Regular Exercise Lowers Odds of Developing Depression, Meta-Analysis Finds

Physical activity can protect against the development of depression, regardless of age and geographical region, according to a meta-analysis published yesterday in AJP in Advance.

Depressive disorders are the second leading cause of global burden of illness and account for more than 44 million years lived with disability, according to Felipe B. Schuch, Ph.D., of LaSalle University in Canoas, Brazil, and colleagues.

While previous reviews have suggested that physical activity can protect against the development of depression, this study is believed to be “the first pooled meta-analysis investigating this relationship, which allows a clearer understanding of a true association between an exposure and outcome, rather than when studies are considered separately,” Schuch and colleagues wrote.

The meta-analysis included 49 studies involving nearly 267,000 participants from across four geographic regions (Asia, Europe, North America, and Oceania), who were followed for an average of 7.4 years. Participants were free of depression or depressive symptoms at the outset of the studies.

The study found overall that people with higher levels of physical activity were significantly less likely to develop depression, compared with people with low levels of physical activity (adjusted odds ratio=0.83). Physical activity had a protective effect against the emergence of depression in young people (adjusted odds ratio=0.90), adults (adjusted odds ratio=0.78), and in elderly people (adjusted odds ratio=0.79). Protective effects against depression were found across geographical regions, with adjusted odds ratios ranging from 0.65 to 0.84 in Asia, Europe, North America, and Oceania, and against major depression diagnosis (adjusted odds ratio=0.86).

“Our meta-analysis suggests that physical activity is associated with a decrease in the risk of developing depression, which raises an inevitable question: How might physical activity offer protection against depression onset?” the authors wrote. “It is likely that no single mechanism can explain this relationship. A range of biochemical and psychosocial factors are likely responsible, including biological mechanisms through which exercise increases neurogenesis and reduces inflammatory and oxidant markers and activates the endocannabinoid system.”

“Our data further emphasize the importance of policies targeting increased physical activity levels,” they concluded. However, randomized, controlled trials are needed to discern whether physical activity can prevent the development of depression in those at highest risk of the disorder.

For related information, see the Psychiatric News article “Minimal Exercise May Help Prevent Future Depression.”

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Substance Use Associated With Conversion From Schizotypal Disorder to Schizophrenia

An estimated 25% to 50% of patients diagnosed with schizotypal disorder develop schizophrenia within five years. A study published today in JAMA Psychiatry suggests that substance use by these patients may be associated with conversion to schizophrenia.

The findings highlight the need to educate this population about the risks associated with substance use and closely monitor patients’ substance use.

Substance use disorders are known to be common in patients with schizotypal disorder, but whether these disorders might be associated with conversion to schizophrenia was previously unclear, according to lead author Carsten Hjorthøj, Ph.D., M.Sc., of Copenhagen University Hospital and colleagues.

Hjorthøj and colleagues relied on data contained in Danish registries to identify a cohort of 2,539 people born in Denmark who had been diagnosed with schizotypal disorder. The researchers then tracked the patients from schizotypal diagnosis until diagnosis of schizophrenia, death, migration, or August 10, 2014.

According to the researchers, 16.3% of those with schizotypal disorder had experienced conversion to schizophrenia after two years. After 20 years, 30.6% of individuals without any substance use disorder had experienced conversion to schizophrenia. For those with cannabis use disorder, the 20-year conversion rate was 58.2%.

Further analysis revealed that cannabis use disorders, amphetamine use disorders, and opioid use disorders were associated with conversion to schizophrenia. “These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders,” Hjorthøj and colleagues wrote.

Though the findings suggest substance use disorders—in particular cannabis, amphetamines, and opioids—may be associated with conversion from schizotypal disorder to schizophrenia, the authors noted that “conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.”

For related information, see the Psychiatric News article “Early End to Substance Use Linked to Better Outcome in First-Episode Psychosis.”

