Major Depressive Disorder Participants Research Articles

Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS.

Accelerated brain aging predicts impulsivity and symptom severity in depression.

Multiple structural and functional neuroimaging measures vary over the course of the lifespan and can be used to predict chronological age. Accelerated brain aging, as quantified by deviations in the MRI-based predicted age with respect to chronological age, is associated with risk for neurodegenerative conditions, bipolar disorder, and mortality. Whether age-related changes in resting-state functional connectivity are accelerated in major depressive disorder (MDD) is unknown, and, if so, it is unclear if these changes contribute to specific cognitive weaknesses that often occur in MDD. Here, we delineated age-related functional connectivity changes in a large sample of normal control subjects and tested whether brain aging is accelerated in MDD. Furthermore, we tested whether accelerated brain aging predicts individual differences in cognitive function. We trained a support vector regression model predicting age using resting-state functional connectivity in 710 healthy adults aged 18-89. We applied this model trained on normal aging subjects to a sample of actively depressed MDD participants (n = 109). The difference between predicted brain age and chronological age was 2.11 years greater (p = 0.015) in MDD patients compared to control participants. An older MDD brain age was significantly associated with increased impulsivity and, in males, increased depressive severity. Unexpectedly, accelerated brain aging was also associated with increased placebo response in a sham-controlled trial of high-frequency repetitive transcranial magnetic stimulation targeting the dorsomedial prefrontal cortex. Our results indicate that MDD is associated with accelerated brain aging, and that accelerated aging is selectively associated with greater impulsivity and depression severity.

Peripheral biopterin and neopterin in schizophrenia and depression

Increasing evidence points to a causal involvement of inflammation in the pathogenesis of neuropsychiatric disorders, including major depressive disorder (MDD) and schizophrenia (SZ). Neopterin and biopterin may link peripheral immune system activation and central neurotransmitter alterations. However, it is not fully established whether these alterations are transdiagnostic or disorder-specific and whether they are associated with reward-related psychopathologies.We investigated group differences in neopterin and biopterin in the plasma of healthy comparison (HC) (n=19), SZ (n=45) and MDD (n=43) participants. We then correlated plasma proteins with CRP as a measure for inflammation. Lastly, plasma proteins were correlated with the reward-related psychopathological domain apathy.We found a trend-level difference in biopterin levels and no significant difference in neopterin levels between groups. Within both patient groups, but not HC, we show a significant positive correlation of CRP with neopterin but not with biopterin. Further, we observed no significant correlations of plasma proteins with reward-related psychopathology in HC, MDD or SZ.While our study shows trend-level alterations of biopterin with relevance for future research, it does not support the hypothesis that peripheral neopterin or biopterin are associated with reward-related psychopathology.

Investigating neural circuits of emotion regulation to distinguish euthymic patients with bipolar disorder and major depressive disorder.

Up to 40% of patients with bipolar disorder (BD) are initially diagnosed as having major depressive disorder (MDD), and emotional lability is a key aspect of both sets of mood disorders. However, it remains unknown whether differences in the regulation of emotions through cognitive reappraisal may serve to distinguish BD and MDD. Therefore, we examined this question in euthymic BD and MDD patients. Thirty-eight euthymic BD, 33 euthymic MDD and 37 healthy control (HC) participants, matched for age, gender and depression severity, engaged in an emotion regulation (ER) cognitive reappraisal task during an fMRI scan were examined. Participants either reappraised (Think condition) or passively watched negative (Watch condition) or neutral (Neutral condition) pictures and rated their affect. Activation and connectivity analyses were used to examine group differences in reappraisal (Think vs Watch) and reactivity (Watch vs Neutral) conditions in ER-specific neural circuits. Irrespective of group, participants rated most negatively the images during the Watch condition relative to Think and Neutral conditions, and more negatively to Think relative to Neutral. Notably, BD participants exhibited reduced subgenual anterior cingulate activation (sgACC) relative to MDD during reappraisal, but exhibited greater sgACC activation relative to MDD during reactivity, whereas MDD participants elicited greater activation in right amygdala relative to BD during reactivity. We found no group differences in task-related connectivity. Euthymic BD and MDD patients engage differential brain regions to process and regulate emotional information. These differences could serve to distinguish the clinical groups and provide novel insights into the underlying pathophysiology of BD.

