Long-wavelength traveling waves of vasomotion modulate the perfusion of cortex.

Brain arterioles are active, multicellular complexes whose diameters oscillate at ∼ 0.1 Hz. We assess the physiological impact and spatiotemporal dynamics of vaso-oscillations in the awake mouse. First, vaso-oscillations in penetrating arterioles, which source blood from pial arterioles to the capillary bed, profoundly impact perfusion throughout neocortex. The modulation in flux during resting-state activity exceeds that of stimulus-induced activity. Second, the change in perfusion through arterioles relative to the change in their diameter is weak. This implies that the capillary bed dominates the hydrodynamic resistance of brain vasculature. Lastly, the phase of vaso-oscillations evolves slowly along arterioles, with a wavelength that exceeds the span of the cortical mantle and sufficient variability to establish functional cortical areas as parcels of uniform phase. The phase-gradient supports traveling waves in either direction along both pial and penetrating arterioles. This implies that waves along penetrating arterioles can mix, but not directionally transport, interstitial fluids.

Identifying tripartite relationship among cortical thickness, neuroticism, and mood and anxiety disorders.

The number of young adults seeking help for emotional distress, subsyndromal-syndromal mood/anxiety symptoms, including those associated with neuroticism, is rising and can be an early manifestation of mood/anxiety disorders. Identification of gray matter (GM) thickness alterations and their relationship with neuroticism and mood/anxiety symptoms can aid in earlier diagnosis and prevention of risk for future mood and anxiety disorders. In a transdiagnostic sample of young adults (n = 252;177 females; age 21.7 ± 2), Hypothesis (H) 1:regularized regression followed by multiple regression examined relationships among GM cortical thickness and clinician-rated depression, anxiety, and mania/hypomania; H2:the neuroticism factor and its subfactors as measured by NEO Personality Inventory (NEO-PI-R) were tested as mediators. Analyses revealed positive relationships between left parsopercularis thickness and depression (B = 4.87, p = 0.002), anxiety (B = 4.68, p = 0.002), mania/hypomania (B = 6.08, p ≤ 0.001); negative relationships between left inferior temporal gyrus (ITG) thickness and depression (B = - 5.64, p ≤ 0.001), anxiety (B = - 6.77, p ≤ 0.001), mania/hypomania (B = - 6.47, p ≤ 0.001); and positive relationships between left isthmus cingulate thickness (B = 2.84, p = 0.011), and anxiety. NEO anger/hostility mediated the relationship between left ITG thickness and mania/hypomania; NEO vulnerability mediated the relationship between left ITG thickness and depression. Examining the interrelationships among cortical thickness, neuroticism and mood and anxiety symptoms enriches the potential for identifying markers conferring risk for mood and anxiety disorders and can provide targets for personalized intervention strategies for these disorders.

Specific Patterns of Endogenous Functional Connectivity Are Associated With Harm Avoidance in Obsessive-Compulsive Disorder.

BACKGROUND: Individuals with obsessive-compulsive disorder (OCD) show persistent avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomical studies of persistent avoidance in rodents and nonhuman primates, our goal was to test whether connections within a hypothesized persistent avoidance-related network predicted OCD-related harm avoidance (HA), a trait measure of persistent avoidance. We hypothesized that 1) HA, not an OCD diagnosis, would be associated with altered endogenous connectivity in at least one connection in the network; 2) HA-specific findings would be robust to comorbid symptoms; and 3) reliable findings would replicate in a holdout testing subsample. METHODS: Using resting-state functional connectivity magnetic resonance imaging, cross-validated elastic net for feature selection, and Poisson generalized linear models, we tested which connections significantly predicted HA in our training subsample (n = 73; 71.8% female; healthy control group n = 36, OCD group n = 37); robustness to comorbidities; and replicability in a testing subsample (n = 30; 56.7% female; healthy control group n = 15, OCD group n = 15). RESULTS: Stronger inverse connectivity between the right dorsal anterior cingulate cortex and right basolateral amygdala and stronger positive connectivity between the right ventral anterior insula and left ventral striatum were associated with greater HA across groups. Network connections did not discriminate OCD diagnostic status or predict HA-correlated traits, suggesting sensitivity to trait HA. The dorsal anterior cingulate cortex-basolateral amygdala relationship was robust to controlling for comorbidities and medication in individuals with OCD and was also predictive of HA in our testing subsample. CONCLUSIONS: Stronger inverse dorsal anterior cingulate cortex-basolateral amygdala connectivity was robustly and reliably associated with HA across groups and in OCD. Results support the relevance of a cross-species persistent avoidance-related network to OCD, with implications for precision-based approaches and treatment.

