Faculty Bibliography

Functional connectivity magnetic resonance imaging (fcMRI) studies in rat brain show brain reorganization following peripheral nerve injury. Subacute neuroplasticity was observed 2 weeks following transection of the four major nerves of the brachial plexus. Direct stimulation of the intact radial nerve reveals a functional magnetic resonance imaging (fMRI) activation pattern in the forelimb regions of the sensory and motor cortices that is significantly different from that observed in normal rats. Results of this fMRI experiment were used to determine seed voxel regions for fcMRI analysis. Intrahemispheric connectivities in the sensorimotor forelimb representations in both hemispheres are largely unaffected by deafferentation, whereas substantial disruption of interhemispheric sensorimotor cortical connectivity occurs. In addition, significant intra- and interhemispheric changes in connectivities of thalamic nuclei were found. These are the central findings of the study. They could not have been obtained from fMRI studies alone-both fMRI and fcMRI are needed. The combination provides a general marker for brain plasticity. The rat visual system was studied in the same animals as a control. No neuroplastic changes in connectivities were found in the primary visual cortex upon forelimb deafferentation. Differences were noted in regions responsible for processing multisensory visual-motor information. This incidental discovery is considered to be significant. It may provide insight into phantom limb epiphenomena.

Functional connectivity analyses of resting-state fMRI data are rapidly emerging as highly efficient and powerful tools for in vivo mapping of functional networks in the brain, referred to as intrinsic connectivity networks (ICNs). Despite a burgeoning literature, researchers continue to struggle with the challenge of defining computationally efficient and reliable approaches for identifying and characterizing ICNs. Independent component analysis (ICA) has emerged as a powerful tool for exploring ICNs in both healthy and clinical populations. In particular, temporal concatenation group ICA (TC-GICA) coupled with a back-reconstruction step produces participant-level resting state functional connectivity maps for each group-level component. The present work systematically evaluated the test-retest reliability of TC-GICA derived RSFC measures over the short-term (<45 min) and long-term (5-16 months). Additionally, to investigate the degree to which the components revealed by TC-GICA are detectable via single-session ICA, we investigated the reproducibility of TC-GICA findings. First, we found moderate-to-high short- and long-term test-retest reliability for ICNs derived by combining TC-GICA and dual regression. Exceptions to this finding were limited to physiological- and imaging-related artifacts. Second, our reproducibility analyses revealed notable limitations for template matching procedures to accurately detect TC-GICA based components at the individual scan level. Third, we found that TC-GICA component's reliability and reproducibility ranks are highly consistent. In summary, TC-GICA combined with dual regression is an effective and reliable approach to exploratory analyses of resting state fMRI data

BACKGROUND: Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins. The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho; and, ii) the anticipated correlations would be more pronounced in the melancholic subtype group. METHODS: Fourteen adolescents with MDD (seven with melancholic features) and six healthy controls were enrolled. Minimums of 6 weeks MDD duration and a severity score of 40 on the Children's Depression Rating Scale-Revised were required. All were scanned at 3T with MRI, multi-voxel 3-dimensional, high, 0.75 cm(3), spatial resolution proton magnetic resonance spectroscopic imaging. Striatal tCho concentrations were assessed using phantom replacement. Spearman correlation coefficients were Bonferroni-corrected. RESULTS: Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate (r=0.93, p=0.03) and the left putamen (r=0.96, p=.006), respectively. CONCLUSIONS: These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD. Larger studies should follow

Principal points are cluster means for theoretical distributions. A discriminant methodology based on principal points is introduced. The principal point classification method is useful in clinical trials where the goal is to distinguish and differentiate between different treatment effects. Particularly, in psychiatric studies where placebo response rates can be very high, the principal point classification is illustrated to distinguish specific drug responders from non-specific placebo responders

This paper describes the process by which child mental health researchers partnered with paraprofessionals called peer family advisors to create a stress-reducing intervention for caregivers of children and adolescents with mental health challenges. The issues that arose as the team strove to develop an intervention that was both relevant to the issues that these caregivers grapple with, as well as palatable and feasible for peers to deliver, are discussed.

Improving outcomes for children and adolescents with mental health needs demands a broad meta-systemic orientation to overcome persistent problems in current service systems. Improving outcomes necessitates inclusion of current and emerging evidence about effective practices for the diverse population of youth and their families. Key components of the meta-system for children with emotional or behavioral needs include families, cultural norms and values, and service sectors such as schools, pediatric health centers, specialty mental health systems, juvenile justice systems, child protection services, and substance use treatment systems. We describe each component of the meta-system, noting challenges to the provision of evidence-based practice (EBP) and highlighting ways to optimize outcomes. Our focus is on the inclusion of evidence-based assessment and interventions, including prevention, within a developmentally driven and culturally responsive contextual model. Recommendations for addressing disparities in research funding and essential steps to foster communication and coordination of EBP across settings are provided.

Quality of life (QoL) describes an individual's subjective perception of their position in life as evidenced by their physical, psychological, and social functioning. QoL has become an increasingly important measure of outcome in child mental health clinical work and research. Here we provide a systematic review of QoL studies in children and young people with attention deficit hyperactivity disorder (ADHD) and address three main questions. (1) What is the impact of ADHD on QoL? (2) What are the relationships between ADHD symptoms, functional impairment and the mediators and moderators of QoL in ADHD? (3) Does the treatment of ADHD impact on QoL? Databases were systematically searched to identify research studies describing QoL in ADHD. Thirty six relevant articles were identified. Robust negative effects on QoL are reported by the parents of children with ADHD across a broad range of psycho-social, achievement and self evaluation domains. Children with ADHD rate their own QoL less negatively than their parents and do not always seeing themselves as functioning less well than healthy controls. ADHD has a comparable overall impact on QoL compared to other mental health conditions and severe physical disorders. Increased symptom level and impairment predicts poorer QoL. The presence of comorbid conditions or psychosocial stressors helps explain these effects. There is emerging evidence that QoL improves with effective treatment. In conclusion, ADHD seriously compromises QoL especially when seen from a parents' perspective. QoL outcomes should be included as a matter of course in future treatment studies

OBJECTIVE: Advanced paternal age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If paternal age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-a-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset age and more severe negative symptoms than females. METHOD: Symptoms were assessed at baseline (admission) and during medication-free and treatment phases for 153 inpatients on a schizophrenia research unit, 38 of whom fulfilled operationally defined criteria for PARS (sporadic cases with paternal age > or = 35). RESULTS: Males and females with PARS had the same age at onset and a similar preponderance of negative symptoms, whereas the other (non-PARS) cases showed the typical earlier onset age and more severe negative symptoms in males. When medications were withdrawn, PARS cases showed significantly worse symptoms than non-PARS cases (higher total PANSS scores and positive, activation, and autistic preoccupation scores). However these symptoms globally improved with antipsychotic treatment, such that the differences between the PARS and other schizophrenia cases receded. CONCLUSION: The lack of sex differences in the age at onset and the greater severity of medication-free symptoms bolster the hypothesis that PARS has a distinct etiopathology. It also suggests that female sex does not exert a protective effect on the course of PARS, as it may in other forms of schizophrenia