A 2012 study by Geoge I. Papkostas and colleagues found that 15mg/day of the nutritional supplement l-methylfolate calcium (a form of the B vitamin folate that the body can more readily use) improved depression in people who had not responded adequately to treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant. In a follow-up study by Richard C. Shelton and colleagues published in the Journal of Clinical Psychiatry in 2015, the same researchers further analyzed these data and found that l-methylfolate worked better in patients who were overweight (with body mass indexes (BMIs) of 30 or above) and those who had higher than average levels of inflammation at the beginning of the study. Inflammatory markers linked to greater improvement with l-methylfolate included TNF-alpha, IL-8, high sensitivity CRP, and leptin. In overweight participants, higher than average levels of IL-6 were also linked to more improvement on l-methylfolate.
Vitamin D3 tends to be low in children and adolescents with mania, but supplements may help. In a small open study published in the Journal of Child and Adolescent Psychopharmacology in 2015, Elif M. Sikoglu and colleagues administered 2000 IU of vitamin D3 per day to youth aged 6–17 for eight weeks. Sixteen of the participants had bipolar spectrum disorders (including subthreshold symptoms) and were exhibiting symptoms of mania. Nineteen participants were typically developing youth.
At the beginning of the study, the youth with bipolar spectrum disorders had lower levels of the neurotransmitter GABA in the anterior cingulate cortex than did the typically developing youth. Following the eight weeks of vitamin D3 supplementation, mania and depression symptoms both decreased in the youth with bipolar spectrum disorders, and GABA in the anterior cingulate cortex increased in these participants.
Editor’s Note: GABA dysfunction has been implicated in the manic phase of bipolar disorder. While larger controlled studies of vitamin D supplementation are needed, given the high incidence of vitamin D deficiency in youth in the US, testing and treating these deficiencies is important, especially among kids with symptoms of bipolar illness.
Chronic fatigue syndrome, or Systemic Exertion Intolerance Disease (SEID), as it is now known, is characterized by extreme fatigue that cannot be explained by any underlying illness. Doctors have long disagreed over how it should be treated, particularly about whether or not exercise should be encouraged. A new small study of adolescents suggests that anti-viral medications can reduce fatigue.
The 2014 article by Theodore A. Henderson in Advanced Mind Body Medicine reports that among 15 adolescents who reported chronic fatigue symptoms, 1000 mg/day of the antiviral valacyclovir (trade name Valtrex) led to improvement in 86% of the patients by 3 months, and 92% of the patients by 5 months. One patient dropped out due to nausea. Symptoms of fatigue, exertion-induced malaise, excessive sleep, napping, unrefreshing sleep, headaches, cognitive symptoms, and emotional symptoms all improved after treatment with the antiviral. Several previous studies have also shown positive effects of antiviral treatments in patients with chronic fatigue.
E-cigarettes are not regulated to the same extent that cigarettes are by the US Food and Drug Administration, so their contents remain a bit of a mystery. A 2016 study by Vicky Yu and colleagues in Oral Oncology determined that even e-cigarettes without nicotine cause cell damage.
The researchers created an extract from two different brands of e-cigarettes. When they added the extract to human cells in a Petri dish, the cells showed signs of damage (including broken DNA strands) and death compared to untreated cells.
The researchers tested e-cigarettes both with and without nicotine, and those that contained nicotine showed even more signs of cell damage and death after exposure to the contents of the e-cigarette.
Other ingredients that have been identified in e-cigarettes include formaldehyde, which is known to be a carcinogen, and diacetyl, a flavoring agent.
Yu and colleagues suggest that e-cigarettes are not as safe as their marketing would suggest. The researchers hope to identify more of the ingredients in e-cigarettes.
Scientists have known for some time that heightened activity of dopaminergic neurons (neurons in the midbrain that contain the neurotransmitter dopamine) can make people vulnerable to depression. New research in animals suggests for the first time that noradrenergic neurons (those that contain the neurotransmitter norepinephrine) control the activity of dopaminergic neurons and that these noradrenergic neurons can make the difference between vulnerability to depression or resilience to stress. The research, published by Elsa Isingrini and colleagues in the journal Nature Neuroscience in 2015, showed that animals that cannot release norepinephrine are vulnerable to depression following chronic stress, but increasing the production of norepinephrine increases the animals’ resilience and reduces depression.
