Elevated decision uncertainty and reduced avoidance drives in depression, anxiety and substance use disorders during approach-avoidance conflict: a replication study.

BACKGROUND: Decision-making under approach-avoidance conflict (AAC; e.g., sacrificing quality of life to avoid feared outcomes) may be affected in multiple psychiatric disorders. Recently, we used a computational (active inference) model to characterize information processing differences during AAC in individuals with depression, anxiety and/or substance use disorders. Individuals with psychiatric disorders exhibited increased decision uncertainty (DU) and reduced sensitivity to unpleasant stimuli. This preregistered study aimed to determine the replicability of this processing dysfunction. METHODS: A new sample of participants completed the AAC task. Individual-level computational parameter estimates, reflecting decision uncertainty and sensitivity to unpleasant stimuli ("emotion conflict"; EC), were obtained and compared between groups. Subsequent analyses combining the prior and current samples allowed assessment of narrower disorder categories. RESULTS: The sample in the present study included 480 participants: 97 healthy controls, 175 individuals with substance use disorders and 208 individuals with depression and/or anxiety disorders. Individuals with substance use disorders showed higher DU and lower EC values than healthy controls. The EC values were lower in females, but not males, with depression and/or anxiety disorders than in healthy controls. However, the previously observed difference in DU between participants with depression and/or anxiety disorders and healthy controls did not replicate. Analyses of specific disorders in the combined samples indicated that effects were common across different substance use disorders and affective disorders. LIMITATIONS: There were differences, although with small effect size, in age and baseline intellectual functioning between the previous and current sample, which may have affected replication of DU differences in participants with depression and/or anxiety disorders. CONCLUSION: The now robust evidence base for these clinical group differences motivates specific questions that should be addressed in future research: can DU and EC become behavioural treatment targets, and can we identify neural substrates of DU and EC that could be used to measure severity of dysfunction or as neuromodulatory treatment targets?

Self-regulation of the posterior cingulate cortex with real-time fMRI neurofeedback augmented mindfulness training in healthy adolescents: A nonrandomized feasibility study.

Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).

Behavioral activation therapy for depression is associated with a reduction in the concentration of circulating quinolinic acid.

BACKGROUND: An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown. METHODS: Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA). RESULTS: BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy. CONCLUSION: The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.

C-Reactive protein and the kynurenic acid to quinolinic acid ratio are independently associated with white matter integrity in major depressive disorder.

Kynurenic acid (KynA) and quinolinic acid (QA) are neuroactive kynurenine pathway (KP) metabolites that have neuroprotective and neurotoxic properties, respectively. At least partly as a result of immune activation, the ratio of KynA to QA in the blood is reduced in major depressive disorder (MDD) and has been reported to be positively correlated with gray matter volume in depression. This study examined whether the inflammatory mediator, C-reactive protein (CRP) and the putative neuroprotective index, KynA/QA, were associated with white matter integrity in MDD, and secondly, whether any such associations were independent of each other or whether the effect of CRP was mediated by KynA/QA. One hundred and sixty-six participants in the Tulsa 1000 study with a DSM-V diagnosis of MDD completed diffusion tensor imaging and provided a serum sample for the quantification of CRP, KynA, and QA. Correlational tractography was performed using DSI Studio to map the specific white matter pathways that correlated with CRP and KynA/QA. CRP was negatively related to KynA/QA (standardized beta coefficient, SBC = -0.35 with standard error, Std.E = 0.13, p < 0.01) after controlling for nine possible confounders, i.e., age, sex, body mass index (BMI), medication status, lifetime alcohol use, severity of depression, severity of anxiety, length of illness, and smoking status. Higher concentrations of CRP were associated with decreased white matter integrity (fractional anisotropy, FA) of the bilateral cingulum and fornix after controlling for the nine potential confounders (SBC = -0.43, Std.E = 0.13, p = 0.002). Greater serum KynA/QA was associated with increased white matter integrity of the bilateral fornix, bilateral superior thalamic radiations, corpus callosum, and bilateral cingulum bundles after controlling for the same possible confounders (SBC = 0.26, Std.E = 0.09, p = 0.005). The relationship between CRP and FA was not mediated by KynA/QA. Exploratory analyses also showed that KynA/QA but not CRP was associated with self-reported positive affect, attentiveness, and fatigue measured with the PANASX (SBCs = 0.17-0.23). Taken together, these results are consistent with the hypothesis that within a subgroup of MDD patients, a higher level of systemic inflammation alters the balance of KP metabolism but also raise the possibility that CRP and neuroactive KP metabolites represent independent molecular mechanisms underlying white matter alterations in MDD.

