Can divorce increase risk of acute myocardial infarction? Circulation. ahead of print.

15.04.2015
Smoking, hypertension and diabetes are the major risk factors for myocardial infarction.Psychological/Social stress can affect cardiac functioning and contribute to myocardial infarctions.Divorce is linked to poorer physical health outcomes. Can divorce  significantly increase the chances of having acute myocardial infarction?
Matthew E. Dupre, Linda K. George, Guangya Liu and Eric D. Peterson from Duke University used a nationally representative sample ( from the Health and Retirement Study) of married people (~15,000) to answer this question.These participants were followed up during 1992 to 2010.

Results:

35% of the cohort had one or more divorces during the observation period.During the 200524 person-years of follow-up, 8% (n=1211) of the cohort had an Acute MI. Age-specific rates of AMI were consistently higher in those who were divorced compared with those who were continuously married. Associations were not accounted for by socioeconomic, psychosocial, behavioral, or physiological factors.

Women with multiple divorces were at especially high risk of AMI; and remarried women had risks that were similar in magnitude to divorced women.
Hazard ratio for women differed according to number of divorces. Those  who had 1 divorce = hazard ratio, 1.24; (95% confidence interval, 1.01–1.55), those with  ≥2 divorces =hazard ratio, 1.77; ( 95% confidence interval, 1.30–2.41). Remarriage didn’t help women. Among the remarried women= hazard ratio, 1.35 (95% confidence interval, 1.07–1.70) All the above ratio is in comparison with continuously married women after adjusting for multiple risk factors.

Men who remarried had no significant increase in risk.

This is the first prospective study on the cumulative association between divorce and MI.This study show that life time exposure to divorce is a serious risk factor for acute MI. Women with multiple divorce are at significant risk. Remarriage protects men but not women.

Factors like loss of income, changes in health insurance, depressive symptoms, smoking , alcohol use etc did not account for the excess risk observed. Authors suggest that direct biological mechanisms of stress ( inflammatory activation) may explain the observed association.

Limitations: Patient reported data was used to find out acute MI event.

Comment: It would be interesting to see the association ( with MI) in subgroups of divorced people. For example among those who consider divorce as an escape from stressful relationships.It will help us explore the cognitive and emotional mediators of divorce and how they may bring about physical effects.  Previous research have shown that cardiac health is affected by emotional status/stress/traumatic events. Higher risk among women needs special attention.Men possibly get along easily with relationship changes where as  women may be continuing to struggle emotionally.

Summary of the article:
Association Between Divorce and Risks for Acute Myocardial Infarction.Matthew E. Dupre, PhD; Linda K. George, PhD; Guangya Liu, PhD; Eric D. Peterson, MD, MPH.Circ Cardiovasc Qual Outcomes. 2015;8:00-00. DOI: 10.1161/CIRCOUTCOMES.114.001291.) Ahead of print.

Do children who were breastfed have sharper minds and better income? Lancet.April 2015.

24.03.2015

Breastfeeding has short-term and longterm beneficial effects on child.It is already known that breastfeeding increase the average IQ by 3.5 points at childhood and adolescence. RCT evidence also support this meta analytic measure from observational studies. In developed countries, longer duration of breastfeeding is associated with higher socio-economic status and thus this might confound the observed associations.The real life effect of small differences in IQ is not known.It is not known whether breastfeeding will influence the income in adults.

This study reported by Cesar G Victora et al from Brasil offers a rare opportunity to unravel such long-term effects. They studied the associations between infant feeding and IQ, educational attainment, and income in participants aged 30 years in a large population-based birth cohort, in Brazil ( a setting where no strong social patterning of breastfeeding exists). The neonatal cohort was recruited in 1982 with 5914 participants.IQ (Wechsler Adult Intelligence Scale) was assessed at mean age of 30. A range of confounders were measured (income, maternal education, smoking,maternal age,gestational age, birth weight etc). Genomic ancestry analysis was also done.

Results

At the age of 30 years, the mean IQ of offspring was 98·0 (SD 12·6) points and the average number of years of education was 11·4. Distribution of monthly income had a median of  R$1000 and a mean of R$1501.

Durations (total/predominant) breastfeeding  were positively associated with IQ, educational attainment, and income.The adjusted differences  between the extreme groups ( on breast feeding) were 3·76 (95% CI 2·20–5·33) IQ points, 0·91 (0·42–1·40) years of education, and R$341 (93·8–588·3) in adult income. Dose-response associations with breastfeeding duration for IQ and educational attainment and income were clear. Income difference was on average of 341·0 Brazilian reals compared to  those who were breastfed for less than 1 month.