Accelerated brain aging in major depressive disorder and antidepressant treatment response: A CAN-BIND report

ObjectivesPrevious studies suggest that major depressive disorder (MDD) may be associated with volumetric indications of accelerated brain aging. This study investigated neuroanatomical signs of accelerated aging in MDD and evaluated whether a brain age gap is associated with antidepressant response. MethodsIndividuals in a major depressive episode received escitalopram treatment (10–20 mg/d) for 8 weeks. Depression severity was assessed at baseline and at weeks 8 and 16 using the Montgomery-Asberg Depression Rating Scale (MADRS). Response to treatment was characterized by a significant reduction in the MADRS (≥50%). Nonresponders received adjunctive aripiprazole treatment (2–10 mg/d) for a further 8 weeks. The brain-predicted age difference (brain-PAD) at baseline was determined using machine learning methods trained on 3377 healthy individuals from seven publicly available datasets. The model used features from all brain regions extracted from structural magnetic resonance imaging data. ResultsBrain-PAD was significantly higher in older MDD participants compared to younger MDD participants [t(147.35) = -2.35, p < 0.03]. BMI was significantly associated with brain-PAD in the MDD group [r(155) = 0.19, p < 0.03]. Response to treatment was not significantly associated with brain-PAD. ConclusionWe found an elevated brain age gap in older individuals with MDD. Brain-PAD was not associated with overall treatment response to escitalopram monotherapy or escitalopram plus adjunctive aripiprazole.

Internal reliability of blame-related functional MRI measures in major depressive disorder

BackgroundIn major depressive disorder (MDD), self-blame-related fMRI measures have shown the potential to be used as prognostic markers for recurrence risk. Like most potential fMRI markers, however, their reliability is unclear. Here, we probed the internal reliability of self-blame-related fMRI measures, as well as the impact of different modelling approaches on reliability metrics and validity. MethodsInternal consistency (i.e. split-half reliability) was calculated for blood oxygen level-dependent (BOLD) responses and psychophysiological interactions (PPI) related to self-blame-related biases in medication-free remitted MDD participants (n = 81) and healthy controls (n = 41). Trial-length was modelled using three durations (0, 2 and 5 s), which was convolved with the haemodynamic response function (HRF) with and without time and dispersion derivatives. Intraclass correlation coefficients (ICCs) were calculated for simple contrasts examining activation to self-blaming emotions and other-blaming emotions and the more complex contrast of the subtraction-based difference between self- and other-blaming emotions within the following a priori ROIs: right superior anterior temporal lobe seed region, anterior subgenual cingulate cortex, posterior subgenual cortex and right striatum / pallidum. ResultsAcross ROIs, we obtained fair reliability (ICC ≥ 0.40) for simple, but poor reliability (ICC < 0.40) for more complex fMRI measures related to self-blame. Despite this low internal consistency of complex measures at the individual level, we observed robust activation at the group-level, reproducing previously published results. ConclusionsWhile simple BOLD contrasts had fair reliability, previously employed PPI models had poor reliability and simple connectivity measures lacked predictive validity. This calls for the development of functional connectivity measures that strike a better balance between reliability and validity for future clinical applications, which require robust measures at the individual rather than group-level.

Altered EEG Oscillatory Brain Networks During Music-Listening in Major Depression.

To examine the electrophysiological underpinnings of the functional networks involved in music listening, previous approaches based on spatial independent component analysis (ICA) have recently been used to ongoing electroencephalography (EEG) and magnetoencephalography (MEG). However, those studies focused on healthy subjects, and failed to examine the group-level comparisons during music listening. Here, we combined group-level spatial Fourier ICA with acoustic feature extraction, to enable group comparisons in frequency-specific brain networks of musical feature processing. It was then applied to healthy subjects and subjects with major depressive disorder (MDD). The music-induced oscillatory brain patterns were determined by permutation correlation analysis between individual time courses of Fourier-ICA components and musical features. We found that (1) three components, including a beta sensorimotor network, a beta auditory network and an alpha medial visual network, were involved in music processing among most healthy subjects; and that (2) one alpha lateral component located in the left angular gyrus was engaged in music perception in most individuals with MDD. The proposed method allowed the statistical group comparison, and we found that: (1) the alpha lateral component was activated more strongly in healthy subjects than in the MDD individuals, and that (2) the derived frequency-dependent networks of musical feature processing seemed to be altered in MDD participants compared to healthy subjects. The proposed pipeline appears to be valuable for studying disrupted brain oscillations in psychiatric disorders during naturalistic paradigms.