Striatal reactivity during emotion and reward relates to approach-avoidance conflict behaviour and is altered in adults with anxiety or depression.

BACKGROUND: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach-avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC. METHODS: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures. RESULTS: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = -0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = -0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = -0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27). LIMITATIONS: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference. CONCLUSION: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach.

It is never as good the second time around: Brain areas involved in salience processing habituate during repeated drug cue exposure in treatment engaged abstinent methamphetamine and opioid users.

The brain response to drug-related cues is an important marker in addiction-medicine. However, the temporal dynamics of this response in repeated exposure to cues are not well known. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations all abstinent during their early recovery (treatment). Sixty-five male participants (35.8 ± 8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample from an abstinence-based residential treatment program. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD from a different residential program and 22 male with opioid use disorder from the same residential program as the discovery sample). The second replication sample was re-tested within two weeks. In the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both a main effect of condition and a condition-by-time interaction, indicating a habituating response to drug-related but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed a consistent lack of drug > neutral and habituation response within all selected clusters in the second cue-exposure session. The VMPFC, amygdala and ventral striatum show habituation in response to drug-related cues which is consistent among different clinical populations. This habituated response in the first session of cue-exposure and lack of reactivity in the second session of exposure may be important for informing the development of cue-desensitization interventions.

Latent variables for region of interest activation during the monetary incentive delay task.

BACKGROUND: The Monetary Incentive Delay task (MID) has been used extensively to probe anticipatory reward processes. However, individual differences evident during this task may relate to other constructs such as general arousal or valence processing (i.e., anticipation of negative versus positive outcomes). This investigation used a latent variable approach to parse activation patterns during the MID within a transdiagnostic clinical sample. METHODS: Participants were drawn from the first 500 individuals recruited for the Tulsa-1000 (T1000), a naturalistic longitudinal study of 1000 participants aged 18-55 (n = 476 with MID data). We employed a multiview latent analysis method, group factor analysis, to characterize factors within and across variable sets consisting of: (1) region of interest (ROI)-based blood oxygenation level-dependent (BOLD) contrasts during reward and loss anticipation; and (2) self-report measures of positive and negative valence and related constructs. RESULTS: Three factors comprised of ROI indicators emerged to accounted for >43% of variance and loaded on variables representing: (1) general arousal or general activation; (2) valence, with dissociable responses to anticipation of win versus loss; and (3) region-specific activation, with dissociable activation in salience versus perceptual brain networks. Two additional factors were comprised of self-report variables, which appeared to represent arousal and valence. CONCLUSIONS: Results indicate that multiview techniques to identify latent variables offer a novel approach for differentiating brain activation patterns during task engagement. Such approaches may offer insight into neural processing patterns through dimension reduction, be useful for probing individual differences, and aid in the development of optimal explanatory or predictive frameworks.

Test-retest reliability of approach-avoidance conflict decision-making during functional magnetic resonance imaging in healthy adults.