Subject-specific maximum entropy model of resting state fMRI shows diagnostically distinct patterns of energy state distributions.

Objective: Existing neuroimaging studies of psychotic and mood disorders have reported regional brain activation differences (first-order properties) and alterations in functional connectivity based on pairwise correlations in activation (second-order properties). This study used a generalized Ising model, also called a pairwise maximum entropy model (MEM), to integrate first- and second-order properties to provide a comprehensive picture of BOLD patterns and a system-wide summary measure called energy. This study examines the usefulness of individual level MEMs, attempts to identify image-derived counterparts of the model, and explores potential applications to psychiatry. Method: MEMs are fit to resting state fMRI data of each individual of a sample of 132 participants consisting of schizophrenia/schizoaffective disorder, bipolar disorder, and major depression, and a demographically matched 132 participants without these diagnoses from the UK Biobank to examine the default mode network (DMN). Results: The model explained observed brain state occurrence probabilities well across all participants, and model parameters were highly correlated to image-derived parameters for all groups. Within clinical groups, schizophrenia/schizoaffective disorder and bipolar disorder patients showed significant differences in averaged energy distribution compared to controls for all sub-systems of the DMN except for depression, where differences in the energy distributions were only detected in the DMN of the regions from the right hemisphere. Conclusions: Subject-specific Ising modeling may offer an improved measure of biological functional correlates relative to traditional approaches. The observation of distinct patterns of energy distribution among the three clinical groups compared to controls suggests relative diagnostic specificity and potential for clinical translation.

Validation of a youth suicide risk calculator in an adult sample with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) conveys the highest risk of suicide of all mental disorders. We sought to externally validate a risk calculator (RC) of suicide attempts developed in youth with BD from the Course and Outcome of Bipolar Youth (COBY) study in an adult sample. METHODS: A prospective cohort of adults with BD from the National Institute of Mental Health Collaborative Depression Study (CDS; N = 427; mean (+/- SD) age at intake (36 +/- 13 years)) was secondarily analyzed to validate the COBY RC for one-year risk of suicide attempts/deaths. Nine of the ten predictor variables from the COBY RC were available in the CDS and used: age, age of mood disorder onset, first and second (partial) degree family history of suicide, history of psychotic symptoms, substance use disorder, prior suicide attempt, socioeconomic status, and non-suicidal self-injury (prospectively, incompletely at baseline). RESULTS: Over a mean (SD) follow-up of 19 (10) years, 29 % of the CDS sample attempted suicide. The RC predicted suicide attempts/deaths over one-year follow-up with an area under the receiver operating characteristic curve (AUC) of 0.78 (95 % CI 0.75-0.80). The RC performed slightly better in those with a younger age of mood disorder onset. LIMITATIONS: Clinical samples may limit generalizability; the RC does not assess more acute suicide risk. CONCLUSIONS: One-year risk of suicide attempts/deaths can be predicted with acceptable accuracy in youth and adults with BD, comparable to commonly used RCs to predict cardiovascular risk. This RC may help identify higher-risk individuals with BD for personalized treatment and research. https://cobysuicideattemptsrc.shinyapps.io/Shiny.

Feasibility and acceptability of the Indian Autism Screening Questionnaire in clinical and community settings.

We developed and tested the Indian Autism Screening Questionnaire (IASQ), which was reported to be reliable and valid as compared to the Indian Scale for Assessment of Autism (ISAA) and the Childhood Autism Rating Scale -2 (CARS2). The present study describes the feasibility, acceptability, sociodemographic and developmental details of IASQ study participants in 5 settings- a psychiatry outpatients' clinic (n = 145), a specialised paediatric clinic (n = 24), a speciality disability centre (n = 174), a primary school (n = 41) and a government housing colony (n = 255). The IASQ could be easily administered and understood. Consistent with prior reports, the male-female ratio of participants with autism was 3.8:1. Developmental complications were reported more frequently in clinical settings, while delivery by Caesarean section was commoner among community-dwelling higher socioeconomic status mothers (53% of the officers' sample). Mothers of participants with autism more frequently reported Caesarean section birth for the proband (χ2 = 41.61, p < .0001) and prenatal and postnatal complications. Binary logistic regression confirmed that perinatal complications in the mother and father's (older) age at birth of the participant were associated with autism. The IASQ is a reliable, practical tool for screening for autism in clinical and non-clinical settings in India.

