Saturday, March 3, 2018

March 2018

Diet Shown To Reduce Stroke Risk May Also Reduce Risk Of Depression


American Academy of Neurology

People who eat vegetables, fruit and whole grains may have lower rates of depression over time, according to a preliminary study released today that will be presented at the American Academy of Neurology’s 70th Annual Meeting in Los Angeles, April 21 to 27, 2018.

The study found that people whose diets adhered more closely to the Dietary Approaches to Stop Hypertension (DASH) diet were less likely to develop depression than people who did not closely follow the diet. In addition to fruit and vegetables, the DASH diet recommends fat-free or low-fat dairy products and limits foods that are high in saturated fats and sugar. Studies have shown health benefits such as lowering high blood pressure and bad cholesterol (LDL), along with lowering body weight.

“Depression is common in older adults and more frequent in people with memory problems, vascular risk factors such as high blood pressure or high cholesterol, or people who have had a stroke,” said study author Laurel Cherian, MD, of Rush University Medical Center in Chicago and a member of the American Academy of Neurology. “Making a lifestyle change such as changing your diet is often preferred over taking medications, so we wanted to see if diet could be an effective way to reduce the risk of depression.”


For the study, 964 participants with an average age of 81 were evaluated yearly for an average of six-and-a-half years. They were monitored for symptoms of depression such as being bothered by things that usually didn’t affect them and feeling hopeless about the future. They also filled out questionnaires about how often they ate various foods, and the researchers looked at how closely the participants’ diets followed diets such as the DASH diet, Mediterranean diet and the traditional Western diet. 


Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition


JAMA Psychiatry

Abstract

Importance  
The menopause transition and early postmenopausal period are associated with a 2- to 4-fold increased risk for clinically significant depressive symptoms. Although a few studies suggest that hormone therapy can effectively manage existing depression during this time, to our knowledge, there have been no studies testing whether hormone therapy can prevent the onset of perimenopausal and early postmenopausal depressive symptoms.

Objective 
To examine the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) in preventing depressive symptom onset among initially euthymic perimenopausal and early postmenopausal women. A secondary aim was to identify baseline characteristics predicting TE+IMP’s beneficial mood effects.


Design, Setting, and Participants 
Double-blind, placebo-controlled randomized trial at the University of North Carolina at Chapel Hill from October 2010 to February 2016. Participants included euthymic perimenopausal and early postmenopausal women from the community, aged 45 to 60 years.


Interventions 
Transdermal estradiol (0.1 mg/d) or transdermal placebo for 12 months. Oral micronized progesterone (200 mg/d for 12 days) was also given every 3 months to women receiving active TE, and identical placebo pills were given to women receiving placebo.


Main Outcome Measures 
Scores on the Center for Epidemiological Studies–Depression Scale (CES-D), assessed at baseline and months 1, 2, 4, 6, 8, 10, and 12 after randomization, and the incidence of clinically significant depressive symptoms, defined as a CES-D score of at least 16.


Results 
Of 172 participants, 130 were white (76%), and 70 were African American (19%), with a mean household income of $50 000 to $79 999. The mean age was 51 years, and 43 developed clinically significant depressive symptoms. Women assigned to placebo were more likely than those assigned to TE+IMP to score at least 16 on the CES-D at least once during the intervention phase (32.3% vs 17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = .03) and had a higher mean CES-D score across the intervention period (P = .03). Baseline reproductive stage moderated the effect of treatment (β, −1.97; SEM, 0.80; P for the interaction = .03) such that mood benefits of TE+IMP vs placebo were evident among women in the early menopause transition (β, −4.2; SEM, 1.2; P < .001) but not the late menopause transition (β, −0.9; SEM, 0.3; P = .23) or among postmenopausal women (β, −0.3; SEM, 1.1; P = .92). Stressful life events in the 6 months preceding enrollment also moderated the effect of treatment on mean CES-D score such that the mood benefits of TE+IMP increased with a greater number of events (β, 1.22; SEM, 0.40; P = .003). Baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not moderate treatment effects.


Conclusions 
Twelve months of TE+IMP were more effective than placebo in preventing the development of clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women
 
 


Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression


JAMA Psychiatry

Abstract

Importance  
Approximately one-third of patients with major depressive disorder (MDD) do not respond to available antidepressants.

Objective 
To assess the efficacy, safety, and dose-response of intranasal esketamine hydrochloride in patients with treatment-resistant depression (TRD).