Knowledge, Risk Perception, Precautionary Behavior and Level of Worry towards the 2019 Coronavirus Disease (COVID-19) among Psychiatric Outpatients

Objective: To identify level of worry towards COVID-19, and related factors among psychiatric outpatients.Methods:A cross-sectional study surveyed psychiatric outpatients at Songklanagarind Hospital; from May to June, 2020. The questionnaires composed of; 1) Demographic inquiry 2) COVID-19 knowledge 3) COVID-19 risk perception 4) COVID-19 precautionary behaviors. 5) Level of worry towards COVID-19. All data were analyzed using descriptive statistics, and associated factors as to the level of worry towards COVID-19 were analyzed by chi-square and logistic regression.Results: There were 400 participants; neurosis (60.0%), and non-neurosis (40.0%). The majority of participants were female (62.0%), with a mean age of; 44.5±14.6 years. Almost all participants reported a good score of COVID-19 knowledge (91.8%), and having good precautionary behavior towards COVID-19 (97.5%). Majority of participants had a low risk perception (54.2%) and a low level of worry towards COVID-19 (67.0%). Generalized anxiety disorder and major depressive disorder participants were the 1st and 2nd group who had a high to moderate level of worry towards COVID-19. Aside from, from the multivariate analysis, this study indicated income, psychiatric disorders and risk perception towards COVID-19 were statistically significant associated factors related to levels of worry.Conclusion: Most psychiatric outpatients had good knowledge, good precautionary behaviors and a low level of worry towards COVID-19; with associated factors to level of worry being income, risk perception and being diagnosed with generalized anxiety disorder. However, major depressive disorder patients should also be concerned.

A hidden menace? Cytomegalovirus infection is associated with reduced cortical gray matter volume in major depressive disorder.

Human cytomegalovirus (HCMV) infection is associated with neuropathology in patients with impaired immunity and/or inflammatory diseases. However, the association between gray matter volume (GMV) and HCMV has never been examined in major depressive disorder (MDD) despite the presence of inflammation and impaired viral immunity in a subset of patients.We tested this relationship in two independent samples consisting of 179 individuals with MDD and 41 healthy controls (HC) (sample 1) and 124 MDD participants and 148 HCs (sample 2). HCMV positive (HCMV+) and HCMV negative (HCMV−) groups within each sample were balanced on up to eleven different clinical/demographic variables using inverse probability of treatment weighting. GMV of 87 regions was measured with FreeSurfer. There was a main effect of HCMV serostatus but not diagnosis that replicated across samples. Relative to HCMV− subjects, HCMV+ subjects in sample 1 showed a significant reduction of volume in six regions (puncorrected<0.05). The reductions in GMV of the right supramarginal gyrus (standardized beta coefficient (SBC)=−0.26) and left fusiform gyrus (SBC=−0.25) in sample 1 were replicated in sample 2: right supramarginal gyrus (puncorrected <0.05, SBC=−0.32), left fusiform gyrus (PFDR<0.01, SBC=−0.51). Posthoc tests revealed that the effect of HCMV was driven by differences between the HCMV+ and HCMV− MDD subgroups. HCMV IgG level, a surrogate marker of viral activity, was correlated with GMV in the left fusiform gyrus (r=−0.19, Puncorrected=0.049) and right supramarginal gyrus (r=−0.19, puncorrected=0.043) in the HCMV+ group of sample 1. Conceivably, HCMV infection may be a treatable source of neuropathology in vulnerable MDD patients.

