Wednesday, May 6, 2015

May 2015

Long-Term Effects Of Being Bullied By Other Kids May Be Worse Than Abuse By Adults:
Adult mental health consequences of peer bullying and maltreatment in childhood


The Lancet Psychiatry

Summary

Background
The adult mental health consequences of childhood maltreatment are well documented. Maltreatment by peers (ie, bullying) has also been shown to have long-term adverse effects. We aimed to determine whether these effects are just due to being exposed to both maltreatment and bullying or whether bullying has a unique effect.

Methods
We used data from the Avon Longitudinal Study of Parents and Children in the UK (ALSPAC) and the Great Smoky Mountains Study in the USA (GSMS) longitudinal studies. In ALSPAC, maltreatment was assessed as physical, emotional, or sexual abuse, or severe maladaptive parenting (or both) between ages 8 weeks and 8·6 years, as reported by the mother in questionnaires, and being bullied was assessed with child reports at 8, 10, and 13 years using the previously validated Bullying and Friendship Interview Schedule. In GSMS, both maltreatment and bullying were repeatedly assessed with annual parent and child interviews between ages 9 and 16 years. To identify the association between maltreatment, being bullied, and mental health problems, binary logistic regression analyses were run. The primary outcome variable was overall mental health problem (any anxiety, depression, or self-harm or suicidality).

Findings
4026 children from the ALSPAC cohort and 1420 children from the GSMS cohort provided information about bullying victimisation, maltreatment, and overall mental health problems. The ALSPAC study started in 1991 and the GSMS cohort enrolled participants from 1993. Compared with children who were not maltreated or bullied, children who were only maltreated were at increased risk for depression in young adulthood in models adjusted for sex and family hardships according to the GSMS cohort (odds ratio [OR] 4·1, 95% CI 1·5–11·7). According to the ALSPAC cohort, those who were only being maltreated were not at increased risk for any mental health problem compared with children who were not maltreated or bullied. By contrast, those who were both maltreated and bullied were at increased risk for overall mental health problems, anxiety, and depression according to both cohorts and self-harm according to the ALSPAC cohort compared with neutral children. Children who were bullied by peers only were more likely than children who were maltreated only to have mental health problems in both cohorts (ALSPAC OR 1·6, 95% CI 1·1–2·2; p=0·005; GSMS 3·8, 1·8–7·9, p<0·0001), with differences in anxiety (GSMS OR 4·9; 95% CI 2·0–12·0), depression (ALSPAC 1·7, 1·1–2·7), and self-harm (ALSPAC 1·7, 1·1–2·6) between the two cohorts.

Interpretation
Being bullied by peers in childhood had generally worse long-term adverse effects on young adults' mental health. These effects were not explained by poly-victimisation. The findings have important implications for public health planning and service development for dealing with peer bullying.

Link: http://www.thelancet.com/


Borderline Personality Disorder May Be as Destructive as Bipolar Disorder:
Psychosocial morbidity associated with bipolar disorder and borderline personality disorder in psychiatric out-patients: comparative study


British Journal of Psychiatry

Abstract

Background
The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such commentary exists for the improved detection of borderline personality disorder. Clinical experience suggests that it is as disabling as bipolar disorder, but no study has directly compared the two disorders.

Aims
To compare the levels of psychosocial morbidity in patients with bipolar disorder and borderline personality disorder.

Method
Patients were assessed with semi-structured interviews. We compared 307 patients with DSM-IV borderline personality disorder but without bipolar disorder and 236 patients with bipolar disorder but without borderline personality disorder.

Results
The patients with borderline personality disorder less frequently were college graduates, were diagnosed with more comorbid disorders, more frequently had a history of substance use disorder, reported more suicidal ideation at the time of the evaluation, more frequently had attempted suicide, reported poorer social functioning and were rated lower on the Global Assessment of Functioning. There was no difference between the two patient groups in history of admission to psychiatric hospital or time missed from work during the past 5 years.