Design, Setting, and Participants 
This phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study was conducted in multiple outpatient referral centers from January 28, 2014, to September 25, 2015. The study consisted of 4 phases: (1) screening, (2) double-blind treatment (days 1-15), composed of two 1-week periods, (3) optional open-label treatment (days 15-74), and (4) posttreatment follow-up (8 weeks). One hundred twenty-six adults with a DSM-IV-TR diagnosis of MDD and history of inadequate response to 2 or more antidepressants (ie, TRD) were screened, 67 were randomized, and 60 completed both double-blind periods. Intent-to-treat analysis was used in evaluation of the findings.


Interventions 
In period 1, participants were randomized (3:1:1:1) to placebo (n = 33), esketamine 28 mg (n = 11), 56 mg (n = 11), or 84 mg (n = 12) twice weekly. In period 2, 28 placebo-treated participants with moderate-to-severe symptoms were rerandomized (1:1:1:1) to 1 of the 4 treatment arms; those with mild symptoms continued receiving placebo. Participants continued their existing antidepressant treatment during the study. During the open-label phase, dosing frequency was reduced from twice weekly to weekly, and then to every 2 weeks.


Main Outcomes and Measures 
The primary efficacy end point was change from baseline to day 8 (each period) in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.


Results 
Sixty-seven participants (38 women, mean [SD] age, 44.7 [10.0] years) were included in the efficacy and safety analyses. Change (least squares mean [SE] difference vs placebo) in MADRS total score (both periods combined) in all 3 esketamine groups was superior to placebo (esketamine 28 mg: −4.2 [2.09], P = .02; 56 mg: −6.3 [2.07], P = .001; 84 mg: −9.0 [2.13], P < .001), with a significant ascending dose-response relationship (P < .001). Improvement in depressive symptoms appeared to be sustained (−7.2 [1.84]) despite reduced dosing frequency in the open-label phase. Three of 56 (5%) esketamine-treated participants during the double-blind phase vs none receiving placebo and 1 of 57 participants (2%) during the open-label phase had adverse events that led to study discontinuation (1 event each of syncope, headache, dissociative syndrome, and ectopic pregnancy).


Conclusions and Relevance 
In this first clinical study to date of intranasal esketamine for TRD, antidepressant effect was rapid in onset and dose related. Response appeared to persist for more than 2 months with a lower dosing frequency. Results support further investigation in larger trials.



The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder


American Psychiatric Association 



Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A Randomized Controlled Trial


The American Journal of Psychiatry

Abstract

Objective
The authors assessed the efficacy of trauma memory reactivation performed under the influence of propranolol, a noradrenergic beta-receptor blocker, as a putative reconsolidation blocker, in reducing symptoms of posttraumatic stress disorder (PTSD).

Method
This was a 6-week, double-blind, placebo-controlled, randomized clinical trial in 60 adults diagnosed with long-standing PTSD. Propranolol or placebo was administered 90 minutes before a brief memory reactivation session, once a week for 6 consecutive weeks. The hypothesis predicted a significant treatment effect of trauma reactivation with propranolol compared with trauma reactivation with placebo in reducing PTSD symptoms on both the Clinician-Administered PTSD Scale (CAPS) and the patient-rated PTSD Checklist–Specific (PCL-S) in an intention-to-treat analysis.

Results
The estimated group difference in posttreatment CAPS score, adjusted for pretreatment values (analysis of covariance), was a statistically significant 11.50. The within-group pre- to posttreatment effect sizes (Cohen’s d) were 1.76 for propranolol and 1.25 for placebo. For the PCL-S, the mixed linear model’s estimated time-by-group interaction yielded an average decrease of 2.43 points per week, for a total significant difference of 14.58 points above that of placebo. The pre- to posttreatment effect sizes were 2.74 for propranolol and 0.55 for placebo. Per protocol analyses for both outcomes yielded similar significant results.

Conclusions
Pre-reactivation propranolol, a treatment protocol suggested by reconsolidation theory, appears to be a novel and efficacious treatment for PTSD. Replication studies using a long-term follow-up in various trauma populations are required.



Major mental illnesses unexpectedly share brain gene activity, raising hope for better diagnostics and therapie


Science

Mental illness affects one in six U.S. adults, but scientists' sense of the underlying biology of most psychiatric disorders remains nebulous. That's frustrating for physicians treating the diseases, who must also make diagnoses based on symptoms that may only appear sporadically. No laboratory blood test or brain scan can yet distinguish whether someone has depression or bipolar disorder, for example.

Now, however, a large-scale analysis of postmortem brains is revealing distinctive molecular traces in people with mental illness. This week, an international team of researchers reports that five major psychiatric disorders have patterns of gene activity that often overlap but also vary in disease-specific—and sometimes counterintuitive—ways. The findings, they say, might someday lead to diagnostic tests and novel therapies, and one has already inspired a clinical trial of a new way to treat overactive brain cells in autism.

