Gray matter volume associations in youth with ADHD features of inattention and hyperactivity/impulsivity.

BACKGROUND: Prior research has shown smaller cortical and subcortical gray matter volumes among individuals with attention-deficit/hyperactivity disorder (ADHD). However, neuroimaging studies often do not differentiate between inattention and hyperactivity/impulsivity, which are distinct core features of ADHD. The present study uses an approach to disentangle overlapping variance to examine the neurostructural heterogeneity of inattention and hyperactivity/impulsivity dimensions. METHODS: We analyzed data from 10,692 9- to 10-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study. Confirmatory factor analysis was used to derive factors representing inattentive and hyperactive/impulsive traits. We employed structural equation modeling to examine these factors' associations with gray matter volume while controlling for the shared variance between factors. RESULTS: Greater endorsement of inattentive traits was associated with smaller bilateral caudal anterior cingulate and left parahippocampal volumes. Greater endorsement of hyperactivity/impulsivity traits was associated with smaller bilateral caudate and left parahippocampal volumes. The results were similar when accounting for socioeconomic status, medication, and in-scanner motion. The magnitude of these findings increased when accounting for overall volume and intracranial volume, supporting a focal effect in our results. CONCLUSIONS: Inattentive and hyperactivity/impulsivity traits show common volume deficits in regions associated with visuospatial processing and memory while at the same time showing dissociable differences, with inattention showing differences in areas associated with attention and emotion regulation and hyperactivity/impulsivity associated with volume differences in motor activity regions. Uncovering such biological underpinnings within the broader disorder of ADHD allows us to refine our understanding of ADHD presentations.

Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium.

Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups-a 'lower brain volume' subgroup (SG1) and an 'higher striatal volume' subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership ('None'), and mixed SG1 + SG2 subgroups ('Mixed'). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of 'lower brain volume' in SG1 and 'higher striatal volume' (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy = 64%; p < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature.

Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence.

BACKGROUND: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. METHODS: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). RESULTS: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. CONCLUSIONS: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.

The Association between Insomnia and Anxiety Symptoms in a Naturalistic Anxiety Treatment Setting.

Objective/Background: Few studies have examined the relationship between insomnia and anxiety treatment outcomes in naturalistic settings. Furthermore, prior studies typically examine insomnia within a single anxiety diagnosis without accounting for the high overlap between disorders. Here we investigate the association between insomnia and multiple anxiety disorders over a course of cognitive behavioral treatment (CBT) in a naturalistic treatment setting. Participants: Insomnia was assessed in 326 patients seeking treatment at a clinic specializing in CBT for anxiety. Methods: Multilevel modeling was used to investigate whether insomnia moderated reductions in anxiety symptoms. A cross-lagged analysis tested for bidirectional effects between insomnia and anxiety. Multiple regression was used to investigate the relationship between insomnia and anxiety while controlling for the other anxiety disorders and depression. Results: While there was a significant reduction in insomnia during treatment in all anxiety disorders, the majority of the most severe patients remained in the clinical range at post-treatment. Baseline insomnia did not significantly moderate anxiety outcomes, suggesting that patients with high or low levels of insomnia will do equally well in CBT for anxiety. The bidirectional effect between insomnia and anxiety did not reach significance. Additionally, posttraumatic stress disorder, generalized anxiety disorder, and panic disorder were associated with the greatest endorsement of insomnia, after controlling for the overlap between disorders. Conclusions: Sleep problems may persist after anxiety treatment, suggesting that CBT for insomnia may be warranted during or after a course of CBT for anxiety. Importantly, baseline insomnia does not impede anxiety reduction during CBT.

Gestational Age is Dimensionally Associated with Structural Brain Network Abnormalities Across Development.

Prematurity is associated with diverse developmental abnormalities, yet few studies relate cognitive and neurostructural deficits to a dimensional measure of prematurity. Leveraging a large sample of children, adolescents, and young adults (age 8-22 years) studied as part of the Philadelphia Neurodevelopmental Cohort, we examined how variation in gestational age impacted cognition and brain structure later in development. Participants included 72 preterm youth born before 37 weeks' gestation and 206 youth who were born at term (37 weeks or later). Using a previously-validated factor analysis, cognitive performance was assessed in three domains: (1) executive function and complex reasoning, (2) social cognition, and (3) episodic memory. All participants completed T1-weighted neuroimaging at 3 T to measure brain volume. Structural covariance networks were delineated using non-negative matrix factorization, an advanced multivariate analysis technique. Lower gestational age was associated with both deficits in executive function and reduced volume within 11 of 26 structural covariance networks, which included orbitofrontal, temporal, and parietal cortices as well as subcortical regions including the hippocampus. Notably, the relationship between lower gestational age and executive dysfunction was accounted for in part by structural network deficits. Together, these findings emphasize the durable impact of prematurity on cognition and brain structure, which persists across development.

