Specialized Therapy, Micronutrient Supplements Fail to Prevent MDD in Overweight Patients

Nutritional supplements and/or a special kind of therapy focused on improving dietary behaviors do not appear to prevent overweight adults with mild symptoms of depression from episodes of major depressive disorder (MDD) within a year, according to a study published today in JAMA. While some studies have found that improving diet reduces depressive symptoms in adults with depression, this study examined its effects on prevention for overweight adults with mild symptoms of depression.

The type of therapy used in this study was food-related behavioral activation. Behavioral activation is a treatment whose goal is to teach people that their behavior is linked to their mood and that by changing their behavior, they can change their mood.

“This study showed that multinutrient supplements containing omega-3 PUFAs [polyunsaturated fatty acids], vitamin D, folic acid, and selenium neither reduced depressive symptoms [and] anxiety symptoms, nor improved health utility measures,” wrote Mariska Bot, Ph.D., of the Amsterdam Public Health research institute and colleagues. “In fact, they appeared to result in slightly poorer depressive and anxiety symptoms scores compared with placebo.”

The trial included 1,025 overweight adults, aged 18 to 75 years, in four western European countries (Germany, the Netherlands, Spain, and the United Kingdom) with mild depressive symptoms (Patient Health Questionnaire-9, or PHQ-9 scores ≥5). The study participants were randomly assigned to one of four groups: multinutrient supplements with food-related behavioral activation therapy; multinutrient supplements without therapy; placebo supplements with food-related behavioral activation therapy; or placebo supplements without therapy. Participants receiving supplements were assigned to take omega-3 polyunsaturated fatty acids, selenium, folic acid, vitamin D3, and calcium for one year. Those assigned to food-related behavioral activation were invited to participate in a maximum of 21 sessions (15 individual, six group) focused on improving dietary habits for one year.

Bot and colleagues followed the participants in the trial for 12 months to evaluate symptoms of depression, anxiety, and more.

In total, 105 participants (10%) developed an MDD episode during the 12-month follow-up: 25 participants (9.7%) had received placebo alone; 26 (10.2%), placebo with therapy; 32 (12.5%), supplements alone; and 22 (8.6%), supplements combined with therapy. Neither of the interventions nor the combination of the two had an effect on decreasing the participants’ likelihood of developing an MDD episode in the following 12 months.

“Despite the large sample size and selection of people with elevated depressive symptoms, the onset of MDD was lower than expected, which reduced the statistical power to detect a statistically significant effect,” Bot and colleagues wrote. Nonetheless, the authors concluded, “These findings do not support the use of these interventions for prevention of major depressive disorder in this population.”

For additional information, see the American Journal of Psychiatry article “Adjunctive Nutraceuticals for Depression: A Systematic Review andMeta-Analyses.”

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Prenatal Exposure to Folic Acid Appears to Promote Healthy Brain Development

Increased prenatal exposure to folic acid, which is known to reduce the risk of neural tube defects, may also promote healthy brain development through adolescence, reports a study published in JAMA Psychiatry. According to the study authors, prenatal exposure to folic acid may protect against psychosis through altered postnatal cortical development. 

Some studies suggest poor maternal nutrition during pregnancy increases subsequent risks for conditions like schizophrenia in offspring; other studies have suggested that prenatal exposure to folic acid may lower the risk of language delay and autism in children. In 1996, the U.S. government mandated that all food manufacturers fortify enriched grain products with folic acid by January 1, 1998. To examine whether prenatal exposure to folic acid is associated with changes in brain development later in life, Hamdi Eryilmaz, Ph.D., of Massachusetts General Hospital and colleagues compared cortical brain development in youth who were born before, during, and after the full implementation of folic acid fortification of U.S. grain products.

Eryilmaz and colleagues analyzed multiple sets of magnetic resonance imaging (MRI) scans taken when children and adolescents born from 1993 to 2001 were ages 8 to 18: one set consisted of normal brain images taken from 292 patients seen at Massachusetts General Hospital; another set included images from 861 participants in the Philadelphia Neurodevelopmental Cohort, a study that assessed psychiatric symptoms in the study participants; and a third included scans collected of youth in an NIH study, who were born prior to folic acid fortification. 

The researchers found that cortical thickness was greatest in youth born after the implementation of folic acid fortification, intermediate in those partially exposed to folic acid fortification, and lowest in those born before fortification. Data from the Philadelphia cohort suggested delayed cortical thinning in the group exposed to full folic acid fortification was associated with a reduced risk of psychosis symptoms. “Collectively, these data suggest an association of prenatal exposure to folic acid fortification with increased cortical thickness through early adolescence, accompanied by delayed onset of cortical thinning and reduced risk of psychosis,” the authors wrote.

“While our results link prenatal exposure to folic acid fortification with changes in cortical development and with a reduced risk of psychotic spectrum symptoms, they cannot directly link folic acid exposure to reduced schizophrenia risk, since the typical age of onset for that disorder is in the early 20s,” senior author Joshua Roffman, M.D., M.M.Sc., of Massachusetts General said in a press release. “But since such symptoms in youth are on the same continuum as schizophrenia, the results hold some promise for schizophrenia prevention.” 

For related news, see the American Journal of Psychiatry review article “Prenatal Primary Prevention of Mental Illness by Micronutrient Supplements in Pregnancy.”

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Review Examines Evidence to Support Use of Prenatal Supplements to Prevent Mental Illness

Previous studies suggest that certain prenatal supplements can enhance fetal brain development, but less is known about whether these supplements decrease the subsequent risk of mental illness in offspring. A review published Wednesday in AJP in Advance suggests that while prenatal nutrients may offer some protective mental health benefits to the offspring, there are some health risks.