Outsiders say the data mark a milestone in psychiatry. "This [work] is changing fundamental views about the nature of psychiatric illness," says Kenneth Kendler, a psychiatric geneticist at Virginia Commonwealth University in Richmond.



EFFECT OF TIME-DEPENDENT SELECTIVE SEROTONIN REUPTAKE INHIBITOR ANTIDEPRESSANTS DURING PREGNANCY ON BEHAVIORAL, EMOTIONAL, AND SOCIAL DEVELOPMENT IN PRESCHOOL-AGE CHILDREN


American Academy of Child and Adolescent Psychiatry

Abstract

Schizophrenia (SZ) is a devastating mental disease caused by complex genetic and environmental factors. The pathological process and clinical manifestation of SZ are heterogeneous among patients, which hampers precise diagnosis and treatment of the disease. Since no objective marker for SZ has been established today, to identify a subgroup of the patients with homogeneous biochemical traits will provide a new angle for both researchers and clinicians to understand and manage the disease. In this study, we employed the niacin skin-flushing test in Chinese population and confirmed a niacin-blunted subgroup of SZ patients distinguishable from mood disorders (MD) and normal individuals. This subgroup accounted for 30.67% of the total SZ patients with a specificity of 88.37% in male subjects and 83.75% in female subjects. We support the notion that bluntness in niacin skin test might reflect abnormalities in membrane fatty acid composition, which could be induced by increased PLA2 enzyme activity, in vivo oxidative stress or lipid metabolism imbalance in SZ. Further studies are encouraged to clarify the molecular origins of niacin-bluntness in SZ, which would provide extra clues for etiological research in schizophrenia and for new targeted treatment.



Clinical Consensus Recommendations for Urine Testing of Adherence to Antipsychotics Among People With Serious Mental Illness


Psychiatric Services

Abstract

Objective
This study developed clinical recommendations for the use of proven urine testing technologies to assess antipsychotic medication adherence among people with serious mental illness.

Methods
Guided by the RAND/UCLA Appropriateness Method, researchers conducted a literature review and semistructured interviews and convened an expert panel to develop clinical consensus recommendations for the use of urine monitoring to assess antipsychotic medication adherence.

Results
The expert panel identified six circumstances in which urine monitoring was recommended at initial evaluation and five scenarios in which monitoring was recommended after initial evaluation. Conducting monitoring at the site where psychiatric medication is prescribed and providing education prior to testing and feedback after testing were recommended.

Conclusions
A consensus was reached on clinical recommendations for use of urine monitoring at intake and during ongoing treatment. There was strong agreement that monitoring can be used to improve assessment and thence clinical care and outcomes.



IMPACT OF SSRI THERAPY ON RISK OF CONVERSION FROM MILD COGNITIVE IMPAIRMENT TO ALZHEIMER’S DEMENTIA IN INDIVIDUALS WITH PREVIOUS DEPRESSION


The American Journal of Psychiatry

Abstract

Objective
Depression is associated with an increased risk of Alzheimer’s disease. Research has shown that the selective serotonin reuptake inhibitor (SSRI) citalopram decreases amyloid-β generation and plaque load. The authors evaluated the impact of SSRI treatment on CSF biomarkers and progression from mild cognitive impairment (MCI) to Alzheimer’s dementia.

Method
Data sets from 755 currently nondepressed participants from the longitudinal Alzheimer’s Disease Neuroimaging Initiative were evaluated by Kaplan-Meier analysis and analyses of variance and covariance with ApoE4 status and age as covariates.

Results
In MCI patients with a history of depression, long-term SSRI treatment (>4 years) was significantly associated with a delayed progression to Alzheimer’s dementia by approximately 3 years, compared with short-term SSRI treatment, treatment with other antidepressants, or no treatment and compared with MCI patients without a history of depression. No differences in CSF biomarker levels were observed between treatment groups.

Conclusions
Long-term SSRI treatment may delay progression from MCI to Alzheimer’s dementia.



CORTICAL AND SUBCORTICAL BRAIN MORPHOMETRY DIFFERENCES BETWEEN PATIENTS WITH AUTISM SPECTRUM DISORDER AND HEALTHY INDIVIDUALS ACROSS THE LIFESPAN: RESULTS FROM THE ENIGMA ASD WORKING GROUP


The American Journal of Psychiatry

Abstract

Objective
Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group.

Method
The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2–64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach.

Results
The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen’s d], 0.13 to –0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, −0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions.

Conclusions
The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.



Online Journals:




Biological Psychiatry - Volume 83, Issue 8, April 2018



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