These findings may open up new avenues to treatment that target norepinephrine rather than or in addition to dopamine or serotonin, which is targeted by SSRI antidepressants, or selective serotonin reuptake inhibitors.
Many studies have linked depression and cardiovascular problems. The solutions may also be linked. A new study found that patients with depression and acute coronary syndrome saw their depression improve most when they took the selective-serotonin reuptake inhibitor (SSRI) antidepressant escitalopram and statins (used to lower cholesterol), while depression improved least among patients who took neither type of drug. Statin use was linked to improvement in depression after one year, while escitalopram was not. In a subset of the study, use of lipophilic statins in particular was linked to improvement in depression.
The study, published in 2015 by S.W. Kim and colleagues in the journal Translational Psychiatry, suggests that statins can improve depression regardless of antidepressant use, but combining statins with an SSRI may have an even more powerful effect on depression.
In 2015 Claudia Chauvet and colleagues reported in the journal Neuropsychopharmacology that the brain-penetrating statins simvastatin and Atorvastatin reduced cocaine seeking behaviors in mice that were taught to self-administer cocaine and then were denied access to it for 21 days compared to pravastatin, a statin that does not penetrate the brain as thoroughly. The researchers found that the brain-penetrating statins also reduced nicotine seeking, but not food reward seeking. The statins also worked in mice that had stopped seeking cocaine but relapsed due to stress, allowing them to abstain from cocaine seeking again.
Statins are considered a very safe treatment in humans. The ability of statins to prevent relapse to addictions in mice may mean that one day they could be used to treat addictions in people as well. A review article by Cassie Redlich and colleagues in the journal BMC Psychiatry in 2014 indicated that statins may reduce recurrence of depression in people. The researchers found that simvastatin had a protective effect while Atorvastatin was associated with increased risk of depression, so the choice of statins may be important for both depression and addiction.
A study by researcher J.H. Newcorn and colleagues published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2013 found that eight weeks of treatment with the drug guanfacine (extended release) improved symptoms of attention deficit hyperactivity disorder (ADHD) in North American children compared to placebo. A 2015 study by M.A. Stein and colleagues in the journal CNS Drugs extended this research, determining that guanfacine also improved academic and social functioning, including family dynamics, in the same group of children.
Children aged 6–12 who had been diagnosed with ADHD received either placebo or 1 to 4 mg of guanfacine extended release either in the morning or evening. The children in both guanfacine groups showed improvements in family interactions, learning and school, social behavior, and risky behavior compared to those taking placebo. No improvements were seen in life skills or self-concept. The improvements in functioning were linked to the drug’s effectiveness in improving ADHD symptoms. Those children whose ADHD symptoms improved on guanfacine were also more likely to see improvements in academic and social functioning.
People with disorders on the schizophrenia spectrum often suffer cognition problems that affect skills such as the processing of information about people and social situations (social cognition) and the execution of plans (executive function). At the 2015 meeting of the Society for Biological Psychiatry, researcher Larry J. Siever reported that the drug guanfacine improved these types of thinking in people with disorders on the schizophrenic spectrum compared to placebo. Participants were enrolled in a 7.5-week training program to improve cognition.
Stimulants are one of the most common medications prescribed to children and adolescents, typically for attention deficit hyperactivity disorder (ADHD). In children of parents with major depression, bipolar disorder, or schizophrenia, stimulant use may come with a risk of psychotic symptoms. A 2016 study by L.E. MacKenzie and colleagues in the journal Pediatrics reported that among children and youth whose parents had one of these psychiatric illnesses, 62.5% of those who had taken stimulants had current psychotic symptoms, compared to only 27.4% of those who had not taken stimulants. The participants with psychotic symptoms tended to have hallucinations that occurred while they were taking stimulants. Doctors may want to consider whether parents have a history of psychiatric illness when deciding whether to prescribe stimulants to children and adolescents with ADHD. Activation is a common side effect of antidepressants in children who have a parent with bipolar disorder. Young people taking stimulants for ADHD should be monitored for psychotic symptoms, particularly if they have a parent with a history of depression, bipolar disorder, or schizophrenia.