AJP Editor Robert Freedman, M.D., of the University of Colorado School of Medicine and colleagues conducted a literature search for human studies that included the keyword “micronutrients” combined with “pregnancy” or “fetal development” that were published between 1990 and 2017. Thirty-five human studies and trials of individual nutrients were identified that included reports on subsequent child behavior, emotion, or cognition in one or more articles. Freedman and colleagues identified four supplements as a result of this literature review: folic acid, omega-3 fatty acids, phosphatidylcholine, and vitamins D and A.

Key findings of the review included the following:

• Folic acid and phosphatidylcholine supplements appear to reduce social and emotional problems in young children that are associated with later mental illness. More research is needed to establish whether these supplements can reduce the risk of psychiatric disorders such as schizophrenia.
• Vitamin A and D supplements appear to decrease the risk for schizophrenia and autism. However, at higher doses these vitamins can be toxic to both mother and child. The authors wrote, “Supplementation should not be greater than the amount in standard multivitamins.” (The daily recommendation in the United States for vitamin D is 600 IU for pregnant women and 400 IU for infants.)
• Omega-3 fatty acid supplements during pregnancy appear to increase the risk for schizophrenia and attention-deficit/hyperactivity disorder (ADHD) symptoms; however, other studies show that omega-3 supplements can substantially reduce the risk of premature birth, which is also a risk factor for ADHD.

Freedman and colleagues noted that more research is needed to understand the relationship between prenatal nutrients and mental health of offspring; of the 35 studies they analyzed for the review, only five were randomized, controlled clinical studies. “To obtain [substantive] evidence for any nutrient will require new research agendas that emphasize prenatal clinical trials of interventions, early biomarkers of their effectiveness developed in translational models, and then longer-term follow-up through childhood developmental stages into adulthood,” the authors wrote.

“In the absence of definitive evidence, parents currently planning pregnancy now have difficult decisions about nutrient supplements,” the authors continued. “The mother is unlikely to receive fully effective levels of the currently studied nutrients from diet alone. Adverse effects of supplements are few at the doses studied, but it would be premature to conclude that they are nonexistent. Conversely, there is only one opportunity in each child’s life for intervention to enhance fetal brain development and protect the child against developmental risks that arise in this period.”

To read more about this topic, see the Psychiatric News article “Long Career Studying Choline Leads to Public Health Payoff.”

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Use of Folic Acid and Multivitamins During Pregnancy May Lower Autism Risk

Women who take folic acid and multivitamins before and during pregnancy appear to reduce their risk of having a child with autism, according to a large study in Israel.

Compared with women who had no exposure to supplements during pregnancy, women who took folic acid and/or multivitamins had a significantly reduced risk of having offspring with autism spectrum disorder (ASD), with a relative risk of 0.27, according to the study published yesterday in JAMA Psychiatry. Mothers who took folic acid and vitamin supplements before pregnancy had a relative risk of 0.41 compared with mothers who did not.

For the study, researchers followed 45,300 Israeli children born between 2003 and 2007, until 2015; 1.3% were diagnosed with ASD, according to the study by Stephen Z. Levine, Ph.D., of the University of Haifa, Israel, and colleagues.

Women are routinely advised to take folic acid or multivitamins during pregnancy to avoid neural tube defects in their children, but previous studies of an association between the supplements and the risk of ASD in their offspring have been inconsistent.

For this observational study, children with ASD were compared with children without it to identify whether maternal use of folic acid and multivitamin supplements might play a role. The researchers examined health care organization data, including pharmacy dispensation of folic acid and multivitamin prescriptions, to pregnant women.

They examined whether supplements were dispensed to the pregnant women before pregnancy (540 days to 271 days before childbirth) and during pregnancy (9 months before childbirth, up to the date of birth). A diagnosis of ASD of their children was made after evaluation by a panel of experts, including a behavioral pediatrician.

Among offspring whose parents had a psychiatric disorder, folic acid supplementation before pregnancy did not provide the same protective effect against ASD, the researchers found. They theorized this finding might reflect noncompliance with the vitamin regimens, or possibly higher rates of vitamin deficiency or poor nutrition among persons with psychiatric conditions.

The researchers found that most supplement dispensations occurred around the first trimester. Only 26% of children were born to mothers who took folic acid and/or multivitamin supplements before pregnancy; about 48 percent were born to mothers who took folic acid and/or multivitamins during pregnancy.

For related information, see the Psychiatric News article “Folinic Acid May ImproveVerbal Skills in Children With ASD.”

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Folic Acid Linked to Lower Autism Risk

A study of 85,176 Norwegian children finds that women who took folic acid supplements beginning a month before conception through eight weeks into pregnancy had a 40 percent lower risk of giving birth to children with autism.

Folic acid has long been recommended for women who may become pregnant because it reduces the risk of neural tube defects in their babies.

Among children whose mothers took folic acid, only 0.10 percent (64/61,042) were diagnosed with autistic disorder, compared to 0.21 percent (50/24,134) among those whose mothers did not take folic acid, wrote Pål Surén, M.D., M.P.H., of the Norwegian Institute of Public Health in Oslo, in the February 13 issue of the Journal of the American Medical Association.

Use of folic acid did not have an effect on rates of other autism spectrum disorders. Starting folic acid supplements midway through pregnancy had no effect, and there was no correlation with maternal intake of folate through food.

“The study does not prove that folic acid supplements can prevent childhood autism,” said Surén, in a statement. “However, the findings are so apparent that they constitute a good argument to further examine possible causal mechanisms.”

For more in Psychiatric News about risk factors for autism, click here.

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