Faculty Bibliography

A schizophrenia phenotype for paternal and maternal age effects on illness risk could benefit etiological research. As odor sensitivity is associated with variability in symptoms and cognition in schizophrenia, we examined if it was related to parental ages in patients and healthy controls. We tested Leukocyte Telomere Length (LTL) as an explanatory factor, as LTL is associated with paternal age and schizophrenia risk. Seventy-five DSM-IV patients and 46 controls were assessed for detection of PEA, WAIS-III for cognition, and LTL, assessed by qPCR. In healthy controls, but not schizophrenia patients, decreasing sensitivity was monotonically related to advancing parental ages, particularly in sons. The relationships between parental aging and odor sensitivity differed significantly for patients and controls (Fisher's R to Z: chi2 = 6.95, P = 0.009). The groups also differed in the association of odor sensitivity with cognition; lesser sensitivity robustly predicted cognitive impairments in patients (<0.001), but these were unassociated in controls. LTL was unrelated to odor sensitivity and did not explain the association of lesser sensitivity with cognitive deficits.Parental aging predicted less sensitive detection in healthy subjects but not in schizophrenia patients. In patients, decreased odor sensitivity strongly predicted cognitive deficits, whereas more sensitive acuity was associated with older parents. These data support separate risk pathways for schizophrenia. A parental age-related pathway may produce psychosis without impairing cognition and odor sensitivity. Diminished odor sensitivity may furthermore be useful as a biomarker for research and treatment studies in schizophrenia. (c) 2015 Wiley Periodicals, Inc.

Approximately three million individuals in the United States sustain traumatic brain injury (TBI) every year, with documented impact on a range of neurological and psychiatric disturbances including mania, depression, and psychosis. Identification of subsets of individuals that may demonstrate increased propensity for posttraumatic symptoms and who may share genetic vulnerabilities for gene-environment interactions can enhance efforts to understand, predict, and prevent these phenomena. A sample of 11,489 cases from the Genomic Psychiatry Cohort (GPC), a NIMH-managed data repository for the investigation of schizophrenia and bipolar disorder, was used for this study. Cases were excluded if TBI was deemed causal to their mental illness. A k-means clustering algorithm was used to probe differences between schizophrenia and bipolar disorder associated with variables including onset age, hallucinations, delusions, head injury, and TBI. Cases were separated into an optimum number of seven clusters, with two clusters including all cases with brain injury. Bipolar disorder with psychosis and TBI were significantly correlated in one cluster in which 72% of cases were male and 99.2% sustained head injury. This cluster also carried the longest average period of unconsciousness. This study demonstrates an association of TBI with psychosis in a subset of bipolar cases, suggesting that traumatic stressors may have the ability to impact gene expression in a vulnerable population, and/or there is a heightened occurrence of TBI in individuals with underlying psychosis. Further studies should more closely examine the interplay between genetic variation in bipolar disorder and susceptibility to psychosis following TBI. (c) 2015 Wiley Periodicals, Inc.

Oppositional defiant disorder (ODD) is a frequent psychiatric disorder seen in children and adolescents with attention-deficit-hyperactivity disorder (ADHD). ODD is also a common antecedent to both affective disorders and aggressive behaviors. Although the heritability of ODD has been estimated to be around 0.60, there has been little research into the molecular genetics of ODD. The present study examined the association of irritable and defiant/vindictive dimensions and categorical subtypes of ODD (based on latent class analyses) with previously described specific polymorphisms (DRD4 exon3 VNTR, 5-HTTLPR, and seven OXTR SNPs) as well as with dopamine, serotonin, and oxytocin genes and pathways in a clinical sample of children and adolescents with ADHD. In addition, we performed a multivariate genome-wide association study (GWAS) of the aforementioned ODD dimensions and subtypes. Apart from adjusting the analyses for age and sex, we controlled for "parental ability to cope with disruptive behavior." None of the hypothesis-driven analyses revealed a significant association with ODD dimensions and subtypes. Inadequate parenting behavior was significantly associated with all ODD dimensions and subtypes, most strongly with defiant/vindictive behaviors. In addition, the GWAS did not result in genome-wide significant findings but bioinformatics and literature analyses revealed that the proteins encoded by 28 of the 53 top-ranked genes functionally interact in a molecular landscape centered around Beta-catenin signaling and involved in the regulation of neurite outgrowth. Our findings provide new insights into the molecular basis of ODD and inform future genetic studies of oppositional behavior. (c) 2015 Wiley Periodicals, Inc.

Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA. The Genomic Psychiatry Cohort established a clinically characterized repository of genomic samples from subjects with a Sz-BP diagnosis or unaffected controls, 12,975 with parental age information. We estimated relative risk ratios for Sz, schizoaffective depressed and bipolar types (SA-D, SA-B), and BP with and without history of psychotic features (PF) relative to the control group, comparing each paternal age group to the reference group 20-24 years. All tests were two-sided with adjustment for multiple comparisons. Subjects with fathers age 45+ had significantly higher risk for all diagnoses except for BP w/o PF. APA also bore no significant relation to family psychiatric history. In conclusion, we replicated APA as a risk factor for Sz. To our knowledge, this is the first published report of APA in a BP sample stratified by psychosis history, extending this association only in BP w/PF. This suggests that phenotypic expression of the APA effect in Sz-BP spectrum is psychosis, per se, rather than other aspects of these complex disorders. The lack of a significant relationship between paternal age and familial disease patterns suggests that underlying mechanisms of the paternal age effect may involve a complex interaction of heritable and non-heritable factors. The authors discuss implications and testable hypotheses, starting with a focus on genetic mechanisms and endophenotypic expressions of dopaminergic function. (c) 2015 Wiley Periodicals, Inc.

OBJECTIVE: Cognitive slowing is a core neuropsychological symptom of Multiple Sclerosis (MS). We aimed to assess the extent to which cognitive slowing in MS was predicted by changes in dorsolateral prefrontal networks. METHOD: We assessed patients with relapsing-remitting MS and healthy controls (HCs) on measures of processing speed. Participants underwent a functional MRI while performing a processing speed task to allow assessment of task-based connectivity. RESULTS: Patients were slower than HCs on the processing speed tasks. Patients showed attenuated connectivity between right and left dorsolateral prefrontal cortex (DLPFC) and task-relevant brain regions compared to HCs during processing speed task performance. Patients' connectivity with DLPFC in these group-disparate networks accounted for significant variability in their performance on processing speed measures administered both in and out of the imaging environment. Specifically, patients who had stronger functional connections with DLPFC in group-disparate networks performed faster than patients with weaker connections with DLPFC in group-disparate networks. CONCLUSION: Results suggest that MS-related cognitive slowing can be accounted for by systemic alterations in executive functional networks. (PsycINFO Database Record

Item response theory (IRT) was separately applied to parent- and teacher-rated symptoms of attention-deficit/hyperactivity disorder (ADHD) from a pooled sample of 526 six- to twelve-year-old children with and without ADHD. The dimensional structure ADHD was first examined using confirmatory factor analyses, including the bifactor model. A general ADHD factor and two group factors, representing inattentive and hyperactive/impulsive dimensions, optimally fit the data. Using the graded response model, we estimated discrimination and location parameters and information functions for all 18 symptoms of ADHD. Parent- and teacher-rated symptoms demonstrated adequate discrimination and location values, although these estimates varied substantially. For parent ratings, the test information curve peaked between -2 and +2 SD, suggesting that ADHD symptoms exhibited excellent overall reliability at measuring children in the low to moderate range of the general ADHD factor, but not in the extreme ranges. Similar results emerged for teacher ratings, in which the peak range of measurement precision was from -1.40 to 1.90 SD. Several symptoms were comparatively more informative than others; for example, is often easily distracted ("Distracted") was the most informative parent- and teacher-rated symptom across the latent trait continuum. Clinical implications for the assessment of ADHD as well as relevant considerations for future revisions to diagnostic criteria are discussed.

