In some studies, vitamin D supplementation (1,500 IU/day) has been found to improve unipolar depression. Recently, researchers led by Wendy K. Marsh found that compared to placebo, 12 weeks of vitamin D3 supplementation (5,000 IU/day) did not produce greater improvement in depressive symptoms. The study, presented at the 2016 meeting of the Society of Biological Psychiatry, included 33 adult participants whose vitamin D levels remained deficient throughout the study.
Editor’s Note: Caution is urged in interpreting this small study, especially because the participants did not achieve healthy levels of vitamin D.
Low levels of vitamin D are common in children and adults with bipolar disorder. Future research may explore whether raising vitamin D levels to healthy levels has a beneficial effect on mood. There are many other benefits to vitamin D supplementation. It can improve cognition, regulate calcium and phosphorus absorption, and maintain healthy bones and teeth. It may also protect against diseases such as cancer, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. Improved cardiovascular health is also a possible benefit of vitamin D supplementation.
Some studies have suggested that omega-3 fatty acids may be helpful in the treatment of schizophrenia, but data to support this idea have been inconsistent. A recent meta-analysis of research on omega-3s and schizophrenia suggests that this nutritional supplement might be more useful in early-stage schizophrenia than in later illness.
At the 2016 meeting of the Society of Biological Psychiatry, researchers led by Alexander T. Chen presented the findings of their meta-analysis. First they analyzed six studies that shared a common scale for measuring schizophrenia symptoms. In these studies, omega-3 fatty acids did not outperform placebo when used as an add-on treatment to antipsychotics for people with schizophrenia.
In four remaining studies of omega-3 fatty acids and schizophrenia, the omega-3s were associated with improvement only in patients in the early stages of schizophrenia. Compared to placebo, the supplements decreased non-psychotic symptoms, decreased the dosage of antipsychotic medication patients required, and improved early treatment response (but not late treatment response) in patients in their first episode of schizophrenia.
In the same study, omega-3 fatty acids also reduced conversion to full-blown schizophrenia and psychotic symptom severity in patients at high risk for schizophrenia who were having preliminary symptoms of the illness.
Editor’s Note: Researcher Paul E. Keck has also found that omega-3 fatty acids may be more effective early in bipolar disorder rather than later. He reported that younger patients with bipolar depression and rapid cycling showed more improvement when taking the omega-3 fatty acid EPA than when taking placebo. In contrast, patients with bipolar depression who were over the age of 45 did worse on EPA than on placebo.
Part of the ambiguity about whether omega-3 fatty acids can help treat or prevent mental illness may be explained by the supplements working better in younger people or earlier in the course of an illness.
In 1996, the US began to require that enriched cereal grain products be fortified with folate, a vitamin that is particularly important to fetal brain development. A new study of children born before and after this policy change suggests that the increased folate in commercial foods after 1996 led to increases in cortical thickness in the children born after the change.
At the 2016 meeting of the Society of Biological Psychiatry, Joshua L. Roffman and colleagues described their research into the effects of folate fortification. The researchers identified 3,309 children born between 1993 and 2001 who had had a magnetic resonance imaging (MRI) brain scan. Analysis of the scans showed that children born after folate fortification began had thicker cortices than those born before the change. The frontal and temporal regions of the brain were particularly affected.
A thin cortex is a risk factor for schizophrenia and other cognitive problems.
Editor’s Note: Folate supplementation has also been shown to enhance the effects of selective serotonin reuptake inhibitor (SSRI) antidepressants in adults with lingering symptoms of depression.
Up to a third of the population may have a deficit of MTHFR, an enzyme important for folate metabolism, and for these people, l-methylfolate is recommended rather than folate itself.
A recently completed clinical trial suggests that NeuroAD, a treatment system that combines transcranial magnetic stimulation and cognitive training targeted at brain regions affected by Alzheimer’s disease, may be effective at treating mild to moderate cases of the illness.
