PCOM Library / Hot Topics in Research / Archive for "Psychology and Psychiatry"

Category: Psychology and Psychiatry

Hot Topics: Ineffective Arthritis Drug Could Treat Opioid Addiction

Jackie Werner Hot Topics in Research, Substance Use Disorders

Slowly Signaling G Protein–Biased CB2 Cannabinoid Receptor Agonist LY2828360 Suppresses Neuropathic Pain with Sustained Efficacy and Attenuates Morphine Tolerance and Dependence

Lin X, Dhopeshwarkar AS, Huibregtse M, Mackie K, Hohmann AG. Slowly Signaling G Protein–Biased CB2 Cannabinoid Receptor Agonist LY2828360 Suppresses Neuropathic Pain with Sustained Efficacy and Attenuates Morphine Tolerance and Dependence. Mol Pharmacol. 2018;93:49-62; doi: 10.1124/mol.117.109355.

The CB2 cannabinoid agonist LY2828360 lacked both toxicity and efficacy in a clinical trial for osteoarthritis. Whether LY2828360 suppresses neuropathic pain has not been reported, and its signaling profile is unknown. In vitro, LY2828360 was a slowly acting but efficacious G protein–biased CB2 agonist, inhibiting cAMP accumulation and activating extracellular signal-regulated kinase 1/2 signaling while failing to recruit arrestin, activate inositol phosphate signaling, or internalize CB2 receptors. In wild-type (WT) mice, LY2828360 (3 mg/kg per day i.p. × 12 days) suppressed chemotherapy-induced neuropathic pain produced by paclitaxel without producing tolerance. Antiallodynic efficacy of LY2828360 was absent in CB2 knockout (KO) mice. Morphine (10 mg/kg per day i.p. × 12 days) tolerance developed in CB2KO mice but not in WT mice with a history of LY2828360 treatment (3 mg/kg per day i.p. × 12 days). LY2828360-induced antiallodynic efficacy was preserved in WT mice previously rendered tolerant to morphine (10 mg/kg per day i.p. × 12 days), but it was absent in morphine-tolerant CB2KO mice. Coadministration of LY2828360 (0.1 mg/kg per day i.p. × 12 days) with morphine (10 mg/kg per day × 12 days) blocked morphine tolerance in WT but not in CB2KO mice. WT mice that received LY2828360 coadministered with morphine exhibited a trend (P = 0.055) toward fewer naloxone-precipitated jumps compared with CB2KO mice. In conclusion, LY2828360 is a slowly signaling, G protein–biased CB2 agonist that attenuates chemotherapy-induced neuropathic pain without producing tolerance and may prolong effective opioid analgesia while reducing opioid dependence. LY2828360 may be useful as a first-line treatment in chemotherapy-induced neuropathic pain and may be highly efficacious in neuropathic pain states that are refractive to opioid analgesics.

Hot Topics: Key Molecule Found To Protect Brain From Depression

Jackie Werner Hot Topics in Research, Mood Disorders, Psychology and Psychiatry

Loss of eIF4E Phosphorylation Engenders Depression-like Behaviors via Selective mRNA Translation

Amorim IS, Kedia S, Kouloulia S, et al. Loss of eIF4E phosphorylation engenders depression-like behaviors via selective mRNA translation. J Neurosci. 2018;38(8):2118-2133. doi: 10.1523/JNEUROSCI.2673-17.2018.

The MAPK/ERK (mitogen-activated protein kinases/extracellular signal-regulated kinase) pathway is a cardinal regulator of synaptic plasticity, learning, and memory in the hippocampus. One of major endpoints of this signaling cascade is the 5′ mRNA cap binding protein eIF4E (eukaryotic Initiation Factor 4E), which is phosphorylated on Ser 209 by MNK (MAPK-interacting protein kinases) and controls mRNA translation. The precise role of phospho-eIF4E in the brain is yet to be determined. Herein, we demonstrate that ablation of eIF4E phosphorylation in male mice (4Eki mice) does not impair long-term spatial or contextual fear memory, or the late phase of LTP. Using unbiased translational profiling in mouse brain, we show that phospho-eIF4E differentially regulates the translation of a subset of mRNAs linked to inflammation, the extracellular matrix, pituitary hormones, and the serotonin pathway. Consequently, 4Eki male mice display exaggerated inflammatory responses and reduced levels of serotonin, concomitant with depression and anxiety-like behaviors. Remarkably, eIF4E phosphorylation is required for the chronic antidepressant action of the selective serotonin reuptake inhibitor fluoxetine. Finally, we propose a novel phospho-eIF4E-dependent translational control mechanism in the brain, via the GAIT complex (gamma IFN activated inhibitor of translation). In summary, our work proposes a novel translational control mechanism involved in the regulation of inflammation and depression, which could be exploited to design novel therapeutics.

