OBJECTIVE: Clinically anxious youth are hypervigilant to emotional stimuli and display difficulty shifting attention from emotional to nonemotional stimuli, suggesting impairments in cognitive control over emotion. However, it is unknown whether the neural substrates of such biases vary across the clinical-to-nonclinical range of anxiety or by age.
METHODS: Youth aged 7 to 17 years with clinical anxiety (n = 119) or without an anxiety diagnosis (n = 41) matched emotional faces or matched shapes flanked by emotional face distractors during magnetic resonance imaging, probing emotion processing and cognitive control over emotion, respectively. Building from the National Institute of Mental Health Research Domain Criteria (RDoC) framework, clinically anxious youth were sampled across diagnostic categories, and non-clinically affected youth were sampled across minimal-to-subclinical severity.
RESULTS: Across both conditions, anxiety severity was associated with hyperactivation in the right inferior parietal lobe, a substrate of hypervigilance. Brain-anxiety associations were also differentiated by attentional state; anxiety severity was associated with greater left ventrolateral prefrontal cortex activation during emotion processing (face matching) and greater activation in the left posterior superior temporal sulcus and temporoparietal junction (and slower responses) during cognitive control over emotion (shape matching). Age also moderated associations between anxiety and cognitive control over emotion, such that anxiety was associated with greater right thalamus and bilateral posterior cingulate cortex activation for children at younger and mean ages, but not for older youth.
CONCLUSIONS: Aberrant function in brain regions implicated in stimulus-driven attention to emotional distractors may contribute to anxiety in youth. Results support the potential utility of attention modulation interventions for anxiety that are tailored to developmental stage.
BACKGROUND: Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety; https://clinicaltrials.gov; NCT02810171.

Siblings of individuals with neurodevelopmental conditions (NDCs) experience distinct challenges and have unique strengths compared to siblings of individuals without NDCs. The present study examined attributes and aspirations of siblings of individuals with and without neurodevelopmental conditions, and analyzed the association between qualitative responses and quantitative measures of growth mindset, positive and negative valence, and mental health diagnoses. A novel mixed methods thematic analysis was employed to explore the experiences of 166 siblings (75 NDC and 91 controls, aged 14-26, 66.27% female) completing an online survey as part of a larger study on sibling mental health. The overarching theme described The Process of Self-Actualization and Integration, reflecting the journey siblings undergo in seeking to understand themselves and others amidst psychological challenges. It encompassed three subthemes: Personal Growth and Identity Formation; Connection and Belonginess; and Societal Perspective and Global Consciousness. Qualitative responses were analyzed within a Research Domain Criteria (RDoC) framework, and associations between phenomenology and mental health diagnoses examined. NDC siblings had higher negative valence and lower positive valence embedded in their responses, and quantitatively lower self-reported growth mindset (i.e., beliefs about the capacity for personal growth), compared to control siblings, which correlated with self-reported mental health diagnoses. Findings suggest clinical practice may focus on optimizing self-identified strengths and offer opportunities for self-actualization of hopes and ambitions, while providing support for families to attenuate bioecological factors impacting mental health.

BACKGROUND: This pilot study aimed to assess patients\' cognitive functioning with the Polish version of the THINC-it tool and to analyze its association with self-reported quality of life (QOL).
METHODS: Twenty-one patients (mean age: 37.8 ± 10.4) were assessed at baseline and after six weeks of a standard therapeutic outpatient program. Participants completed the World Health Organization QOL Questionnaire (WHOQOL-BREF) and the THINC-it tool at both visits. The tool consists of tasks evaluating working memory (SYMBOL CHECK), attention (SPOTTER), executive functions (TRIALS), and cognitive skills (CODEBREAKER).
RESULTS: During the second visit, patients showed significant improvements in mean latency of correct responses of SPOTTER: p = 0.021, Cohen\'s d = 0.38 and in the Physical health domain: p = 0.007, Cohen\'s d = 0.37. The number of correct responses for CODEBREAKER was positively associated with the Physical health domain at visit 1 (r = 0.53, p = 0.014) and visit 2 (r = 0.42, p = 0.058). The number of correct responses at SYMBOL CHECK was positively related to QOL in the Environment domain only at visit 2 (r = 0.45, p = 0.042).
CONCLUSIONS: These results suggest the THINC-it tool has utility as a cognitive measure in adults with schizophrenia in both clinical and research settings.

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability - mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing-externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

Alcohol use confers risk for suicidal thoughts and behaviors (ideation, attempt) in early adolescents. The Research Domain Criteria provides a framework for examination of multidimensional and modifiable risk factors. We examined distinct latent profiles based on patterns of positive valence (reward responsivity) and cognitive systems (neurocognition) from the ABCD Study (age 9−10, N = 10,414) at baseline enrollment. Longitudinal associations were determined between baseline positive valence and cognitive profiles and group classification (alcohol use, suicidal thoughts and behaviors, or their co-occurrence) two-years after initial assessment (ages 11−12). Three unique profiles of positive valence, cognition, alcohol use, and suicidal thoughts and behaviors were identified. Two baseline profiles predicted alcohol use and suicidal thoughts and behaviors, two-years after initial assessment. Low positive valence with high cognition (but low impulsivity) predicted alcohol use (OR = 1.414, p< 0.001), while high positive valence with low cognition (but high impulsivity) predicted suicidal thoughts and behaviors (OR = 1.25, p = 0.038), compared to average positive valence and cognition. Unique profiles of positive valence and cognitive systems among 9−12-year-olds may be predictive of alcohol use and suicidal thoughts and behaviors over a two-year period. Findings underscore the potential for trajectory research on positive valence and cognitive profiles to enhance prevention for early-adolescents.