Neural and behavioral mechanisms during approach-avoidance conflict decision-making are relevant across various psychiatric disorders, particularly anxiety disorders. Studies using approach-avoidance conflict paradigms in healthy adults have identified preliminary neural mechanisms, but findings must be replicated and demonstrated as reliable before further application. This study sought to replicate previous findings and examine test-retest reliability of behavioral (approach behavior, reaction time) and neural (regions of interest [ROIs]) responses during an approach-avoidance conflict task conducted during functional magnetic resonance imaging (fMRI). Thirty healthy adults completed an approach-avoidance conflict task during fMRI on two occasions (mean interval: 17 days; range: 11-32). Effects of task condition during three task phases (decision-making, affective outcome and monetary reward) and intraclass correlation coefficients (ICCs) were calculated across time points. Results replicated that approach behavior was modulated by conflict during decision-making. ROI activations were replicated such that dorsal anterior cingulate cortex (dACC) was modulated by conflict during decision-making, and dACC, striatum, and anterior insula were modulated by valence during affective outcomes (p's <.0083). Approach behavior during conflict demonstrated excellent reliability (ICCs ≥.77). Activation of dACC during conflict decision-making and anterior insula during negative outcomes demonstrated fair reliability (ICCs = .51 and .54), and dACC and striatum activation demonstrated good reliability during negative outcomes (ICCs = .63 and .69). Two additional ROIs (amygdala, left dorsolateral prefrontal cortex) showed good reliability during negative outcomes (ICCs ≥.60). These results characterize several specific behavioral and neuroimaging responses that are replicable and sufficiently reliable during approach-avoidance conflict decision-making to support future utility.

Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial.

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have shown initial promise in producing antidepressant effects. This is perhaps due to these drugs being peroxisome proliferator-activated receptor gamma (PPARγ) agonists, in addition to their inhibition of cyclooxygenase enzymes. Some, albeit mixed, evidence suggests that PPARγ agonists have antidepressant effects in humans and animals. This double-blind, placebo-controlled, pharmacologic functional magnetic resonance imaging (ph-fMRI) study aimed to elucidate the impact of ibuprofen on emotion-related neural activity and determine whether observed effects were due to changes in PPARγ gene expression. Twenty healthy volunteers completed an emotional face matching task during three fMRI sessions, conducted one week apart. Placebo, 200 mg, or 600 mg ibuprofen was administered 1 h prior to each scan in a pseudo-randomized order. Peripheral blood mononuclear cells were collected at each session to isolate RNA for PPARγ gene expression. At the doses used, ibuprofen did not significantly change PPARγ gene expression. Ibuprofen dose was associated with decreased blood oxygen level-dependent (BOLD) activation in the dorsolateral prefrontal cortex and fusiform gyrus during emotional face processing (faces-shapes). Additionally, PPARγ gene expression was associated with increased BOLD activation in the insula and transverse and superior temporal gyri (faces-shapes). No interaction effects between ibuprofen dose and PPARγ gene expression on BOLD activation were observed. Thus, results suggest that ibuprofen and PPARγ may have independent effects on emotional neurocircuitry. Future studies are needed to further delineate the roles of ibuprofen and PPARγ in exerting antidepressant effects in healthy as well as clinical populations.

Greater decision uncertainty characterizes a transdiagnostic patient sample during approach-avoidance conflict: a computational modelling approach.