SIGNIFICANCE STATEMENT We demonstrate that downstream of the MAPK (mitogen-activated protein kinase) pathway, eukaryotic Initiation Factor 4E (eIF4E) Ser209 phosphorylation is not required for classical forms of hippocampal LTP and memory. We reveal a novel role for eIF4E phosphorylation in inflammatory responses and depression-like behaviors. eIF4E phosphorylation is required for the chronic action of antidepressants, such as fluoxetine in mice. These phenotypes are accompanied by selective translation of extracellular matrix, pituitary hormones, and serotonin pathway genes, in eIF4E phospho-mutant mice. We also describe a previously unidentified translational control mechanism in the brain, whereby eIF4E phosphorylation is required for inhibiting the translation of gamma IFN activated inhibitor of translation element-containing mRNAs. These findings can be used to design novel therapeutics for depression.

 

Hot Topics: Shaming Overweight Children is Harmful

Jackie Werner Hot Topics in Research, Nutrition, Pediatrics, Psychology and Psychiatry

Stigma Experienced by Children and Adolescents With Obesity

Pont, S. J., Puhl, R., Cook, S. R., Slusser, W., Section on Obesity , & The Obesity Society. (2017). Stigma experienced by children and adolescents with obesity. Pediatrics, doi:10.1542/peds.2017-3034

The stigmatization of people with obesity is widespread and causes harm. Weight stigma is often propagated and tolerated in society because of beliefs that stigma and shame will motivate people to lose weight. However, rather than motivating positive change, this stigma contributes to behaviors such as binge eating, social isolation, avoidance of health care services, decreased physical activity, and increased weight gain, which worsen obesity and create additional barriers to healthy behavior change. Furthermore, experiences of weight stigma also dramatically impair quality of life, especially for youth. Health care professionals continue to seek effective strategies and resources to address the obesity epidemic; however, they also frequently exhibit weight bias and stigmatizing behaviors. This policy statement seeks to raise awareness regarding the prevalence and negative effects of weight stigma on pediatric patients and their families and provides 6 clinical practice and 4 advocacy recommendations regarding the role of pediatricians in addressing weight stigma. In summary, these recommendations include improving the clinical setting by modeling best practices for nonbiased behaviors and language; using empathetic and empowering counseling techniques, such as motivational interviewing, and addressing weight stigma and bullying in the clinic visit; advocating for inclusion of training and education about weight stigma in medical schools, residency programs, and continuing medical education programs; and empowering families to be advocates to address weight stigma in the home environment and school setting.

Hot Topics: Daily Light Therapy May Provide Relief for Bipolar Depression

Jackie Werner Hot Topics in Research, Mood Disorders, Psychology and Psychiatry

Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial

Sit, D. K., McGowan, J., Wiltrout, C., Diler, R. S., Dills, J., et al. (2017). Adjunctive bright light therapy for bipolar depression: A randomized double-blind placebo-controlled trial. American Journal of Psychiatry. doi:10.1176/appi.ajp.2017.16101200

Objective:
Patients with bipolar disorder have recurrent major depression, residual mood symptoms, and limited treatment options. Building on promising pilot data, the authors conducted a 6-week randomized double-blind placebo-controlled trial to investigate the efficacy of adjunctive bright light therapy at midday for bipolar depression. The aims were to determine remission rate, depression symptom level, and rate of mood polarity switch, as well as to explore sleep quality.

Method:
The study enrolled depressed adults with bipolar I or II disorder who were receiving stable dosages of antimanic medication (excluding patients with hypomania or mania, mixed symptoms, or rapid cycling). Patients were randomly assigned to treatment with either 7,000-lux bright white light or 50-lux dim red placebo light (N=23 for each group). Symptoms were assessed weekly with the Structured Interview Guide for the Hamilton Depression Scale With Atypical Depression Supplement (SIGH-ADS), the Mania Rating Scale, and the Pittsburgh Sleep Quality Index. Remission was defined as having a SIGH-ADS score of 8 or less.

Results:
At baseline, both groups had moderate depression and no hypomanic or manic symptoms. Compared with the placebo light group, the group treated with bright white light experienced a significantly higher remission rate (68.2% compared with 22.2%; adjusted odds ratio=12.6) at weeks 4–6 and significantly lower depression scores (9.2 [SD=6.6] compared with 14.9 [SD=9.2]; adjusted β=–5.91) at the endpoint visit. No mood polarity switches were observed. Sleep quality improved in both groups and did not differ significantly between them.

Conclusions:
The data from this study provide robust evidence that supports the efficacy of midday bright light therapy for bipolar depression.