Threshold Selection for Brain Connectomes.

Introduction: Structural and functional brain connectomes represent macroscale data collected through techniques such as magnetic resonance imaging (MRI). Connectomes may contain noise that contributes to false-positive edges, thereby obscuring structure-function relationships and data interpretation. Thresholding procedures can be applied to reduce network density by removing low-signal edges, but there is limited consensus on appropriate selection of thresholds. This article compares existing thresholding methods and introduces a novel alternative "objective function" thresholding method. Methods: The performance of thresholding approaches, based on percolation and objective functions, is assessed by (1) computing the normalized mutual information (NMI) of community structure between a known network and a simulated, perturbed networks to which various forms of thresholding have been applied, and by (2) comparing the density and the clustering coefficient (CC) between the baseline and thresholded networks. An application to empirical data is provided. Results: Our proposed objective function-based threshold exhibits the best performance in terms of resulting in high similarity between the underlying networks and their perturbed, thresholded counterparts, as quantified by NMI and CC analysis on the simulated functional networks. Discussion: Existing network thresholding methods yield widely different results when graph metrics are subsequently computed. Thresholding based on the objective function maintains a set of edges such that the resulting network shares the community structure and clustering features present in the original network. This outcome provides a proof of principle that objective function thresholding could offer a useful approach to reducing the network density of functional connectivity data.

Multipronged investigation of morphometry and connectivity of hippocampal network in relation to risk for psychosis using ultrahigh field MRI.

Hippocampal abnormalities are associated with psychosis-risk states. Given the complexity of hippocampal anatomy, we conducted a multipronged examination of morphometry of regions connected with hippocampus, and structural covariance network (SCN) and diffusion-weighted circuitry among 27 familial high-risk (FHR) individuals who were past the highest risk for conversion to psychoses and 41 healthy controls using ultrahigh-field high-resolution 7 Tesla (7T) structural and diffusion MRI data. We obtained fractional anisotropy and diffusion streams of white matter connections and examined correspondence of diffusion streams with SCN edges. Nearly 89 % of the FHR group had an axis-I disorder including 5 with schizophrenia. Therefore, we compared the entire FHR group regardless of the diagnosis (All_FHR = 27) and FHR-without-schizophrenia (n = 22) with 41 controls in this integrative multimodal analysis. We found striking volume loss in bilateral hippocampus, particularly the head, bilateral thalamus, caudate, and prefrontal regions. All_FHR and FHR-without-SZ SCNs showed significantly lower assortativity and transitivity but higher diameter compared to controls, but FHR-without-SZ SCN differed on every graph metric compared to All_FHR suggesting disarrayed network with no hippocampal hubs. Fractional anisotropy and diffusion streams were lower in FHR suggesting white matter network impairment. White matter edges showed significantly higher correspondence with SCN edges in FHR compared to controls. These differences correlated with psychopathology and cognitive measures. Our data suggest that hippocampus may be a "neural hub" contributing to psychosis risk. Higher correspondence of white matter tracts with SCN edges suggest that shared volume loss may be more coordinated among regions within the hippocampal white matter circuitry.

Adolescents' Hormonal Responses to Social Stress and Associations with Adolescent Social Anxiety and Maternal Comfort: A Preliminary Study.

Both social support and social stress can impact adolescent physiology including hormonal responses during the sensitive transition to adolescence. Social support from parents continues to play an important role in socioemotional development during adolescence. Sources of social support and stress may be particularly impactful for adolescents with social anxiety symptoms. The goal of the current study was to examine whether adolescent social anxiety symptoms and maternal comfort moderated adolescents' hormonal response to social stress and support. We evaluated 47 emotionally healthy 11- to 14-year-old adolescents' cortisol and oxytocin reactivity to social stress and support using a modified version of the Trier Social Stress Test for Adolescents that included a maternal comfort paradigm. Findings demonstrated that adolescents showed significant increases in cortisol and significant decreases in oxytocin following the social stress task. Subsequently, we found that adolescents showed significant decreases in cortisol and increases in oxytocin following the maternal comfort paradigm. Adolescents with greater social anxiety symptoms showed higher levels of cortisol at baseline but greater declines in cortisol response following maternal social support. Social anxiety symptoms were unrelated to oxytocin response to social stress or support. Our findings provide further evidence that mothers play a key role in adolescent regulation of physiological response, particularly if the stressor is consistent with adolescents' anxiety. More specifically, our findings suggest that adolescents with higher social anxiety symptoms show greater sensitivity to maternal social support following social stressors. Encouraging parents to continue to serve as a supportive presence during adolescent distress may be helpful for promoting stress recovery during the vulnerable transition to adolescence.