BACKGROUND: Imbalances in approach-avoidance conflict (AAC) decision-making (e.g., sacrificing rewards to avoid negative outcomes) are considered central to multiple psychiatric disorders. We used computational modelling to examine 2 factors that are often not distinguished in descriptive analyses of AAC: decision uncertainty and sensitivity to negative outcomes versus rewards (emotional conflict). METHODS: A previously validated AAC task was completed by 478 participants, including healthy controls (n = 59), people with substance use disorders (n = 159) and people with depression and/or anxiety disorders who did not have substance use disorders (n = 260). Using an active inference model, we estimated individual-level values for a model parameter that reflected decision uncertainty and another that reflected emotional conflict. We also repeated analyses in a subsample (59 healthy controls, 161 people with depression and/or anxiety disorders, 56 people with substance use disorders) that was propensity-matched for age and general intelligence. RESULTS: The model showed high accuracy (72%). As further validation, parameters correlated with reaction times and self-reported task motivations in expected directions. The emotional conflict parameter further correlated with self-reported anxiety during the task (r = 0.32, p < 0.001), and the decision uncertainty parameter correlated with self-reported difficulty making decisions (r = 0.45, p < 0.001). Compared to healthy controls, people with depression and/or anxiety disorders and people with substance use disorders showed higher decision uncertainty in the propensity-matched sample (t = 2.16, p = 0.03, and t = 2.88, p = 0.005, respectively), with analogous results in the full sample; people with substance use disorders also showed lower emotional conflict in the full sample (t = 3.17, p = 0.002). LIMITATIONS: This study was limited by heterogeneity of the clinical sample and an inability to examine learning. CONCLUSION: These results suggest that reduced confidence in how to act, rather than increased emotional conflict, may explain maladaptive approach-avoidance behaviours in people with psychiatric disorders.

Independent and Synergistic Associations Between TBI Characteristics and PTSD Symptom Clusters on Cognitive Performance and Postconcussive Symptoms in Iraq and Afghanistan Veterans.

OBJECTIVE: The investigators sought to evaluate the independent and interactive associations between mild traumatic brain injury (mTBI) characteristics and posttraumatic stress disorder (PTSD) symptoms with regard to postconcussive symptoms and cognition among treatment-seeking veterans of the U.S. conflicts in Iraq and Afghanistan. METHODS: Sixty-seven Iraq and Afghanistan veterans who had a history of mTBI and comorbid PTSD were grouped based on injury mechanism (blast versus nonblast) and number of lifetime mTBIs (one to two versus three or more). Independent associations between mTBI characteristics and PTSD symptom clusters were evaluated with regard to cognition and postconcussive symptoms. Follow-up analyses were conducted to determine any interactive associations between TBI characteristics and PTSD symptom clusters. RESULTS: Higher PTSD symptoms, particularly hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. No direct relationships were observed between PTSD symptom clusters and memory or processing speed. The relationship between hyperarousal and processing speed was moderated by lifetime mTBIs, such that those with a history of at least three mTBIs demonstrated a negative association between hyperarousal and processing speed. Blast-related mTBI history was associated with reduced processing speed, compared with non-blast-related mTBI. However, an interaction was observed such that among those with blast-related mTBI history, higher re-experiencing symptoms were associated with poorer processing speed, whereas veterans without history of blast-related mTBI did not demonstrate an association between processing speed and re-experiencing symptoms. CONCLUSIONS: Higher hyperarousal and re-experiencing symptoms were associated with reduced processing speed among veterans with repetitive and blast-related mTBI history, respectively. PTSD symptoms, specifically hyperarousal, were associated with poorer executive functioning and higher postconcussive symptoms. Limited associations were found between injury characteristics and cognition chronically following mTBI. However, these results support synergistic effects of specific PTSD symptom clusters and TBI characteristics.

Gastric symptoms and low perceived maternal warmth are associated with eating disorder symptoms in young adolescent girls.

OBJECTIVE: This study sought to determine whether gastric symptoms are associated with later eating disorder (ED) symptoms during early adolescence, and whether this relationship is moderated by parental warmth/acceptance and/or the child's sex. METHOD: Longitudinal data from the Adolescent Brain Cognitive DevelopmentSM Study were utilized. Participants ages 9-10 years old (N = 4,950; 2,370 female) completed measures at baseline and 1 year later (Y1). At baseline, gastric symptoms were measured by parent-reported items from the Child Behavior Checklist (CBCL), and perceived parental acceptance was measured by youth report on the Children's Report of Parent Behavior Inventory (CRPBI) Acceptance subscale separately for mothers and fathers. ED symptoms at Y1 were assessed by parent report on a computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Linear mixed-effects models were conducted separately for maternal and paternal acceptance to test relationships among variables. RESULTS: A three-way interaction between baseline gastric symptoms, sex, and maternal acceptance predicted Y1 ED symptoms (𝛽 = 0.08; p < .01). Post-hoc analyses revealed that the interaction between gastric symptoms and maternal acceptance was significant for girls only (𝛽 = -0.06, p < .01), such that low maternal acceptance was associated with a stronger relationship between baseline gastric symptoms and Y1 ED symptoms. No statistically significant main effects or interactions were found in the model for paternal acceptance. DISCUSSION: Gastric symptoms and low perceived maternal acceptance may interact to result in heightened risk for EDs in young adolescent girls.

