Saturday, February 15, 2014

Neuropsychopharmacoly and Neuroscience News, February 2014

Religion, Spirituality May Build Resilience Against Depression by Toughening the Brain


JAMA Psychiatry

Importance
We previously reported a 90% decreased risk in major depression, assessed prospectively, in adult offspring of depressed probands who reported that religion or spirituality was highly important to them. Frequency of church attendance was not significantly related to depression risk. Our previous brain imaging findings in adult offspring in these high-risk families also revealed large expanses of cortical thinning across the lateral surface of the right cerebral hemisphere.
Objective 
To determine whether high-risk adults who reported high importance of religion or spirituality had thicker cortices than those who reported moderate or low importance of religion or spirituality and whether this effect varied by family risk status.
Design, Setting, and Participants 
Longitudinal, retrospective cohort, familial study of 103 adults (aged 18-54 years) who were the second- or third-generation offspring of depressed (high familial risk) or nondepressed (low familiar risk) probands (first generation). Religious or spiritual importance and church attendance were assessed at 2 time points during 5 years, and cortical thickness was measured on anatomical images of the brain acquired with magnetic resonance imaging at the second time point.
Main Outcomes and Measures
Cortical thickness in the parietal regions by risk status.
Results 
Importance of religion or spirituality, but not frequency of attendance, was associated with thicker cortices in the left and right parietal and occipital regions, the mesial frontal lobe of the right hemisphere, and the cuneus and precuneus in the left hemisphere, independent of familial risk. In addition, the effects of importance on cortical thickness were significantly stronger in the high-risk than in the low-risk group, particularly along the mesial wall of the left hemisphere, in the same region where we previously reported a significant thinner cortex associated with a familial risk of developing depressive illness. We note that these findings are correlational and therefore do not prove a causal association between importance and cortical thickness.
Conclusions and Relevance 
A thicker cortex associated with a high importance of religion or spirituality may confer resilience to the development of depressive illness in individuals at high familial risk for major depression, possibly by expanding a cortical reserve that counters to some extent the vulnerability that cortical thinning poses for developing familial depressive illness.

Link: http://goo.gl/BwgpTm


Microvascular Abnormality in Schizophrenia as Shown by Retinal Imaging


The American Journal of Psychiatry

Objective  
Retinal and cerebral microvessels are structurally and functionally homologous, but unlike cerebral microvessels, retinal microvessels can be noninvasively measured in vivo by retinal imaging. The authors tested the hypothesis that individuals with schizophrenia exhibit microvascular abnormality and evaluated the utility of retinal imaging as a tool for schizophrenia research. 
Method  
Participants were members of the Dunedin Study, a population-representative cohort followed from birth with 95% retention. Study members underwent retinal imaging at age 38. The authors assessed retinal arteriolar and venular caliber for all members of the cohort, including individuals who developed schizophrenia. 
Results  
Study members who developed schizophrenia were distinguished by wider retinal venules, suggesting microvascular abnormality reflective of insufficient brain oxygen supply. Analyses that controlled for confounding health conditions suggested that wider retinal venules are not simply an artifact of co-occurring health problems in schizophrenia patients. Wider venules were also associated with a dimensional measure of adult psychosis symptoms and with psychosis symptoms reported in childhood.
Conclusions
The findings provide initial support for the hypothesis that individuals with schizophrenia show microvascular abnormality. Moreover, the results suggest that the same vascular mechanisms underlie subthreshold symptoms and clinical disorder and that these associations may begin early in life. These findings highlight the promise of retinal imaging as a tool for understanding the pathogenesis of schizophrenia.

Link: http://goo.gl/6yCvs2


January 2014 Drug Safety Labeling Changes includes 23 products with revisions to Prescribing Information


FDA Medwatch

The MedWatch January 2014 Safety Labeling Changes posting includes 39 products with safety labeling changes to the following sections: BOXED WARNINGS, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS and PATIENT PACKAGE INSERT.
The "Summary Page" provides a listing of product names and safety labeling sections revised.