Mother-child neural synchronization is time linked to mother-child positive affective state matching.

In the first years of life, in which self-regulation occurs via external means, mother-child synchronization of positive affect (PA) facilitates regulation of child homeostatic systems. Mother-child affective synchrony may contribute to mother-child synchronization of neural systems, but limited research has explored this possibility. Participants were 41 healthy mother-child dyads (56% girls; Mage = 24.76 months; s.d. = 8.77 months, Range = 10-42 months). Mothers' and children's brain activities were assessed simultaneously using near-infrared spectroscopy while engaging in dyadic play. Mother and child PA during play were coded separately to characterize periods in which mothers and children (i) matched on high PA, (ii) matched on low/no PA or (iii) showed a mismatch in PA. Models evaluated moment-to-moment correlations between affective matching and neural synchrony in mother-child dyads. Greater positive affective synchrony, in which mother and child showed similarly high levels of PA but not similarly low levels of PA, was related to greater synchrony in medial and lateral frontal and temporoparietal regions. Age moderated associations between mother and child neural activities but only during moments of high PA state matching. Positive, synchronous mother-child interactions may foster greater neural responding in affective and social regions important for self-regulation and interpersonal bonds.

Early indicators of bipolar risk in preschool offspring of parents with bipolar disorder.

BACKGROUND: Offspring of parents with bipolar disorder (BD-I/II) are at increased risk to develop the disorder. Previous work indicates that bipolar spectrum disorder (BPSD) is often preceded by mood/anxiety symptoms. In school-age offspring of parents with BD, we previously built a risk calculator to predict BPSD onset, which generates person-level risk scores. Here, we test whether preschool symptoms predict school-age BPSD risk. METHODS: We assessed 113 offspring of parents with BD 1-3 times during preschool years (2-5 years old) and then approximately every 2 years for a mean of 10.6 years. We used penalized (lasso) regression with linear mixed models to assess relationships between preschool mood, anxiety, and behavioral symptoms (parent-reported) and school-age predictors of BPSD onset (i.e., risk score, subthreshold manic symptoms, and mood lability), adjusting for demographics and parental symptomatology. Finally, we conducted survival analyses to assess associations between preschool symptoms and school-age onset of BPSD and mood disorder. RESULTS: Of 113 preschool offspring, 33 developed new-onset mood disorder, including 19 with new-onset BPSD. Preschool irritability, sleep problems, and parental factors were lasso-selected predictors of school-age risk scores. After accounting for demographic and parental factors, preschool symptoms were no longer significant. Lasso regressions to predict mood lability and subthreshold manic symptoms yielded similar predictors (irritability, sleep problems, and parental affective lability), but preschool symptoms remained predictive even after adjusting for parental factors (ps < .005). Exploratory analyses indicated that preschool irritability univariately predicted new-onset BPSD (p = .02) and mood disorder (p = .02). CONCLUSIONS: These results provide initial prospective evidence that, as early as preschool, youth who will develop elevated risk scores, mood lability, and subthreshold manic symptoms are already showing symptomatology; these preschool symptoms also predict new-onset BPSD. While replication of findings in larger samples is warranted, results point to the need for earlier assessment of risk and development of early interventions.

Altered patterns of central executive, default mode and salience network activity and connectivity are associated with current and future depression risk in two independent young adult samples.

Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders.

A Statewide Randomized Controlled Trial to Compare Three Models for Implementing Parent Child Interaction Therapy.