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Antidepressants May Be Less Effective in Patients With Mild General Anxiety Disorder, Panic Disorder

Patients with mild general anxiety disorder (GAD) or panic disorder (PD) may be less likely to benefit from antidepressants than patients with severe cases of these disorders, suggests a meta-analysis in Depression and Anxiety.

While previous studies have suggested that the benefits of antidepressants are smaller in patients with mild versus severe symptoms of depression, few have examined how symptom severity might influence other conditions for which antidepressants are prescribed.

Ymkje Anna de Vries, Ph.D., and colleagues of the University of Groningen, The Netherlands, combined patient data from randomized, controlled trials of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in 3,430 patients with GAD; 1,195 with social anxiety disorder (SAD); 1,132 with obsessive-compulsive disorder (OCD); 1,071 with posttraumatic stress disorder (PTSD); and 2,151 with panic disorder (PD). All of the trials involved patients who were treated with either duloxetine, fluoxetine, paroxetine, or placebo.

The authors found that symptom severity moderated antidepressant efficacy in patients with GAD and PD. For GAD, the symptom improvements in patients taking an antidepressant relative to those taking placebo were 1.4 points on the Hamilton Anxiety Rating Scale (HAM-A) for participants with mild anxiety (baseline HAM-A score=10), 2.7 points for patients with moderate anxiety (baseline HAM-A score=20), and 4.0 points for severe anxiety (baseline HAM-A score=30). Compared with patients taking placebo, patients with mild PD (10 panic attacks every two weeks at baseline) experienced 0.4 fewer panic attacks every two weeks, patients with moderate PD (20 panic attacks/two weeks at baseline) experienced 0.9 fewer panic attacks every two weeks, and patients with severe PD (40 panic attacks/two weeks at baseline) experienced 4.7 fewer panic attacks every two weeks.

Regardless of initial symptom severity, patients with SAD, OCD, and PTSD responded similarly to antidepressants.

“To understand the implications of these findings, it should be noted that the clinical relevance of a treatment effect is context-specific, depending on such factors as the expected sequelae of the disease, the costs and drawbacks of the treatment, and the efficacy of alternative treatments,” de Vries and colleagues wrote.

“[I]t is clear that the risk-benefit ratio for GAD and PD becomes less favorable as initial severity decreases. It is therefore imperative that clinicians transparently discuss the expected benefits of antidepressants with patients with mild to moderate symptoms,” they concluded.

For related information, see the Psychiatric News article “Percentage of Americans Taking Antidepressants Climbs.”

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Handgrip Strength May Offer Clues About Cognitive Function in People With Mood Disorders

Handgrip strength may provide a useful indicator of cognitive impairment in people with major depression and bipolar disorder, according to a study in JAMA Psychiatry. 

Joseph Firth, Ph.D., of the University of Western Sydney and colleagues found that greater grip strength in individuals with major depression and bipolar disorder was associated with better performance on measures of reasoning, reaction time, and memory.

Firth and colleagues analyzed data from the UK Biobank—a nationwide, health-oriented, cohort study conducted across the United Kingdom. The final analysis included 110,067 people who had their handgrip strength evaluated (each participant received a single, maximum score indicating the greatest strength for each hand). The participants also performed a variety of cognitive functioning tasks on a computer (these tasks evaluated visuospatial memory, reaction time, reasoning, prospective memory, and numeric memory).

Of the group, 85,893 participants had no indication of any mood disorders, 22,699 reported recurrent major depression, and 1,475 reported bipolar disorder (type I or type II). The mean age of the healthy control, bipolar disorder, and major depression samples was 53.7 years, 54.4 years, and 55.5 years, respectively.

In participants with major depression and no indication of any mood disorders, greater handgrip strength was a significant predictor of better cognitive performance in all five domains: visual memory, reaction time, reasoning, number memory, and prospective memory. In people with bipolar disorder, greater handgrip strength was significantly associated with visual memory, reaction time, reasoning, and prospective memory. 