Link: http://goo.gl/xO7jSp 


Elevated Serum Pesticide Levels and Risk for Alzheimer Disease


JAMA Neurology

Importance 
The causes of late-onset Alzheimer disease (AD) are not yet understood but likely include a combination of genetic, environmental, and lifestyle factors. Limited epidemiological studies suggest that occupational pesticide exposures are associated with AD. Previously, we reported that serum levels of dichlorodiphenyldichloroethylene (DDE), the metabolite of the pesticide dichlorodiphenyltrichloroethane (DDT), were elevated in a small number of patients with AD (n=20).
Objective 
To evaluate the association between serum levels of DDE and AD and whether the apolipoprotein E (APOE) genotype modifies the association.
Design, Setting, and Participants  
A case-control study consisting of existing samples from patients with AD and control participants from the Emory University Alzheimer’s Disease Research Center and the University of Texas Southwestern Medical School’s Alzheimer’s Disease Center. Serum levels of DDE were measured in 79 control and 86 AD cases.
Main Outcomes and Measures 
Serum DDE levels, AD diagnosis, severity of AD measured by the Mini-Mental State Examination score, and interaction with APOE4 status.
Results 
Levels of DDE were 3.8-fold higher in the serum of those with AD (mean [SEM], 2.64 [0.35] ng/mg cholesterol) when compared with control participants (mean [SEM], 0.69 [0.1] ng/mg cholesterol; P < .001). The highest tertile of DDE levels was associated with an odds ratio of 4.18 for increased risk for AD (95% CI, 2.54-5.82; P < .001) and lower Mini-Mental State Examination scores (−1.605; range, −3.095 to −0.114; P < .0001). The Mini-Mental State Examination scores in the highest tertile of DDE were −1.753 points lower in the subpopulation carrying an APOE ε4 allele compared with those carrying an APOE ε3 allele (P interaction = .04). Serum levels of DDE were highly correlated with brain levels of DDE (ρ = 0.95). Exposure of human neuroblastoma cells to DDT or DDE increased levels of amyloid precursor protein.
Conclusions and Relevance 
Elevated serum DDE levels are associated with an increased risk for AD and carriers of an APOE4 ε4 allele may be more susceptible to the effects of DDE. Both DDT and DDE increase amyloid precursor protein levels, providing mechanistic plausibility for the association of DDE exposure with AD. Identifying people who have elevated levels of DDE and carry an APOE ε4 allele may lead to early identification of some cases of AD.

Link: http://goo.gl/gzKrlz



Prevalence of Diagnosed Depression in Adolescents With History of Concussion
 

Journal of Adolescent Health

Purpose
Previous studies in adults have suggested concussion and other brain injury presents a risk factor for depression. The goal of our study was to analyze the association between previous concussion and current depression diagnosis in a large nationally representative adolescent data set.
Methods
Retrospective cohort study using the National Survey of Children's Health 2007–2008, a nationally representative survey conducted via random digit dialing. Data were obtained by parental report. We included youth 12–17 years old without a current concussion (N = 36,060), and evaluated the association between previous concussion (binary) and current depression diagnosis (binary) using multiple logistic regression to control for age, sex, parental mental health, and socioeconomic status.
Results
After controlling for age, sex, parental mental health, and socioeconomic status, history of concussion was associated with a 3.3-fold greater risk for depression diagnosis (95% CI: 2.0–5.5). Other factors significantly associated with depression diagnosis included poor or fair parental mental health (OR: 3.7, 95% CI: 2.8–4.9), and older age (15–17 years vs. 12–14 years, OR: 1.4, 95% CI: 1.1–1.8). Sex of the subject was not significantly related to depression diagnosis. Being above 200% of the poverty level was associated with approximately a 50% decreased risk of depression diagnosis (95% CI: 35%–70%).
Conclusions
History of concussion was associated with a higher prevalence of diagnosed depression in a large nationally representative adolescent data set. Clinicians should screen for depression in their adolescent patients with concussion. Future studies should confirm this association using prospective methodology and examine potential treatment approaches.

Link: http://goo.gl/1OorLu


Mitigation of Sociocommunicational Deficits of Autism Through Oxytocin-Induced Recovery of Medial Prefrontal Activity


JAMA Psychiatry

Importance  
Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin’s beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide.
Objective  
To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures.
Design, Setting, and Participants 
At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject–crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial.
Interventions 
Single-dose intranasal administration of oxytocin (24 IU) and placebo.
Main Outcomes and Measures  
Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information–based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs.
Results  
Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the magnitude of these neural effects was predictive of the behavioral effects (P ≤ .01).
Conclusions and Relevance 
These findings provide the first neurobiological evidence for oxytocin’s beneficial effects on sociocommunicational deficits of ASD and give us the initial account for neurobiological mechanisms underlying any beneficial effects of the neuropeptide.

Link: http://goo.gl/mWFTOI


Study Finds That Persistent Internalizing Disorders May Lead to Accelerated Aging


Molecular Psychiatry

There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose–response manner, specifically in men (β=−0.137, 95% confidence interval (CI): −0.232, −0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (β=−0.111, 95% CI: −0.184, −0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.

Link: http://goo.gl/KMJddi


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