Conclusions
The level of psychosocial morbidity associated with borderline personality disorder was as great as (or greater than) that experienced by patients with bipolar disorder. From a public health perspective, efforts to improve the detection and treatment of borderline personality disorder might be as important as efforts to improve the recognition and treatment of bipolar disorder.

Link: http://bjp.rcpsych.org/


Reporting Bias in Clinical Trials Investigating the Efficacy of Second-Generation Antidepressants in the Treatment of Anxiety Disorders


JAMA Psychiatry

Abstract 

Importance  
Studies have shown that the scientific literature has overestimated the efficacy of antidepressants for depression, but other indications for these drugs have not been considered.

Objective  
To examine reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantify the extent to which these biases inflate estimates of drug efficacy.

Data Sources and Study Selection  
We included reviews obtained from the US Food and Drug Administration (FDA) for premarketing trials of 9 second-generation antidepressants in the treatment of anxiety disorders. A systematic search for matching publications (until December 19, 2012) was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials.

Data Extraction and Synthesis  
Double data extraction was performed for the FDA reviews and the journal articles. The Hedges g value was calculated as the measure of effect size.

Main Outcomes and Measures  
Reporting bias was examined and classified as study publication bias, outcome reporting bias, or spin (abstract conclusion not consistent with published results on primary end point). Separate meta-analyses were conducted for the 2 sources, and the effect of publication status on the effect estimates was examined using meta-regression.

Results  
The findings of 41 of the 57 trials (72%) were positive according to the FDA, but 43 of the 45 published article conclusions (96%) were positive (P < .001). Trials that the FDA determined as positive were 5 times more likely to be published in agreement with that determination compared with trials determined as not positive (risk ratio, 5.20; 95% CI, 1.87 to 14.45; P < .001). We found evidence for study publication bias (P < .001), outcome reporting bias (P = .02), and spin (P = .02). The pooled effect size based on the published literature (Hedges g, 0.38; 95% CI, 0.33 to 0.42; P < .001) was 15% higher than the effect size based on the FDA data (Hedges g, 0.33; 95% CI, 0.29 to 0.38; P < .001), but this difference was not statistically significant (β = 0.04; 95% CI, –0.02 to 0.10; P = .18).

Conclusions and Relevance  
Various reporting biases were present for trials on the efficacy of FDA-approved second-generation antidepressants for anxiety disorders. Although these biases did not significantly inflate estimates of drug efficacy, reporting biases led to significant increases in the number of positive findings in the literature.

Link: http://archpsyc.jamanetwork.com/


Efficacy and Safety of Brexpiprazole for the Treatment of Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Trial


The American Journal of Psychiatry

Abstract

Objective
The efficacy, safety, and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia.

Method
This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with schizophrenia experiencing an acute exacerbation were randomly assigned to daily brexpiprazole at a dosage of 0.25, 2, or 4 mg or placebo (1:2:2:2) for 6 weeks. Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score (primary endpoint measure), Clinical Global Impressions Scale (CGI) severity score (key secondary endpoint measure), and other efficacy and tolerability measures.

Results
The baseline overall mean PANSS total score was 95.2, and the CGI severity score was 4.9. Study completion rates were 62.2%, 68.1%, and 67.2% for patients in the 0.25-, 2-, and 4-mg brexpiprazole groups, respectively, versus 59.2% in the placebo group. At week 6, compared with placebo, brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score (treatment differences: –8.72 and –7.64, respectively) and CGI severity score (treatment differences: –0.33 and –0.38). The most common treatment-emergent adverse event for brexpiprazole was akathisia (2 mg: 4.4%; 4 mg: 7.2%; placebo: 2.2%). Weight gain with brexpiprazole was moderate (1.45 and 1.28 kg for 2 and 4 mg, respectively, versus 0.42 kg for placebo at week 6). There were no clinically or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings.

