-II, bipolar type II: n = 3) and 125 healthy controls. Waist circumference, body mass index, body fat, blood pressure, cholesterol levels, triglycerides, and blood glucose were considered as cardiovascular risk markers. CRF was assessed with a submaximal ergometer test. Differences between groups were examined via χ2-tests and (multivariate) analyses of covariance. Compared to healthy controls, patients with depression had a higher cardiovascular risk as evident from about half of the examined indicators. In the total sample, participants with good CRF had more favourable scores across nearly all risk markers than counterparts with poor CRF. For most variables, no interaction occurred between group and fitness, indicating that in patients and controls, similar differences existed between participants with poor and good CRF. Few differences in risk markers were found between patients with mild, moderate and severe depression, and no interaction occurred between depression severity and CRF. Patients with depression and healthy controls differ in several cardiovascular risk markers, putting patients at increased risk for CVDs. In contrast, people with good CRF show more favourable cardiovascular risk scores, a relationship which was observed in both healthy controls and patients with depression. Physical health of psychiatric patients should receive the clinical attention that it deserves. Lifestyle interventions targeting healthy diet and/or physical activity are recommended as a physically active and healthy lifestyle contributes equally to patients' mental well-being and cardiovascular health.

Brain-Cognition Associations in Older Patients With Remitted Major Depressive Disorder or Mild Cognitive Impairment: A Multivariate Analysis of Gray and White Matter Integrity

BackgroundAlmost half of older patients with major depressive disorder (MDD) present with cognitive impairment, and one-third meet diagnostic criteria for mild cognitive impairment (MCI). However, mechanisms linking MDD and MCI remain unclear. We investigated multivariate associations between brain structural alterations and cognition in 3 groups of older patients at risk for dementia, remitted MDD (rMDD), MCI, and rMDD+MCI, as well as cognitively healthy nondepressed control participants. MethodsWe analyzed magnetic resonance imaging data and cognitive domain scores in participants from the PACt-MD (Prevention of Alzheimer’s Disease With Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression) study. Following quality control, we measured cortical thickness and subcortical volumes of selected regions from 283 T1-weighted scans and fractional anisotropy of white matter tracts from 226 diffusion-weighted scans. We assessed brain-cognition associations using partial least squares regressions in the whole sample and in each subgroup. ResultsIn the entire sample, atrophy in the medial temporal lobe and subregions of the motor and prefrontal cortex was associated with deficits in verbal and visuospatial memory, language skills, and, to a lesser extent, processing speed (p < .0001; multivariate r = 0.30, 0.34, 0.26, and 0.18, respectively). Widespread reduced white matter integrity was associated with deficits in executive functioning, working memory, and processing speed (p = .008; multivariate r = 0.21, 0.26, 0.35, respectively). Overall, associations remained significant in the MCI and rMDD+MCI groups, but not the rMDD or healthy control groups. ConclusionsWe confirm findings of brain-cognition associations previously reported in MCI and extend them to rMDD+MCI, but similar associations in rMDD are not supported. Early-onset and treated MDD might not contribute to structural alterations associated with cognitive impairment.

0638 Comparison of social jet lag between individuals with seasonal affective disorder and controls

Abstract Introduction Social jet lag (SJL) occurs when a person’s social time (weekdays) is out of phase with their circadian time (weekend). Not much is known about the relationship between Seasonal Affective Disorder (SAD) and SJL; however, the sleep/wake cycle is very vulnerable to disruption by external factors. In a previous study in adolescents and young adults, self-reported chronotype was used to calculate SJL, and winter mood variation and SJL were found to be higher after the time change in fall and winter. Our study will directly compare SAD and non-depressed controls in the winter on SJL calculated with actigraphy in a sample of adults. Methods Participants (N=46) ages 21-64 were recruited during winter months and included individuals with SAD (n=21) and nonseasonal, never depressed controls (n=25). Midsleep timing was measured using actigraphy (average number nights = 7), and SJL was calculated by subtracting average week midsleep from average weekend midsleep corrected for number of days. Regression analysis included diagnostic group as a predictor, age and gender as covariates, and SJL as the outcome. Results While the seasonally depressed group had a slightly higher average SJL (M =61.8 minutes, SD = 181.2 minutes) than the control group (M = 60.6 minutes, SD = 165 minutes; mean difference 1.2 minutes), there was no significant difference in SJL between the participants with seasonal depression and the controls (p=0.778). However, age was a significant predictor, as the younger half of the sample had a mean SJL of 94 minutes (SD=180 minutes) and the older half of the sample had a mean SJL of 24 minutes (SD= 156 minutes; mean difference= 70 minutes). There was no group*age interaction in post-hoc tests. Conclusion This is the first study to test whether individuals with SAD have greater SJL than non-depressed controls, and the data do not support such a hypothesis. Results do, however, confirm prior findings that SJL decreases with age. Future studies should compare SJL in individuals with SAD during winter compared to spontaneous summer remission to test whether a change in SJL correlates with winter depression onset. Support (if any) NIMH K.A.R. MH103303

