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What is the experience of psychiatry residents learning to prescribe? A qualitative research inquiry

Tue, 04/25/2017 - 10:28pm

BACKGROUND: Understanding how psychiatry residents learn to prescribe is important for the future of psychiatry. Prescribing is a complicated act that involves much more than signing a prescription. During residency, psychiatrists develop seminal attitudes and habits about prescribing. There have been no published studies focusing on psychiatry residents' experience when learning to prescribe.

AIMS: Qualitative methodology lends itself to a deep exploration of the process of learning how to prescribe. We undertook a qualitative study questioning psychiatry residents about their prescribing.

METHODS: Psychiatry residents were recruited from three residency programs and focus groups were conducted at each program. The focus groups were audiotaped and transcribed by a professional service. Thematic analysis was used to analyze the data and triangulation to increase the rigor of the study.

RESULTS: A total of 12 residents participated. Three themes were identified concerning identity development as a psychiatrist, uncertainty and fear about prescribing, and the centrality of collaborating with the patient during the prescribing process.

CONCLUSION: Psychiatry residents struggle with significant anxiety and frustration in their experience of learning to prescribe, suggesting a place for mentors and supervisors to focus.

Games for Health for Children-Current Status and Needed Research

Tue, 04/25/2017 - 10:28pm

Videogames for health (G4H) offer exciting, innovative, potentially highly effective methods for increasing knowledge, delivering persuasive messages, changing behaviors, and influencing health outcomes. Although early outcome results are promising, additional research is needed to determine the game design and behavior change procedures that best promote G4H effectiveness and to identify and minimize possible adverse effects. Guidelines for ideal use of different types of G4H by children and adolescents should be elucidated to enhance effectiveness and minimize adverse effects. G4H stakeholders include organizational implementers, policy makers, players and their families, researchers, designers, retailers, and publishers. All stakeholders should be involved in G4H development and have a voice in setting goals to capitalize on their insights to enhance effectiveness and use of the game. In the future, multiple targeted G4H should be available to meet a population's diverse health needs in developmentally appropriate ways. Substantial, consistent, and sophisticated research with appropriate levels of funding is needed to realize the benefits of G4H.

Receipt of pharmacotherapy for opioid use disorder by justice-involved U.S. Veterans Health Administration patients

Tue, 04/25/2017 - 10:28pm

BACKGROUND: Pharmacotherapy - methadone, buprenorphine, or naltrexone - is an evidence-based treatment for opioid use disorder, but little is known about receipt of these medications among veterans involved in the justice system. The current study examines receipt of pharmacotherapy for opioid use disorder among veterans with a history of justice involvement at U.S. Veterans Health Administration (VHA) facilities compared to veterans with no justice involvement.

METHODS: Using national VHA clinical and pharmacy records, we conducted a retrospective cohort study of veterans with an opioid use disorder diagnosis in fiscal year 2012. Using a mixed-effects logistic regression model, we examined receipt of pharmacotherapy in the 1-year period following diagnosis as a function of justice involvement, adjusting for patient and facility characteristics.

RESULTS: The 1-year rate of receipt for pharmacotherapy for opioid use disorder was 27% for prison-involved veterans, 34% for jail/court-involved veterans, and 33% for veterans not justice-involved. Compared to veterans not justice-involved, those prison-involved had 0.75 lower adjusted odds (95% confidence interval [CI]: 0.65-0.87) of receiving pharmacotherapy whereas jail/court-involved veterans did not have significantly different adjusted odds.

CONCLUSIONS: Targeted efforts to improve receipt of pharmacotherapy for opioid use disorder among veterans exiting prison is needed as they have lower odds of receiving these medications.

microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration

Tue, 04/25/2017 - 10:27pm

The aggregation of Abeta42-peptides and the formation of drusen in age-related macular degeneration (AMD) are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Abeta42-peptides from the extracellular space. The triggering receptor expressed in myeloid/microglial cells-2 (TREM2), a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical component of Abeta42-peptide clearance. Here we report a significant deficit in TREM2 in AMD retina and in cytokine- or oxidatively-stressed microglial (MG) cells. RT-PCR, miRNA-array, LED-Northern and Western blot studies indicated up-regulation of a microglial-enriched NF-small ka, CyrillicB-sensitive miRNA-34a coupled to a down-regulation of TREM2 in the same samples. Bioinformatics/transfection-luciferase reporter assays indicated that miRNA-34a targets the 299 nucleotide TREM2-mRNA-3'UTR, resulting in TREM2 down-regulation. C8B4-microglial cells challenged with Abeta42 were able to phagocytose these peptides, while miRNA-34a down-regulated both TREM2 and the ability of microglial-cells to phagocytose. Treatment of TNFalpha-stressed MG cells with phenyl-butyl nitrone (PBN), caffeic-acid phenethyl ester (CAPE), the NF-kB - [corrected] inhibitor/resveratrol analog CAY10512 or curcumin abrogated these responses. Incubation of anti-miRNA-34a (AM-34a) normalized miRNA-34a abundance and restored TREM2 back to homeostatic levels. These data support five novel observations: (i) that a ROS- and NF-kB - [corrected] sensitive, miRNA-34a-mediated modulation of TREM2 may in part regulate the phagocytic response; (ii) that gene products encoded on two different chromosomes (miRNA-34a at chr1q36.22 and TREM2 at chr6p21.1) orchestrate a phagocytic-Abeta42-peptide clearance-system; (iii) that this NF-kB-mediated-miRNA-34a-TREM2 mechanism is inducible from outside of the cell; (iv) that when operating normally, this pathway can clear Abeta42 peptide monomers from the extracellular medium; and (v) that anti-NF-kB and/or anti-miRNA (AM)-based therapeutic strategies may be useful against deficits in TREM-2 receptor-based-sensing and -phagocytic signaling that promote pathogenic amyloidogenesis.

Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment

Tue, 04/25/2017 - 10:27pm

BACKGROUND: Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent.

METHOD: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons.

RESULTS: At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018).

CONCLUSIONS: White matter deficits were validated in the present study by a relatively large sample of medication naive and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.

5-HT1A Autoreceptors in the Dorsal Raphe Nucleus Convey Vulnerability to Compulsive Cocaine Seeking

Tue, 04/25/2017 - 10:27pm

Cocaine addiction and depression are comorbid disorders. Although it is well recognized that 5-hydroxytryptamine (5-HT; serotonin) plays a central role in depression, our understanding of its role in addiction is notably lacking. The 5-HT system in the brain is carefully controlled by a combined process of regulating 5-HT neuron firing through 5-HT autoreceptors, neurotransmitter release, enzymatic degradation, and reuptake by transporters. This study tests the hypothesis that activation of 5-HT1A autoreceptors, which would lessen 5-HT neuron firing, contributes to cocaine-seeking behaviors. Using 5-HT neuron-specific reduction of 5-HT1A autoreceptor gene expression in mice, we demonstrate that 5-HT1A autoreceptors are necessary for cocaine conditioned place preference. In addition, using designer receptors exclusively activated by designer drugs (DREADDs) technology, we found that stimulation of the serotonergic dorsal raphe nucleus (DRN) afferents to the nucleus accumbens (NAc) abolishes cocaine reward and promotes antidepressive-like behaviors. Finally, using a rat model of compulsive-like cocaine self-administration, we found that inhibition of dorsal raphe 5-HT1A autoreceptors attenuates cocaine self-administration in rats with 6 h extended access, but not 1 h access to the drug. Therefore, our findings suggest an important role for 5-HT1A autoreceptors, and thus DRNshort right arrowNAc 5-HT neuronal activity, in the etiology and vulnerability to cocaine reward and addiction. Moreover, our findings support a strategy for antagonizing 5-HT1A autoreceptors for treating cocaine addiction.

Pharmacogenetics of Ketamine-Induced Emergence Phenomena: A Pilot Study

Tue, 04/25/2017 - 9:51pm

BACKGROUND: Up to 55% of patients who are administered ketamine experience an emergence phenomena (EP) that closely mimics schizophrenia and increases their risk of injury; however, to date, no studies have investigated genetic association of ketamine-induced EP in healthy patients.

OBJECTIVES: The aim of the study was to investigate the feasibility and sample sizes required to explore the relationship between CYP2B6*6 and GRIN2B single-nucleotide polymorphisms and ketamine-induced EP.

METHODS: This cross-sectional, pharmacogenetic candidate, gene pilot study recruited 75 patients having minor elective outpatient surgeries. EP was measured with the Clinician Administered Dissociative State Scale. Genetic association of CYP2B6*6 and GRIN2B (rs1019385 and rs1806191) single-nucleotide polymorphisms and ketamine-induced EP occurrence and severity were tested using logistic and linear regression.

