Behavioral Improvements but Limited Change in Callous-Unemotional Traits in Adolescents Treated for Conduct Problems

Callous-unemotional (CU) traits have been linked to more severe and sustained behavior problems among adolescents. The aims of this study were to examine the treatment impact and malleability of CU traits among adolescents and explore potential moderation effects of treatment condition and CU sub-typology. A sample of 159 adolescents (45.9% girls; M age = 14.7 years, SD = 1.47) and their parents participated in a randomized controlled trial of Functional Family Therapy with three assessments (baseline, 6-months and 18-months) of behavior problems, CU traits, prosocial skills and the parent-youth relationship. Latent growth curve model (LGCM) analyses revealed that children with higher CU traits had greater reductions in aggressive and rule-breaking behavior and greater improvements in social skills (|standardized coefficients| = 0.27–0.32). Similarly, higher CU traits were linked to larger increases in parent-ratings of family cohesion and youth-ratings of maternal support (standardized coefficients = 0.26–0.27). Reliable Change Index summaries showed that CU traits remained unchanged for the majority of participants (73.6% and 72.6% had no reliable short- and long-term change, respectively). Baseline anxiety linked to CU sub-typology moderated some of the study results. Findings show that adolescents with co-occurring behavior problems and elevated CU traits can obtain improvement in behavioral and relational outcomes in out-patient treatment. Strikingly, such improvements can occur notwithstanding a limited reduction in CU traits. Future work should investigate whether the treatment gains would be more substantial and stable if treatment adjuncts modifying the CU traits themselves were concurrently deployed

The anabolic androgenic steroid treatment gap: a national study of substance use disorder treatment

Background Anabolic-androgenic steroid (AAS) use is associated with serious mental and physical health problems. Evidence indicates that AAS use amongst people who use psychoactive substances is higher than in the general population. This study aims to estimate lifetime AAS use among patients in substance use disorder (SUD) treatment, compare characteristics of AAS and non-AAS users and identify whether AAS use was addressed during treatment. Methods This cross-sectional survey included 563 (142 women, 24.2%) patients in 38 SUD-treatment facilities in Norway. Respondents reported on AAS and substance use, and treatment experiences. Results Lifetime AAS use was reported by 156 (28.3%) SUD-patients, thereof 35.6 % of the men and 8.0% of the women. Lifetime AAS use was highest among men with stimulants (55.8%) as preferred substance, and lowest among men who preferred alcohol (14.6%). Initiation of AAS use due to getting thinner following substance use was reported by 44.5% of the AAS using men. AAS users reported more severe substance use than non-AAS users. More than half (58%)of all patients had not been asked about AAS use, and 42.4% of those who were asked, experienced that treatment providers lacked expertise about AAS. Conclusion Lifetime AAS use in this sample of SUD patients is common practice and comprise an underrecognized problem in SUD treatment. Given the deleterious implications to the individual and society that concomitant use of AAS may cause, it would be essential to raise the awareness about AAS use amongst SUD patients, and the level of competence among health professionals

Neurogenomic Evidence for a Shared Mechanism of the Antidepressant Effects of Exercise and Chronic Fluoxetine in Mice

Several different interventions improve depressed mood, including medication and environmental factors such as regular physical exercise. The molecular pathways underlying these effects are still not fully understood. In this study, we sought to identify shared mechanisms underlying antidepressant interventions. We studied three groups of mice: mice treated with a widely used antidepressant drug – fluoxetine, mice engaged in voluntary exercise, and mice living in an enriched environment. The hippocampi of treated mice were investigated at the molecular and cellular levels. Mice treated with fluoxetine and mice who exercised daily showed, not only similar antidepressant behavior, but also similar changes in gene expression and hippocampal neurons. These changes were not observed in mice with environmental enrichment. An increase in neurogenesis and dendritic spine density was observed following four weeks of fluoxetine treatment and voluntary exercise. A weighted gene co-expression network analysis revealed four different modules of co-expressed genes that were correlated with the antidepressant effect. This network analysis enabled us to identify genes involved in the molecular pathways underlying the effects of fluoxetine and exercise. The existence of both neuronal and gene expression changes common to antidepressant drug and exercise suggests a shared mechanism underlying their effect. Further studies of these findings may be used to uncover the molecular mechanisms of depression, and to identify new avenues of therapy