Neuronix Ltd, the company that produces the device used to deliver transcranial magnetic stimulation in the trial, plans to seek Food and Drug Administration approval for NeuroAD. It would be the first device approved for the treatment of Alzheimer’s in the US. The device is already in use in Europe and Asia.
In the clinical trial, 131 patients received six weeks of the NeuroAD treatment or a sham treatment used as a comparison. Those participants who received the real intervention performed better on an assessment of Alzheimer’s and experienced minimal side effects.
In transcranial magnetic stimulation, a non-invasive procedure, magnets placed near the skull stimulate electrical impulses in the brain. This activates neurons, releasing excitatory transmitters and brain-derived neurotrophic factor (BDNF), which is important for new synapse formation and long-term learning and memory.
Editor’s Note: This editor (Robert Post) has long advocated the use of repeated transcranial magnetic stimulation (rTMS) with simultaneous cognitive behavioral or other positive therapy to activate and enhance specific neural circuits and relieve depression. The trial of NeuroAD adds evidence of the positive effects of this approach in domains other than depression. Cognitive training enhanced by rTMS may be helpful with a variety of cognitive difficulties.
Several researchers have found that lithium has some value in fighting dementia. The researcher Lars Kessing has published several studies showing that people taking clinical doses of lithium for bipolar disorder have a lower incidence of dementia in old age.
In 2011, another researcher, Oreste Vicentes Forlenza, reported that a year of low-dose lithium (typically around 300mg/day) slowed deterioration in people with mild cognitive impairment compared to placebo.
In an article published in the journal Current Alzheimer Research in 2013, researchers led by Marielza Andrade Nunes reported that very small doses of lithium (more than a thousand times lower than doses used to treat mood disorders) also improved mild cognitive impairment in people with Alzheimer’s disease.
In Nunes’ study, participants with Alzheimer’s disease were randomly assigned to receive either 300 micrograms of lithium daily or a placebo. Beginning at three months of treatment, those receiving the microdoses of lithium showed stable performance on a common Alzheimer’s evaluation tool that measures how well patients remember, recall information, and follow directions; while those taking placebo got worse.
This continued over the 15 months of the study, with the difference between the two groups intensifying over time—those taking placebo got worse, while those getting the microdoses of lithium remained stable.
There were no complaints of side effects from the microdoses of lithium, and participants showed no sign of impairment to their kidney or thyroid function (a risk with the higher doses of lithium used to treat bipolar disorder).
In 2015, Nunes and colleagues reported in the journal PLOS ONE that in a mouse model of Alzheimer’s disease, mice treated with chronic low doses of lithium in their water had less memory disruption, fewer plaques in the brain, and fewer reductions in cortex and hippocampus size compared to mice given plain water.
These studies suggest that low or micro doses of lithium may be a promising treatment for Alzheimer’s disease. Much more research is needed to determine appropriate lithium dosing for the treatment of dementia or cognition problems.
People with unipolar depression and bipolar disorder may experience cognitive difficulties, even when they’re not currently depressed. In a study published in the journal European Neuropsychopharmacology in 2016, researchers led by Caroline Vintergaard Ott determined that treatment with the hormone erythropoietin (EPO) may help. EPO is produced in the kidney and increases the production of hemoglobin and red cells.
Seventy-nine participants with unipolar or bipolar disorder were randomized to receive infusions of either EPO or a saline solution once a week for eight weeks. By the end of the study, those who received EPO showed significant improvements in the speed of their complex cognitive processing compared to those who received saline. EPO is known to induce the production of red blood cells. The improvements in processing speed lasted for at least another six weeks after red blood cell production would have normalized.
Those participants who received EPO not only had improved scores on tests of processing speed, they also reported fewer cognitive complaints. The EPO treatment was most likely to be effective in participants who had more impaired cognition at the beginning of the study.
In previous research by the same research group presented by Kamilla W. Miskowiak at the 2014 meeting of the International Society of Bipolar Disorders, EPO also improved sustained attention and recognition of happy faces.
