Human emotion processing accuracy, negative biases, and fMRI activation are associated with childhood trauma.

Introduction: Emerging literature suggests that childhood trauma may influence facial emotion perception (FEP), with the potential to negatively bias both emotion perception and reactions to emotion-related inputs. Negative emotion perception biases are associated with a range of psychiatric and behavioral problems, potentially due or as a result of difficult social interactions. Unfortunately, there is a poor understanding of whether observed negative biases are related to childhood trauma history, depression history, or processes common to (and potentially causative of) both experiences. Methods: The present cross-sectional study examines the relation between FEP and neural activation during FEP with retrospectively reported childhood trauma in young adult participants with remitted major depressive disorder (rMDD, n = 41) and without psychiatric histories (healthy controls [HC], n = 34). Accuracy of emotion categorization and negative bias errors during FEP and brain activation were each measured during exposure to fearful, angry, happy, sad, and neutral faces. We examined participant behavioral and neural responses in relation to total reported severity of childhood abuse and neglect (assessed with the Childhood Trauma Questionnaire, CTQ). Results: Results corrected for multiple comparisons indicate that higher trauma scores were associated with greater likelihood of miscategorizing happy faces as angry. Activation in the right middle frontal gyrus (MFG) positively correlated with trauma scores when participants viewed faces that they correctly categorized as angry, fearful, sad, and happy. Discussion: Identifying the neural mechanisms by which childhood trauma and MDD may change facial emotion perception could inform targeted prevention efforts for MDD or related interpersonal difficulties.

Memory differences by sex, but not by previous diagnosis of major depressive disorder.

Memory difficulties are consistently reported in Major Depressive Disorder (MDD). Nonetheless, it has not been thoroughly investigated as to whether these deficits persist during remission from MDD. A group of 32 healthy young adults with no history of a mood disorder (Mage = 20.8, SD = 2.1) and 62 remitted depressed young adults (Mage = 21.1, SD = 1.9) completed a neuropsychological battery. The test battery included two measures of nonverbal memory, two measures of verbal memory, and a measure of performance validity. The testing session was repeated three to six weeks later to determine performance stability. No differences were found between healthy controls and remitted depressed patients in either memory domain (all ps > .05) and improvement in performance was exhibited over time for both groups (p = 0.004). Potential practice effects are examined. We found a stronger performance for women than men (p = 0.003), particularly for the Semantic List Learning Task (SLLT) (p = .047). Verbal and nonverbal memory and effort may not be impacted in those who are in a remitted state of MDD, early in the course of the illness. Women demonstrated auditory memory superiority over men, similar to prior research.

Pre-scan cortisol is differentially associated with enhanced connectivity to the cognitive control network in young adults with a history of depression.

BACKGROUND: We have previously demonstrated that pre-scan salivary cortisol is associated with attentuated frontal-subcortical brain activation during emotion processesing and semantic list-learning paradigms in depressed subjects. Additionally, altered functional connectivity is observed after remission of acute depression symptoms (rMDD). It is unknown whether cortisol also predicts altered functional connectivity during remission. METHODS: Participants were 47 healthy controls (HC) and 73 rMDD, 18-30 years old who provided salivary cortisol samples before and after undergoing resting-state fMRI. We tested whether salivary cortisol by diagnosis interactions were associated with seed-based resting connectivity of the default mode (DMN) and salience and emotion (SN) networks using whole-brain, cluster-level corrected (p < .01) regression in SPM8. RESULTS: Pre-scan cortisol predicted decreased (HC) and increased (rMDD) cross-network connectivity to the dorsal anterior cingulate, dorso-medial and lateral- prefrontal cortex, brain stem and cerebellum (all seeds) and precuneus (DMN seeds). By and large, pre/post-scan cortisol change predicted the same pattern of findings. In network analyses, cortisol predominantly predicted enhanced cross-network connectivity to cognitive control network regions in rMDD. CONCLUSIONS: The association of cortisol with connections of default and salience networks to executive brain networks differs between individuals with and without a history of depression. Further investigation is needed to better understand the role of cortisol and related stress hormones as a potential primary and interactive driver of network coherence in depression.

