Faculty Bibliography

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimaging had not kept pace. In response, we introduce the Autism Brain Imaging Data Exchange (ABIDE)-a grassroots consortium aggregating and openly sharing 1112 existing resting-state functional magnetic resonance imaging (R-fMRI) data sets with corresponding structural MRI and phenotypic information from 539 individuals with ASDs and 573 age-matched typical controls (TCs; 7-64 years) (http://fcon_1000.projects.nitrc.org/indi/abide/). Here, we present this resource and demonstrate its suitability for advancing knowledge of ASD neurobiology based on analyses of 360 male subjects with ASDs and 403 male age-matched TCs. We focused on whole-brain intrinsic functional connectivity and also survey a range of voxel-wise measures of intrinsic functional brain architecture. Whole-brain analyses reconciled seemingly disparate themes of both hypo- and hyperconnectivity in the ASD literature; both were detected, although hypoconnectivity dominated, particularly for corticocortical and interhemispheric functional connectivity. Exploratory analyses using an array of regional metrics of intrinsic brain function converged on common loci of dysfunction in ASDs (mid- and posterior insula and posterior cingulate cortex), and highlighted less commonly explored regions such as the thalamus. The survey of the ABIDE R-fMRI data sets provides unprecedented demonstrations of both replication and novel discovery. By pooling multiple international data sets, ABIDE is expected to accelerate the pace of discovery setting the stage for the next generation of ASD studies.Molecular Psychiatry advance online publication, 18 June 2013; doi:10.1038/mp.2013.78.

Brain operation is profoundly rhythmic. Oscillations of neural excitability shape sensory, motor, and cognitive processes. Intrinsic oscillations also entrain to external rhythms, allowing the brain to optimize the processing of predictable events such as speech. Moreover, selective attention to a particular rhythm in a complex environment entails entrainment of neural oscillations to its temporal structure. Entrainment appears to form one of the core mechanisms of selective attention, which is likely to be relevant to certain psychiatric disorders. Deficient entrainment has been found in schizophrenia and dyslexia and mounting evidence also suggests that it may be abnormal in attention-deficit/hyperactivity disorder (ADHD). Accordingly, we suggest that studying entrainment in selective-attention paradigms is likely to reveal mechanisms underlying deficits across multiple disorders.

OBJECTIVE:Clinicians caring for children rely on measures of linear growth as a biomarker of development and overall health. Current reference ranges for height velocity (HV) for US children are unable to provide HV percentiles or Z-scores for early maturing and late maturing children at ages other than age at peak velocity. We present empirically acquired, age-specific reference ranges for HV from a contemporary sample of US youth. STUDY DESIGN/METHODS:Subjects were enrolled in the Bone Mineral Density in Childhood Study, a large, multicenter, multiethnic, contemporary cohort of children (aged 5-19 y at enrollment) from the United States followed for up to 7 years. More than 4000 annual (12 ± 1 mo) HV measurements from approximately 1500 children were available. Pubertal status was determined by breast stage or testicular volume assessed by experienced health providers. Age-specific reference ranges were determined using the LMS method. RESULTS:Reference ranges (third to 97th percentiles) were generated for the entire cohort and for subgroups whose pubertal timing was defined as "earlier," "average," or "later." African American girls experienced earlier pubertal onset and had greater HV at younger ages and lower HV at older ages, compared to non-African American girls; differences did not persist after adjustment for pubertal timing. These differences were not observed for males. CONCLUSIONS:These reference ranges for annual HV can be used to assess growth relative to peers of the same age and sex, with consideration of pubertal timing. Z-scores and exact percentiles for HV can also be determined for population studies.

Previous research has shown that healthy individuals who fail to differentiate among emotional states (i.e., those with low emotional granularity; EG) have poorer social functioning (SF) than those with high EG. It is unknown, however, whether these associations extend to clinical disorders characterized by impaired SF, such as schizophrenia. In the present study, we compared SF and EG in individuals with schizophrenia and healthy controls, and then, within the schizophrenia group, we examined the links between EG and SF. Employing an Experience Sampling Method approach, 77 individuals with schizophrenia and 27 healthy controls rated their momentary emotions (sadness, anxiety, anger, and happiness) up to 10 times/day over a two-day period using mobile electronic devices. For each participant, we then calculated the within-subject average correlations among the momentary emotion ratings, producing two EG indices - EGIall for all emotions and EGIneg for negative ones. A subsample of participants with schizophrenia also completed self-report, interview, and ability-based measures of SF. Compared to healthy controls, individuals with schizophrenia displayed significantly poorer SF and lower EGIall, but comparable EGIneg. Within the schizophrenia group, hierarchical multiple regression analyses indicated that EGIall, but not EGIneg, significantly predicted social dysfunction after controlling for emotional awareness, symptoms, and emotional intensity and variability. Our findings indicate that individuals with schizophrenia have a relatively intact ability to differentiate among negative emotions in everyday life. However, they experience significant difficulties differentiating between positive and negative emotions, and this may contribute to their social difficulties.

A long tradition in sound symbolism describes a host of sound-meaning linkages, or associations between individual speech sounds and concepts or object properties. Might sound symbolism extend beyond sound-meaning relationships to linkages between sounds and modes of thinking? Integrating sound symbolism with construal level theory, we investigate whether vowel sounds influence the mental level at which people represent and evaluate targets. We propose that back vowels evoke abstract, high-level construal, while front vowels induce concrete, low-level construal. Two initial studies link front vowels to the use of greater visual and conceptual precision, consistent with a construal account. Three subsequent studies explore construal-dependent tradeoffs as a function of vowel sound contained in the target's name. Evaluation of objects named with back vowels was driven by their high- over low-level features; front vowels reduced or reversed this differentiation. Thus, subtle linguistic cues appear capable of influencing the very nature of mental representation.

