BACKGROUND: Autism spectrum conditions (ASC) and quantitative autistic traits (QATs) are associated with sensory symptoms, which may contribute to anxiety and adversely affect social and cognitive development. Although sensory symptoms can occur across all senses, the relative roles of specific sensory modalities as contributors to the autistic phenotype and to anxiety are not well understood. The objective of this study was to examine which sensory symptoms were most predictive of high anxiety.
METHODS: We recruited 257 female primary caregivers of children aged 6 to 11 years (49% girls) to a questionnaire study comprising parent-report measures for classical QATs (social, communicative, and rigid), autism-related sensorimotor symptoms (visual, auditory, tactile, olfactory, gustatory, vestibular, proprioceptive, and motor), and anxiety symptoms. First, Bayesian stochastic search variable selection (SSVS) was used to identify the most probable sensorimotor predictors of specific QATs as well as diagnosed ASC. Then, the selected predictors were used in another SSVS, using anxiety symptoms as a dependent variable, to identify which of the autism-relevant sensorimotor symptoms were most robustly predictive of anxiety. Finally, the effect sizes of anxiety-related sensory symptoms were estimated with linear regressions.
RESULTS: We found that auditory symptoms and motor difficulties were most predictive of ASC diagnosis. Developmental motor difficulties were also strongly related to all individual QATs, whereas auditory symptoms were more selectively predictive of rigid traits. Tactile symptoms robustly predicted social interaction QATs, and proprioceptive symptoms predicted communicative QATs. Anxiety outcomes were most strongly predicted by difficulties with auditory and olfactory processing.
CONCLUSIONS: The results support the clinical importance of being alert to complaints about sounds and hearing in neurodevelopmental populations, and that auditory processing difficulties may be evaluated as an early marker of poor mental health in children with and without diagnosed autism. Olfactory processing differences appeared to be an anxiety marker less strongly associated with ASC or QATs, while motor difficulties were highly autism-relevant but not equally strongly associated with anxiety outcomes. We suggest that future studies may focus on the mechanisms and consequences of neurodevelopmental central auditory processing dysfunction and its potential relationship to anxiety disorders.

For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute\'s ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives-Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia; and Research Domain Criteria-and related funding announcements that span basic experimental studies, efficacy and comparative effectiveness trials, and implementation research designed to promote cognitive healthcare in real-world treatment settings. We discuss how trends in science and public health policy since the early 2000s have influenced NIMH treatment development activities, resulting in greater attention to (1) inclusive teams that reflect end-user perspectives on the utility of proposed studies; (2) measurement of discrete neurocognitive processes to inform targeted interventions; (3) clinical trials that produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects; and (4) \"productive urgency\" in pursuing feasible and effective cognitive interventions for psychosis. Programs employing these principles have catalyzed cognitive measurement, drug development, and behavioral intervention approaches that aim to improve neurocognition and community functioning among persons with schizophrenia. NIMH will maintain support for innovative and impactful investigator-initiated research that advances patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional brain areas involved. We evaluated the relationships between brain microstructural features and causality orientation in patients with schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) using diffusional kurtosis imaging (DKI) techniques. Methods Forty patients with MDD, 36 with BD, and 30 with schizophrenia underwent DKI and assessment using the General Causality Orientation Scale (GCOS). We analyzed the DKI index and the GCOS subscales. Results The psychiatric patients showed significant positive correlations between the GCOS-autonomy orientation score and the mean kurtosis (MK) values in the prefrontal regions, orbitofrontal regions, and posterior cingulate cortex. When the analyses were performed separately by disease and gender, a positive correlation was found between the GCOS-autonomy orientation score and the MK values in the left prefrontal regions transdiagnostically, especially among female patients with MDD, BD, and schizophrenia. Conclusions A similar association between intrinsic motivation and MK value in the left prefrontal cortex was suggested in patients with schizophrenia, MDD, and BD. The commonality of this association among these disorders might lead to the discovery of a new biomarker for psychiatric clinical research.

