In response to shortcomings with the current diagnostic classification system for mental health disorders, such as poor validity and reliability of categorical diagnoses, the National Institute of Mental Health proposed the Research Domain Criteria (RDoC) initiative to move towards a dimensional approach using translational research. The current study examined associations between measures of behaviors, cognitions, and mental health symptoms and how they overlap in the Negative Valence Systems (NVS) domain. Specifically, we examined how the Self-Reports unit of analysis reflects the RDoC NVS constructs of acute threat, potential threat, sustained threat, frustrative nonreward, and loss. The overall goal was to identify additional self-report measures that reflect these constructs. Participants, two student samples and two community samples (total N = 1,509), completed online self-reported measures. Questionnaire total and subscale scores were submitted to a principal-axis factor analysis with Promax rotation separately for each sample. For both student samples and one community sample six-factor solutions emerged reflecting major aspects of the RDoC NVS and positive valence systems, particularly acute threat (i.e., fear/panic), potential threat (i.e., inhibition/worry), sustained threat (i.e., chronic stress), loss (i.e., low well-being), frustrative nonreward (i.e., reactive aggression), and reduced behavioral activation. The second community sample differed in that fear/panic and frustration/anger was combined in a general distress factor. Recommendations for additional NVS self-report markers are discussed.

Recent debates have evolved regarding the classification/conceptualization of compulsive sexual behavior disorder (CSBD). Conclusions regarding an agreed upon CSBD model are hindered by reliance on the latent disease model. Competing biological-based frameworks are moving forward to replace latent disease classification more broadly but have been met with limited success. We suggest that CSBD researchers move towards developing dimensional, transtheoretical, process-based models. We further suggest additional research, particularly mixed methods and longitudinal studies. Finally, we request that federal funding bodies take a more active role in supporting CSBD research.

Given the high prevalence of depressive symptoms reported by adolescents and associated risk of experiencing psychiatric disorders as adults, differentiating the trajectories of the symptoms related to negative valence at an individual level could be crucial in gaining a better understanding of their effects later in life.
A longitudinal deep learning framework is presented, identifying self-reported and behavioral measurements that detect the depressive symptoms associated with the Negative Valence System domain of the NIMH Research Domain Criteria (RDoC).
Applied to the annual records of 621 participants (age range: 12 to 17 years) of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), the deep learning framework identifies predictors of negative valence symptoms, which include lower extraversion, poorer sleep quality, impaired executive control function and factors related to substance use.
The results rely mainly on self-reported measures and do not provide information about the underlying neural correlates. Also, a larger sample is required to understand the role of sex and other demographics related to the risk of experiencing symptoms of negative valence.
These results provide new information about predictors of negative valence symptoms in individuals during adolescence that could be critical in understanding the development of depression and identifying targets for intervention. Importantly, findings can inform preventive and treatment approaches for depression in adolescents, focusing on a unique predictor set of modifiable modulators to include factors such as sleep hygiene training, cognitive-emotional therapy enhancing coping and controllability experience and/or substance use interventions.

DiGeorge\'s syndrome is one of the most frequent microdeletion syndromes and is associated with a high risk for neuropsychiatric disorders of intelligence, social communication and executive functioning as well as psychotic disorders. The male patient described here represents one of the rare descriptions of Tourette\'s syndrome on the basis of a 22q11.2 microdeletion syndrome. The following two case studies demonstrate the variety of related clinical presentations. A characterization of these patients in a clinical and scientific context by the means of Research Domain Criteria (RDoC) enables a transdiagnostic description of overlapping as well as specific neuropsychiatric functional impairments. Possibly, this dimensional characterization might also facilitate a more exact differentiation of pleiotropic associations between genotype and phenotype.
UNASSIGNED: Das DiGeorge-Syndrom ist eines der häufigsten Mikrodeletionssyndrome und bedingt ein erhöhtes Risiko für neuropsychiatrische Störungen der Intelligenz, der sozialen Kommunikation und der Exekutivfunktionen sowie psychotische Störungen. Im Falle des vorgestellten männlichen Patienten handelt es sich um die seltene Beschreibung eines Tourette-Syndroms auf der Grundlage eines 22q11.2-Mikrodeletionssyndroms. Die folgenden zwei Fallbeispiele demonstrieren die Vielfalt assoziierter klinischer Präsentationen, selbst auf der Grundlage einer übereinstimmenden und umschriebenen genetischen Aberration. Eine Charakterisierung solcher Patient*innen im Kontext der klinisch-wissenschaftlichen Praxis anhand der Research Domain Criteria (RDoC) ermöglicht eine transdiagnostische Beschreibung der überlappenden wie auch spezifischen neuropsychiatrischen Funktionseinschränkungen. Eine solche dimensionale Charakterisierung erlaubt somit potenziell auch eine genauere Differenzierung pleiotroper Assoziationen zwischen Genotyp und Phänotyp.

