Faculty Bibliography

Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable and prevalent neurodevelopmental disorder that frequently persists into adulthood. Strong evidence from genetic studies indicates that single nucleotide polymorphisms (SNPs) harboured in the ADGRL3 (LPHN3), SNAP25, FGF1, DRD4, and SLC6A2 genes are associated with ADHD. We genotyped 26 SNPs harboured in genes previously reported to be associated with ADHD and evaluated their potential association in 386 individuals belonging to 113 nuclear families from a Caribbean community in Barranquilla, Colombia, using family-based association tests. SNPs rs362990-SNAP25 (T allele; p = 2.46 × 10-4), rs2282794-FGF1 (A allele; p = 1.33 × 10-2), rs2122642-ADGRL3 (C allele, p = 3.5 × 10-2), and ADGRL3 haplotype CCC (markers rs1565902-rs10001410-rs2122642, OR = 1.74, Ppermuted = 0.021) were significantly associated with ADHD. Our results confirm the susceptibility to ADHD conferred by SNAP25, FGF1, and ADGRL3 variants in a community with a significant African American component, and provide evidence supporting the existence of specific patterns of genetic stratification underpinning the susceptibility to ADHD. Knowledge of population genetics is crucial to define risk and predict susceptibility to disease.

A report in this issue of Acta Physiologica describes how leptin, a hormone released by fat cells in the body, modulates olfactory system neural activity and odor perception in a manner that could promote homeostatic regulation of responses to food odor. The mammalian olfactory system serves dual chemosensory functions. Its classic sensory role is to monitor and identify volatile molecules in the air through orthonasal olfaction or in foods in the mouth through retronasal olfaction. This external chemosensory monitoring drives or modulates diverse behaviors including feeding, mate selection, kin recognition, predator avoidance, and spatial orientation/homing. However, it is now well established that this external monitoring occurs in the context of an internal chemical monitoring of nutritional status, reproductive status, and more general internal state. This article is protected by copyright. All rights reserved.

BACE1 is a transmembrane aspartic protease that cleaves various substrates and it is required for normal brain function. BACE1 expression is high during early development, but it is reduced in adulthood. Under conditions of stress and injury, BACE1 levels are increased; however, the underlying mechanisms that drive BACE1 elevation are not well understood. One mechanism associated with brain injury is the activation of injurious p75 neurotrophin receptor (p75), which can trigger pathological signals. Here we report that within 72 h after controlled cortical impact (CCI) or laser injury, BACE1 and p75 are increased and tightly co-expressed in cortical neurons of mouse brain. Additionally, BACE1 is not up-regulated in p75 null mice in response to focal cortical injury, while p75 over-expression results in BACE1 augmentation in HEK-293 and SY5Y cell lines. A luciferase assay conducted in SY5Y cell line revealed that BACE1 expression is regulated at the transcriptional level in response to p75 transfection. Interestingly, this effect does not appear to be dependent upon p75 ligands including mature and pro-neurotrophins. In addition, BACE1 activity on amyloid precursor protein (APP) is enhanced in SY5Y-APP cells transfected with a p75 construct. Lastly, we found that the activation of c-jun n-terminal kinase (JNK) by p75 contributes to BACE1 up-regulation. This study explores how two injury-induced molecules are intimately connected and suggests a potential link between p75 signaling and the expression of BACE1 after brain injury.

AIM/OBJECTIVE:To strengthen the theoretical understanding of illness acceptance in adolescents and to inform healthcare strategies geared toward supporting adolescents with chronic illness. BACKGROUND:Illness acceptance is associated with positive health outcomes. Though well understood in adults with chronic illness, less is known about how this phenomenon ensues in adolescents. Adolescents may have a difficult time accepting an illness due to their unique developmental needs. Consequently, they are vulnerable to poor health outcomes. DESIGN/METHODS:Concept analysis. DATA SOURCES/METHODS:A literature search through 2 databases (PubMed and PsycINFO) and a hand-search through Google were conducted to identify uses of the concept. REVIEW METHODS/METHODS:The Walker and Avant method of concept analysis. RESULTS:Four attributes of illness acceptance were identified: understanding of illness, overcoming limitations, normalization, and readiness for responsibility. Antecedents that predisposed illness acceptance included peer and family support, disease management education, and developmental readiness. Positive consequences of illness acceptance included high self-esteem, improved quality of life, resilience, identity formation, and better disease control. CONCLUSIONS:Establishing a standardized conceptual understanding of how illness acceptance ensues in adolescents can enable nurses and other health professionals to tailor developmentally appropriate care strategies and optimize the overall quality of life for this unique patient population.

During healthy brain aging, different brain regions show anatomical or functional declines at different rates, and some regions may show compensatory increases in functional activity. However, few studies have explored interregional influences of brain activity during the aging process. We proposed a causality analysis framework combining high dimensionality independent component analysis (ICA), Granger causality, and least absolute shrinkage and selection operator regression on longitudinal brain metabolic activity data measured by Fludeoxyglucose positron emission tomography (FDG-PET). We analyzed FDG-PET images from healthy old subjects, who were scanned for at least five sessions with an averaged intersession interval of 1 year. The longitudinal data were concatenated across subjects to form a time series, and the first-order autoregressive model was used to measure interregional causality among the independent sources of metabolic activity identified using ICA. Several independent sources with reduced metabolic activity in aging, including the anterior temporal lobe and orbital frontal cortex, demonstrated causal influences over many widespread brain regions. On the other hand, the influenced regions were more distributed, and had smaller age-related declines or even relatively increased metabolic activity. The current data demonstrated interregional spreads of aging on metabolic activity at the scale of a year, and have identified key brain regions in the aging process that have strong influences over other regions.