Extracurricular Activities, Screen Media Activity, and Sleep May Be Modifiable Factors Related to Children's Cognitive Functioning: Evidence From the ABCD Study®.

This study used a machine learning framework in conjunction with a large battery of measures from 9,718 school-age children (ages 9-11) from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study to identify factors associated with fluid cognitive functioning (FCF), or the capacity to learn, solve problems, and adapt to novel situations. The identified algorithm explained 14.74% of the variance in FCF, replicating previously reported socioeconomic and mental health contributors to FCF, and adding novel and potentially modifiable contributors, including extracurricular involvement, screen media activity, and sleep duration. Pragmatic interventions targeting these contributors may enhance cognitive performance and protect against their negative impact on FCF in children.

Visual cortical regions show sufficient test-retest reliability while salience regions are unreliable during emotional face processing.

Functional magnetic resonance imaging studies frequently use emotional face processing tasks to probe neural circuitry related to psychiatric disorders and treatments with an emphasis on regions within the salience network (e.g., amygdala). Findings across previous test-retest reliability studies of emotional face processing have shown high variability, potentially due to differences in data analytic approaches. The present study comprehensively examined the test-retest reliability of an emotional faces task utilizing multiple approaches to region of interest (ROI) analysis and by examining voxel-wise reliability across the entire brain for both neural activation and functional connectivity. Analyses included 42 healthy adult participants who completed an fMRI scan concurrent with an emotional faces task on two separate days with an average of 25.52 days between scans. Intraclass correlation coefficients (ICCs) were calculated for the 'FACES-SHAPES' and 'FACES' (compared to implicit baseline) contrasts across the following: anatomical ROIs identified from a publicly available brain atlas (i.e., Brainnetome), functional ROIs consisting of 5-mm spheres centered on peak voxels from a publicly available meta-analytic database (i.e., Neurosynth), and whole-brain, voxel-wise analysis. Whole-brain, voxel-wise analyses of functional connectivity were also conducted using both anatomical and functional seed ROIs. While group-averaged neural activation maps were consistent across time, only one anatomical ROI and two functional ROIs showed good or excellent individual-level reliability for neural activation. The anatomical ROI was the right medioventral fusiform gyrus for the FACES contrast (ICC â€‹= â€‹0.60). The functional ROIs were the left and the right fusiform face area (FFA) for both FACES-SHAPES and FACES (Left FFA ICCs â€‹= â€‹0.69 & 0.79; Right FFA ICCs â€‹= â€‹0.68 & 0.66). Poor reliability (ICCs â€‹< â€‹0.4) was identified for almost all other anatomical and functional ROIs, with some exceptions showing fair reliability (ICCs â€‹= â€‹0.4-0.59). Whole-brain voxel-wise analysis of neural activation identified voxels with good (ICCs â€‹= â€‹0.6-0.74) to excellent reliability (ICCs â€‹> â€‹0.75) that were primarily located in visual cortex, with several clusters in bilateral dorsal lateral prefrontal cortex (DLPFC). Whole-brain voxel-wise analyses of functional connectivity for amygdala and fusiform gyrus identified very few voxels with good to excellent reliability using both anatomical and functional seed ROIs. Exceptions included clusters in right cerebellum and right DLPFC that showed reliable connectivity with left amygdala (ICCs â€‹> â€‹0.6). In conclusion, results indicate that visual cortical regions demonstrate good reliability at the individual level for neural activation, but reliability is generally poor for salience regions often focused on within psychiatric research (e.g., amygdala). Given these findings, future clinical neuroimaging studies using emotional faces tasks to examine individual differences might instead focus on visual regions and their role in psychiatric disorders.

Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry.

Appetite change is a defining feature of major depressive disorder (MDD), yet little neuroscientific evidence exists to explain why some individuals experience increased appetite when they become depressed while others experience decreased appetite. Previous research suggests depression-related appetite changes can be indicative of underlying neural and inflammatory differences among MDD subtypes. The present study explores the relationship between systemic inflammation and brain circuitry supporting food hedonics for individuals with MDD. Sixty-four participants (31 current, unmedicated MDD and 33 healthy controls [HC]) provided blood samples for analysis of an inflammatory marker, C-reactive protein (CRP), and completed a functional magnetic resonance imaging (fMRI) scan in which they rated the perceived pleasantness of various food stimuli. Random-effects multivariate modeling was used to explore group differences in the relationship between CRP and the coupling between brain activity and inferred food pleasantness (i.e., strength of the relationship between activity and pleasantness ratings). Results revealed that for MDD with increased appetite, higher CRP in blood related to greater coupling between orbitofrontal cortex and anterior insula activity and inferred food pleasantness. Compared to HC, all MDD exhibited a stronger positive association between CRP and coupling between activity in striatum and inferred food pleasantness. These findings suggest that for individuals with MDD, systemic low-grade inflammation is associated with differences in reward and interoceptive-related neural circuitry when making hedonic inferences about food stimuli. In sum, altered immunologic states may affect appetite and inferences about food reward in individuals with MDD and provide evidence for physiological subtypes of MDD.

A pragmatic clinical trial examining the impact of a resilience program on college student mental health.

BACKGROUND: One in three college students experience significant depression or anxiety interfering with daily functioning. Resilience programs that can be administered to all students offer an opportunity for addressing this public health problem. The current study objective was to assess the benefit of a brief, universal resilience program for first-year college students. METHOD: First-year students at a private, midwestern university participated. This trial used a pragmatic design, delivering the intervention within university-identified orientation courses and was not randomized. The four-session resilience program included goal-building, mindfulness, and resilience skills. The comparison was orientation-as-usual. Primary outcomes included PROMIS® Depression and Anxiety and Connor-Davidson Resilience Scale. Secondary and exploratory outcomes included the Perceived Stress Scale, Emotion Regulation, and Cognitive Behavioral Therapy (CBT) Skills Questionnaires, and Freiburg Mindfulness Inventory. Time by treatment interactions at post-training and semester-end were examined using linear mixed models. RESULTS: Analysis included 252 students, 126 who completed resilience programming and a matched comparison sample. Resilience programming did not relate to improvements in depression at post-training (CI: -2.53 to 1.02; p = .404, d =-0.08), but did at semester-end (95% CI: -4.27 to -0.72; p = .006, d = -0.25) and improvements in perceived stress were observed at post-training (CI: -3.31 to -0.44; p = .011, d = -0.24) and semester-end (CI: -3.30 to -0.41; p = .013, d = -0.24). Emotion regulation, mindfulness, and CBT skills increased, with CBT skills mediating clinical improvements. CONCLUSIONS: Universal implementation of a brief, resilience intervention may be effective for improving college student mental health.

SMART-CPT for veterans with comorbid post-traumatic stress disorder and history of traumatic brain injury: a randomised controlled trial.