The National Institute of Mental Health Research Domain Criteria (RDoC) framework promotes the dimensional and transdiagnostic operationalization of psychopathology, but consideration of the neurodevelopmental foundations of mental health problems requires deeper examination. Irritability, the dispositional tendency to angry emotion that has both mood and behavioral elements, is dimensional, transdiagnostic, and observable early in life-a promising target for the identification of early neural indicators or risk factors for psychopathology. Here, we examine functional brain networks linked to irritability from preschool to adulthood and discuss how development and early experience may influence these neural substrates. Functional connectivity measured with fMRI varies according to irritability and indicates the atypical coordination of several functional networks involved in emotion generation, emotion perception, attention, internalization, and cognitive control. We lay out an agenda to improve our understanding and detection of atypical brain:behavior patterns through advances in the characterization of both functional networks and irritability as well as the consideration and operationalization of developmental and early life environmental influences on this pathway.

Inherited metabolic disorders (IMDs) can present with psychiatric signs that vary widely from one disease to another. This picture is further complicated by the fact that these features occur at very different illness time points, which may further delay appropriate diagnosis and treatment. In this case series of 62 children and adolescents suffering from IMDs, we clustered psychiatric signs (on the basis of the fifth edition of the Diagnostic and Statistical Manual for Mental Disorders classification) as well as impaired cognitive domains (on the basis of the Research Domain Criteriamatrix) according to their mean age of onset (5.7 ± 4 years). We observed consistent patterns of occurrence across disorders. Externalizing symptoms, sleep problems, and cross-domain self-regulation deficits were found to precede the IMD diagnosis. Repetitive thoughts and behaviors as well as emotional dysregulation were found to occur around the disease onset. Finally, late-onset features included dissociative or eating disorders, together with impaired emotion knowledge. Clinicians should specifically look for the co-occurrence of age-specific atypical signs, such as treatment resistance or worsening with psychotropic medication in the earliest stages and symptom fluctuation, confusion, catatonia, or isolated visual hallucinations. We believe that the combined characterizations of psychiatric signs and impaired neurocognitive domains may enable the earliest detection of IMDs and the appropriate care of these particular manifestations.
CONCLUSIONS: Psychiatric signs are common in inherited metabolic disorders (IMDs) and may occur in the same age-range as other clinical manifestations.Three clusters of psychiatric signs and two clusters of neurocognitive domains can be defined according to their mean age of onset.Warning signs to be used in liaison psychiatry should include age-specific cognitive impairments.