0648 Retinal responsivity is associated with light and season-related cognitions in older adults with seasonal depression

Abstract Introduction Maladaptive cognitions associated with lower light availability in winter and the changing of the seasons are elevated in winter depression and are treatment targets in psychotherapy. Mechanisms underlying the development of SAD-specific cognitions may be related to seasonal variation in melanopsin-driven retinal responsivity to light. Prior work has shown reduced retinal responsivity to light during the winter in seasonal depression. We hypothesized maladaptive seasonal cognitions would be associated with reduced retinal responses to light. We also tested whether age moderated this relationship, hypothesizing that this learned association may only appear in older individuals who have experienced a greater number of seasonal depressive episodes. Methods Participants ages 19-65 (M=36.13, SD=12.81) with seasonal depression (n=37) and non-depressed controls (n=32) completed assessments in winter months (21st December to 21st March). Maladaptive seasonal cognitions were measured by the Seasonal Beliefs Questionnaire (SBQ). Melanopsin-driven retinal responsivity was assessed using the post illumination pupil response (PIPR). Net PIPR as a percent of baseline was averaged across the 10-30 seconds post-stimulus for use in analyses. Using multiple regression, we tested (1) if seasonal beliefs predict the PIPR and (2) if an interaction between seasonal beliefs and age predicts the PIPR, controlling for gender, the pupillary light reflex (PLR), and circadian time of testing from Dim Light Melatonin Onset. Results Seasonal beliefs were not associated with the PIPR (b= -0.86e-5, SE=0.27e-3, p=0.98). There was a significant interaction between seasonal beliefs and age on the PIPR (b= -0.56e-4, SE=0.23e-4, p=0.02), in which greater seasonal beliefs were associated with reduced PIPR in older individuals but not younger individuals. The Johnson-Neyman interval indicated that in participants above age 49, greater seasonal beliefs were significantly associated with lower retinal responsivity (PIPR; p&amp;lt; 0.05). Conclusion Greater seasonal beliefs were associated with reduced retinal responsivity, but only in older adults with seasonal depression. It is possible that reduced retinal responsivity creates learned maladaptive schemas regarding seasonal changes that are reinforced with annually recurring winter depressive episodes. However, longitudinal data focused on changes in seasonal beliefs resulting from reduced retinal sensitivity is necessary to test whether retinal responsivity is a mechanism in the formation of these seasonal-specific cognitions. Support (if any)

Deep phenotyping as a contribution to personalized depression therapy: the GEParD and DaCFail protocols

Depressive patients suffer from a complex of symptoms of varying intensity compromising their mood, emotions, self-concept, neurocognition, and somatic function. Due to a mosaic of aetiologies involved in developing depression, such as somatic, neurobiological, (epi-)genetic factors, or adverse life events, patients often experience recurrent depressive episodes. About 20–30% of these patients develop difficult-to-treat depression. Here, we describe the design of the GEParD (Genetics and Epigenetics of Pharmaco- and Psychotherapy in acute and recurrent Depression) cohort and the DaCFail (Depression-associated Cardiac Failure) case–control protocol. Both protocols intended to investigate the incremental utility of multimodal biomarkers including cardiovascular and (epi-)genetic markers, functional brain and heart imaging when evaluating the response to antidepressive therapy using comprehensive psychometry. From 2012 to 2020, 346 depressed patients (mean age 45 years) were recruited to the prospective, observational GEParD cohort protocol. Between 2016 and 2020, the DaCFail case–control protocol was initiated integrating four study subgroups to focus on heart-brain interactions and stress systems in patients > 50 years with depression and heart failure, respectively. For DaCFail, 120 depressed patients (mean age 60 years, group 1 + 2), of which 115 also completed GEParD, and 95 non-depressed controls (mean age 66 years) were recruited. The latter comprised 47 patients with heart failure (group 3) and 48 healthy subjects (group 4) of a population-based control group derived from the Characteristics and Course of Heart Failure Stages A–B and Determinants of Progression (STAAB) cohort study. Our hypothesis-driven, exploratory study design may serve as an exemplary roadmap for a standardized, reproducible investigation of personalized antidepressant therapy in an inpatient setting with focus on heart comorbidities in future multicentre studies.