This is the first study to show a positive association of breastfeeding  with adult earnings. The analysis also show that this effect was  largely mediated through intelligence levels.

Comments: Breastfeeding’s effect on IQ , education and income need to be brought in to antenatal discussions/public health campaign . The positive effects  shown here are very much likely to contribute to better mental health as well.

Summary of the article:

Association between breastfeeding and intelligenceeducational attainment, and income at 30years of age: a prospective birth cohort study from Brazil.

Victora CG, Horta BL, Loret de Mola C, Quevedo L, Pinheiro RT, Gigante DP, Gonçalves H, Barros FC.

Lancet Glob Health. 2015 Apr;3(4):e199-205.

First episode psychosis : Are we prescribing well?

17.03.2015

There are suggestions that we should adopt different pharmacological strategies for first episode schizophrenia and multi episode illness.The state of present practice in treating first episode is important to see how we stick to guidances and what factors  are associated with choices we make.

Delbert G. Robinson et al report  prescription practices in USA, using data from NIMH funded RAISE-ETP (Recovery After an Initial Schizophrenia Episode (RAISE) Project :Early Treatment Program (ETP)) study.Patients included were those between ages 15 yrs-40yrs with diagnosis of non affective psychosis with no previous discrete psychotic episode. Site randomisation was used to compare a  specialty care treatment program for first-episode psychosis that includes medical management guided by a decision support system and community care where treatment is by physician choice.Thirty-four  community treatment sites in 21 US states participated.

Results

There were 404 patients in the sample.12.6% did not have prescriptions for any psychotropic medications at study entry. of the 337 patients who were on antipsychotics at entry, 12% received First Generation Antipsychotic (FGA)including those who had both FGA and Second Generation Antispychotic (SGA).10% were on LA depot injections: half of this were  paliperidone depot and one third were haloperidol depot.Nearly 90% received only one antipsychotic agent.10% had two antipsychotics. Risperidone accounted for one-third of antipsychotic monotherapy. 17% were for olanzapine. Aripiprazole, Paliperidone, and Quetiapine, each accounting for around 10% of prescriptions.Few patients received higher than recommended doses. This was particularly more if they were on olanzapine. 21% of those who received antipsychotics also had perception for anticholinergic agents.11% of those pn antipsychotics also received anti anxiety medications.One third of those on antipsychotics also received antidepressants i.e. 115/337, though only half them had any documented life time depression/anxiety disorders.Negative symptoms possibly explained only 10% of the remaining 58 patients ( after accounting for depression).

Women were more likely to get lower doses. They were more likely to be on depot and receive antidepressants. African Americans were  more likely to get FGA.Young patients were more likely to get risperidone. Specific diagnosis had no effect on choice of medications.

Prescriptions were initiated mostly by inpatients units, after which patients were referred to community centres. Information on decision making reasons/indications /patient choices is not available to offer further interpretations.

A large number of first episode patients received antidepressants without clear indications.Preference for SGA is clear. Choice of agents with in SGA,  esp with regard to metabolic side effects need to be considered.

Potentially problematic prescribing was identified in 40% of the sample.This include 1. use of antidepressants where there was no clear indication 2. use of olanzapine (PORT recommends against using olanzapine as first choice due to metabolic side effects) 3. use of more than one antipsychotic.

It is important to audit and reflect on local prescribing patterns. It is essential that  patients and their families are engaged in a comprehensive discussion of the risks and benefits of different medication choices. This is the only way to ensure well-informed decisions are made.

Prescription Practices in the Treatment of First-Episode Schizophrenia Spectrum DisordersData From the National RAISE-ETPStudy.

Robinson DG, Schooler NR, John M, Correll CU, Marcy P, Addington J, Brunette MF, Estroff SE, Mueser KT, Penn D, Robinson J, Rosenheck RA, Severe J, Goldstein A, Azrin S, Heinssen R, Kane JM.

Am J Psychiatry. 2015 Mar 1;172(3):237-48.

How do maternal thinking during pregnancy affect offsprings at age 13 ? Translational psych.Feb 2015

Stress have long-lasting effect on human body. Prenatal maternal stress is shown to have many negative effects in the offspring, some lasting in to adulthood. Stress can bring about epigenetic changes , like DNA methylation.It is unclear which aspect of stress is the active ingredient in these changes. Is it the objective  severity of stress that matters? Or is it  the  cognitive appraisal of the stressor, or the subjective degree of distress?

How can you study this question?  You need a major independent stressor affecting a large population  to control for genetic bias and to differentiate the objective degree of exposure to an event from the cognitive appraisal and subjective degree of distress.