OBJECTIVE: The aetiology of ADHD is complex, with genetic and environmental factors both implicated in the disorder. The most recent ADHD genome-wide association study identified 12 loci that showed significant association with the disorder. However, as highlighted by the authors, these loci \"only capture a tiny fraction\" of the risk for ADHD. It has been suggested that it may be important to disentangle: (1) the clinical complexity of the disorder, and (2) the complex interaction between genetic and environmental factors, in order to better dissect the aetiology of the disorder.
METHODS: We have conducted a clinically-relevant Pharmaco-Behavioural Genetic study in a large group of children with ADHD (~850 families) over the last 15 years. The study includes detailed evaluation of quantitative behavioural and neuropsychological phenotypes, as well as short-term response of these phenotypes to treatment with a fixed dose of methylphenidate (0.5mg/kg in a b.i.d. dose). Specific genetic markers and environmental factors were examined for their association with these dimensions.
RESULTS: Here we present results that highlight the importance of examining genetic association with quantitative traits, including those constructs having relevance to Research Domain Criteria (RDoC). Further, we demonstrate that by conducting association analysis in groups of children stratified based on exposure to key environmental exposure (maternal smoking or stress during pregnancy), we are able to increase the sensitivity for finding genes involved in the disorder.
CONCLUSIONS: These results suggest that deep phenotyping and heterogeneity reduction may be imperative in order to uncover the \"missing heritability\" of the disorder.
OBJECTIVE: L’étiologie du trouble de déficit d’attention avec hyperactivité (TDAH) est complexe, puisque des facteurs tant génétiques qu’environnementaux y sont impliqués. L’étude d’association pangénomique du TDAH la plus récente a identifié 12 loci qui présentaient une association significative avec le trouble. Toutefois, comme le soulignent les auteurs, ces loci ne « représentent qu’une infime fraction » du risque de TDAH. Il est suggéré qu’il peut être important de démêler: (1) la complexité clinique du trouble et (2) l’interaction complexe entre les facteurs génétiques et environnementaux, afin de mieux décortiquer l’étiologie du trouble.
UNASSIGNED: Nous avons mené une étude de génétique pharmaco-comportementale importante sur le plan clinique auprès d’un groupe nombreux d’enfants souffrant du TDAH (~850 familles) au cours des 15 dernières années. L’étude comporte une évaluation détaillée des phénotypes comportementaux et neuropsychologiques quantitatifs, ainsi que la réponse à court terme de ces phénotypes au traitement par dose fixe de méthylphénidate (0,5 mg/kg dans une dose deux fois par jour). Les marqueurs génétiques spécifiques et les facteurs environnementaux ont été examinés relativement à leur association à ces dimensions.
UNASSIGNED: Nous présentons ici les résultats qui soulignent l’importance d’examiner l’association génétique avec les traits quantitatifs, y compris ces construits qui ont rapport aux critères du domaine de recherche (RDoC). En outre, nous démontrons qu’en menant une analyse d’association dans des groupes d’enfants stratifiés selon leur exposition à une exposition environnementale principale (le tabagisme maternel ou le stress durant la grossesse), nous sommes capables d’accroître la sensibilité propice à trouver des gènes impliqués dans le trouble.
CONCLUSIONS: Ces résultats suggèrent qu’un phénotypage profond et une réduction de l’hétérogénéité peuvent être impératifs afin de découvrir « l’héritabilité manquante » du trouble.

The objective of this pilot study was to explore the use of a closed-loop, allostatic, acoustic stimulation neurotechnology for individuals with self-reported symptoms of post-traumatic stress, as a potential means to impact symptomatology, temporal lobe high frequency asymmetry, heart rate variability (HRV), and baroreflex sensitivity (BRS).
From a cohort of individuals participating in a naturalistic study to evaluate use of allostatic neurotechnology for diverse clinical conditions, a subset was identified who reported high scores on the Posttraumatic Stress Disorder Checklist (PCL). The intervention entailed a series of sessions wherein brain electrical activity was monitored noninvasively at high spectral resolutions, with software algorithms translating selected brain frequencies into acoustic stimuli (audible tones) that were delivered back to the user in real time, to support auto-calibration of neural oscillations. Participants completed symptom inventories before and after the intervention, and a subset underwent short-term blood pressure recordings for HRV and BRS. Changes in temporal lobe high frequency asymmetry were analyzed from baseline assessment through the first four sessions, and for the last four sessions.
Nineteen individuals (mean age 47, 11 women) were enrolled, and the majority also reported symptom scores that exceeded inventory thresholds for depression. They undertook a median of 16 sessions over 16.5 days, and 18 completed the number of sessions recommended. After the intervention, 89% of the completers reported clinically significant decreases in post-traumatic stress symptoms, indicated by a change of at least 10 points on the PCL. At a group level, individuals with either rightward (n = 7) or leftward (n = 7) dominant baseline asymmetry in temporal lobe high frequency (23-36 Hz) activity demonstrated statistically significant reductions in their asymmetry scores over the course of their first four sessions. For 12 individuals who underwent short-term blood pressure recordings, there were statistically significant increases in HRV in the time domain and BRS (Sequence Up). There were no adverse events.
Closed-loop, allostatic neurotechnology for auto-calibration of neural oscillations appears promising as an innovative therapeutic strategy for individuals with symptoms of post-traumatic stress.
ClinicalTrials.gov #NCT02709369 , retrospectively registered on March 4, 2016.