A machine learning analysis of risk and protective factors of suicidal thoughts and behaviors in college students.

OBJECTIVE: To identify robust and reproducible factors associated with suicidal thoughts and behaviors (STBs) in college students. METHODS: 356 first-year university students completed a large battery of demographic and clinically-relevant self-report measures during the first semester of college and end-of-year (n = 228). Suicide Behaviors Questionnaire-Revised (SBQ-R) assessed STBs. A machine learning (ML) pipeline using stacking and nested cross-validation examined correlates of SBQ-R scores. RESULTS: 9.6% of students were identified at significant STBs risk by the SBQ-R. The ML algorithm explained 28.3% of variance (95%CI: 28-28.5%) in baseline SBQ-R scores, with depression severity, social isolation, meaning and purpose in life, and positive affect among the most important factors. There was a significant reduction in STBs at end-of-year with only 1.8% of students identified at significant risk. CONCLUSION: Analyses replicated known factors associated with STBs during the first semester of college and identified novel, potentially modifiable factors including positive affect and social connectedness.

A randomized clinical trial of behavioral activation and exposure-based therapy for adults with generalized anxiety disorder.

Objective: Exposure-based therapy (EXP) and behavioral activation (BA) are empirically-supported behavioral intervention techniques that target avoidance and approach behavior to alleviate symptoms. Although EXP is an established treatment for generalized anxiety disorder (GAD), the effectiveness of BA for GAD has not been directly tested or compared with that of EXP. This study examined the efficacy of EXP and BA for adults with GAD. Method: In a randomized clinical trial (clinicaltrials.gov: NCT02807480) with partial blinding in Tulsa, OK, 102 adults with GAD were allocated to manualized, 10-session EXP or BA between April 2016-April 2021. Primary analyses were intention-to-treat and included the 94 (46 EXP, 48 BA) participants who started treatment. The GAD-7 self-report scale was the primary outcome measure. Results: Similar GAD-7 declines were observed at post-treatment for EXP (d=-0.97 [95% CI -1.40 to -0.53]) and BA (d=-1.14 [95% CI -1.57 to -0.70]), and were maintained through 6-month follow-up (EXP: d=-2.13, BA: d=-1.98). Compared to EXP, BA yielded more rapid declines in anxiety and depression scores during therapy (d=0.75-0.77), as well as lower anxiety and depression scores (d=0.13-0.14) and greater participant-rated improvement (d=0.64) at post-treatment. Bayesian analyses indicated 74-99% probability of greater change in BA than EXP at post-treatment. Conclusions: BA and EXP are both effective in treating GAD, and BA may confer greater benefit during treatment. Future research is warranted to inform personalized treatment approaches.

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.

Active coping strategies and less pre-pandemic alcohol use relate to college student mental health during the COVID-19 pandemic.

Objective: To further delineate risk and resilience factors contributing to trajectories of mental health symptoms experienced by college students through the pandemic. Participants: n = 183 college students (67.2% female). Methods: Linear mixed models examined time effects on depression and anxiety. Propensity-matched subgroups exhibiting "increased" versus "low and stable" depression symptoms from before to after the pandemic-onset were compared on pre-pandemic demographic and psychological factors and COVID-related experiences and coping strategies. Results: Students experienced worsening of mental health symptoms throughout the pandemic, particularly during Fall 2020 compared with Fall 2019 (Depression scale d = -0.43 [95% CI: -0.65 to -0.21]). The propensity-matched subgroup exhibiting relative resilience ("low and stable" symptoms) reported less alcohol use prior to the pandemic, greater use of active coping strategies, and less of an impact on their college progress. Conclusions: Results point to several potential targets of screening and intervention to decrease residual impacts of the pandemic.

Real-Time Functional Magnetic Resonance Imaging Dyadic Neurofeedback for Emotion Regulation: A Proof-of-Concept Study.