“To our knowledge, this study is the first to identify handgrip strength as a marker of cognitive function in mood disorders,” Firth and colleagues wrote. “However, the cross-sectional design of this investigation means that further longitudinal and mechanistic research must be conducted to determine the causative nature of the association between handgrip strength and cognition in psychiatric populations.”

Noting that strength training exercise interventions have been shown to improve cognitive functioning in aging populations, the authors suggested that improving muscular fitness may be a “therapeutic target” for individuals with mood disorders. 

“Future research should investigate causality, assess the functional implications of handgrip strength in psychiatric populations, and examine how interventions to improve muscular fitness affect neurocognitive status and socio-occupational functioning,” they concluded.   

For related information, see the Psychiatric News article “Minimal Exercise May Help Prevent Future Depression.”

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Identifying, Treating Mothers’ Depression Could Positively Impact Children’s Neurodevelopment, Study Suggests

Children whose mothers experienced depression during and after pregnancy may be slower to hit early childhood developmental milestones than children whose mothers did not experience depression, suggests a study published this week in Depression & Anxiety. The findings demonstrate the benefit that early recognition and treatment of maternal depression symptoms can have on both mothers and children.

While previous studies have suggested symptoms of depression during and after pregnancy are associated with poorer neurodevelopmental outcomes in offspring, questions remain about whether such symptoms during pregnancy and postpartum as well as early childhood periods exert different, independent, or additive effects on child neurodevelopment.

For the current study, Soile Tuovinen, Ph.D., of the University of Helsinki in Finland and colleagues examined maternal depression and child development data collected from women in Finland as part of the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study. A total of 2,231 mothers in the PREDO study completed the Center for Epidemiological Studies Depression Scale biweekly up to 14 times during pregnancy and twice up to 12 months after pregnancy. When the children were between 1.9 and 5.7 years old, the mothers completed the Beck Depression Inventory-II and filled out the Ages and Stages Questionnaire (ASQ), which asks caregivers to assess children’s fine and gross motor, problem solving, communication, and personal/social skills.

The researchers found that higher depression symptoms during and after pregnancy predicted lower ASQ total scores and subscale scores in fine and gross motor, communication, problem solving, and personal/social skills in children.

“The after-pregnancy effects were additive to those during pregnancy: children whose mothers had chronically elevated depressive symptoms during and after pregnancy had the poorest developmental milestones scores,” Tuovinen and colleagues wrote. “Compared with children whose mothers never had clinically significant depressive symptoms, neurodevelopmental scores were significantly worse for children whose mothers had clinically relevant depressive symptoms either only during pregnancy, both during and up to 12 months after pregnancy, or across all three developmental stages.”

The authors concluded, “[I]ntervention in early pregnancy may benefit both mothers and children: early treatment may prevent the accumulative cascade of depressive symptoms from pregnancy onwards, which may all possibly reflect positively on child neurodevelopment.”

For related information on efforts to recognize and treat pregnant and postpartum women with depression, see the Psychiatric News article “UMass Researcher Turns Idea Into a Nationally Recognized Program.”

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Naltrexone May Reduce Stimulant-Related Euphoria

Stimulants are a preferred option for treating attention-deficit/hyperactivity disorder (ADHD), but concerns remain about their potential for misuse. A small study in the Journal of Clinical Psychiatry now suggests that treating patients with ADHD with a combination of the opioid blocker naltrexone and methylphenidate could reduce the feelings of euphoria some patients experience when taking stimulants.

For the study, Thomas Spencer, M.D., the assistant chief of the Pediatric Psychopharmacology Research Program at Massachusetts General Hospital, and colleagues enrolled 37 young adults (aged 18 to 30) with ADHD who reported a feeling of euphoria when taking stimulants. The participants were randomly assigned to take either placebo or 50 mg naltrexone in the morning along with an extended-release methylphenidate formulation taken in the morning and afternoon (up to 80 mg/day). 

