An Elemental Effect on Mental Health

Zinc, copper, iron—these and many other elements play a crucial role in health and sickness. Beyond the well-known toxic effects of lead, it can be difficult to determine the precise impacts of these metals because they interact with one another and with many types of molecules found in our body. Recent research has led to some key insights, however, which may lead to new treatments for mental illnesses.

Linking Zinc to Depression

Depression is tricky to treat because many patients do not respond to antidepressant medications. A growing body of evidence suggests that zinc deficiency may be a factor underlying depression in some cases—and zinc supplements can be an effective treatment for people whose levels are low.

A meta-analysis published in December 2013 in Biological Psychiatry analyzed 17 studies and found that depressed people tended to have about 14 percent less zinc in their blood than most people do on average, and the deficiency was greater among those with more severe depression. In the brain, zinc is concentrated in glutamatergic neurons, which increase brain activity and play a role in neuroplasticity, explains one of the paper's co-authors, Krista L. Lanctôt, a professor of psychiatry and pharmacology at the University of Toronto. “Those neurons feed into the mood and cognition circuitry,” she says.

Newer results increasingly point to a causal relation. Last September researchers at the University of Newcastle in Australia reported findings of two longitudinal studies that demonstrated an inverse relation between depression risk and dietary zinc intake. After adjusting for all known potential confounders, they found that the odds of developing depression among men and women with the highest zinc intake was about 30 to 50 percent lower than those with the lowest intake. Although previous studies have shown that zinc supplementation can augment the effects of antidepressant medications, research published in May in Nutritional Neuroscience is the first to investigate the effects of zinc alone on depressive symptoms. In the double-blind, randomized, placebo-controlled trial, researchers assigned participants to one of two groups: every day for 12 weeks, one group received 30 milligrams of zinc; the other group received a placebo. At the end of the study period, the zinc group showed a steeper decline in its scores on a rigorous inventory of depression symptoms.

“The future treatment of depression is zinc sulfate,” says Atish Prakash, a postdoctoral fellow in the department of pharmacy at the MARA University of Technology in Malaysia, who co-authored a thorough review of studies on the role of zinc in brain disorders, published in April in Fundamental and Clinical Pharmacology. Researchers strongly caution against people trying zinc supplements on their own, however—when levels are too high, zinc can cause other complications. Working with a doctor is essential, and in most cases, eating a healthier diet is probably a better way to ensure optimal zinc levels than supplementation. Yet for those with depression who are also at high risk for zinc deficiency, including vegetarians, people with alcoholism, gastrointestinal issues or diabetes, and pregnant or lactating women, zinc may be just what the doctor ordered.

Improving Lithium Treatment

Lithium has been providing relief to patients with bipolar disorder for decades. Although it is considered the standard treatment for the illness, how it works—and why it does not work for at least half of patients who try it—remains largely a mystery. Recent study findings suggest that a hormonal mechanism may be a factor.

In research published in July in the Journal of Molecular Neuroscience, scientists from several universities expanded on earlier work investigating the role of insulinlike growth factor (IGF1) in lithium sensitivity. (Scientific American is part of Springer Nature.) A 2013 paper by some of the authors of the newer study had found higher levels of the hormone in blood cells of bipolar patients who were responsive to lithium treatment, as compared with nonresponders. In the current study, researchers tested the effects of administering IGF1 to the blood cells of those same patients.

Adding the hormone increased lithium sensitivity only in cells of nonresponders, which “proves that indeed IGF1 is strongly implicated in determining clinical response or resistance to lithium,” says study co-author Elena Milanesi, a postdoctoral fellow at the Sackler Faculty of Medicine at Tel Aviv University in Israel. Further research will be needed to discern treatment possibilities, including supplemental use of the hormone or a similarly acting drug in lithium-resistant patients. Synthetic human IGF1 is already FDA-approved for human use in other kinds of disorders, Milanesi says, so she hopes clinical trials can get under way quickly.

Other Metals and the Mind

IRON. Iron deficiency impedes neurotransmission and cell metabolism, and research findingshave linked it with cognitive deficits in children and adults.

MAGNESIUM. Low magnesium intake has been implicated in anxiety and depression in studies of humans and rodents, and new research published in Acta Neuropsychiatrica suggests the relation is mediated by altered gut microbes, which have previously been linked with depression. In the study, mice fed a magnesium-deficient diet displayed an increase in depressive behavior and alterations in gut microbiota that were positively associated with neuroinflammation in the hippocampus.

MANGANESE. In research reported in theJournal of Alzheimer's Disease, scientists from China and Japan investigated the role of manganese—a known neurotoxin at high levels—in the progression of cognitive decline. In 40 older adults, they found that manganese levels were significantly correlated with scores on assessments of cognitive function and dementia and that levels of the characteristic protein tangles of Alzheimer's disease increased as manganese levels did. Excessive manganese is usually caused by airborne pollutants or pesticides, but eating too little iron can increase manganese absorption—so a healthy diet is key here, too.

Beware of Supplements

That headline may sound alarmist—if your doctor advises you to take a supplement, by all means, you should take it. Yet we cannot emphasize enough the importance of consulting a health care provider before starting any kind of supplement regimen, especially one that includes the trace elements discussed in this overview. Many of these elements can cause serious complications at high levels as well as low levels, and it is easy to accidentally go overboard. In addition, it can be hard to tell whether a person truly needs supplements—zinc, for example, cannot be reliably measured in blood or urine. Researchers use a complex variety of measurements and indicators to determine patients' zinc levels—something the average doctor's office cannot replicate.

In addition, most researchers and physicians believe that improving a person's diet is a far better way to reach healthy levels of these elements. Eating whole foods such as fresh meats, vegetables, fruits, nuts and seeds will give most people the nutrients they need. Avoiding highly processed foods with added sugars and fats is key, too, because those types of foods can impede your body's absorption of nutrients. In other words, that spinach salad is actually rendered less healthy if you chase it with a candy bar.