Real-time fMRI (rt-fMRI) neurofeedback can be used to non-invasively modulate brain activity and has shown initial effectiveness in symptom reduction for psychiatric disorders. Neurofeedback paradigms often target the neurocircuitry underlying emotion regulation, as difficulties with emotion regulation are common across many psychiatric conditions. Adolescence is a key period for the development of emotion regulation, with the parent-adolescent relationship providing an important context for learning how to modulate one's emotions. Here, we present evidence for a novel extension of rt-fMRI neurofeedback wherein a second person (the parent) views neurofeedback from the focal participant (adolescent) and attempts to regulate the other person's brain activity. In this proof-of-concept study, mother-adolescent dyads (n = 6; all female) participated in a dyadic neurofeedback protocol, during which they communicated via active noise-canceling microphones and headphones. During the scan, adolescents described current emotionally upsetting situations in their lives, and their mothers responded while viewing neurofeedback from the adolescent's right anterior insular cortex (aIC)-a key hub for emotion-related processing. The mother was instructed to supportively respond to her daughter's negative emotions and attempt to downregulate the aIC activity. Mean right aIC activation during each run was calculated for each adolescent participant, and results revealed a downward trend across the session (ß = -0.17, SE ß = 0.19, Cohen's f 2 = 0.03). Results of this proof-of-concept study support further research using dyadic neurofeedback to target emotion-related processing. Future applications may include therapist-client dyads and continued research with parents and children. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03929263].

Limits to the generalizability of resting-state functional magnetic resonance imaging studies of youth: An examination of ABCD Study® baseline data.

This study examined how resting-state functional magnetic resonance imaging (rs-fMRI) data quality and availability relate to clinical and sociodemographic variables within the Adolescent Brain Cognitive Development Study. A sample of participants with an adequate sample of quality baseline rs-fMRI data containing low average motion (framewise displacement ≤ 0.15; low-noise; n = 4,356) was compared to a sample of participants without an adequate sample of quality data and/or containing high average motion (higher-noise; n = 7,437) using Chi-squared analyses and t-tests. A linear mixed model examined relationships between clinical and sociodemographic characteristics and average head motion in the sample with low-noise data. Relative to the sample with higher-noise data, the low-noise sample included more females, youth identified by parents as non-Hispanic white, and youth with married parents, higher parent education, and greater household incomes (ORs = 1.32-1.42). Youth in the low-noise sample were also older and had higher neurocognitive skills, lower BMIs, and fewer externalizing and neurodevelopmental problems (ds = 0.12-0.30). Within the low-noise sample, several clinical and demographic characteristics related to motion. Thus, participants with low-noise rs-fMRI data may be less representative of the general population and motion may remain a confound in this sample. Future rs-fMRI studies of youth should consider these limitations in the design and analysis stages in order to optimize the representativeness and clinical relevance of analyses and results.

Impact of serotonergic medication on interoception in major depressive disorder.

Unmedicated individuals with major depressive disorder (MDD) show abnormal interoception, but it is unclear whether antidepressant treatment via serotonergic medication alters this relationship. The current cross-sectional study examined associations between neural and behavioral indices of interoceptive processing and chronic serotonergic medication administration in MDD. 47 selective serotonin reuptake inhibitor (SSRI)-medicated MDD (MDD-SSRI) individuals were propensity-matched with 48 unmedicated current MDD (MDD-UnMed) and 41 healthy comparison (HC) participants on demographics including age, sex, body mass index, education, as well as on dimensional scales of symptom severity including depression and anxiety. All participants completed an interoceptive attention task during functional magnetic resonance imaging, and a behavioral heartbeat tapping task under three conditions: Guessing, No Guessing, and Breath Hold. Relative to HC, both MDD groups: (1) exhibited lower mid-insula, amygdala, putamen, and caudate activation during interoceptive versus exteroceptive attention; and (2) showed poorer heartbeat tapping performance during the Breath Hold condition. However, the MDD-SSRI group reported higher intensity ratings of heartbeat and stomach sensations than MDD-UnMed and HC during the interoceptive attention task. These findings suggest that the attenuated patterns of neural activation observed in depressed individuals during interoceptive attention are not ameliorated by the chronic administration of serotonergic medications. However, amplified interoceptive sensation ratings suggest a potential impact of chronic serotonergic medication on conscious experiences of internal body states. Future investigations will need to determine the extent to which serotonergic medications acutely influence interoceptive processing, and whether such changes play a role in therapeutic responses during treatment initiation.

Effects of Parent Emotion Socialization on the Neurobiology Underlying Adolescent Emotion Processing: A Multimethod fMRI Study.