Conclusions
Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation.

Link: http://ajp.psychiatryonline.org/


Molecular Signatures of Major Depression


Current Biology

Summary

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease.

Link: http://www.cell.com/


A rest-activity biomarker to predict response to SSRIs in major depressive disorder


Journal of Psychiatric Research

Abstract

Most adults with Major Depressive Disorder (MDD) will not experience a remission with the first antidepressant trial. No practical biomarkers presently exist to predict responsiveness to antidepressants. Herein we report pilot data for a rest-activity biomarker of antidepressant response.

Fifty-eight medication-free adults with MDD underwent a week-long collection of actigraphic data before beginning a 9 week open label trial of fluoxetine, coupled with blinded randomized assignment to eszopiclone/placebo. Depression severity was repeatedly measured with the Hamilton Rating Scale for Depression (HRSD). Baseline actigraphic data was analyzed with functional data analysis to create smoothed 24-h curves of activity. The time of the lowest point of activity (the bathyphase) was calculated for each patient, as well the mean difference between bedtime and the bathyphase (BBD). At the end of treatment, patients were characterized as treatment responders (50% reduction in HRSD) or non-responders, and receiver operating curves were calculated to find the optimal cut point of the BBD for prediction of treatment response.

The best cut point for BBD was at 260.2 min, resulting in an effect size of 1.45, and with a positive predictive value of 0.75 and a negative predictive value of 0.88.

We conclude that actigraphically-determined measures of rest-activity patterns show promise as potential biomarker predictors of antidepressant response. However, this conclusion is based upon a small number of patients who received only one choice of antidepressant, for a single trial. Replication with a larger sample is needed.

Link: http://www.sciencedirect.com/


A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood 


Brain, Behavior and Inmunity

Abstract

Background
Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression.

Objective
Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals.

Design
In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics, while 20 control participants received an inert placebo for the same period. In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale.

Results
Compared to participants who received the placebo intervention, participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts.

Conclusion 
These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research as a potential preventive strategy for depression.

Link: http://www.sciencedirect.com/


Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi


Translational Psychiatry

Abstract

Depression affects 10–15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q<0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P=0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring.

Link: http://www.nature.com/


Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial


The American Journal of Psychiatry

Abstract

Objective
The study aims were 1) to describe the proportions of individuals who met criteria for melancholic, atypical, and anxious depressive subtypes, as well as subtype combinations, in a large sample of depressed outpatients, and 2) to compare subtype profiles on remission and change in depressive symptoms after acute treatment with one of three antidepressant medications.

Method
Participants 18–65 years of age (N=1,008) who met criteria for major depressive disorder were randomly assigned to 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine. Participants were classified by subtype. Those who met criteria for no subtype or multiple subtypes were classified separately, resulting in eight mutually exclusive groups. A mixed-effects model using the intent-to-treat sample compared the groups’ symptom score trajectories, and logistic regression compared likelihood of remission (defined as a score ≤5 on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report).

Results
Thirty-nine percent of participants exhibited a pure-form subtype, 36% met criteria for more than one subtype, and 25% did not meet criteria for any subtype. All subtype groups exhibited a similar significant trajectory of symptom reduction across the trial. Likelihood of remission did not differ significantly between subtype groups, and depression subtype was not a moderator of treatment effect.

Conclusions
There was substantial overlap of the three depressive subtypes, and individuals in all subtype groups responded similarly to the three antidepressants. The consistency of these findings with those of the Sequenced Treatment Alternatives to Relieve Depression trial suggests that subtypes may be of minimal value in antidepressant selection.

Link: http://ajp.psychiatryonline.org/


Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people


The Lancet

Summary

Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society.

Link: http://www.thelancet.com/

Online Journals:

Journal of Clinical Psychopharmacology - June 2015 - Volume 35, Issue 3



Biological Psychiatry - Volume 77, Issue 10, May 2015



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