RESULTS: Forty-seven patients (63%) received ketamine and were genotyped, and 40% of them experienced EP. Occurrence and severity of EP were not associated with CYP2B6*6 or GRIN2B (p > .10). Exploratory analysis of nongenotype models containing age, ketamine dose, duration of anesthesia, and time from ketamine administration to assessment for EP significantly predicted EP occurrence (p = .001) and severity (p = .007). This pilot study demonstrates feasibility for implementing a pharmacogenetic study in a clinical setting, and we estimate that between 380 and 570 cases will be needed to adequately power future genetic association studies.

DISCUSSION: Younger age, higher dose, and longer duration of anesthesia significantly predicted EP occurrence and severity among our pilot sample. Although the small sample size limited our ability to demonstrate significant genotype differences, we generated effect sizes, sample size estimates, and nongenetic covariates information in order to support future pharmacogenetic study design for evaluating this adverse event.

Ensuring Competent Care by Senior Physicians

Tue, 04/25/2017 - 9:35pm

The increasing number of senior physicians and calls for increased accountability of the medical profession by the public have led regulators and policymakers to consider implementing age-based competency screening. Some hospitals and health systems have initiated age-based screening, but there is no agreed upon assessment process. Licensing and certifying organizations generally do not require that senior physicians pass additional assessments of health, competency, or quality performance. Studies suggest that physician performance, on average, declines with increasing years in medical practice, but the effect of age on an individual physician's competence is highly variable. Many senior physicians practice effectively and should be allowed to remain in practice as long as quality and safety are not endangered. Stakeholders in the medical profession should consider the need to develop guidelines and methods for monitoring and/or screening to ensure that senior physicians provide safe and effective care for patients. Any screening process needs to achieve a balance between protecting patients from harm due to substandard practice, while at the same time ensuring fairness to physicians and avoiding unnecessary reductions in workforce.

The Social Life of Data

Sun, 04/23/2017 - 10:04pm

Summary:

So, besides this amusing parallel between data and children, what have we learned? We are reminded to get identifiers for our data, encourage our data to socialize with other data, and plan in advance for the long-term archival of our data. If we can do this in a well-controlled environment, the benefits, individually and as a community, in terms credit, value and reproducibility, are substantial.

In short, if you love your data, set it free, and watch what happens! Its social life may surprise you.

Integrating Permanent Supportive Housing and Co-Occurring Disorders Treatment for Individuals Who Are Homeless

Sun, 04/23/2017 - 10:04pm

OBJECTIVES: While permanent housing, addictions, and mental health treatment are often critical needs to achieve housing stability and community reintegration, few studies have systematically integrated them into a single comprehensive approach for people experiencing chronic homelessness. This pilot study examined the feasibility and preliminary outcomes of systematically integrating permanent supportive housing and an evidence-based co-occurring disorders intervention called Maintaining Independence and Sobriety Through Systems Integration, Outreach, and Networking (MISSION).

METHODS: This single-group open pilot enrolled 107 people with co-occurring disorders experiencing chronic homelessness from two Massachusetts inner-city and rural areas. Enrolled subjects were interested in receiving permanent supportive housing along with 1 year of MISSION services. Data were collected through baseline and 6- and 12-month follow-up assessments.

RESULTS: Participants (Mage = 49.52 years, SD = 10.61) were mostly male (76.6%), Caucasian (52.3%), and unemployed (86.0%), with an average of 8.34 years (SD = 8.01) of homelessness. Self-reported lifetime problems with anxiety (75.7%) and depression (76.6%) were common, as was use of alcohol (30.8%), cannabis (31.8%), and cocaine (15.9%). Almost all participants (95.3%) were placed into permanent housing, which took on average 42.6 days from enrollment (SD = 50.09). Among those placed, nearly 80% of the clients were able to retain housing through the end of the study. Overall retention was high, with 86.0% remaining in MISSION treatment until the end of the study. While there were no significant changes in rehospitalization, service utilization, or substance use, there were modest significant mental health symptom improvements from baseline to program completion.

CONCLUSIONS: This pilot study suggests that co-occurring disorder interventions like MISSION are feasible to integrate with permanent supportive housing despite the somewhat differing philosophies, and preliminary data suggested substantial improvements in housing and modest improvements in mental health symptoms. While caution is warranted given the lack of a comparison group, these findings are consistent with other rigorous studies using MISSION among homeless individuals who did not receive permanent supportive housing.

Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry

Sun, 04/23/2017 - 10:04pm

X-linked congenital cerebellar ataxia is a heterogeneous nonprogressive neurodevelopmental disorder with onset in early childhood. We searched for a genetic cause of this condition, previously reported in a Buryat pedigree of Mongolian ancestry from southeastern Russia. Using whole-genome sequencing on Illumina HiSeq 2000 platform, we found a missense mutation in the ABCB7 (ABC-binding cassette transporter B7) gene, encoding a mitochondrial transporter, involved in heme synthesis and previously associated with sideroblastic anemia and ataxia. The mutation resulting in a substitution of a highly conserved glycine to serine in position 682 is apparently a major causative factor of the cerebellar hypoplasia/atrophy found in affected individuals of a Buryat family who had no evidence of sideroblastic anemia. Moreover, in these affected men we also found the genetic defects in two other genes closely linked to ABCB7 on chromosome X: a deletion of a genomic region harboring the second exon of copper-transporter gene (ATP7A) and a complete deletion of PGAM4 (phosphoglycerate mutase family member 4) retrogene located in the intronic region of the ATP7A gene. Despite the deletion, eliminating the first of six metal-binding domains in ATP7A, no signs for Menkes disease or occipital horn syndrome associated with ATP7A mutations were found in male carriers. The role of the PGAM4 gene has been previously implicated in human reproduction, but our data indicate that its complete loss does not disrupt male fertility. Our finding links cerebellar pathology to the genetic defect in ABCB7 and ATP7A structural variant inherited as X-linked trait, and further reveals the genetic heterogeneity of X-linked cerebellar disorders.

Telephone Smoking-Cessation Counseling for Smokers in Mental Health Clinics: A Patient-Randomized Controlled Trial

Sun, 04/23/2017 - 10:04pm

INTRODUCTION: People with a mental health diagnosis have high rates of tobacco use and encounter limited availability of tobacco treatment targeted to their needs. This study compared the effectiveness of a specialized telephone smoking-cessation intervention developed for mental health patients with standard state quit-line counseling. DESIGN: RCT. SETTING/PARTICIPANTS: The study was conducted at six Veterans Health Administration facilities in the Northeast U.S. Participants were 577 mental health clinic patients referred by their providers for smoking-cessation treatment. INTERVENTION: From 2010 to 2012, the study implemented a telephone program that included patient referral from a mental health provider, mailed cessation medications, and telephone counseling. Participants were randomized to receive a specialized multisession telephone counseling protocol (n=270) or transfer to their state's quit-line for counseling (n=307). MAIN OUTCOME MEASURES: Participants completed telephone surveys at baseline, 2 months, and 6 months. The study's primary outcome was self-reported 30-day abstinence at 6 months. Secondary outcomes were self-reported 30-day abstinence, counseling satisfaction and counseling content at 2 months, and self-reported use of cessation treatment and quit attempts at 6 months. Logistic regression was used to compare treatment groups on outcomes, controlling for baseline cigarettes per day and site. Inverse probability weighting and multiple imputation were used to handle missing abstinence outcomes. Data were analyzed in 2014-2015. RESULTS: At 6 months, participants in the specialized counseling arm were more likely to report 30-day abstinence (26% vs 18%, OR=1.62, 95% CI=1.24, 2.11). There was no significant group difference in abstinence at 2 months (18% vs 14%, OR=1.31, 95% CI=0.49, 3.49). Participants in the specialized arm were more likely to be assisted with developing a quit plan; receive follow-up calls after quitting; and receive counseling on several domains, including motivation, confidence, smoking triggers, coping with urges, and mental health symptoms (all p<0.05). Specialized counseling participants were more satisfied with treatment and more likely to find the counseling useful (p<0.05). CONCLUSIONS: The specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line. Patients were more satisfied with the specialized counseling program. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT00724308.

Women's Behavioral Responses to the Threat of a Hypothetical Date Rape Stimulus: A Qualitative Analysis

Sun, 04/23/2017 - 10:03pm

One in four college women experience sexual assault on campus; yet, campuses rarely provide the in-depth self-defense programs needed to reduce sexual assault risk. Further, little is known about the range of possible behaviors elicited by sexual assault threat stimuli besides assertion. To fill this gap, the aim of the current study was to explore qualitative themes in women's intended behavioral responses to a hypothetical sexual assault threat, date rape, by using a laboratory-controlled threat. College women (N = 139) were randomly assigned to one of four different levels of sexual assault threat presented via an audio-recorded vignette. Participants articulated how they would hypothetically respond to the experimentally assigned threat. Responses were blinded and analyzed using Consensual Qualitative Research methodology. Six major themes emerged: assertion, compliance/acceptance, conditional decision making, avoidance, expressions of discomfort, and allusion to future contact. Although almost all participants described assertion, a number of non-assertive responses were described that are not currently recognized in the literature. These non-assertive responses, including compliance/acceptance, conditional decision making, and avoidance, may represent unique behavioral response styles and likely reflect the complex psychological process of behavioral response to threat. The variety of themes found illustrates the great range of behavioral responses to threat. This broad range is not currently well represented or measured in the literature and better understanding of these responses can inform future interventions, advocacy efforts, and policies focused on sexual assault.