Parents' emotion socialization (ES) practices impact socioemotional development throughout adolescence. Little is known, however, regarding the neurobiology underlying these effects. This study used functional magnetic resonance imaging (fMRI) to examine how parent ES practices relate to adolescent brain function during emotion processing. Thirty-three adolescents (ages 14-16) reported on ES practices of a focal parent (primarily mothers) using the Emotions as a Child (EAC) Scale. Adolescents also completed a conflict discussion task with this parent, and parents' statements were coded for emotional valence. Adolescents performed two fMRI tasks: a standard emotion processing (EP) task (n = 32) and the Testing Emotional Attunement and Mutuality (TEAM) task (n = 27). The EP task consisted of viewing emotional pictures and either reacting naturally or using cognitive reappraisal to regulate emotional responses. The TEAM task was performed with the parent and included trials during which adolescents were shown that their parent made an error, costing the dyad $5. Parent negative verbalizations during the conflict discussion were associated with greater activity in the thalamus during the emotion reactivity condition of the EP task and in the thalamus, superior medial and superior frontal gyri, anterior insula, and dorsolateral prefrontal cortex during the costly error condition of the TEAM task. Unsupportive ES was associated with greater activity in the supplementary motor area and less activity in the paracentral gyrus and amygdala during the costly error condition of the TEAM task. This study supports the premise that ES influences adolescents' emotion-related neural processing, particularly when using ecologically valid tasks in social contexts.

The Role of Neurobiological Bases of Dyadic Emotion Regulation in the Development of Psychopathology: Cross-Brain Associations Between Parents and Children.

Daily interactions between parents and children play a large role in children's emotional development and mental health. Thus, it is important to investigate the neural mechanisms underlying this association within the context of these dyadic social interactions. We suggest that examining cross-brain associations, coordinated brain responses, among parents and children increases our understanding of patterns of social and emotion-related processes that occur during parent-child interactions, which may influence the development of child emotion regulation and psychopathology. Therefore, we extend the Parent-Child Emotion Regulation Dynamics Model (Morris et al., in: Cole and Hollenstein (eds) Dynamics of emotion regulation: A matter of time, Taylor & Francis, 2018) to include cross-brain associations involved in dyadic emotion regulation during parent-child social emotional interactions and discuss how this model can inform future research and its broader applications.

We Know Even More Things: A Decade Review of Parenting Research.

In this article, we highlight the important ideas that have emerged from research on parenting and adolescent development over the past decade. Beginning with research on authoritative parenting, we examine key elements of this parenting style and its influence across diverse contexts and populations. We turn our attention to four topics that have generated much research in the past decade: (1) how parenting contributes to adolescent peer and romantic relationships; (2) the impact of parenting on adolescent brain development; (3) gene-environment interactions in parenting research; and (4) parents' involvement in adolescents' social media use. We discuss contemporary challenges and ways parents can promote healthy development. We consider the integration of research, practice, and policy that best supports parents and adolescents.

Into the Unknown: Examining Neural Representations of Parent-Adolescent Interactions.

The parent-adolescent relationship is important for adolescents' emotion regulation (ER), yet little is known regarding the neural patterns of dyadic ER that occur during parent-adolescent interactions. A novel measure that can be used to examine such patterns is cross-brain connectivity (CBC)-concurrent and time-lagged connectivity between two individuals' brain regions. This study sought to provide evidence of CBC and explore associations between CBC, parenting, and adolescent internalizing symptoms. Thirty-five adolescents (mean age = 15 years, 69% female, 72% Non-Hispanic White, 17% Black, 11% Hispanic or Latino) and one biological parent (94% female) completed an fMRI hyperscanning conflict discussion task. Results revealed CBC between emotion-related brain regions. Exploratory analyses indicated CBC is associated with parenting and adolescent depressive symptoms.

The Impact of COVID-19 on Adolescent Mental Health: Preliminary Findings From a Longitudinal Sample of Healthy and At-Risk Adolescents.

Background: The COVID-19 pandemic has brought on far-reaching consequences for adolescents. Adolescents with early life stress (ELS) may be at particular risk. We sought to examine how COVID-19 impacted psychological functioning in a sample of healthy and ELS-exposed adolescents during the pandemic. Methods: A total of 24 adolescents (15 healthy, nine ELS) completed self-report measures prior to and during the COVID-19 pandemic. The effect of COVID-19 on symptoms of depression and anxiety were explored using linear mixed-effect analyses. Results: With the onset of the pandemic, healthy but not ELS-exposed adolescents evidenced increased symptoms of depression and anxiety (ps < 0.05). Coping by talking with friends and prioritizing sleep had a protective effect against anxiety for healthy adolescents (t = -3.76, p = 0.002). Conclusions: On average, this study demonstrated large increases in depression and anxiety in adolescents who were healthy prior to the COVID-19 pandemic, while ELS-exposed adolescents evidenced high but stable symptoms over time.