BACKGROUND: To enable greater use of National Institute of Mental Health Research Domain Criteria (RDoC) in real-world settings, we applied large language models (LLMs) to estimate dimensional psychopathology from narrative clinical notes.
METHODS: We conducted a cohort study using health records from individuals age ≤18 years evaluated in the psychiatric emergency department of a large academic medical center between November 2008 and March 2015. Outcomes were hospital admission and length of emergency department stay. RDoC domains were estimated using a Health Insurance Portability and Accountability Act-compliant LLM (gpt-4-1106-preview) and compared with a previously validated token-based approach.
RESULTS: The cohort included 3059 individuals (median age 16 years [interquartile range, 13-18]; 1580 [52%] female, 1479 [48%] male; 105 [3.4%] identified as Asian, 329 [11%] as Black, 288 [9.4%] as Hispanic, 474 [15%] as other race, and 1863 [61%] as White), of whom 1695 (55%) were admitted. Correlation between LLM-extracted RDoC scores and the token-based scores ranged from small to medium as assessed by Kendall\'s tau (0.14-0.22). In logistic regression models adjusting for sociodemographic and clinical features, admission likelihood was associated with greater scores on all domains, with the exception of the sensorimotor domain, which was inversely associated (p < .001 for all adjusted associations). Tests for bias suggested modest but statistically significant differences in positive valence scores by race (p < .05 for Asian, Black, and Hispanic individuals).
CONCLUSIONS: An LLM extracted estimates of 6 RDoC domains in an explainable manner, which were associated with clinical outcomes. This approach can contribute to a new generation of prediction models or biological investigations based on dimensional psychopathology.

Schizotypy refers to a latent personality organization that reflects liability to schizophrenia. Because schizotypy is a multidimensional construct, people with schizotypy vary in behavioral and neurobiological features. In this article, we selectively review the neuropsychological and neurobiological profiles of people with schizotypy, with a focus on negative schizotypy. Empirical evidence is presented for alterations of neuropsychological performance in negative schizotypy. We also cover the Research Domain Criteria domains of positive valence, social process, and sensorimotor systems. Moreover, we systematically summarize the neurobiological correlates of negative schizotypy at the structural, resting-state, and task-based neural levels, as well as the neurochemical level. The convergence and inconsistency of the evidence are critically reviewed. Regarding theoretical and clinical implications, we argue that negative schizotypy represents a useful organizational framework for studying neuropsychology and neurobiology across different psychiatric disorders.
This perspective paper provides empirical evidence to show that schizotypy, and especially negative schizotypy, are associated with alterations of positive valence, social process, and sensorimotor systems domains within the Research Domain Criteria (RDoC). This perspective paper also systematically summarizes the neurobiological correlates of negative schizotypy at the structural, resting-state, and task-based neural levels, as well as the neurochemical level. We argue that negative schizotypy represents a useful organizational framework for studying neuropsychology and neurobiology across different psychiatric disorders.

BACKGROUND: Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps.
METHODS: Across 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task. Using partial least squares regression, we investigated genes whose expression in the Allen Human Brain Atlas was associated with anatomical patterns of stress-related FC change. Finally, we correlated stress-related FC change maps with opioid and GABAA (gamma-aminobutyric acid A) receptor distribution maps derived from positron emission tomography.
RESULTS: Results revealed robust effects of stress on global cortical connectivity, with increased global FC in frontoparietal and attentional networks and decreased global FC in the medial default mode network. Moreover, robust increases emerged in FC of the caudate, putamen, and amygdala with regions from the ventral attention/salience network, frontoparietal network, and motor networks. Such regions showed preferential expression of genes involved in cell-to-cell signaling (OPRM1, OPRK1, SST, GABRA3, GABRA5), similar to previous genetic MDD studies.
CONCLUSIONS: Acute stress altered global cortical connectivity and increased striatal connectivity with cortical regions that express genes that have previously been associated with imaging abnormalities in MDD and are rich in μ and κ opioid receptors. These findings point to overlapping circuitry underlying stress response, reward, and MDD.

Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active targets to create more effective interventions for SUD treatment and prevention. Recent large-scale cohort studies from early childhood are generating multiple levels of neuroscience-based information with the potential to inform the development and refinement of future preventive strategies. However, there are still no available well-recognized frameworks to guide the integration of these multi-level datasets into prevention interventions. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioral domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science and adapted the framework for the existing preventive interventions. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents, we identified 22 unique preventive interventions. By teasing apart these 22 interventions into the RDoC domains, we proposed distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, to be targeted, engaged and modified for effective addiction prevention.

