Saturday, March 4, 2017

March 2017

Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year


Depression and Anxiety

Abstract

Background
Due to its potent effects on social behavior, including maternal behavior, oxytocin has been identified as a potential mediator of postpartum depression and anxiety. The objective of this study was to examine the relationship between peripartum synthetic oxytocin administration and the development of depressive and anxiety disorders within the first year postpartum. We hypothesized that women exposed to peripartum synthetic oxytocin would have a reduced risk of postpartum depressive and anxiety disorders compared with those without any exposure.

Methods
Population-based data available through the Massachusetts Integrated Clinical Academic Research Database (MiCARD) were used to retrospectively (2005–2014) examine this relationship and calculate the relative risk of peripartum synthetic oxytocin for the development of postpartum depressive and anxiety disorders in exposed (n = 9,684) compared to unexposed (n = 37,048) deliveries.

Results
Among deliveries to women with a history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 36% (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.20–1.55). In deliveries to women with no history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 32% compared to those not exposed (RR: 1.32; 95% CI: 1.23-1.42).

Conclusions
Contrary to our hypothesis, results indicate that women with peripartum exposure to synthetic oxytocin had a higher relative risk of receiving a documented depressive or anxiety disorder diagnosis or antidepressant/anxiolytic prescription within the first year postpartum than women without synthetic oxytocin exposure.


The Effect of Substance Use on 10-Year Outcome in First-Episode Psychosis


Schizophrenia Bulletin

Abstract

Substance use is common in first-episode psychosis (FEP) and has been linked to poorer outcomes with more severe psychopathology and higher relapse rates. Early substance discontinuation appears to improve symptoms and function. However, studies vary widely in their methodology, and few have examined patients longitudinally, making it difficult to draw conclusions for practice and treatment. We aimed to investigate the relationship between substance use and early abstinence and the long-term course of illness in a representative sample of FEP patients. Out of 301 included patients, 266 could be divided into 4 groups based on substance use patterns during the first 2 years of treatment: persistent users, episodic users, stop-users and nonusers. Differences in clinical and functional measures during the follow-up period were assessed using linear mixed effects models for the analysis of repeated measures data. Patients who stopped using substances within the first 2 years after diagnosis had outcomes similar to those who had never used with fewer symptoms than episodic or persistent users. Both episodic and persistent users had lower rates of symptom remission than nonusers, and persistent users also had more negative symptoms than those who stopped using. Our findings emerge from one of very few long-term longitudinal studies examining substance use cessation in FEP with 10-year follow-up. The results convey hope that the detrimental effects of substance abuse on mental health may be significantly reversed if one stops the abuse in time. This can help patients who struggle with addiction with their motivation to embrace abstinence.
 


Predictors of Major Depression and Posttraumatic Stress Disorder Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis


The Journal of Neuropsychiatry

Abstract

Although major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are prevalent after traumatic brain injury (TBI), little is known about which patients are at risk for developing them. The authors systematically reviewed the literature on predictors and multivariable models for MDD and PTSD after TBI. The authors included 26 observational studies. MDD was associated with female gender, preinjury depression, postinjury unemployment, and lower brain volume, whereas PTSD was related to shorter posttraumatic amnesia, memory of the traumatic event, and early posttraumatic symptoms. Risk of bias ratings for most studies were acceptable, although studies that developed a multivariable model suffered from methodological shortcomings.



Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study


Biological Psychiatry 

Abstract
  
Background
Cognitive dysfunction is a core feature of depression and tends to persist even after mood symptoms recover, leading to detrimental effects on clinical and functional outcomes. However, most currently available treatments have not typically addressed cognition. Modafinil has been shown to have beneficial effects on cognitive function and therefore has the potential to improve cognition in depression. The objective of this double-blind, placebo-controlled study was to investigate the effects of modafinil on cognitive functions in patients with remitted depression.

Methods
In total, 60 patients with remitted depression participated in the study. Cognitive functions were evaluated with tests of working memory, planning, attention, and episodic memory from the Cambridge Neuropsychological Test Automated Battery at the baseline session and after treatment. A double-blind, randomized, placebo-controlled, parallel groups design was used to assess the effects of single-dose (200 mg) modafinil (n = 30) or placebo (n = 30) on cognition and fatigue. The main outcome measures were neurocognitive test scores from the Cambridge Neuropsychological Test Automated Battery. Visual analogue scales for subjective feelings and fatigue were used as secondary measures.

Results
The modafinil group had significantly better performance on tests of episodic memory (p = .01, ηp2 = .10) and working memory (p = .04, ηp2 = .06). Modafinil did not improve planning or sustained attention.

Conclusions
This study suggested that modafinil (200 mg) could improve episodic memory and working memory performance in patients with remitted depression. Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.

Source: http://www.biologicalpsychiatrycnni.org/


Association of Serum Docosahexaenoic Acid With Cerebral Amyloidosis


JAMA Neurology

Importance  
Higher dietary intake of the essential fatty acid docosahexaenoic (DHA) has been associated with better cognitive performance in several epidemiological studies. Animal and in vitro studies also indicate that DHA prevents amyloid deposition in the brain.

Objective  
To determine the association between serum DHA levels, cerebral amyloidosis, and the volumes of brain areas affected by Alzheimer disease.