OBJECTIVE: This study (NIMH RO1 MH095750; ClinicalTrials.gov Identifier: NCT02543359) evaluated the effectiveness of three training models to implement a well-established evidence-based treatment, Parent-Child Interaction Therapy (PCIT). METHOD: Fifty licensed outpatient clinics, including 100 clinicians, 50 supervisors, and 50 administrators were randomized to one of three training conditions: 1) Learning Collaborative (LC), 2) Cascading Model (CM) or 3) Distance Education (DE). Data to assess training and implementation outcomes were collected at 4 time points coinciding with the training period: baseline, 6- (mid), 12- (post), and 24-months (1-year follow-up). RESULTS: Multi-level hierarchical linear growth modeling was used to examine changes over time in training outcomes. Results indicate that clinicians in CM were more likely to complete training, reported high levels of training satisfaction and better learning experiences compared to the other training conditions. However, supervisors in the LC condition reported greater learning experiences, higher levels of knowledge, understanding of treatment, and satisfaction compared to supervisors in other conditions. Although clinicians and supervisors in the DE condition did not outperform their counterparts on any outcomes, their performance was comparable to both LC and CM in terms of PCIT use, supervisor perceived acceptability, feasibility, system support, and clinician satisfaction. CONCLUSIONS: Through the use of a randomized controlled design and community implementation, this study contributes to the current understanding of the impact of training design on implementation of PCIT. Results also indicate that although in-person training methods may produce more positive clinician and supervisor outcomes, training is not a one-size-fits-all model, with DE producing comparable results on some variables.

The Role of Puberty and Sex on Brain Structure in Adolescents With Anxiety Following Concussion.

BACKGROUND: Adolescence represents a window of vulnerability for developing psychological symptoms following concussion, especially in girls. Concussion-related lesions in emotion regulation circuits may help explain these symptoms. However, the contribution of sex and pubertal maturation remains unclear. Using the neurite density index (NDI) in emotion regulation tracts (left/right cingulum bundle [CB], forceps minor [FMIN], and left/right uncinate fasciculus), we sought to elucidate these relationships. METHODS: No adolescent had a history of anxiety and/or depression. The Screen for Child Anxiety Related Emotional Disorders and Children's Depression Rating Scale were used at scan to assess anxiety and depressive symptoms in 55 concussed adolescents (41.8% girls) and 50 control adolescents with no current/history of concussion (44% girls). We evaluated if a mediation-moderation model including the NDI (mediation) and sex or pubertal status (moderation) could help explain this relationship. RESULTS: Relative to control adolescents, concussed adolescents showed higher anxiety (p = .003) and lower NDI, with those at more advanced pubertal maturation showing greater abnormalities in 4 clusters: the left CB frontal (p = .002), right CB frontal (p = .011), FMIN left-sided (p = .003), and FMIN right-sided (p = .003). Across all concussed adolescents, lower NDI in the left CB frontal and FMIN left-sided clusters partially mediated the association between concussion and anxiety, with the CB being specific to female adolescents. These effects did not explain depressive symptoms. CONCLUSIONS: Our findings indicate that lower NDI in the CB and FMIN may help explain anxiety following concussion and that adolescents at more advanced (vs less advanced) status of pubertal maturation may be more vulnerable to concussion-related injuries, especially in girls.

Working memory updating in individuals with bipolar and unipolar depression: fMRI study.

Understanding neurobiological characteristics of cognitive dysfunction in distinct psychiatric disorders remains challenging. In this secondary data analysis, we examined neurobiological differences in brain response during working memory updating among individuals with bipolar disorder (BD), those with unipolar depression (UD), and healthy controls (HC). Individuals between 18-45 years of age with BD (n = 100), UD (n = 109), and HC (n = 172) were scanned using fMRI while performing 0-back (easy) and 2-back (difficult) tasks with letters as the stimuli and happy, fearful, or neutral faces as distractors. The 2(n-back) × 3(groups) × 3(distractors) ANCOVA examined reaction time (RT), accuracy, and brain activation during the task. HC showed more accurate and faster responses than individuals with BD and UD. Difficulty-related activation in the prefrontal, posterior parietal, paracingulate cortices, striatal, lateral occipital, precuneus, and thalamic regions differed among groups. Individuals with BD showed significantly lower difficulty-related activation differences in the left lateral occipital and the right paracingulate cortices than those with UD. In individuals with BD, greater difficulty-related worsening in accuracy was associated with smaller activity changes in the right precuneus, while greater difficulty-related slowing in RT was associated with smaller activity changes in the prefrontal, frontal opercular, paracingulate, posterior parietal, and lateral occipital cortices. Measures of current depression and mania did not correlate with the difficulty-related brain activation differences in either group. Our findings suggest that the alterations in the working memory circuitry may be a trait characteristic of reduced working memory capacity in mood disorders. Aberrant patterns of activation in the left lateral occipital and paracingulate cortices may be specific to BD.