January 1998 ice storm in Quebec offered such an opportunity and was used to examine this issue. This project ( project Ice storm) have already shown that higher levels of maternal stress is associated with poorer physical, behavioral, motor and cognitive measures among the offspring from those pregnancies. DNA methylation levels among offsprings at  age 13 higher and correlated with maternal objective stress.

The team now try to address whether cognitive appraisal ( as reported by participants in 1998: about the overall consequences of the ice storm on them and their families, and to provide a rating on a five-point scale from very negative to neutral to very positive) is correlated with DNA methylation at age 13.

Results

Among 218 women who completed the assessments in 1998, nearly 35% rated the effect of storm as negative and 65% rated the effect as neutral or positive.  The three aspects of the stress experience (the objective hardship, the cognitive appraisal of the storm’s consequences and the enduring subjective distress) were  relatively independent of each other. At age, 13, offsprings blood study showed that 2872 candidate genes were significantly differentially methylated between these two appraisal groups. These are mostly those  involved in immune function. Some changes were uniquely associated with maternal cognitive appraisal of the ice storm, and not with their objective exposure.

So,  mothers cognitive appraisal of the situation is transmitted to the unborn child and this is perhaps NOT through the subjective stress and its physiological effects. Cognitive appraisal may have direct effect on stress hormone release.

Limitations:

Study has a small sample size.It is possible that the studied aspect of stress might have affected other areas of child development resulting in observed methylation changes.Peripheral DNA methylation is studied, this may not be truly reflective of brain levels.

This is the first human prenatal maternal stress study investigating the effect of maternal cognitive appraisal from an independent stressor that detects DNA methylation differences throughout the genome in the offspring during adolescence.

Summary of the article:

Pregnant women’s cognitive appraisal of a natural disaster affects DNA methylation in their children 13 years laterProject IceStorm. Cao-Lei L, Elgbeili G, Massart R, Laplante DP, Szyf M, King S. Transl Psychiatry. 2015 Feb 24;5:e515.

Do depression affect platelet function? Jl Psych Research.Feb.2015

04.02.2015

Depression is an independent risk factor for cardiovascular disease. Reduced NO (Nitric Oxide) bioavailability is considered to be one mechanism linking depression to CVD. Oxidative stress can reduce NO bioavailability. Oxidative stress produce Reactive Oxygen Species (ROS) .Usual antioxidants who neutralise ROS   include antioxidant enzymes ( copper-zinc superoxide dismutase (SOD), catalase and glutathione peroxidase) and  non-enzymatic antioxidants (like bilirubin, uric acid, glutathione, and vitamins A, C, and E) . ROS have direct effects on platelets. ROS can also reduce NO.

Depressed individuals show heightened level of platelet activation.Platelet dysfunction is a possible mechanism through which depression may increase cardiovascular risk

Monique B.O. Ormonde do Carmo et al studied the factors that modulate NO bioavailability and platelet dysfunction in depression.

Treatment naive major depression patients and controls participated in this study. Platelet aggregation, ,oxidative state and antioxidant enzyme activities were studied.

Results

Platelet aggregation was higher in depression group.

Depression group showed higher  activity of arginase II in platelets. Activation of the arginase can shift L-arginine to the urea cycle rather than to NO synthesis.  ( resulting in less NO)

MDD patients has higher PDE5 expression. NO regulate  cyclic GMP levels in platelet and this play a key role in platelet activity. PDE5 is responsible for breakdown of CGMP. Over expression of PDE5 would thus result in increased degradation of cGMP. cGMP signalling can thus be down regulated leading to platelet reactivity.

Indicator of oxidative damage  ( =protein carbonylation)  was markedly increased in platelets in MDD

Limitations:  Small study.Cross sectional in nature.

Comments: Psychological states/ conditions exert  significant effect on physical health. Knowledge on biological pathways that link them is expanding. These are building blocks for understanding the interplay between mind, body, and society .

Summary of the article

Major depression induces oxidative stress and platelet hyperaggregability.

Ormonde do Carmo MB, Mendes-Ribeiro AC, Matsuura C, Pinto VL, Mury WV, Pinto NO, Moss MB, Ferraz MR, Brunini TM.