Hot Topics: Frequent Vaping Encourages Smokers to Quit Tobacco

Jackie Werner Hot Topics in Research, Substance Use Disorders

The Relationship of E-Cigarette Use to Cigarette Quit Attempts and Cessation: Insights From a Large, Nationally Representative U.S. Survey

David T Levy, PhD, Zhe Yuan, MS, Yuying Luo, MS, David B Abrams, PhD; The Relationship of E-Cigarette Use to Cigarette Quit Attempts and Cessation: Insights From a Large, Nationally Representative U.S. Survey. Nicotine & Tobacco Research. https://doi.org/10.1093/ntr/ntx166

Objectives
While cessation from cigarettes is a top priority for public health, controversy surrounds the role of e-cigarettes for quitting cigarettes. This study examines the role of e-cigarettes in quit attempts and 3-month cigarette abstinence using a large, recent nationally representative US sample.

Methods
Data from the 2014/15 Tobacco Use Supplement-Current Population Survey (TUS-CPS) on cigarette and e-cigarette use and individual characteristics were supplemented with information on state tobacco control policies. We estimated frequencies and multivariate logistic equations for making a quit attempt among those who smoked 1 year earlier and for remaining abstinent at least 3 months among those making a quit attempt. These two outcomes were related to demographic characteristics, tobacco control policies and different frequency measures of e-cigarette use (ever, at least 1, 5, 20 of the last 30 days, a continuous measure of days use).

Results
Having made a quit attempt was more likely among smokers using e-cigarettes than non-users. Among those making at least one quit attempt, quit success was lower among ever users, but higher among those with at least 5 days use of e-cigarettes in the last month. Both quit attempts and quit success were linearly related to the frequency of e-cigarette use.

Conclusions
Consistent with randomized trials and those observational studies that measure frequency of e-cigarette use, both quit attempts and quit success were positively associated with increased frequency of e-cigarette use. Frequency of e-cigarette use was important in gauging the nature of these relationships.

Implications
Previous studies have obtained mixed results regarding the relationship of e-cigarette use to cigarette smoking cessation. This study provides a more precise methodology for considering the relationship of e-cigarette use to quit attempts and to quit success, and finds that quit attempts and quit success increase with the number of days use in the past month.

Hot Topic: Mind-Body Therapies Dramatically Reduce Pain in Hospital Patients

Jackie Werner Hot Topics in Research, Neurology, Psychology and Psychiatry

Randomized Controlled Trial of Brief Mindfulness Training and Hypnotic Suggestion for Acute Pain Relief in the Hospital Setting

Garland EL, Baker AK, Larsen P, et al. Randomized controlled trial of brief mindfulness training and hypnotic suggestion for acute pain relief in the hospital setting. Journal of General Internal Medicine. 2017. https://doi.org/10.1007/s11606-017-4116-9.

Background

Medical management of acute pain among hospital inpatients may be enhanced by mind-body interventions.

Objective

We hypothesized that a single, scripted session of mindfulness training focused on acceptance of pain or hypnotic suggestion focused on changing pain sensations through imagery would significantly reduce acute pain intensity and unpleasantness compared to a psychoeducation pain coping control. We also hypothesized that mindfulness and suggestion would produce significant improvements in secondary outcomes including relaxation, pleasant body sensations, anxiety, and desire for opioids, compared to the control condition.

Methods

This three-arm, parallel-group randomized controlled trial conducted at a university-based hospital examined the acute effects of 15-min psychosocial interventions (mindfulness, hypnotic suggestion, psychoeducation) on adult inpatients reporting “intolerable pain” or “inadequate pain control.” Participants (N = 244) were assigned to one of three intervention conditions: mindfulness (n = 86), suggestion (n = 73), or psychoeducation (n = 85).

Key Results

Participants in the mind-body interventions reported significantly lower baseline-adjusted pain intensity post-intervention than those assigned to psychoeducation (p < 0.001, percentage pain reduction: mindfulness = 23%, suggestion = 29%, education = 9%), and lower baseline-adjusted pain unpleasantness (p < 0.001). Intervention conditions differed significantly with regard to relaxation (p < 0.001), pleasurable body sensations (p = 0.001), and desire for opioids (p = 0.015), but all three interventions were associated with a significant reduction in anxiety (p < 0.001).

Conclusions

Brief, single-session mind-body interventions delivered by hospital social workers led to clinically significant improvements in pain and related outcomes, suggesting that such interventions may be useful adjuncts to medical pain management.

Hot Topics: Benefits of Autism Diets and Supplements Questionable

Jackie Werner Developmental Disorders, Hot Topics in Research

Nutritional and Dietary Interventions for Autism Spectrum Disorder: A Systematic Review

Sathe N, Andrews JC, McPheeters ML, Warren ZE. Nutritional and dietary interventions for autism spectrum disorder: A systematic review. Pediatrics. 2017. doi: 10.1542/peds.2017-0346

CONTEXT: Children with autism spectrum disorder (ASD) frequently use special diets or receive nutritional supplements to treat ASD symptoms.