OBJECTIVE: To better concurrently address emotional and neuropsychological symptoms common in veterans with comorbid post-traumatic stress disorder (PTSD) and history of traumatic brain injury (TBI), we integrated components of compensatory cognitive training from the Cognitive Symptom Management and Rehabilitation Therapy (CogSMART) programme into cognitive processing therapy (CPT) for PTSD to create a hybrid treatment, SMART-CPT (CogSMART+CPT). This study compared the efficacy of standard CPT with SMART-CPT for treatment of veterans with comorbid PTSD and history of TBI reporting cognitive symptoms. METHODS: One hundred veterans with PTSD, a history of mild to moderate TBI and current cognitive complaints were randomised and received individually delivered CPT or SMART-CPT for 12 weeks. Participants underwent psychological, neurobehavioural and neuropsychological assessments at baseline, on completion of treatment and 3 months after treatment. RESULTS: Both CPT and SMART-CPT resulted in clinically significant reductions in PTSD and postconcussive symptomatology and improvements in quality of life. SMART-CPT resulted in additional improvements in the neuropsychological domains of attention/working memory, verbal learning/memory and novel problem solving. CONCLUSION: SMART-CPT, a mental health intervention for PTSD, combined with compensatory cognitive training strategies, reduces PTSD and neurobehavioural symptoms and also provides added value by improving cognitive functioning.

Contributions to Executive Dysfunction in Operation Enduring Freedom/Operation Iraqi Freedom Veterans With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury.

OBJECTIVE: Posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (mTBI), and executive function (EF) difficulties are prevalent in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We evaluated the contributions of injury variables, lower-order cognitive component processes (processing speed/attention), and psychological symptoms to EF. PARTICIPANTS: OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were administered neuropsychological tests of EF and self-report assessments of PTSD and depression. RESULTS: Those impaired on one or more EF measures had higher PTSD and depression symptoms and lower processing speed/attention performance than those with intact performance on all EF measures. Across participants, poorer attention/processing speed performance and higher psychological symptoms were associated with worse performance on specific aspects of EF (eg, inhibition and switching) even after accounting for injury variables. Although direct relationships between EF and injury variables were equivocal, there was an interaction between measures of injury burden and processing speed/attention such that those with greater injury burden exhibited significant and positive relationships between processing speed/attention and inhibition/switching, whereas those with lower injury burden did not. CONCLUSION: Psychological symptoms as well as lower-order component processes of EF (attention and processing speed) contribute significantly to executive dysfunction in OEF/OIF Veterans with PTSD and history of mTBI. However, there may be equivocal relationships between injury variables and EF that warrant further study. Results provide groundwork for more fully understanding cognitive symptoms in OEF/OIF Veterans with PTSD and history of mTBI that can inform psychological and cognitive interventions in this population.

PTSD and cognitive symptoms relate to inhibition-related prefrontal activation and functional connectivity.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with reduced executive functioning and verbal memory performance, as well as abnormal task-specific activity in prefrontal cortex (PFC) and anterior cingulate cortices (ACC). The current study examined how PTSD symptoms and neuropsychological performance in combat veterans relates to (1) medial PFC and ACC activity during cognitive inhibition, and (2) task-independent PFC functional connectivity. METHODS: Thirty-nine male combat veterans with varying levels of PTSD symptoms completed the multisource interference task during functional magnetic resonance imaging. Robust regression analyses were used to assess relationships between percent signal change (PSC: incongruent-congruent) and both PTSD severity and neuropsychological performance. Analyses were conducted voxel-wise and for PSC extracted from medial PFC and ACC regions of interest. Resting-state scans were available for veterans with PTSD. Regions identified via task-based analyses were used as seeds for resting-state connectivity analyses. RESULTS: Worse PTSD severity and neuropsychological performance related to less medial PFC and rostral ACC activity during interference processing, driven partly by increased activation to congruent trials. Worse PTSD severity related to reduced functional connectivity between these regions and bilateral, lateral PFC (Brodmann area 10). Worse neuropsychological performance related to reduced functional connectivity between these regions and the inferior frontal gyrus. CONCLUSIONS: PTSD and associated neuropsychological deficits may result from difficulties regulating medial PFC regions associated with "default mode," or self-referential processing. Further clarification of functional coupling deficits between default mode and executive control networks in PTSD may enhance understanding of neuropsychological and emotional symptoms and provide novel treatment targets.