Comparing the Indian Autism Screening Questionnaire (IASQ) and the Indian Scale for Assessment of Autism (ISAA) with the Childhood Autism Rating Scale-Second Edition (CARS2) in Indian settings.

The Indian Autism Screening Questionnaire (IASQ), derived from the Indian Scale for Assessment of Autism ISAA (the mandated tool for autism in India), is an autism screening instrument for use in the general population by minimally trained workers. While ISAA has 40 items with four anchor points, the IASQ is a 10-item questionnaire with yes/no answers. It was initially validated using the ISAA. During its development the ISAA was itself compared to the Childhood Autism Rating Scale version 1 (ISAA Manual). In the present study, we evaluated both the ISAA and the IASQ in relation to the Childhood Autism Rating Scale version 2 (CARS-2). METHODS: Participants were recruited from three settings: a referral clinic for neurodevelopmental conditions run by the Department of Paediatrics of a tertiary care teaching hospital (NDC OPD), the outpatient department of an institute for disability and rehabilitation (NIEPID), and from the community (CGOC). Persons between ages 3-18 were recruited following consent or assent (parent and child/adolescent). The IASQ was administered by a minimally trained administrator. It was followed by ISAA and the CARS-2 (in alternating order, by different evaluators blind to each other) (CARS2 SV (Standard Version) and CARS2 HF (High Functioning) as applicable). Sensitivity, specificity and area under the Receiver Operator Characteristics (ROC) curve were calculated for IASQ and CARS2, as well as for ISAA and CARS2. Concordance between CARS2 and ISAA was calculated using kappa coefficient. RESULTS: A total of 285 participants (NIEPD n = 124; NDC OPD, n = 4; CGOC n = 157) (a total of 70 with autism and 215 controls) participated. IASQ and CARS2 were administered on 285 participants, while IASQ and ISAA were administered on 264 participants. When IASQ was compared to CARS2, sensitivity was 97%, specificity 81%, PPV 63%, NPV 99% at cut off 1 while these values were 97%, 92%, 79% and 99% respectively at cut off 2. There was high concordance between CARS2 and ISAA (Kappa 0.907, p<0.0001). CONCLUSIONS: IASQ has satisfactory sensitivity, specificity and concordance when compared with CARS2; it can be used for screening children with autism in community. The ISAA also showed a high concordance with CARS2, as it had with the older version of CARS.

The role of sleep quality on white matter integrity and concussion symptom severity in adolescents.