OBJECTIVES: Our objective was to evaluate the effectiveness and safety of dietary interventions or nutritional supplements in ASD.

DATA SOURCES: Databases, including Medline and PsycINFO.

STUDY SELECTION: Two investigators independently screened studies against predetermined criteria.

DATA EXTRACTION: One investigator extracted data with review by a second investigator. Investigators independently assessed the risk of bias and strength of evidence (SOE) (ie, confidence in the estimate of effects).

RESULTS: Nineteen randomized controlled trials (RCTs), 4 with a low risk of bias, evaluated supplements or variations of the gluten/casein-free diet and other dietary approaches. Populations, interventions, and outcomes varied. Ω-3 supplementation did not affect challenging behaviors and was associated with minimal harms (low SOE). Two RCTs of different digestive enzymes reported mixed effects on symptom severity (insufficient SOE). Studies of other supplements (methyl B12, levocarnitine) reported some improvements in symptom severity (insufficient SOE). Studies evaluating gluten/casein-free diets reported some parent-rated improvements in communication and challenging behaviors; however, data were inadequate to make conclusions about the body of evidence (insufficient SOE). Studies of gluten- or casein-containing challenge foods reported no effects on behavior or gastrointestinal symptoms with challenge foods (insufficient SOE); 1 RCT reported no effects of camel’s milk on ASD severity (insufficient SOE). Harms were disparate.

LIMITATIONS: Studies were small and short-term, and there were few fully categorized populations or concomitant interventions.

CONCLUSIONS: There is little evidence to support the use of nutritional supplements or dietary therapies for children with ASD.

Hot Topics: PTSD in Women Strongly Linked to Genetics

Jackie Werner Anxiety Disorders, Hot Topics in Research, Psychology and Psychiatry

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

Duncan L,E., Ratanatharathorn A, Aiello A,E., et al. Largest GWAS of PTSD (N=20thinsp]070) yields genetic overlap with schizophrenia and sex differences in heritability. Mol Psychiatry. 2017.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ~10000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Hot Topics: First Tardive Dyskinesia Drug Approved by FDA

Jackie Werner Hot Topics in Research, Neurology, Psychology and Psychiatry

FDA approves first drug to treat tardive dyskinesia

Food and Drug Administration, U.S. Department of Health and Human Services. (2017). FDA approves first drug to treat tardive dyskinesia. Retrieved from https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm552418.htm.

The U.S. Food and Drug Administration today [April 11, 2017] approved Ingrezza (valbenazine) capsules to treat adults with tardive dyskinesia. This is the first drug approved by the FDA for this condition.

Tardive dyskinesia is a neurological disorder characterized by repetitive involuntary movements, usually of the jaw, lips and tongue, such as grimacing, sticking out the tongue and smacking the lips. Some affected people also experience involuntary movement of the extremities or difficulty breathing.

Hot Topics: Training Medical Students to Organize Needle Exchange Programs

Jackie Werner Hot Topics in Research, Substance Use Disorders

Students as effective harm reductionists and needle exchange organizers

Barbour K, McQuade M, Brown B. Students as effective harm reductionists and needle exchange organizers. Substance Abuse Treatment, Prevention, and Policy. 2017;12(15). http://dx.doi.org/10.1186/s13011-017-0099-0.

Background
Needle exchange programs are safe, highly effective programs for promoting health among people who inject drugs. However, they remain poorly funded, and often illegal, in many places worldwide due to fear and stigma surrounding drug use. Continued advocacy, education, and implementation of new needle exchanges are thus essential to improve public health and reduce structural inequality.

Commentary
We argue that students, and especially professional and graduate students, have the potential to play an important role in advancing harm reduction. Students benefit from the respect given to the professions they are training to enter, which gives them leverage to navigate the political hurdles often faced by needle exchange organizers, especially in areas that presently lack services. In addition, due to their relative simplicity, needle exchanges do not require much of the licensing, clinical knowledge, and infrastructure associated with more traditional student programs, such as student-run free medical clinics. Students are capable of learning harm reduction cultural approaches and techniques if they remain humble, open-minded, and seek the help of the harm reduction community. Consequently, students can generate tremendous benefits to their community without performing beyond their appropriate clinical limitations.

Students benefit from organizing needle exchanges by gaining applied experience in advocacy, organization-building, and political finesse. Working in a needle exchange significantly helps erode stigma against multiple marginalized populations. Students in health-related professions additionally learn clinically-relevant knowledge that is often lacking from their formal training, such as an understanding of structural violence and inequality, root causes of substance use, client-centered approaches to health services, and interacting with clients as peers, rather than through the standard hierarchical medical interaction.

Conclusion
We therefore encourage students to learn about and consider organizing needle exchanges during their training. Our experience is that students can be successful in developing sustainable programs which benefit their clients, the broader harm reduction movement, and themselves alike.