Family support: A possible buffer against disruptive events for individuals with and without remitted depression.

The current study sought to test the role of family support as a buffer of life stress for depressive symptoms in a sample of young adults at low- and high-risk for depression based on a previous history of depression. Ninety-seven young adults, 54 with remitted depression and 43 without prior history of depression, completed reports of family relationships, disruptive life events, and depressive symptoms at baseline and every 2 months for 10 months. Results revealed significant interactions between family environment and life events predicting Beck Depressive Inventory (BDI) scores at baseline, such that individuals with better family support were buffered from risk associated with life stress, and this was true even after accounting for a previous history of depression. Longitudinal analyses utilizing the Patient Health Questionnaire-9 (PHQ-9) as a depressive symptom measure did not find significant associations with family environment, but did find that more stressful events at baseline were associated with increasing levels of symptoms over time. Exploratory analyses suggest that discrepant findings for baseline versus longitudinal analyses may be due to differences in symptom measurement and to associations between family environment and cognitive features of depression. These findings provide qualified support for the continued relevance of families as stress buffers in young adulthood across a spectrum of risk for depression. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Differential engagement of cognitive control regions and subgenual cingulate based upon presence or absence of comorbid anxiety with depression.

BACKGROUND: Major depressive disorder (MDD) and anxiety disorders are highly comorbid, sharing many similar symptoms, including impairments in cognitive control. Deficits in cognitive control could be a potential mechanism underlying impaired emotion regulation in mood disorders. METHODS: Participants were 44 individuals with no history of mental illness (healthy controls, HC), 31 individuals in the remitted state of MDD (rMDD), and 18 individuals who met lifetime DSM-IV-TR criteria for rMDD and an anxiety disorder in remission (Comorbid). Participants completed a Parametric Go/No-Go (PGNG) test during fMRI. Event-related analyses modeled activity for cognitive control successes (Hits for Targets, Rejections for Lures) and failures (Commissions on Lures) on the PGNG task. RESULTS: The rMDD group showed significantly reduced activity within the cognitive control network (CCN) during Commission errors, including the middle frontal gyrus and inferior parietal lobule (IPL). The Comorbid group showed significantly reduced activity in several clusters within the CCN during correct Rejections, including the left IPL and right inferior frontal gyrus and greater subgenual cingulate. Notably, during correct Rejections, 60% of activation for the Comorbid group was within the Salience and Emotion Network (SEN), with 0% within the CCN. LIMITATIONS: The size of the Comorbid subgroup was modest, preventing subanalysis of the different AD subtypes. CONCLUSIONS: There is evidence that CCN activity declines in rMDD and that there may be compensatory SEN activity in individuals with Comorbid rMDD and anxiety. Our findings support the identification of comorbid anxiety as a meaningful subtype of MDD that may obscure group differences between rMDD and HCs.

Reliability, Convergent Validity and Time Invariance of Default Mode Network Deviations in Early Adult Major Depressive Disorder.

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.

Individuals with more severe depression fail to sustain nucleus accumbens activity to preferred music over time.

We investigated the ability of preferred classical music to activate the nucleus accumbens in patients with Major depressive disorder (MDD). Twelve males with MDD and 10 never mentally ill male healthy controls (HC) completed measures of anhedonia and depression severity, and listened to 90-second segments of preferred classical music during fMRI. Compared to HCs, individuals with MDD showed less activation of the left nucleus accumbens (NAcc). Individuals with MDD showed attenuation of the left NAcc response in later compared to earlier parts of the experiment, supporting theories that MDD involves an inability to sustain reward network activation. Counter intuitively, we found that NAcc activity during early music listening was associated with greater depression severity. In whole-brain analyses, anhedonia scores predicted activity in regions within the default mode network, supporting previous findings. Our results support theories that MDD involves an inability to sustain reward network activation. It also highlights that pleasant classical music can engage critical neural reward circuitry in MDD.