Trajectories of drinking urges and the initiation of abstinence during cognitive-behavioral alcohol treatment

Sun, 04/23/2017 - 10:03pm

BACKGROUND AND AIMS: Drinking urges during treatment for alcohol use disorders (AUDs) are common, can cause distress and predict relapse. Clients may have little awareness of how their drinking urges might be expected to change during AUD treatment in general and in response to initiating abstinence. The aim of the present study was to test whether drinking urges change on a daily level during treatment and after initiating abstinence.

DESIGN: Secondary data analysis was performed using daily drinking urge ratings from two randomized clinical trials.

SETTING AND PARTICIPANTS: Women (n = 98) and men (n = 79) with AUDs in separate clinical trials of out-patient AUD-focused cognitive-behavioral therapy.

MEASUREMENTS: Daily dichotomous indicators of any drinking urges or acute escalations in urges (i.e. at least two more urges compared with the previous day) were examined using generalized linear mixed growth-curve modeling.

FINDINGS: Participants who initiated abstinence reported reductions in urges immediately thereafter (log odds ratios: women B = -0.701, P < 0.001; men B = -0.628, P = 0.018), followed by additional, gradual reductions over time (women B = -0.118, P < 0.001; men B = -0.141, P < 0.001). Participants who entered treatment abstaining from alcohol also reported significant reductions in urges over time (women B = -0.147, P < 0.001; men B = -0.142, P < 0.001). Participants who drank throughout treatment had smaller (women B = -0.042, P = 0.012) or no reductions in urges (men B = 0.015, P = 0.545). There was no evidence that urges increased systematically in response to initiating abstinence.

CONCLUSIONS: Drinking urges during out-patient behavioral treatment for alcohol use disorders may be maintained in part by alcohol consumption. Initiating abstinence is associated with reductions in drinking urges immediately and then more gradually over time.

rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System

Sun, 04/23/2017 - 10:03pm

Aspartoacylase (AspA) gene mutations cause the pediatric lethal neurodegenerative Canavan disease (CD). There is emerging promise of successful gene therapy for CD using recombinant adeno-associated viruses (rAAVs). Here, we report an intracerebroventricularly delivered AspA gene therapy regime using three serotypes of rAAVs at a 20-fold reduced dose than previously described in AspA(-/-) mice, a bona-fide mouse model of CD. Interestingly, central nervous system (CNS)-restricted therapy prolonged survival over systemic therapy in CD mice but failed to sustain motor functions seen in systemically treated mice. Importantly, we reveal through histological and functional examination of untreated CD mice that AspA deficiency in peripheral tissues causes morphological and functional abnormalities in this heretofore CNS-defined disorder. We demonstrate for the first time that AspA deficiency, possibly through excessive N-acetyl aspartic acid accumulation, elicits both a peripheral and CNS immune response in CD mice. Our data establish a role for peripheral tissues in CD pathology and serve to aid the development of more efficacious and sustained gene therapy for this disease.

Does psychosis increase the risk of suicide in patients with major depression? A systematic review

Sun, 04/23/2017 - 10:03pm

OBJECTIVE: Over the years studies have shown conflicting results about the risk of suicide in psychotic depression (MD-psych). To understand this association, we undertook a comprehensive review of the literature to ascertain whether individuals with MD-psych have higher rates of completed suicides, suicide attempts or suicidal ideation compared to those with non-psychotic depression (MD-nonpsych).

METHODS: We searched Pubmed, PsycINFO and Ovid in English language, from 1946-October 2015. Studies were included if suicidal ideation, attempts or completed suicides were assessed.

RESULTS: During the acute episode of depression, patients with MD-psych have higher rates of suicide, suicide attempts, and suicidal ideation than patients with MD-nonpsych, especially when the patient is hospitalized on an inpatient psychiatric unit. Studies done after the acute episode has resolved are less likely to show this difference, likely due to patients having received treatment.