Altered topological properties of functional brain networks in patients with first episode, late-life depression before and after antidepressant treatment.

To preliminarily explore the functional activity and information integration of the brains under resting state based on graph theory in patients with first-episode, late-life depression (LLD) before and after antidepressant treatment. A total of 50 patients with first-episode LLD and 40 non-depressed controls (NCs) were recruited for the present research. Participants underwent the RBANS test, the 17-item Hamilton depression rating scale (HAMD-17) test, and resting-state functional MRI scans (rs-fMRI). The RBANS test consists of 12 sub-tests that contribute to a total score and index scores across the five domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Escitalopram or sertraline was adopted for treating depression, and the dosage of the drug was adjusted by the experienced psychiatrists. Of the 50 LLD patients, 27 cases who completed 6-month follow-ups and 27 NCs matched with age, sex, and education level were included for the final statistical analysis. There were significant differences in RBANS total score, immediate memory, visuospatial/constructional, language, attention, and delayed memory between LLD baseline group and NCs group (P < 0.05). Considering the global attribute indicators, the clustering coefficient of global indicators was lower in the LLD baseline group than in the NCs group, and the small-world attribute of functional brain networks existed in all three groups. The degree centrality and node efficiency of some brains were lower in the LLD baseline group than in the NCs group. After 6 months of antidepressant therapy, the scores of HAMD-17, immediate memory, language, and delayed memory in the LLD follow-up group were higher than those in the LLD baseline group. Compared with the LLD baseline group, the degree centrality and node efficiency of some brains in the cognitive control network were decreased in the LLD follow-up group. The ability to integrate and divide labor of functional brain networks declines in LLD patients and linked with the depression severity. After the relief of depressive symptoms, the small-world attribute of functional brain networks in LLD patients persists. However, the information transmission efficiency and centrality of some brain regions continue to decline over time, perhaps related to their progressive cognitive impairment.

Influences on Stress Load in Young Girls with Major Depression

Based on former empirical studies and theoretical models the present study investigated, whether stress symptoms, stress coping, and activity of HPA axis are different in girls with major depression compared to non-depressed controls. 148 girls with a mean age of 15 years were studied twice with 6 months between the two assessments. 74 fulfilled DSM IV criteria for major depression at first assessment. Stress symptoms and stress coping were measured with validated German questionnaires. The cortisol awakening response was analyzed by collecting saliva samples. Depressed girls showed a greater stress load, which was significantly influenced by stress coping strategies. HPA axis activity was heightened in depressed girls, but does not seem to have an influence on stress load.

Predictive potential of somatic symptoms for the identification of subthreshold depression and major depressive disorder in primary care settings.

The presence of heterogenous somatic symptoms frequently obscures the recognition of depression in primary care. We aimed to explore the association between somatic symptoms and subthreshold depression (SD) and Major Depressive Disorder (MDD), as well as to determine the predictive potential of somatic symptoms in identifying SD and MDD in primary care. Data were derived from the Depression Cohort in China study (ChiCTR registry number: 1900022145). The Patient Health Questionnaire-9 (PHQ-9) was used to assess SD by trained general practitioners (GPs), and the Mini International Neuropsychiatric Interview depression module was used to diagnose MDD by professional psychiatrists. Somatic symptoms were assessed using the 28-item Somatic Symptoms Inventory (SSI). In total of 4,139 participants aged 18-64 years recruited from 34 primary health care settings were included. The prevalence of all 28 somatic symptoms increased in a dose-dependent manner from non-depressed controls to SD, and to MDD (P for trend <0.001). Hierarchical clustering analysis grouped the 28 heterogeneous somatic symptoms into three clusters (Cluster 1: energy-related symptoms, Cluster 2: vegetative symptoms, and Cluster 3: muscle, joint, and central nervous symptoms). Following adjustment for potential confounders and the other two clusters of symptoms, per 1 increase of energy-related symptoms exhibited significant association with SD (OR = 1.24, 95% CI, 1.18-1.31) and MDD (OR = 1.50, 95% CI, 1.41-1.60) The predictive performance of energy-related symptoms in identifying individuals with SD (AUC = 0.715, 95% CI, 0.697-0.732) and MDD (AUC = 0.941, 95% CI, 0.926-0.963) was superior to the performance of total SSI and the other two clusters (P < 0.05). Somatic symptoms were associated with the presence of SD and MDD. In addition, somatic symptoms, notably those related to energy, showed good predictive potential in identifying SD and MDD in primary care. The clinical implication of the present study is that GPs should consider the closely related somatic symptoms for early recognition for depression in practice.