Motivational interviewing as a positive response to high‐school bullying

Intervention approaches to bullying are largely preventive in nature, and even these have been shown to be ineffective, if not iatrogenic, with adolescents. Responses to bullying are limited to traditional punitive approaches or “no‐blame” approaches aiming to restore the relationship between the targeted students. Neither of these approaches may effectively engage the perpetrator of bullying at a motivational level, and we propose motivational interviewing (MI) as a means of promoting meaningful behavioral change among youths who bully. We provide a narrative review of MI and map its core features onto the extant literature on self‐reported motivations for bullying, highlighting the ways that MI fits with bullying and could serve as a potent solution that could be deployed by school psychologists and other student support staff members. Qualitative preliminary feedback and initial competency in MI from trained practitioners are presented as preliminary data from a cluster‐randomized control trial, documenting school staff perspectives on the integration of MI into their approach to bullying with recommendations for integrating MI into school settings.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143780/1/pits22120_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143780/2/pits22120.pd

Conditional ablation and recovery of forebrain neurogenesis in the mouse

Forebrain neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Several strategies have been employed to eliminate adult neurogenesis and thereby determine whether depleting adult-born neurons disrupts specific brain functions, but some approaches do not specifically target neural progenitors. We have developed a transgenic mouse line to reversibly ablate adult neural stem cells and suppress neurogenesis. The nestin-tk mouse expresses herpes simplex virus thymidine kinase (tk) under the control of the nestin 2nd intronic enhancer, which drives expression in neural progenitors. Administration of ganciclovir (GCV) kills actively dividing cells expressing this transgene. We found that peripheral GCV administration suppressed SVZ-olfactory bulb and DG neurogenesis within 2 weeks but caused systemic toxicity. Intracerebroventricular GCV infusion for 28 days nearly completely depleted proliferating cells and immature neurons in both the SVZ and DG without systemic toxicity. Reversibility of the effects after prolonged GCV infusion was slow and partial. Neurogenesis did not recover 2 weeks after cessation of GCV administration, but showed limited recovery 6 weeks after GCV that differed between the SVZ and DG. Suppression of neurogenesis did not inhibit antidepressant responsiveness of mice in the tail suspension test. These findings indicate that SVZ and DG neural stem cells differ in their capacity for repopulation, and that adult-born neurons are not required for antidepressant responses in a common behavioral test of antidepressant efficacy. The nestin-tk mouse should be useful for studying how reversible depletion of adult neurogenesis influences neurophysiology, other behaviors, and neural progenitor dynamics. J. Comp. Neurol. 514:567–582, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62155/1/22052_ftp.pd

Physical activity and depression in adolescents: cross-sectional findings from the ALSPAC cohort

Purpose: Few studies have examined the association between physical activity (PA), measured objectively, and adolescent depressive symptoms. The aim of this study was to determine whether there is an association between objective measures of PA (total PA and time spent in moderate and vigorous PA (MVPA)) and adolescent depressive symptoms. Methods: Data on 2,951 adolescents participating in ALSPAC were used. Depressive symptoms were measured using the self-report Mood and Feelings Questionnaire (MFQ) (short version). Measures of PA were based on accelerometry. The association between PA and MFQ scores was modelled using ordinal regression. Results: Adolescents who were more physically active (total PA or minutes of MVPA) had a reduced odds of depressive symptoms [ORadj total PA (tertiles): medium 0.82 (95% CI: 0.69, 0.97); high 0.69 (95% CI: 0.57, 0.83)]; ORadj per 15 min MVPA: 0.92 (95% CI: 0.86, 0.98). In a multivariable model including both total PA and the percentage of time spent in MVPA, total PA was associated with depressive symptoms (ORadj total PA (tertiles): medium 0.82 (95% CI: 0.70, 0.98); high 0.70 (95% CI: 0.58, 0.85) but the percentage of time spent in MVPA was not independently associated with depressive symptoms [ORadj MVPA (tertiles) medium 1.05 (95% CI: 0.88, 1.24), high 0.91 (95% CI: 0.77, 1.09)]. Conclusions: The total amount of PA undertaken was associated with adolescent depressive symptoms, but the amount of time spent in MVPA, once total PA was accounted for, was not. If confirmed in longitudinal studies and randomised controlled trials, this would have important implications for public health messages.Nicola J. Wiles, Anne M. Haase, Debbie A. Lawlor, Andy Ness, Glyn Lewi

Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress

Impact of Treadmill Running and Sex on Hippocampal Neurogenesis in the Mouse Model of Amyotrophic Lateral Sclerosis

Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a ‘ceiling effect’ of an already heightened basal levels of hippocampal neurogenesis and BDNF expression

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base