Diminished Cortical Thickness Is Associated with Impulsive Choice in Adolescence.

Adolescence is characterized by both maturation of brain structure and increased risk of negative outcomes from behaviors associated with impulsive decision-making. One important index of impulsive choice is delay discounting (DD), which measures the tendency to prefer smaller rewards available soon over larger rewards delivered after a delay. However, it remains largely unknown how individual differences in structural brain development may be associated with impulsive choice during adolescence. Leveraging a unique large sample of 427 human youths (208 males and 219 females) imaged as part of the Philadelphia Neurodevelopmental Cohort, we examined associations between delay discounting and cortical thickness within structural covariance networks. These structural networks were derived using non-negative matrix factorization, an advanced multivariate technique for dimensionality reduction, and analyzed using generalized additive models with penalized splines to capture both linear and nonlinear developmental effects. We found that impulsive choice, as measured by greater discounting, was most strongly associated with diminished cortical thickness in structural brain networks that encompassed the ventromedial prefrontal cortex, orbitofrontal cortex, temporal pole, and temporoparietal junction. Furthermore, structural brain networks predicted DD above and beyond cognitive performance. Together, these results suggest that reduced cortical thickness in regions known to be involved in value-based decision-making is a marker of impulsive choice during the critical period of adolescence.SIGNIFICANCE STATEMENT Risky behaviors during adolescence, such as initiation of substance use or reckless driving, are a major source of morbidity and mortality. In this study, we present evidence from a large sample of youths that diminished cortical thickness in specific structural brain networks is associated with impulsive choice. Notably, the strongest association between impulsive choice and brain structure was seen in regions implicated in value-based decision-making; namely, the ventromedial prefrontal and orbitofrontal cortices. Moving forward, such neuroanatomical markers of impulsivity may aid in the development of personalized interventions targeted to reduce risk of negative outcomes resulting from impulsivity during adolescence.

The Influence of Posttraumatic Stress Disorder on Health Functioning in Active-Duty Military Service Members.

Researchers have suggested that posttraumatic stress disorder (PTSD) is associated with significant healthcare burden and utilization of medical services. The purpose of this study was to examine the impact of PTSD symptoms on health functioning among active-duty military personnel. Participants in the study were 366 treatment-seeking service members who had returned from deployment and were participating in a larger PTSD treatment study. Assessments included measures of PTSD symptom severity, combat experiences, life stress, health functioning, alcohol use, and depression. We hypothesized that at baseline, PTSD severity and its symptom clusters would be significantly associated with poorer physical and mental health functioning. We conducted separate hierarchical multiple regressions to examine the predictive contribution the hypothesized factors would have on the variance in physical and mental health scores. Consistent with previous literature, we found that PTSD severity was significantly associated with poorer mental health functioning, B = -0.25, SE = 0.08, ß = -0.15, t(342) = -3.07, R2 = .37, p = .002; however, contrary to our hypotheses, PTSD severity was not associated with poorer physical health functioning. Further, the hyperarousal symptom cluster was significantly associated with poorer physical health functioning, B = -0.83, SE = 0.26, ß = -0.18, t(340) = -3.16, R2 = .11, p = .002, but not mental health functioning. Limitations of our study included the use of self-report measures only and lack of objective measures. Future directions for study include examination of how health functioning perceptions change over a longer duration of PTSD symptoms and after treatment.

Factor Structure and Psychometric Properties of the Peritraumatic and Posttraumatic Emotions Questionnaires Among Active Duty Military Personnel With Posttraumatic Stress Disorder.