Worry and rumination enhance a positive emotional contrast based on the framework of the Contrast Avoidance Model

The Contrast Avoidance Model (CAM) suggests that worry increases negative affect and decreases positive affect. CAM also suggests that in response to a positive event, higher worry enhances the probability of experiencing greater decreased negative affect and increased positive affect (positive emotional contrasts; PECs). Consequently, worrying may be reinforced by repeated PECs. However, no study has tested whether rumination enhances PECs. Also, emotional specificity in these processes has not been considered. Therefore, we tested whether both rumination and worry enhanced PECs related to specific emotions. After resting baseline, participants with pure generalized anxiety disorder (GAD group, n = 91), pure depression symptoms (depression group, n = 91), and non-GAD and non-depressed healthy controls (HCs, n = 93) engaged with randomly assigned induction tasks (either worry, rumination, or relaxation), and then watched an amusement video. Regardless of group, both worry and rumination increased sadness and fear and decreased amusement more than relaxation from baseline. However, worry increased fear more than rumination, and rumination increased sadness more than worry. Although all inductions led to PECs during the video, worry enhanced fear PECs more than rumination, and rumination enhanced sadness PECs more than worry. The GAD group who worried experienced the most salient PECs of amusement relative to other groups.

A comparative evaluation of resting state proxies of sympathetic and parasympathetic nervous system activity in adolescent major depression.

Major depressive disorder (MDD) is associated with autonomic nervous system (ANS) dysfunction, characterized by decreased parasympathetic (PNS) and increased sympathetic (SNS) activity. Although findings on reduced PNS activity in adult MDD have been replicated in adolescents, comprehensive studies assessing PNS and SNS proxies in underage patients with MDD are scarce. Proxies of resting PNS (heart rate variability (HRV) and SNS activity (skin conductance response [SCR] and salivary alpha amylase [sAA], as well as mixed activity (heart rate [HR]) were collected in adolescents with MDD (n = 29) and non-depressed controls (n = 29). Primary analyses addressed differences between groups and correlations with depression severity. Patients with MDD showed significantly decreased HRV (g = -0.87; 95% CI [-1.39; -0.35]) and increased HR (g = 0.66; 95% CI [0.14; 1.18]). Proxies of pure SNS activity showed no significant differences between groups. HR (positive) and HRV (negative) were significantly correlated with self- and clinician-rated depression severity. Alterations of ANS activity are evident in adolescent MDD, but characterized by decreased PNS activity only. We found no evidence for altered SNS activity. Findings suggest that ANS dysfunction early in the course of MDD might be predominantly driven by decreased PNS activity.

Feasibility of performing a multi-arm clinical trial examining the novel combination of repetitive transcranial magnetic stimulation and aerobic exercise for post-stroke depression

ABSTRACT Background Post-stroke depression (PSD) occurs in approximately one-third of chronic stroke survivors. Although pharmacotherapy reduces depressive symptoms, side effects are common and stroke survivors have increased likelihood of multimorbidity and subsequent polypharmacy. Thus, alternative non-pharmacological treatments are needed. Combining two non-pharmacological anti-depressant treatments, aerobic exercise (AEx) and repetitive transcranial magnetic stimulation (rTMS), has been demonstrated to be feasible and well-tolerated in chronic stroke survivors. Objectives The purpose of this trial was to determine the feasibility of conducting a multi-arm combinatorial trial of rTMS and AEx and to provide an estimate of effect size of rTMS+AEx on PSD symptoms. Methods Twenty-four participants were allocated to one of four treatment arms AEx, rTMS, rTMS+AEx, or non-depressed Control receiving AEx. All participants received a total of 24 treatment sessions. Participant adherence was the primary outcome measure for feasibility and within group effect sizes in Patient Health Questionnaire-9 (PHQ-9) score was the primary outcome for preliminary efficacy. Results Mean adherence rates to the exercise intervention for AEx, rTMS+AEx, and Control subjects were 83%, 98%, and 95%, respectively. Mean adherence rates for rTMS and rTMS+AEx subjects were 97% and 99%, respectively. The rTMS and rTMS+AEx treatment groups demonstrated clinically significant reductions of 10.5 and 6.2 points in PHQ-9 scores, respectively. Conclusion Performing a multi-arm combinatorial trial examining the effect of rTMS+AEx on PSD appears feasible. All treatment arms demonstrated strong adherence to their respective interventions and were well received. rTMS and the combination of AEx with rTMS may be alternative treatments for PSD.