Deficit schizophrenia is a subtype of schizophrenia presenting primary and enduring negative symptoms (NS). Although one of the most updated hypotheses indicates a relationship between NS and impaired motivation, only a few studies have investigated abnormalities of motivational circuits in subjects with deficit schizophrenia (DS). Our aim was to investigate structural connectivity within motivational circuits in DS. We analyzed diffusion tensor imaging (DTI) data from 46 subjects with schizophrenia (SCZ) and 35 healthy controls (HCs). SCZ were classified as DS (n = 9) and non-deficit (NDS) (n = 37) using the Schedule for Deficit Syndrome. The connectivity index (CI) and the Fractional Anisotropy (FA) of the connections between selected brain areas involved in motivational circuits were examined. DS, as compared with NDS and HCs, showed increased CI between the right amygdala and dorsal anterior insular cortex and increased FA of the pathway connecting the left nucleus accumbens with the posterior insular cortex. Our results support previous evidence of distinct neurobiological alterations underlying different clinical subtypes of schizophrenia. DS, as compared with NDS and HCs, may present an altered pruning process (consistent with the hyperconnectivity) in cerebral regions involved in updating the stimulus value to guide goal-directed behavior.

The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia.
We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses.
Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample.
Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.

Disparate diagnostic categories from the Diagnostic and Statistical Manual of Mental Disorders (DSM), including generalized anxiety disorder, major depressive disorder and post-traumatic stress disorder, share common behavioral and phenomenological dysfunctions. While high levels of comorbidity and common features across these disorders suggest shared mechanisms, past research in psychopathology has largely proceeded based on the syndromal taxonomy established by the DSM rather than on a biologically-informed framework of neural, cognitive and behavioral dysfunctions. In line with the National Institute of Mental Health\'s Research Domain Criteria (RDoC) framework, we present a Human Connectome Study Related to Human Disease that is intentionally designed to generate and test novel, biologically-motivated dimensions of psychopathology. The Dimensional Connectomics of Anxious Misery study is collecting neuroimaging, cognitive and behavioral data from a heterogeneous population of adults with varying degrees of depression, anxiety and trauma, as well as a set of healthy comparators (to date, n = 97 and n = 24, respectively). This sample constitutes a dataset uniquely situated to elucidate relationships between brain circuitry and dysfunctions of the Negative Valence construct of the RDoC framework. We present a comprehensive overview of the eligibility criteria, clinical procedures and neuroimaging methods of our project. After describing our protocol, we present group-level activation maps from task fMRI data and independent components maps from resting state data. Finally, using quantitative measures of neuroimaging data quality, we demonstrate excellent data quality relative to a subset of the Human Connectome Project of Young Adults (n = 97), as well as comparable profiles of cortical thickness from T1-weighted imaging and generalized fractional anisotropy from diffusion weighted imaging. This manuscript presents results from the first 121 participants of our full target 250 participant dataset, timed with the release of this data to the National Institute of Mental Health Data Archive in fall 2020, with the remaining half of the dataset to be released in 2021.

The present study aimed to objectively examine the Research Domain Criteria (RDoC) subconstructs of reward anticipation and initial response to reward in adult suicide attempters, compared with nonattempters, using electroencephalography (EEG) and event-related potentials (ERPs) within the context of the RDoC-recommended experimental paradigms for these subconstructs.
Participants had either a history of at least 1 suicide attempt (n = 30) or no history of attempting suicide (n = 30). They completed diagnostic interviews, self-report questionnaires, and 2 computer-based tasks-the monetary incentive delay task and the doors task-during which continuous EEG was recorded. Temporospatial principal component analysis was used to isolate each of the ERP components of interest from other temporally or spatially overlapping components. Exploratory time-frequency analyses were also conducted to supplement the ERP analyses.
Suicide attempters, compared with nonattempters, exhibited specific deficits in reward anticipation (i.e., blunted cue-P3 ERP during the monetary incentive delay task) and in initial response to reward (i.e., reduced feedback-related delta power in the gain condition of the doors task). These results were at least partially independent of current symptoms or diagnoses of depression and anxiety.
These findings constitute an important step in obtaining a more fine-grained understanding of the specific reward-related abnormalities that might contribute to suicide risk.

The Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health (NIMH) established a dimensional framework for understanding psychiatric constructs. Initial Responsiveness to Reward Attainment (IRRA) was identified as a dimensional construct relevant to several psychiatric disorders. The current study aimed to (1) examine IRRA as a predictor of psychopathology and impairment in children and their parents, and (2) examine the potential effects of sex and ancestry on the relationship between IRRA and psychopathology. Participants included 1127 children ages 6 to 12, and 1018 of their parents. Parents and children completed self-report measures of IRRA. Psychopathology and impairment were measured using self-report for adults, and parent-report and semi-structured interview for children. In adults, IRRA was significantly, but modestly, related to adaptive functioning. In children, IRRA was significantly, but modestly, related to overall, school, spare time, home, and peer functioning. Findings suggest IRRA may be a helpful construct for understanding adaptive functioning in adults and children, however it may be less helpful for understanding specific dimensions of psychopathology. Additionally, ancestry should be taken into consideration when examining how IRRA relates to psychopathology and functioning.