LIMITATIONS: Diagnostic interviews were not conducted in all studies. Many studies did not report whether psychotic symptoms in MD-psych patients were mood-congruent or mood-incongruent; hence it is unclear whether the type of delusion increases suicide risk. Studies did not describe whether MD-psych patients experienced command hallucinations encouraging them to engage in suicidal behavior. Only 24 studies met inclusion criteria; several of them had small sample size and a quality score of zero, hence impacting validity.

CONCLUSIONS: This review indicates that the seemingly conflicting data in suicide risk between MD-psych and MD-nonpsych in previous studies appears to be related to whether one looks at differences during the acute episode or over the long-term.

Habenula cholinergic neurons regulate anxiety during nicotine withdrawal via nicotinic acetylcholine receptors

Sun, 04/23/2017 - 10:03pm

Cholinergic neurons in the medial habenula (MHb) modulate anxiety during nicotine withdrawal although the molecular neuroadaptation(s) within the MHb that induce affective behaviors during nicotine cessation is largely unknown. MHb cholinergic neurons are unique in that they robustly express neuronal nicotinic acetylcholine receptors (nAChRs), although their behavioral role as autoreceptors in these neurons has not been described. To test the hypothesis that nAChR signaling in MHb cholinergic neurons could modulate anxiety, we expressed novel "gain of function" nAChR subunits selectively in MHb cholinergic neurons of adult mice. Mice expressing these mutant nAChRs exhibited increased anxiety-like behavior that was alleviated by blockade with a nAChR antagonist. To test the hypothesis that anxiety induced by nicotine withdrawal may be mediated by increased MHb nicotinic receptor signaling, we infused nAChR subtype selective antagonists into the MHb of nicotine naive and withdrawn mice. While antagonists had little effect on nicotine naive mice, blocking alpha4beta2 or alpha6beta2, but not alpha3beta4 nAChRs in the MHb alleviated anxiety in mice undergoing nicotine withdrawal. Consistent with behavioral results, there was increased functional expression of nAChRs containing the alpha6 subunit in MHb neurons that also expressed the alpha4 subunit. Together, these data indicate that MHb cholinergic neurons regulate nicotine withdrawal-induced anxiety via increased signaling through nicotinic receptors containing the alpha6 subunit and point toward nAChRs in MHb cholinergic neurons as molecular targets for smoking cessation therapeutics.

Impairments of Social Motor Synchrony Evident in Autism Spectrum Disorder

Sun, 04/23/2017 - 10:03pm

Social interactions typically involve movements of the body that become synchronized over time and both intentional and spontaneous interactional synchrony have been found to be an essential part of successful human interaction. However, our understanding of the importance of temporal dimensions of social motor synchrony in social dysfunction is limited. Here, we used a pendulum coordination paradigm to assess dynamic, process-oriented measures of social motor synchrony in adolescents with and without autism spectrum disorder (ASD). Our data indicate that adolescents with ASD demonstrate less synchronization in both spontaneous and intentional interpersonal coordination. Coupled oscillator modeling suggests that ASD participants assembled a synchronization dynamic with a weaker coupling strength, which corresponds to a lower sensitivity and decreased attention to the movements of the other person, but do not demonstrate evidence of a delay in information transmission. The implication of these findings for isolating an ASD-specific social synchronization deficit that could serve as an objective, bio-behavioral marker is discussed.

A Systematic Review of Evidence for the Clubhouse Model of Psychosocial Rehabilitation

Sun, 04/23/2017 - 10:03pm

The Clubhouse Model has been in existence for over sixty-five years; however, a review that synthesizes the literature on the model is needed. The current study makes use of the existing research to conduct a systematic review of articles providing a comprehensive understanding of what is known about the Clubhouse Model, to identify the best evidence available, as well as areas that would benefit from further study. Findings are summarized and evidence is classified by outcome domains. Fifty-two articles met the selection criteria of Randomized Clinical Trials (RCT's), quasi-experimental studies, or observational studies for domains of employment (N = 29); quality of life/satisfaction (N = 10); reductions in psychiatric hospitalization(s) (N = 10); social relationships (N = 10); education (N = 3); and health promotion activities (N = 2). RCT results support the efficacy of the Clubhouse Model in promoting employment, reducing hospitalization(s), and improving quality of life. Quasi-experimental and observational studies offer support in education and social domains. The findings from this review indicate that Clubhouses are a promising practice but additional studies using rigorous methods that report the strength of the outcomes are needed to evaluate Clubhouse programs with fidelity to the Clubhouse Model.