Ketamine Alters Electrophysiological Responses to Emotional Faces in Major Depressive Disorder

BackgroundThe glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (MDD). However, ketamine's effects on emotional processing biases remain largely unknown, and understanding these processes may help elucidate ketamine's mechanism of action. MethodsMagnetoencephalography (MEG) was used to investigate ketamine's effects on early visual responses to affective stimuli in individuals with MDD (n=31) and healthy volunteers (HVs; n=24). Participants were enrolled in a double-blind, placebo-controlled, crossover clinical trial and were assessed at baseline and after subanesthetic-dose ketamine and placebo-saline infusions. During MEG recording, participants completed an emotional evaluation task in which they indicated the sex or emotional valence (happy-neutral or sad-angry) of facial stimuli. Source-localized event-related field (ERF) M100 and M170 amplitudes and latencies were extracted from regions of interest. Linear fixed effects models examined interactions between diagnosis, stimulus valence, and drug session for behavioral and MEG data. ResultsIn baseline behavioral analyses, MDD participants exhibited higher accuracy for sad-angry than happy-neutral faces, and HVs responded faster to happy-neutral than sad-angry faces. In the MEG post-infusion analyses, calcarine M100 amplitudes were larger in MDD than HV participants post-placebo but became more similar post-ketamine. Finally, fusiform M170 amplitudes were associated with antidepressant response in MDD participants. LimitationsThe modest sample size and the need to collapse across responses to happy and neutral faces to increase statistical power limit the generalizability of the findings. ConclusionsKetamine rapidly altered emotional stimulus processing in MDD, laying the groundwork for future investigations of biomarkers of antidepressant treatment response. Clinical TrialClinicaltrials.gov, NCT#00088699

Sadness and the continuum from well-being to depressive disorder: Findings from a representative US population sample

Sadness is a common symptom in the general population. We tested the hypothesis that sadness is an intermediate state on a continuum from well-being to major depressive disorder (MDD). Using data from The National Epidemiologic Study of Alcohol and Related Conditions III (NESARC-III), a large and representative US population sample, we assessed the prevalence of sadness, its sociodemographic and clinical correlates, using three non-overlapping groups: (i) non-depressed sad participants, (ii) non-sad non-depressed participants and (iii) depressed participants. We estimated sensitivity and specificity of sadness. Sadness was frequent in the general population 34.3%), and present in almost all participants with MDD (99.6%). Sad (N=4593) and MDD participants (N=4593) and 7889 respectively) shared common sociodemographic characteristics. Compared to controls, sad and MDD participants presented more psychiatric disorders, including anxiety, substance use, psychotic, eating and personality disorders. Sadness was an intermediate state, sad individuals reporting more psychiatric disorders than controls, but less than participants with MDD. Sadness demonstrated a very high sensitivity (99.6%), with a good specificity (83.8%) for MDD. The NESARC assessed sadness over lifetime, which may involve memorization bias. Our study confirms the existence of a depressive continuum. Sadness is frequent in general population, and shares correlates with MDD. We have also shown a continuum where sadness is an intermediate state between well-being and psychiatric disorders. With high sensitivity and specificity, sadness appears as a clear MDD prodrome and at-risk state, and may be a symptom of a transdiagnostic distress process.

Neurocognitive subgroups in major depressive disorder.

Major depressive disorder (MDD) is commonly associated with neurocognitive dysfunction. However, there remains substantial heterogeneity between patients and inconsistent findings regarding the magnitude and prevalence of specific neurocognitive deficits. This study aimed to investigate the potential for different neurocognitive subgroups in patients diagnosed with MDD. Data were pooled from 4 different clinical trials that involved adults diagnosed with MDD. Neurocognitive outcomes included measures of verbal learning and memory, executive function, attention, and processing speed. Latent class analysis was conducted to examine for different subgroups based on neurocognitive profiles of performance across outcome measures. Subgroups were compared to a separate sample of age-matched adult healthy controls, across illness factors, and individual mood items on the Montgomery-Åsberg Depression Rating Scale (MADRS). Within the MDD cohort (N = 149), 45% of participants were considered relatively "cognitively preserved," with the remainder "cognitively reduced" (39%) or "cognitively impaired" (16%). Verbal memory performance was significantly poorer compared to attention and processing speed only in the "cognitively impaired" subgroup. There was no association between subgroup membership and relevant illness factors, including ratings on individual MADRS items. Data were pooled from several studies that included different neurocognitive measures and cohorts. Approximately half of MDD participants had no or minimal objective cognitive difficulties, and neurocognitive functioning was found generally unrelated to illness factors. Future longitudinal research is warranted to determine whether the people who are relatively cognitively impaired are at increased risk for further cognitive decline. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Covariation between Childhood-Trauma Related Resting-State Functional Connectivity and Affective Temperaments is Impaired in Individuals with Major Depressive Disorder