Brain structure and connectivity in psoriasis and associations with depression and inflammation; findings from the UK biobank

BackgroundPsoriasis is a chronic systemic inflammatory skin disease, coexisting with depression in up to 25% of patients. Little is known about the drivers of comorbidity, including shared neurobiology and depression brain imaging patterns in patients. An immune-mediated crosstalk between the brain and skin has been hypothesized in psoriasis. With the aim of investigating brain structure and connectivity in psoriasis in relation to depression comorbidity, we conducted a brain imaging study including the largest psoriasis patient sample to date (to our knowledge) and the first to investigate the role of depression and systemic inflammation in brain measures. Effects of coexisting psoriatic arthritis (PsA), which represents joint involvement in psoriasis and a higher putative inflammatory state, were further explored. MethodsBrain magnetic resonance imaging (MRI) data of 1,048 UK Biobank participants were used (131 comorbid patients with psoriasis and depression, age-and sex-matched to: 131 non-depressed psoriasis patients; 393 depressed controls; and 393 non-depressed controls). Interaction effects of psoriasis and depression on volume, thickness and surface of a-priori defined regions of interest (ROIs), white matter tracts and 55x55 partial correlation resting-state connectivity matrices were investigated using general linear models. Linear regression was employed to test associations of brain measures with C-reactive protein (CRP) and neutrophil counts. ResultsNo differences in regional or global brain volumes or white matter integrity were found in patients with psoriasis compared to controls without psoriasis or PsA. Thickness in right precuneus was increased in psoriasis patients compared to controls, only when depression was present (β = 0.26, 95% CI [Confidence Intervals] 0.08, 0.44; p = 0.02). In further analysis, psoriasis patients who had PsA exhibited fronto-occipital decoupling in resting-state connectivity compared to patients without joint involvement (β = 0.39, 95% CI 0.13, 0.64; p = 0.005) and controls (β = 0.49, 95% CI 0.25, 0.74; p < 0.001), which was unrelated to depression comorbidity. Precuneus thickness and fronto-occipital connectivity were not predicted by CRP or neutrophil counts. Precuneus thickening among depressed psoriasis patients showed a marginal correlation with recurrent lifetime suicidality. ConclusionsOur findings provide evidence for a combined effect of psoriasis and depression on the precuneus, which is not directly linked to systemic inflammation, and may relate to suicidality or altered somatosensory processing. The use of the UK Biobank may limit generalizability of results in populations with severe disease.

Serum levels of carnosine may be associated with the duration of MDD episodes

BackgroundMajor depressive disorder (MDD) is a recurrent disorder that incurs a high societal burden. However, the etiology of MDD remains unclear. The functioning of several systems associated with the etiopathogenesis of MDD, such as inflammatory and stress systems, is partially modulated by the dipeptide carnosine. MethodsThe study comprised 99 MDD patients and 253 non-depressed controls aged 20–71 years. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of carnosine and its constituent, histidine. We compared these metabolites in three different settings: 1) MDD patients vs. non-depressed controls and 2) remitted vs. non-remitted MDD patients, as well as 3) changes in the metabolite levels during the follow-up period within a) the remitted group and b) the non-remitted group. In addition, we assessed the possible effect of medications on the measured metabolites. ResultsWe observed higher serum levels of carnosine in the MDD group compared to the control group at baseline (OR = 1.895, 95%CI = 1.223–2.937, p = 0.004). Elevated serum levels of carnosine were also associated with a longer duration of the depressive episode (Z = 0.406, p = 0.001). However, the use of any antipsychotic medication (n = 36) was associated with lowered carnosine levels (p = 0.010 for use vs. non-use). At the follow-up, remitted and non-remitted participants displayed no significant differences in their carnosine levels (Z = -0.14, p = 0.891) or histidine (Z = −1.39 p = 0.164). ConclusionsAn increase in circulating carnosine may characterize depressive episodes and may represent a protective homeostatic reaction against MDD-related oxidative stress and inflammation.