At baseline and three and six weeks later, the participants were asked to take a drug likeability test, where they answered questions about how good they felt after taking their medications. On the days they were given the drug likeability test, the participants took either an immediate-release methylphenidate pill in the morning or afternoon instead of their regular extended-release medication.

Spencer and colleagues observed that naltrexone significantly diminished the euphoric effect of immediate-release methylphenidate during the first three weeks of the study (the titration phase) but not during weeks 4 to 6 (the maintenance phase) of the study. Research has shown that stimulants pose the most risk for abuse when introduced abruptly and unevenly, such as the first few weeks of treatment when the optimal dose is being determined. “It is possible that the experience of euphoria attenuated because the study subjects only had mild euphoria at outset. Our nonsignificant effect for euphoria at week 6 should be viewed with caution due to the possibility of a floor effect, which would have reduced statistical power,” they wrote.

“[T]his double-blind, randomized clinical trial showed that treatment with naltrexone diminished the euphoric effect of immediate-release methylphenidate during the initial methylphenidate titration period of heightened vulnerability,” Spencer and colleagues continued. “If confirmed, these findings could lead to the development of a nonaddictive form of stimulant treatment for ADHD, which could facilitate access to an effective ADHD treatment.”

For related information, see the Psychiatric News article “Six-Question Screen for ADHD Developed for Adults.”

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Timing of First, Second Deployments May Influence Soldiers’ Risk of Suicide, Study Suggests

Soldiers who deployed overseas within their first year of service in the Army are twice as likely as their peers to attempt suicide after a subsequent deployment, reports a study published today in JAMA Psychiatry. Soldiers who have less than six months between their first two deployments are also at greater risk of attempting suicide.

“These time-related deployment variables are potentially modifiable risk factors for SA [suicide attempt],” wrote Robert J. Ursano, M.D., of the Uniformed Services University of the Health Sciences in Bethesda, Md., and colleagues. “Further consideration should be given to how well the timing of first deployment corresponds with the U.S. Army’s training and preparedness goals for new soldiers.”

While a previous study found that soldiers who were deployed in their first year of service were at an elevated risk of death by suicide in the short term, it was unknown what long-term impact deployment within the first year may have on suicidal behavior during or after subsequent deployments.

Ursano and colleagues analyzed data from Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS), which includes health information on more than 1.5 million soldiers who were on active duty between January 1, 2004, and December 31, 2009. They identified 593 soldiers with a medically documented suicide attempt during or after their second deployment, as well as 19,034 matched controls with two deployments.

After adjusting for sociodemographic factors, service-related characteristics (such as age at entry into U.S. Army) and mental health history, Ursano and colleagues found that the odds of a suicide attempt during or after the second deployment were twice as high among soldiers whose first deployment occurred within the first 12 months of service compared with those who deployed after 12 months.

Although the duration of the first deployment was not associated with a higher risk for suicide attempt, the researchers found that the length of time between the first and second deployments (dwell time) was a factor in suicide attempts during or following the second deployment. Soldiers with a dwell time of six months or less had 1.6 higher odds of suicide attempt compared with those with dwell times of more than six months.

Further analysis suggested that suicide attempts might be reduced by about 14% if all soldiers served in the U.S. Army for more than 12 months before their first deployment. Additionally, dwell time of longer than six months for all soldiers could result in a 4% reduction in suicide attempts among those who have deployed twice, the authors noted.

“Future research that examines factors associated with DT [dwell time], including type and extent of social support at home, training and reset opportunities, parenting and household responsibilities and challenges, and family and financial stressors, would provide a better understanding of the association between this period and SA [suicide attempt] risk,” Ursano and colleagues concluded.

To read more on this topic, see the Psychiatric News article “Suicide Attempts Linked to Previous Attempts in Soldiers’ Unit, Says Army Study.”

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