Oxytocin, a hormone that promotes emotional bonding, also benefits people having trouble dealing with stress. A new study suggests that giving oxytocin for a week shortly following a traumatic experience reduces the risk that the recipient will develop post-traumatic stress disorder (PTSD).
In the study by researcher Mirjam van Zuiden and colleagues, people who visited an emergency room following some kind of trauma were randomized to receive either a placebo nasal spray or intranasal oxytocin twice daily for 7.5 days beginning within 12 days after the trauma. The dosage was 40 IU twice daily.
For those participants with severe PTSD symptoms at baseline, repeated oxytocin administration prevented worsening PTSD. The research was presented at the 2016 meeting of the Society of Biological Psychiatry.
In a new study by Keiho Owada and colleagues, 18 people with autism spectrum disorders had more neutral facial expressions and fewer surprised expressions than 17 typically developing people while interacting socially. Oxytocin, a hormone that promotes social bonding, was delivered to the autism group via a nasal spray for six weeks, and made the faces of the people with autism more expressive. Oxytocin also improved their reciprocity in social interactions and increased activity in the dorsomedial prefrontal cortex, as observed via functional magnetic resonance imaging (fMRI).
The study suggests not only that oxytocin can normalize facial expressions, but also that the counting of facial expressions on videos of social interactions can be used as a measure of social symptoms of autism. The research was presented at the 2016 meeting of the Society of Biological Psychiatry.
Oxytocin, the hormone that promotes emotional bonding, also regulates a variety of behaviors. Two recent studies suggest that in rats, an injection of oxytocin can prevent drug-seeking behavior.
In the first study, researcher Gary Aston-Jones found that oxytocin reduced the rats’ interest in methamphetamine. The effect was strongest in the rats that started out with the strongest interest in the methamphetamine.
In the second study, researcher Luyi Zhou and colleagues determined that oxytocin also reduced cocaine-seeking behavior in rats. In addition, the oxytocin reversed changes in the brain’s glutamate signaling pathway that were caused by cocaine use.
Both studies, which were presented at the 2016 meeting of the Society of Biological Psychiatry, suggest that oxytocin is a promising potential treatment for drug addictions.
PANS is a neuropsychiatric syndrome characterized by the acute onset of obsessive compulsive and other abnormal behaviors, tics, and mood changes that appear in a child following a bacterial or viral infection. PANS refers to any pediatric acute-onset neuropsychiatric syndrome of this type, while PANDAS refers more specifically to such a syndrome that occurs after exposure to streptococcal infections.
New research suggests that treatment with the antibiotic azithromycin can treat PANS. In a study presented at the 2016 meeting of the Society of Biological Psychiatry, Tanya K. Murphy and colleagues found that among 32 children aged 4–14 who showed obsessive compulsive symptoms following an infection, those who were given a 4-week course of azithromycin (10mg/kg of body weight, up to 500 mg/day) saw a 26% drop in symptoms, compared to a 1% drop in symptoms in those who received placebo instead.
At the end of the four weeks, 38.9% of the azithromycin group were classified as much improved or very much improved, while no one in the placebo group achieved this level of improvement. Azithromycin treatment increased the QTc interval (a measure of heart rate) and pulse in the study participants, but did not have any other notable side effects.
PANS is thought to arise from an immune response to infection that goes awry and begins attacking neurons in the brain, particularly in the thalamus. For a more complete review of PANS, see several of our earlier articles about PANS and an excellent review article by researcher Kiki Chang and colleagues in the Journal of Child and Adolescent Psychopharmacology in 2015.
It is important to work up a child suspected of having PANS, as the syndrome does not usually respond to conventional psychiatric treatment and often requires anti-inflammatory drugs (steroids or immunosuppressants), intravenous immunoglobulin (IVIG), plasma exchange, the TNF alpha blocker infliximab, or antibiotics.