The Peritraumatic Emotions Questionnaire (Peri-TEQ) and Posttraumatic Emotions Questionnaire (Post-TEQ) are self-report measures of emotions experienced during and after a traumatic event, respectively. The factor structure and psychometric properties of the Peri- and Post-TEQ were investigated among 474 military personnel with posttraumatic stress disorder (PTSD) following deployment. Exploratory factor analysis and confirmatory factor analysis were conducted to test the factor structure of the scales. Internal consistency, composite reliability, convergent validity, and discriminant validity were also assessed. Four factors were identified for the Peri-TEQ (Fear, Humiliation, Anger, and Sadness), and three factors were identified for the Post-TEQ (Fear, Anger-Hurt, and Humiliation). The full scales and all subscales demonstrated adequate-to-good internal consistency, Cronbach's αs = .722-.893. The subscales demonstrated adequate-to-good composite reliability, Cronbach's αs = .763-.861. The Peri- and Post-TEQ demonstrated good convergent validity with measures of PTSD symptoms, rs = .229-.601, ps < .001, and depressive symptoms, rs = .284-.470, ps < .001, and good discriminate validity with measures of resilience, ps = .116-.940, and unit cohesion, Peri-TEQ, p = .304 and Post-TEQ, r = -.123, p = .008. The Humiliation subscales demonstrated good convergent validity with guilt cognitions, rs = .315-.341, ps < .001, and the Anger subscales demonstrated good convergent validity with state anger, rs = .260-.347, ps < .001. The Peri- and Post-TEQ are reliable, valid self-report measures of emotions during and in response to remembering a trauma. The results support the use of these measures in research investigating trauma-related emotions.

The effect of treatment on quality of life and functioning in OCD.

BACKGROUND: Given that obsessive compulsive disorder (OCD) is associated with impaired quality of life (QoL) and functioning, it is important examine whether therapeutic recovery from OCD leads to improvements on these important secondary outcomes. Only a few studies have examined how measures of OCD symptom severity relate to QoL and functioning among patients receiving treatment for OCD. METHODS: OCD severity was measured with the Obsessive-Compulsive Inventory-Revised (OCI-R), a self-report scale of OCD, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), an interview measure of OCD. Participants were 100 adults with a primary diagnosis of OCD on serotonin reuptake inhibitors (SRIs) enrolled in a randomized clinical trial comparing SRI augmentation with either exposure and response prevention (EX/RP) therapy, risperidone, or pill placebo. At baseline, mid-treatment, and post-treatment, patients completed assessments for OCD symptoms and QoL/functioning measures. Multilevel modeling was used to assess changes in QoL/functioning over the course of treatment and to compare such changes across treatment conditions. RESULTS: Improvements in QoL/functioning were significantly greater among those receiving EX/RP compared to those receiving risperidone. Compared to pill placebo, EX/RP performed better on measures of functioning but not QoL. Greater improvement in individual OCI-R scores was associated with greater improvements in QoL/functioning, regardless of condition. In addition, Y-BOCS scores appeared to moderate improvements in QoL over the course of all treatment conditions, such that those with higher Y-BOCS scores showed the greatest improvements in QoL over time. CONCLUSIONS: Improvements in QoL/functioning were associated with reduction in OCD symptom severity. The implications on OCD treatment and clinical research are discussed.

Cognitive Emotion Regulation Strategies Associated With the DSM-5 Posttraumatic Stress Disorder Criteria.

Maladaptive cognitive emotion regulation strategies have been proposed to contribute to the maintenance of posttraumatic stress disorder (PTSD). Prior work has focused on the relationship between these strategies and PTSD as a whole, rather than on how they are related to each PTSD symptom cluster. The purpose of the current study was to determine whether cognitive emotion regulation strategies are predictive of certain PTSD symptom clusters under the Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-5; American Psychiatric Association, 2013) criteria (intrusive thoughts, avoidance, negative alterations in cognitions and mood, and hyperarousal). Participants included 365 treatment-seeking, active-duty military personnel with PTSD. The negative alterations in cognitions and mood cluster were associated with dysfunctional cognitions: greater negative cognitions about the self, negative cognitions about the world, and self-blame, as well as catastrophizing (Rc2 = .519). The negative alterations in cognitions and mood cluster did not show a strong relationship with blaming others, possibly due to the complex nature of self- and other-blame in this primarily deployment-related PTSD sample. Finally, the intrusive thoughts cluster was associated with catastrophizing (Rc2 = .211), suggesting an association between frequent intrusive memories and excessively negative interpretation of those memories.