Affective temperaments and childhood-trauma experiences are associated with major depressive disorder (MDD). So far, how the covariation between distinct affective temperaments and childhood-trauma insulted brain functional connectivities (FCs) contribute to MDD remains unclear. Here, we aimed to investigate whether certain brain FC patterns are related to certain affective temperaments and whether the FCs contribute to depressive symptom dimensions of MDD patients. Twenty-nine medication-free MDD patients and 58 healthy controls underwent magnetic resonance imaging scanning and completed the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), the Childhood Trauma Questionnaire-Short Form (CTQ-SF), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Two multivariate analyses of partial least squares (PLS) regression were used to explore the associations among childhood-trauma related resting-state FCs, affective temperaments and depressive symptom dimensions. In all participants, a linear combination of 81 FCs (involving parahippocampus, amygdala, cingulate cortex, insula, frontal–temporal–parietal–occipital cortex, pallidum, and cerebellum) were associated with a linear combination of increased depressive, irritable, anxious, and cyclothymic temperaments. Moreover, the covariation between the PLS FC profile and the PLS affective-temperament profile were enhanced in the MDD patients compared to healthy controls. In MDD participants alone, the affective-temperament modulated FC profile (mainly of the lingual and temporal cortex) was associated with the somatization symptom dimension when age, sex, ill-duration, age-of-onset, and HARS scores were adjusted. The findings imply possible neural correlates of affective temperaments and may find applications in intervention of the somatization-depression symptoms by stimulation of the related neural correlates.

The effects of ketamine on typical and atypical depressive symptoms.

Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using the Scale for Atypical Symptoms (SAS)). Data from 68 participants with treatment-resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double-blind, placebo-controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic-dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14days postinfusion. Effect sizes were calculated for days 1 and 3 postinfusion. The primary measures of interest for this exploratory analysis were total MADRS, MADRS5, and SAS scores. Individual symptoms were also analyzed in an exploratory manner. Scores improved significantly at Day 1 postinfusion (MADRS: Cohen's d=0.64; MADRS5: Cohen's d=0.61; SAS: Cohen's d=0.41) and continued to be significantly improved over placebo at Day 3 (MADRS: Cohen's d=0.49; MADRS5: Cohen's d=0.43; SAS: Cohen's d=0.39). Effect sizes were greater for typical/melancholic than atypical symptoms at Day 1 postinfusion. Ketamine appears to effectively treat both the typical/melancholic and atypical symptoms of depression, but may have early preferential effects for the former.

The Effect of Ketamine on Electrophysiological Connectivity in Major Depressive Disorder.

Major depressive disorder (MDD) is highly prevalent and frequently disabling. Only about 30% of patients respond to a first-line antidepressant treatment, and around 30% of patients are classified as “treatment-resistant” after failing to respond to multiple adequate trials. While most antidepressants target monoaminergic targets, ketamine is an N-methyl-D-aspartate (NMDA) antagonist that has shown rapid antidepressant effects when delivered intravenously or intranasally. While there is evidence that ketamine exerts its effects via enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput, its mechanism for relieving depressive symptoms is largely unknown. This study acquired resting-state magnetoencephalography (MEG) recordings after both ketamine and placebo infusions and investigated functional connectivity using a multilayer amplitude-amplitude correlation technique spanning the canonical frequency bands. Twenty-four healthy volunteers (HVs) and 27 unmedicated participants with MDD took part in a double-blind, placebo-controlled, crossover trial of 0.5 mg/kg IV ketamine. Order of infusion was randomized, and participants crossed over to receive the second infusion after two weeks. The results indicated widespread ketamine-induced reductions in connectivity in the alpha and beta bands that did not correlate with magnitude of antidepressant response. In contrast, the magnitude of ketamine's antidepressant effects in MDD participants was associated with cross-frequency connectivity for delta-alpha and delta-gamma bands, with HVs and ketamine non-responders showing connectivity decreases post-ketamine and ketamine responders demonstrating small increases in connectivity. These results may indicate functional subtypes of MDD and also suggest that neural responses to ketamine are fundamentally different between responders and non-responders.