Design, Settings, and Participants  
Cross-sectional analysis of serum DHA levels together with measures of amyloid deposition (Pittsburgh Compound B index), brain volumes, and neuropsychological testing scores from 61 participants in the Aging Brain Study. The study was conducted between June 2008 and May 2013, and the data were analyzed between October 2015 and April 2016. Linear models were adjusted for age, sex, years of education, and apolipoprotein E status.

Main Outcomes and Measures  
Serum DHA levels with cerebral amyloidosis measured using PIB PET.

Results  
Samples were available from 61 Aging Brain Study participants (41 women and 20 men) who underwent amyloid PET imaging. The mean (SD) age of the participants was 77 (6) years and ranged from 67 to 88 years. Serum DHA levels (percentage of total fatty acids) were 23% lower in participants with cerebral amyloidosis than those without (0.97 vs 1.25, P = .007) and were inversely correlated with brain amyloid load (r = −0.32, P = .01) independent of age, sex, apolipoprotein E genotype, and years of education. Moreover, greater serum DHA levels were positively associated with brain volume in several subregions affected by AD, in particular the left subiculum (r = 0.38, P = .005) and the left entorhinal volumes (r = 0.51, P = .001). Serum DHA levels were also associated with nonverbal memory scores (r = 0.28, P = .03).

Conclusions and Relevance  
In this study, serum DHA levels were associated with pathogenesis of cerebral amyloidosis and with preservation of entorhinal and hippocampal volumes. These findings suggest an important role for DHA metabolism in brain amyloid deposition during the preclinical or early symptomatic stages of Alzheimer disease.



Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder


The Journal of Clinical Psychiatry

Abstract

Objective
To evaluate efficacy, safety, and tolerability of long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) as maintenance treatment for bipolar I disorder (BP-I).

Methods
In a double-blind, placebo-controlled, 52-week randomized withdrawal study conducted from August 2012 to April 2016, patients with a DSM-IV-TR diagnosis of BP-I currently experiencing a manic episode were stabilized sequentially on oral aripiprazole and AOM 400 and then randomized to AOM 400 or placebo. The primary end point was time from randomization to recurrence of any mood episode. Other end points included proportion of patients with recurrence of any mood episode and recurrence by mood episode type.

Results
Of 266 randomized patients, 64 (48.1%) of 133 in the AOM 400 group and 38 (28.6%) of 133 in the placebo group completed the study. AOM 400 significantly delayed the time to recurrence of any mood episode compared with placebo (hazard ratio: 0.45; 95% CI, 0.30 to 0.68; P < .0001). Significantly fewer patients (P < .0001) experienced recurrence of any mood episode with AOM 400 (35/132; 26.5%) compared with placebo (68/133; 51.1%), with the effects observed predominantly on manic episodes (P < .0001). Patients were not depressed at study entry, and between-group differences in depressive episodes were not significant (P < .864). The treatment-emergent adverse events (incidence > 5%) that were reported at higher rates with AOM 400 than placebo were weight increase, akathisia, insomnia, and anxiety.

Conclusions 
AOM 400 delayed the time to and reduced the rate of recurrence of mood episodes and was generally safe and well tolerated. These findings support the use of AOM 400 for maintenance treatment of BP-I.



Antidepressant use and risk of hip fractures among community-dwelling persons with and without Alzheimer's disease


Geriatric Psychiatry

Abstract

Objective
To study whether antidepressant use is associated with an increased risk of hip fracture among community-dwelling persons with and without Alzheimer's disease (AD), and to compare the risk according to duration of use and between antidepressant groups.

Methods
Retrospective cohort study, including 50,491 persons with AD (mean age 80) and 100,982 comparison persons without AD from Finnish register-based MEDALZ cohort. Antidepressant use was compared with nonuse with Cox proportional hazard models. Incident users were identified with a one year washout period from Prescription register data. Main outcome was hospitalization due to hip fracture.

Results
During antidepressant use, the age-adjusted rate of hip fractures per 100 person-years was 3.01 (95% CI 2.75–3.34) among persons with and 2.28 (1.94–2.61) among persons without AD. Antidepressant use was associated with an increased risk of hip fracture among persons with and without AD (adjusted HR 1.61, 95% CI 1.45–1.80 and 2.71, 2.35–3.14, respectively) compared with nonuse. The risk was most prominent in the beginning of use and was elevated even up to 4 years. The risk was increased with all of the most frequently used antidepressants.

Conclusion
Antidepressant use is associated with an increased risk of hip fracture among older persons. 



Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study


The Lancet

Abstract

Background
Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events.

Methods
Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses.

Findings
293 patients (median age 55 years [IQR 45·0–65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7–4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27–1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210).

Interpretation
In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings.



An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents


Molecular Psychiatry

Abstract

Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear whether differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal epigenetic, neuroimaging and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status (SES) predict changes in risk-related brain function. Specifically, we find that lower SES during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention among high-risk individuals.



Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder


The Journal of Clinical Psychiatry

Abstract

Objective
Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders—social phobia and generalized anxiety disorder (GAD).

Methods
Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed.

Results
Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0–2.6]), cardiac (OR = 1.8 [95% CI, 1.1–3.1]), neurologic (OR = 2.6 [95% CI, 1.6–4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7–5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects.

Conclusions
Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time.



Online Journals:




Biological Psychiatry - Volume 81, Issue 7, April 2017



Join us on LinkedIn: Neurosychopharmacology News Group