A narrative synthesis was conducted to determine typical patient- and family-centered care (PFCC) components and their link to outcomes in pediatric populations. 68 studies with PFCC interventions and experimental designs were included. Study features were synthesized based on 5 core PFCC components (i.e., education from the provider to the patient and/or family, information sharing from the family to the provider, social-emotional support, adapting care to match family background, and/or s decision-making) and 4 outcome categories (health status; the experience, knowledge, and attitudes of the patient/family; patient/family behavior; or provider behavior). The most common PFCC component was education; the least common was adapting care to family background. The presence of social-emotional support alone, as well as educational interventions augmented with shared decision-making, social-emotional support, or adaptations of care based on family background, predicted improvements in families' knowledge, attitudes, and experience. Interventions that targeted the family were associated with positive outcomes.

The spontaneous cerebral hemodynamic fluctuations observed during the resting state have been frequently visualized using functional magnetic resonance imaging (rsfMRI). However, the neuronal populations and neuroelectric characteristics underlying the functional connectivity of cerebrohemodynamic activities are poorly understood. We investigated the characteristics of bi-hemispheric functional connectivity via electrophysiology and rsfMRI in the primary sensory cortex of rats anesthetized by alpha-chloralose. Unlike the evoked responses, the spontaneous electrophysiological activity was concentrated in the infragranular layers and could be classified into subtypes with distinctive current sources and sinks. Both neuroelectric and rsfMRI signals were interhemispherically correlated in a layer-specific manner, suggesting that there are independent neural inputs to infragranular and granular/supragranular layers. The majority of spontaneous electrophysiological activities were bilaterally paired with delays of up to ~50 ms between each pair. The variable interhemispheric delay implies the involvement of indirect, multi-neural pathways. Our findings demonstrated the diverse activity patterns of layer-specific electrophysiological substrates and suggest the recruitment of multiple, non-specific brain regions in construction of interhemispheric functional connectivity.

Various studies have indicated that the thalamus is involved in controlling both cortico-cortical information flow and cortical communication with the rest of the brain. Detailed anatomy and functional connectivity patterns of the thalamocortical system are essential to understanding the cortical organization and pathophysiology of a wide range of thalamus-related neurological and neuropsychiatric diseases. The current study used resting-state fMRI to investigate the topography of the human thalamocortical system from a functional perspective. The thalamus-related cortical networks were identified by performing independent component analysis on voxel-based thalamic functional connectivity maps across a large group of subjects. The resulting functional brain networks were very similar to well-established resting-state network maps. Using these brain network components in a spatial regression model with each thalamic voxel's functional connectivity map, we localized the thalamic subdivisions related to each brain network. For instance, the medial dorsal nucleus was shown to be associated with the default mode, the bilateral executive, the medial visual networks; and the pulvinar nucleus was involved in both the dorsal attention and the visual networks. These results revealed that a single nucleus may have functional connections with multiple cortical regions or even multiple functional networks, and may be potentially related to the function of mediation or modulation of multiple cortical networks. This observed organization of thalamocortical system provided a reference for studying the functions of thalamic sub-regions. The importance of intrinsic connectivity-based mapping of the thalamocortical relationship is discussed, as well as the applicability of the approach for future studies.

The present study used a community partnered research method to develop and pilot a classroom-focused measurement feedback system (MFS) for school mental health providers to support teachers' use of effective universal and target classroom practices related to student emotional and behavioral issues. School personnel from seven urban elementary and middle school classrooms participated. Phase I involved development and refinement of the system through a baseline needs assessment and rapid-cycle feedback. Phase II involved detailed case study analysis of pre-to-post quantitative and implementation process data. Results suggest that teachers who used the dashboard along with consultation showed improvement in observed classroom organization and emotional support. Results also suggest that MFS use was tied closely to consultation dose, and that broader support at the school level was critical. Classroom-focused MFSs are a promising tool to support classroom improvement, and warrant future research focused on their effectiveness and broad applicability.