Data on the relationship between sleep disturbances and refractory epileptic encephalopathies (EEs) are scarce. Our aim was to assess, by means of nocturnal polysomnography, if children with EEs present with objective alterations in sleep organization. Twenty-three children with EEs (12 males; mean age: 8.7+/-1.4years) and 40 healthy controls (22 males; mean age: 8.8+/-1.1years) underwent an overnight full polysomnography (PSG). Relative to controls, children with EEs showed a significant reduction in all PSG parameters related to sleep duration time in bed (TIB-min p<0.001), total sleep time (TST-min p<0.001), and sleep percentage (SPT-min p<0.001), as well as significantly higher REM latency (FRL-min p<0.001), rate in stage shifting (p=0.005), and number of awakenings/hour (p=0.002). Relative to controls, children with EEs also showed significant differences in respiratory parameters (AHI/h p<0.001, ODI/h p<0.001, SpO2% p<0.001, SpO2 nadir% p<0.001) and a higher rate of periodic limb movements (PLMs% p<0.001). Our findings suggest that sleep evaluation could be considered mandatory in children with refractory epileptic encephalopathy in order to improve the clinical management and the therapeutic strategies.

OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) is a new disorder for DSM-5 that is uncommon and frequently co-occurs with other psychiatric disorders. Here, the authors test whether meeting diagnostic criteria for this disorder in childhood predicts adult diagnostic and functional outcomes. METHOD: In a prospective, population-based study, individuals were assessed with structured interviews up to six times in childhood and adolescence (ages 10 to 16 years; 5,336 observations of 1,420 youths) for symptoms of DMDD and three times in young adulthood (ages 19, 21, and 24-26 years; 3,215 observations of 1,273 young adults) for psychiatric and functional outcomes (health, risky/illegal behavior, financial/educational functioning, and social functioning). RESULTS: Young adults with a history of childhood DMDD had elevated rates of anxiety and depression and were more likely to meet criteria for more than one adult disorder relative to comparison subjects with no history of childhood psychiatric disorders (noncases) or individuals meeting criteria for psychiatric disorders other than DMDD in childhood or adolescence (psychiatric comparison subjects). Participants with a history of DMDD were more likely to have adverse health outcomes, be impoverished, have reported police contact, and have low educational attainment as adults compared with either psychiatric or noncase comparison subjects. CONCLUSIONS: The long-term prognosis of children with DMDD is one of pervasive impaired functioning that in many cases is worse than that of other childhood psychiatric disorders.

Purpose Given the metabolic and neurologic side effects of antipsychotics and concerns about the increased risks associated with concomitant use, antipsychotic polypharmacy is a quality concern. This study assessed the operating characteristics of a Medicaid claims-based measure of antipsychotic polypharmacy. Methods A random sample from 10 public mental health clinics and 312 patients met criteria for this study. Medical record extractors were blind to measure status. We examined the prevalence, sensitivity, specificity, and positive predictive value (PPV) in Medicaid claims, testing nine different definitions of antipsychotic polypharmacy, including >14, >60, or >90 days concurrent use of >/=2 antipsychotic agents, each with allowable gaps of up to 0, 14, or 32 days in days' supply of antipsychotic medications. Results All Medicaid claims measure definitions tested had excellent specificity and PPV (>91%). Good to excellent sensitivity was dependent upon use of a 32-day gap allowance, particularly as duration of concurrent antipsychotic use increased. The proposed claims-based measure (90-day concurrent use of >/=2 or more antipsychotics, allowing for a 32-day gap) had excellent specificity (99.1%, 95%CI: 98.2-99.6) and PPV (90.9%, 95%CI: 83.1-95.7) with good sensitivity (79.4%, 95%CI: 70.4-86.6). The overall level of concordance between claims and medical record-based categorization of antipsychotic polypharmacy was high (96.4%, n = 301/312 clients, Cohen's K = 84.7, 95%CI: 75.9-93.5). Discrepant cases were reviewed, and implications are discussed. Conclusions Administrative claims data can be used to construct valid measures of antipsychotic polypharmacy

PURPOSE: To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). MATERIALS AND METHODS: Twenty-seven patients and 27 age-matched controls were recruited. The 3 Tesla fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFFs were computed with filtering (0.01-0.08 Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. RESULTS: In comparison with controls, MTBI patients exhibited significantly decreased fALFFs in the thalamus (and frontal/temporal subsegments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/ thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P < 0.05). This thalamic and cortical disruption also existed at task-related condition in patients. CONCLUSION: The decreased fALFFs (i.e., lower neuronal activity) in the thalamus and its segments provide additional evidence of thalamic injury in patients with MTBI. Our findings of fALFFs and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI. J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc.

Previous work on peer victimization has focused primarily on academic outcomes and negative indicators of youth involved in bullying. Few studies have taken a strength-based approach to examine attributes associated with bullies and victims of bullying. As such, we examined developmental trajectories of moral, performance, and civic character components, and their links to bully status using data from 713 youth (63% female) who participated in Wave 3 (approximately Grade 7) through Wave 6 (approximately Grade 10) of the 4-H Study of Positive Youth Development. Latent growth curve analyses indicated that moral character was stable across waves, whereas civic character increased slightly by Wave 6. Trajectories for performance character varied; some youth alternatively displayed positive versus negative growth. Youth who reported bullying behavior reported lower initial levels of moral, performance, and civic character as compared to youth not involved in bullying. Bully-victims reported lower initial levels of moral and civic character as compared to youth not involved in bullying. Implications for future work examining character-related components in the context of peer victimization are discussed.