OBJECTIVES/OBJECTIVE:Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment for body dysmorphic disorder (BDD), but access to treatment around the world is limited. One way to increase access is to administer CBT remotely via the internet. This study represents the first effort to remotely deliver a therapist-supported, internet-based CBT treatment with no restrictions on enrolment based on geographical location, and it aims to assess whether this treatment can be delivered safely across international borders, with outcomes comparable to previous BDD-NET trials. DESIGN/METHODS:Uncontrolled clinical trial. PARTICIPANTS/METHODS:Patients (n=32) in nine different countries were recruited primarily through internet advertisements. INTERVENTION/METHODS:BDD-NET is a 12-week treatment, consisting of eight treatment modules previously shown to be effective in a Swedish version. SETTING/METHODS:Therapists based at a single, secondary care centre in Sweden provided active guidance and feedback throughout the treatment via asynchronous electronic messages. MAIN OUTCOME MEASURE/METHODS:The clinician-administered Yale-Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS). Symptom severity was assessed pretreatment, mid-treatment (6 weeks), post-treatment and at the 3-month follow-up. RESULTS:There were significant improvements on BDD-YBOCS scores (F(3, 71.63)=31.79, p<0.001), that were maintained at 3-month follow-up. Mean differences from baseline in BDD-YBOCS scores were -8.12 (week 6), -12.63 (post-treatment) and -11.71 (3-month follow-up). 47% and 50% of participants were considered treatment responders at post-treatment and 3-month follow-up, respectively. Additionally, remission rates were 28% at post-treatment and 44% at 3-month follow-up. The treatment was also deemed acceptable by patients. CONCLUSIONS:The results suggest that BDD-NET can be safely and effectively delivered across international borders to a culturally diverse sample. Larger scale randomised controlled trials with more participants from non-Western cultures are warranted to further validate the cross-cultural generalisability of this treatment. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT03517384.

BACKGROUND:As efforts intensify to intervene early among those at risk for psychosis, examination of the relationship between presenting psychopathology and long-term functional outcome may guide treatment decision-making and offer a means to prevent or reduce chronic disability. METHODS:Data were collected through the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP), a multisite national trial testing the efficacy of an early intervention for youth at risk of developing psychosis. Participants were followed prospectively and completed comprehensive evaluations at 6, 12, and 24 months, including the Structured Interview for Prodromal Syndromes (SIPS) and the Global Social and Role Functioning Scales. The present analyses included 327 participants and examined the relationships between baseline symptoms and longitudinal global social and role functioning using a linear mixed modeling approach. RESULTS:Higher baseline negative symptoms and deteriorated thought process predicted worse social and role functioning in the follow-up period. The effect of negative symptoms on social functioning, however, was moderated by positive symptoms, and the relationship between positive symptoms and social functioning changed over time. Baseline positive symptoms, distress, and level of symptom severity were not predictors of either social or role functioning. CONCLUSIONS:Baseline negative symptoms and thought disorder appear to predict functional outcome for up to two years among adolescents and young adults at risk for psychosis. Developing effective interventions to target these symptoms may be critical to promote functional recovery among those experiencing attenuated symptoms or a first episode of psychosis.

Regulatory agencies are increasingly taking on the important issue of effective risk assessment, risk stratification, and treatment planning for youth with psychiatric illness.¹ The Joint Commission mandates a suicide assessment for patients "who exhibit suicidal behavior or who have screened positive for suicidal ideation" followed by risk stratification: after "this assessment, patients should be classified as high, medium or low risk of suicide."² We anticipate that just as screening for depression and suicidality was initially restricted to emergency departments and inpatient units before being rolled out across all care settings, so risk stratification requirements will roll out to these other settings as well.

OBJECTIVE:Very few controlled trials have evaluated targeted treatment methods for childhood selective mutism (SM); the availability of evidence-based services remains limited. This study is the first controlled trial to evaluate an intensive group behavioral treatment (IGBT) for children with SM. METHOD/METHODS:Twenty-nine children with SM (5-9 years; 76% female; 35% ethnic minority) were randomized to immediate SM 5-day IGBT or to a 4-week waitlist with psychoeducational resources (WLP), and were assessed at Week 4 and again 8 weeks into the following school year. RESULTS:IGBT was associated with high satisfaction and low perceived barriers to treatment participation. At Week 4, 50% of the immediate IGBT condition and 0% of the WLP condition were classified as "clinical responders." Further, Time × Condition interactions were significant for social anxiety severity, verbal behavior in social situations, and global functioning (but not for SM severity, verbal behavior in home settings, or overall anxiety). School-year follow-up assessments revealed significant improvements across all outcomes. Eight weeks into the following school year, 46% of IGBT-treated children were free of an SM diagnosis. In addition, teachers in the post-IGBT school year rated less school impairment and more classroom verbal behavior relative to teachers in the pre-IGBT school year. CONCLUSIONS:Findings provide the first empirical support for the efficacy and acceptability of IGBT for SM. Further study is needed to examine mechanisms of IGBT response, and other effective SM treatment methods, in order to clarify which treatment formats work best for which affected children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).