From its inception, development and psychopathology theorists have sought to uncover the earliest forms of risk for mental health challenges in children, to prevent the development of more severe, intractable manifestations of psychopathology. Large familial risk registries have advanced our understanding of early, potentially modifiable factors that could prevent or mitigate the expression of challenging symptoms of neurodevelopmental conditions, and similar registries have been proposed to advance understanding of ADHD and related phenotypes. Data from single-site studies, largely focused on perinatal exposure to maternal mood disorders, reveal that a robust predictor of child psychopathology is parental psychopathology. However, early developmental trajectories of psychopathology risk may be better captured using transdiagnostic approaches in pregnancy, capturing the full range of mental health symptoms. We describe here the need for a parental mental health registry that begins prenatally that includes deep behavioral phenotyping across a range of transdiagnostic indicators of mental health risk to prevent psychopathology in children. This registry has the potential to uncover pathways to psychopathology risk in childhood and support the discovery of novel mechanisms to be targeted for prevention and intervention.

BACKGROUND: The Probabilistic Reward Task (PRT) is a signal detection task that assesses reward learning. In laboratory versions of the task, individuals with current or past major depressive disorder (MDD) were characterized by reduced response bias towards a more frequently rewarded stimuli, compared to controls. Our main goal was to develop and validate a novel online version of the PRT, and, in exploratory analyses, evaluate whether lifetime history of depression was associated with blunted reward learning.
METHODS: 429 participants recruited via CloudResearch completed questionnaires assessing psychiatric history and an online PRT featuring visually appealing stimuli. 108 participants reported either current or past diagnosis of MDD (lifetime MDD group), and were compared to 321 without lifetime MDD.
RESULTS: Participants showed overall increase in response bias, validating the online PRT. Females with lifetime MDD (N = 43), compared to females without prior history of MDD (N = 173), exhibited blunted response bias towards the more frequently rewarded stimulus (i.e., reduced reward learning).
CONCLUSIONS: Participants did not undergo a structured clinical interview, thus we cannot confirm whether they met full diagnostic criteria for depression.
CONCLUSIONS: The online PRT yielded similar psychometric properties as laboratory versions of the task. In exploratory analyses, females with lifetime MDD showed a lower propensity to modulate behavior as a function of rewards, which might contribute to heightened vulnerability for developing MDD in females. Future studies should consider social, cultural, and neurobiological factors contributing to sex differences in reward responsiveness and how factors may relate to disease prognosis and treatment outcomes.

Research on the psychophysiology of stress is expanding rapidly, but the field lacks a clear integrative framework to help translate research findings into empirically supported stress interventions. The Research Domain Criteria (RDoC) is an excellent candidate to explore as a framework to integrate stress research. The RDoC framework is a dimensional, multi-modal approach to psychopathology proposed as an alternative to categorical approaches used by the International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual (DSM). The goal of this paper is to explore the RDoC as a framework to integrate psychophysiology research into therapeutic interventions for stress. The RDoC consists of six domains: negative valence systems, positive valence systems, cognitive systems, social processes systems, arousal/regulatory systems, and sensorimotor systems, and provides an excellent structure for integrating information from multiple levels of functioning including physiology, behavior, and self-report, as well as genes, molecules, cells, and brain circuits. Integrating psychophysiological research on stress using the RDoC framework can direct and amplify stress management and psychotherapeutic interventions. First, the RDoC provides a clear foundation for conceptualizing the stress response in terms of important concepts such as allostasis and adaptation. In this perspective, the terms \"allostatic response\" or \"adaptation response\" are more descriptive terms than \"stress response\" in understanding bodily responses to life threats and challenges. Second, psychophysiological approaches can be used in the context of modalities such as biofeedback and mindfulness to both collect psychophysiological data and then integrate that data into a broader therapeutic framework. Heart rate variability (HRV) biofeedback is being used more frequently as part of a therapeutic intervention package with stress management and psychotherapy, and HRV data is also used to provide outcome evidence on the efficacy of treatment. Mindfulness practices are commonly used in combination with stress management and psychotherapy, and psychophysiological data (HRV, EEG, blood pressure, etc.) is often collected to explore and understand mind/body relationships. In conclusion, the lack of a clear framework to assess and understand mind/body functioning limits current stress research and interventions. The RDoC provides a strong framework to assess and integrate physiological and psychological data and improve stress interventions.