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.

The effect of a mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: a randomized feasibility study.

BACKGROUND: Early life stress (ELS) has been linked to poor mental and physical health outcomes in adolescence and adulthood. Mindfulness reduces symptoms of depression and anxiety and improves cognitive and social outcomes in both youth and adults. However, little is known whether mindfulness can mitigate against the adverse neurobiological and psychological effects of ELS. This study aimed to examine the feasibility of conducting a group mindfulness intervention in adolescents with ELS and provide preliminary indication of potential effects on stress-related biomarkers and mental health symptoms. METHODS: Forty adolescents were randomized to receive either eight sessions of Mindfulness-Based Stress Reduction for Teens in group format (MBSR-T; n = 21) or Treatment as Usual Control group (CTRL; n = 17). Outcomes were assessed at baseline and follow-up and included measures associated with neurobiological functioning (immune and endocrine biomarkers) and self-reported mental health (depressive) symptoms. Linear mixed effects models were used to assess the effects of group and time on these outcome measures. RESULTS: Sixteen of the 21 adolescents completed the intervention, attending an average of 6.5 sessions. The model examining cortisol responses to stress induction revealed medium effects trending toward significance (Cohen's d = .56) for anticipatory cortisol levels in the MBSR-T relative to CTRL groups. No significant effects were found in models examining C-reactive protein or interleukin 6 inflammatory markers. The model examining depressive symptoms revealed a medium effect for symptom reduction (Cohen's d = .69) in the MBSR-T relative to CTRL groups. CONCLUSIONS: This study demonstrated feasibility of conducting a group-based MBSR-T intervention for adolescents with ELS. There was some evidence for efficacy on a symptom level with potential subtle changes on a biological level. Future larger studies are needed to determine the efficacy of group-based mindfulness interventions in this population. TRIAL REGISTRATION: Identifier # NCT03633903 , registered 16/08/2018.

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.

Beyond synchrony: the capacity of fMRI hyperscanning for the study of human social interaction.

Hyperscanning-simultaneous brain scanning of two or more individuals-holds great promise in elucidating the neurobiological underpinnings of social cognitive functions. This article focuses on functional magnetic resonance imaging (fMRI) hyperscanning and identifies promising targets for studying the neuroscience of social interaction with fMRI hyperscanning. Specifically, we present applications of fMRI hyperscanning in the study of social interaction along with promising analysis approaches for fMRI hyperscanning, with its high spatial and low temporal resolution. We first review fMRI hyperscanning studies in social neuroscience and evaluate the premise of using this costly neuroimaging paradigm. Many second-person social neuroscience studies are possible without fMRI hyperscanning. However, certain fundamental aspects of social cognition in real-life social interactions, including different roles of interactors, shared intention emerging through interaction and history of interaction, can be addressed only with hyperscanning. We argue that these fundamental aspects have not often been investigated in fMRI hyperscanning studies. We then discuss the implication of the signal coupling found in fMRI hyperscanning and consider analysis approaches that make fair use of it. With fMRI hyperscanning, we can explore not only synchronous brain activations but whole-brain asymmetric activation patterns with a lagged association between interacting individuals.

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.

TEAMwork: Testing Emotional Attunement and Mutuality During Parent-Adolescent fMRI.

The parent-child relationship and family context influence the development of emotion regulation (ER) brain circuitry and related skills in children and adolescents. Although both parents' and children's ER neurocircuitry simultaneously affect how they interact with one another, neuroimaging studies of parent-child relationships typically include only one member of the dyad in brain imaging procedures. The current study examined brain activation related to parenting and ER in parent-adolescent dyads during concurrent fMRI scanning with a novel task - the Testing Emotional Attunement and Mutuality (TEAM) task. The TEAM task includes feedback trials indicating the other dyad member made an error, resulting in a monetary loss for both participants. Results indicate that positive parenting practices as reported by the adolescent were positively correlated with parents' hemodynamic activation of the ventromedial prefrontal cortex, a region related to empathy, during these error trials. Additionally, during feedback conditions both parents and adolescents exhibited fMRI activation in ER-related regions, including the dorsolateral prefrontal cortex, anterior insula, fusiform gyrus, thalamus, caudate, precuneus, and superior parietal lobule. Adolescents had higher left amygdala activation than parents during the feedback condition. These findings demonstrate the utility of dyadic fMRI scanning for investigating relational processes, particularly in the parent-child relationship.