BACKGROUND: Sleep problems are common after concussion; yet, to date, no study has evaluated the relationship between sleep, white matter integrity, and post-concussion symptoms in adolescents. Using self-reported quality of sleep measures within the first 10 days of injury, we aimed to determine if quality of sleep exerts a main effect on white matter integrity in major tracts, as measured by diffusion Magnetic Resonance Imaging (dMRI), and further examine whether this effect can help explain the variance in post-concussion symptom severity in 12- to 17.9-year-old adolescents. METHODS: dMRI data were collected in 57 concussed adolescents (mean age[SD] = 15.4[1.5] years; 41.2 % female) with no history of major psychiatric diagnoses. Severity of post-concussion symptoms was assessed at study entry (mean days[SD] = 3.7[2.5] days since injury). Using the Pittsburgh Sleep Quality Index (PSQI), concussed adolescents were divided into two groups based on their quality of sleep in the days between injury and scan: good sleepers (PSQI global score ≤ 5; N = 33) and poor sleepers (PSQI global score > 5; N = 24). Neurite Orientation Dispersion and Dispersion Index (NODDI), specifically the Neurite Density Index (NDI), was used to quantify microstructural properties in major tracts, including 18 bilateral and one interhemispheric tract, and identify whether dMRI differences existed in good vs poor sleepers. Since the interval between concussion and neuroimaging acquisition varied among concussed adolescents, this interval was included in the analysis along with an interaction term with sleep groups. Regularized regression was used to identify if quality of sleep-related dMRI measures correlated with post-concussion symptom severity. Due to higher reported concussion symptom severity in females, interaction terms between dMRI and sex were included in the regularized regression model. Data collected in 33 sex- and age-matched non-concussed controls (mean age[SD] = 15.2[1.5]; 45.5 % female) served as healthy reference and sex and age were covariates in all analyses. RESULTS: Relative to good sleepers, poor sleepers demonstrated widespread lower NDI (18 of the 19 tracts; FDR corrected P < 0.048). This group effect was only significant with at least seven days between concussion and neuroimaging acquisition. Post-concussion symptoms severity was negatively correlated with NDI in four of these tracts: cingulum bundle, optic radiation, striato-fronto-orbital tract, and superior longitudinal fasciculus I. The multiple linear regression model combining sex and NDI of these four tracts was able to explain 33.2 % of the variability in symptom severity (F[7,49] = 4.9, P < 0.001, Adjusted R2 = 0.332). Relative to non-concussed controls, poor sleepers demonstrated lower NDI in the cingulum bundle, optic radiation, and superior longitudinal fasciculus I (FDR corrected P < 0.040). CONCLUSIONS: Poor quality of sleep following concussion is associated with widespread lower integrity of major white matter tracts, that in turn helped to explain post-concussion symptom severity in 12-17.9-year-old adolescents. The effect of sleep on white matter integrity following concussion was significant after one week, suggesting that acute sleep interventions may need this time to begin to take effect. Our findings may suggest an important relationship between good quality of sleep in the days following concussion and integrity of major white matter tracts. Moving forward, researchers should evaluate the effectiveness of sleep interventions on white matter integrity and clinical outcomes following concussion.

White Matter Correlates of Early-Onset Bipolar Illness and Predictors of One-Year Recurrence of Depression in Adults with Bipolar Disorder.

Diffusion Magnetic Resonance Imaging (dMRI) studies have reported abnormalities in emotion regulation circuits in BD; however, no study has examined the contribution of previous illness on these mechanisms. Using global probabilistic tractography, we aimed to identify neural correlates of previous BD illness and the extent to which these can help predict one-year recurrence of depressive episodes. dMRI data were collected in 70 adults with early-onset BD who were clinically followed for up to 18 years and 39 healthy controls. Higher number of depressive episodes during childhood/adolescence and higher percentage of time with syndromic depression during longitudinal follow-up was associated with lower fractional anisotropy (FA) in focal regions of the forceps minor (left, F = 4.4, p = 0.003; right, F = 3.1, p = 0.021) and anterior cingulum bundle (left, F = 4.7, p = 0.002; right, F = 7.0, p < 0.001). Lower FA in these regions was also associated with higher depressive and anxiety symptoms at scan. Remarkably, those having higher FA in the right cluster of the forceps minor (AOR = 0.43, p = 0.017) and in a cluster of the posterior cingulum bundle (right, AOR = 0.50, p = 0.032) were protected against the recurrence of depressive episodes. Previous depressive symptomatology may cause neurodegenerative effects in the forceps minor that are associated with worsening of BD symptomatology in subsequent years. Abnormalities in the posterior cingulum may also play a role.

White matter predictors of worsening of subthreshold hypomania severity in non-bipolar young adults parallel abnormalities in individuals with bipolar disorder.

BACKGROUND: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD. While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals. METHODS: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy (FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF). RESULTS: Lower FA in left CB (middle, ß = -0.22, P = 0.022; posterior, ß = -0.32, P < 0.001), right CB (anterior, ß = -0.30, P = 0.003; posterior, ß = -0.27, P = 0.005), and right UF (frontal, ß = -0.29, P = 0.002; temporal, ß = -0.40, P < 0.001) predicted worsening of subthreshold hypomania severity in non-BD individuals. BD versus healthy individuals showed lower FA in several of these segments: middle left CB (F = 8.7, P = 0.004), anterior right CB (F = 9.8, P = 0.002), and frontal right UF (F = 7.0, P = 0.009). Non-BD individuals with worsening 6-month hypomania had lower FA in these three segments versus HC and non-BD individuals without worsening hypomania, but similar FA to BD individuals. LIMITATIONS: Relatively short follow-up. CONCLUSIONS: White matter predictors of worsening subthreshold hypomania in non-BD individuals parallel abnormalities in BD individuals, and can guide early risk identification and interventions.