Difference in binocular rivalry rate between major depressive disorder and generalized anxiety disorder

Binocular rivalry (BR) occurs when monocular images are presented simultaneously to corresponding regions of the two eyes. Rather than forming a stable composite, perception alternates spontaneously between each monocular view. Over recent decades, considerable interest in examining BR in psychiatric populations has demonstrated clear differences in the dynamics of BR when compared to healthy populations. However, the available data with respect to rivalry rates in depression and anxiety are limited, and previous studies have shown inconsistent results. Also, depression and anxiety are highly comorbid and can be difficult to distinguish. Therefore, we aimed to investigate whether patients with depression and anxiety have abnormal rivalry rates and whether rivalry rates differ between these conditions. Thirty-five patients with major depressive disorder (MDD), 30 patients with generalized anxiety disorder (GAD), and 30 control participants matched on sex, age and education were recruited. Our results showed MDD participants had slower BR rates than controls and GAD, and controls were significantly slower than GAD. Our findings raise prospects that BR could be a promising behavioral tool to differentiate depressive and anxiety disorders.

S119. A DIMENSIONAL APPROACH TO UNDERSTANDING COST-BENEFIT DECISION-MAKING IN SCHIZOPHRENIA AND DEPRESSION

BackgroundReductions in motivation figure prominently in the clinical presentation of schizophrenia (SZ) and major depressive disorder (MDD). One critical nexus in the motivation system that drives real-world behaviour is effort-based decision-making (EBDM), which refers to the cost-benefit calculations involved in computing the amount of effort one is willing to expend in order to obtain a desired reward. Important individual differences are associated with these processes, and impairments in motivation can arise if any relevant cost-benefit information is not properly computed, appraised, or integrated. Thus, in order to better understand the computations guiding choice behaviour, the present study sought to utilize a more person-centric approach to characterize individual differences in the effort-cost computations that underlie cost-benefit decision-making in individuals with SZ and MDD.MethodsA sample of 51 individuals with SZ, 43 individuals with MDD, and 51 healthy control (HC) participants underwent a comprehensive clinical and cognitive characterization, and completed the Effort Expenditure for Rewards Task (EEfRT) as a measure of EBDM. Random effects modelling was conducted to estimate the subject-specific predictors of reward magnitude, probability, and perceived cost on choice behaviour. Cluster analysis was subsequently applied to these predictors in order to identify subtypes of impairments within the entire sample, irrespective of diagnostic status.ResultsData-driven cluster analysis identified unique subgroups of individuals with distinct patterns of utilizing cost-benefit information to guide effort-based decision-making. Analyses of variance revealed significant differences between clusters with respect to their utilization of reward (F (3, 133) = 51.58, p < .001), probability (F (3, 133) = 48.71, p < .001), and cost (F (3, 133) = 45.24, p < .001). The first cluster was characterized by an indifference to all cost-benefit information, the second cluster was more influenced by perceived cost, the third cluster demonstrated a preference for reward-based information, and the fourth cluster mainly utilized probability to guide their decision-making. While the clusters did not differ in their severity of clinical amotivation (p = .11), there was a significant effect for cognition, specifically with impairments in clusters 1 and 2. All diagnostic groups were represented in each cluster, but the distribution of SZ, MDD, and HC participants was significantly different (X2 (6, N = 137) = 16.18, p = .013).DiscussionThe emergence of four distinct subgroups in our sample suggests that there are individual differences amongst SZ, MDD, and HC participants in their utilization of cost-benefit information to guide choice behaviour. Moreover, with elevated levels of clinical amotivation present in all four clusters, it is possible that these unique cost-benefit decision-making patterns represent different underlying motivational impairments, the nature of which depending on how reward magnitude, probability, and perceived cost are weighed. Thus, by characterizing the specific mechanisms underlying EBDM in SZ and MDD, the results of this work may be able to help guide the identification of more precise targets for the effective treatment of motivation deficits.

Emotion-behavior decoupling in individuals with schizophrenia, bipolar disorder, and major depressive disorder.