J Psychiatr Res. 2015 Feb;61:19-24

Arginase

How does positive affect reduce mortality? Int.J. Behav. Med. Feb.2015

Positive affect is associated with lower mortality and morbidity.Prospective studies have found that positive affect (PA) and other positive traits (e.g., optimism, hopefulness, life satisfaction, sense of humor) predicted a reliable reduction in mortality of 28 % in healthy individuals (Chida Y, Steptoe A,2008)

How does positive affect lead to less mortality? There are likely to be multiple pathways. One biological pathway is likely to be via HRV ( Heart Rate Variability= cardiac vagal tone). Greater Positive Affect is associated with high HRV and this has shown to have beneficial effects.

Andreas R. Schwerdtfeger, Peter Friedrich-Mai & Ann Kathrin S. Gerteis from Austria looked at relationship between PA and nocturnal cardiac activation.

Participants  rated various affective states several times a day via mobile electronic devices and this was related to the aggregated ratings to nocturnal cardiac activity. A small device attached to chest measured HRV and HR. Body movements were also monitored.

Results

PA ( specifically:  relaxed, content, even-tempered, calm) throughout the day was positively associated with HRV and negatively associated with HR throughout a time interval between 1 am and 5 a.m. Daily affect accounted for approximately 12–13 % of the variance in nocturnal cardiac activation.

Other studies have shown that attenuated nocturnal HRV and elevated HR is linked to  increased risk for all-cause mortality. PA experienced throughout the day might constitute a buffer against cardiac morbidity and mortality.

Previous study has  found that daily worry (a component of Negative Affect) to be accompanied by lower HRV during sleep. NA failed to show any effect in this study.

Limitations: It is possible that quality of sleep may explain the observed association. i.e. more relaxing sleep as evidenced by lower HR and higher HRV could impact affect. Poor subjective sleep quality has been found to be associated with lower ambulatory PA the next day.Physical exercise can lead to both elevated HRV and PA. Sleep and physical exercise measures are required to understand such possibilities. Directionality of association is not clear in this study.

Conclusion: Positive affect  may have beneficial effects on heart that is exerted via HRV. Mental health risk factors to morbidity and mortality are emerging topics where investigation like this adds to the evidence base.

Daily positive affect and nocturnal cardiac activation.

Schwerdtfeger AR, Friedrich-Mai P, Gerteis AK.

Int J Behav Med. 2015 Feb;22(1):132-8.

“decade of life lost”: excess mortality due to mental disorders. JAMA Psych. ahead of print.2015

24.02.2015

Burden of mental illness is growing worldwide. It is widely known that mental disorders are associated with excess disability as well as excess mortality.

Elizabeth Reisinger Walker,Robin E. McGee & Benjamin G. Druss from Emeroy University report the results of a meta analysis of studies looking at excess mortality in mental disorders.

Comprehensive search ( up to 2014)  was carried out to identify all cohort studies that used appropriate methods to identify mental disorders and  where outcomes ( mortality) were reported in comparison to control/ general population . They estimated one estimate of risk from each study analysis. 203 studies met all criteria.These came form 29 countries. Mental disorders were mostly identified from medical records or administrative data .Quarter of studies did this by diagnostic interviews. Follow up ranged between one to 52 years, with a median of 10 years.

Results

The overall pooled Relative Risk for mortality among people with mental disorders was 2.22 (95% CI, 2.12-2.33). All-cause mortality was significantly elevated for psychoses, mood disorders, and anxiety.Mortality risk for psychoses was significantly higher than those for depression,bipolar disorder , and anxiety.Analysis of natural causes of death resulted in a pooled RR of 1.80 . For unnatural causes, the pooled RR from 106 studies was 7.22.The authors estimate that 67.3% of deaths were due to natural causes and 17.5% were due to unnatural causes, with the remainder being unknown or unidentified.

The reduction in life expectancy ranged from 1.4 to 32 years, with a median of 10.1 years .

8 million deaths worldwide are attributable to mental disorders each year.

Conclusions:

People with mental disorders have a mortality rate that is 2.22 times higher than the general population or people without mental disorders, with a decade of potential life lost.

Estimation of Population Attributable Risk show that nearly 15% of deaths worldwide, (= 8 million deaths each year), are attributable to mental disorders.

Natural causes accounted for more than two-thirds of deaths among people with mental disorders, suggesting that physical health problems ( like Cardiovascular health) requires much more attention. Behavioral and lifestyle factors, access to and quality of health care, and social determinants of health, such as poverty and social connectedness, all are important factors contributing to this excess mortality among mentally ill.

Summary of the article:

Mortality in Mental Disorders and Global Disease Burden Implications A Systematic Review and Meta-analysis.  Elizabeth Reisinger Walker, PhD, MPH, MAT; Robin E. McGee, MPH; Benjamin G. Druss, MD, MPH. JAMA Psychiatry.  Published online February 11, 2015.