Failure in translating emotional salience into effortful behavior is thought to be a core feature of anhedonia and avolition in individuals with schizophrenia (SCZ), but little is known about emotion-behavior coupling in individuals with bipolar disorder (BD) and major depressive disorder (MDD). In this study, we compared emotion-behavior correspondence in participants with SCZ, BD, and MDD. Forty-two participants with SCZ, 44 participants with MDD, 43 participants with BD, and 43 healthy controls were recruited. A computerized anticipatory and consummatory pleasure task was used to evaluate emotion-behavior correspondence. Clinical ratings of negative symptoms and self-report anhedonia questionnaires were also administered. We found that participants with SCZ, MDD, and BD exhibited different levels of negative symptoms and self-reported anhedonia, as well as emotion-behavior decoupling. In SCZ participants, both desirable and undesirable images elicited lower correspondence between self-reported liking and behavior. In MDD and BD participants, undesirable images elicited lower emotion-behavior correspondence under both direct stimulus presentation and representation conditions, whereas deficits in emotion-behavior coupling under desirable conditions were only observed when stimuli were present. Taken together, emotion-behavior decoupling showed both common and unique patterns in participants with SCZ, MDD, and BD, and showed some associations with negative symptoms and anhedonia across the combined clinical sample. This finding may be helpful for early identification and the development of novel interventions for different psychiatric diagnoses. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Smaller left hippocampal subfield CA1 volume is associated with reported childhood physical and/or sexual abuse in major depression: A pilot study

BackgroundSmaller hippocampal volumes are reported in adults with major depressive disorder (MDD) and in reported childhood abuse. The hippocampus is a complex structure with distinct functional subfields. We sought to examine the effect of MDD diagnosis and childhood abuse on hippocampal subfields. MethodsForty-one MDD participants (17 reported abuse and 24 did not) and 46 healthy volunteers (HV) (2 reported abuse) underwent T1- weighted structural magnetic resonance imaging (MRI) and clinical characterization in a retrospective design. A subfield segmentation program was used to measure the whole and subfield hippocampal volumes. Linear mixed-effects models were fitted for group comparisons. ResultsNo main effect of diagnosis interaction effect between diagnosis and subfield region was observed. However, a comparison of abused MDD vs. HVs showed a group by region interaction. A significant interaction between childhood abuse and region was observed. Effects were confined to the left side of the brain, and post hoc, exploratory region-specific tests indicated smaller left CA1 volume in abused MDD compared with non-abused MDD. In addition, smaller amygdala volume was found in all MDD compared with HVs. LimitationsWe did not have a sample of healthy volunteers with reported childhood abuse. ConclusionsThe diagnosis of pure MDD may not be sufficient to exert effects on hippocampal volumes, indicating the importance of taking into account childhood trauma in studies on psychopathological mechanisms. Left CA1 might be the hippocampal subfield most relevant to reported childhood abuse. Smaller amygdala volume may be related to MDD diagnosis independent of childhood abuse.

Multiple Facets of Value-Based Decision Making in Major Depressive Disorder

Depression is clinically characterized by obvious changes in decision making that cause distress and impairment. Though several studies suggest impairments in depressed individuals in single tasks, there has been no systematic investigation of decision making in depression across tasks. We compare participants diagnosed with Major Depressive Disorder (MDD) (n = 64) to healthy controls (n = 64) using a comprehensive battery of nine value-based decision-making tasks which yield ten distinct measures. MDD participants performed worse on punishment (d = −0.54) and reward learning tasks (d = 0.38), expressed more pessimistic predictions regarding winning money in the study (d = −0.47) and were less willing to wait in a persistence task (d = −0.39). Performance on learning, expectation, and persistence tasks each loaded on unique dimensions in a factor analysis and punishment learning and future expectations each accounted for unique variance in predicting depressed status. Decision-making performance alone could predict depressed status out-of-sample with 72% accuracy. The findings are limited to MDD patients ranging between moderate to severe depression and the effects of medication could not be accounted for due to the cross sectional nature of the study design. These results confirm hints from single task studies that depression has the strongest effects on reinforcement learning and expectations about the future. Our results highlight the decision processes that are impacted in major depression, and whose further study could lead to a more detailed computational understanding of distinct facets of this heterogeneous disorder.