Researchers are looking for better ways of predicting whether children at risk for bipolar disorder will go on to develop the illness. A 2015 study by David Axelson and colleagues in the American Journal of Psychiatry reported that in the offspring of parents with bipolar disorder, diagnoses of sub-threshold mania, depression, and disruptive behavior disorders were associated with subsequent diagnosis of full-blown Bipolar I or Bipolar II disorders six to seven years later.
More recently, in an article by Danella M. Hafeman and colleagues in the American Journal of Psychiatry, the same group of investigators has examined how symptoms (rather than categorical diagnoses, as in the earlier study) predict the development of bipolar disorder. In children and adolescents at high risk for bipolar disorder (because they have a parent with the disorder) three types of symptoms were the best predictors of later bipolar disorder: anxiety/depression at the time participants entered the study, unstable mood or irritability both when entering the study and shortly before a bipolar diagnosis, and low-level manic symptoms observed shortly before diagnosis.
The earlier the age at which a parent was diagnosed with a mood disorder, the greater the risk that the offspring would also be diagnosed with bipolar disorder. Youth with all four risk factors (anxiety or depression, mood changes, low-level mania, and a parent who was diagnosed with a mood disorder at an early age) had a 49 percent chance of developing bipolar disorder, compared to a 2 percent chance among those without those risk factors.
Childhood onset of bipolar disorder and long delays until first treatment for depression or mania are both significant predictors of a poor outcome in adulthood compared to adult onsets and shorter delays to treatment. Read more
A recent study confirms that women who are depressed during pregnancy are more likely to experience adverse pregnancy outcomes such as preterm or cesaerean delivery and small or underweight babies. However, antidepressant treatment improved outcomes for pregnant women with depression.
The 2016 study by Kartik K. Venkatesh and colleagues in the journal Obstetrics & Gynecology included 7,267 women who gave birth after at least 20 weeks of pregnancy. About 11% of the women screened positive for depression during their pregnancy. Depressed mothers-to-be were more likely to give birth before 37 weeks and before 32 weeks compared to nondepressed mothers-to-be. The depressed women were also more likely to deliver small babies or babies weighing under 2500g.
About 7% of the women in the study received antidepressant medication. Compared to nondepressed women, the women taking antidepressants did not have greater rates of early delivery or small babies. However, the authors caution that because so few women received antidepressants, the study does not reveal whether antidepressants improve outcomes for depressed pregnant women.
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.
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 a recent BNN article on potential drugs for memory loss, we omitted two conventional classes of drugs used to treat Alzheimer’s Disease—acetylcholine esterase inhibitors (AChE-Is) and the blocker of glutamate NMDA receptors memantine (Namenda). This was intentional, as we hoped to suggest possible approaches prior to the use of these drugs for full-blown dementia. However, we neglected to cite a 1999 study by Fred Jacobsen in the Journal of Clinical Psychiatry that indicated that the AChE-I drug donepezil (Aricept) was effective in improving drug-induced memory dysfunction in patients without dementia. Side effects included insomnia, nausea, vomiting, and diarrhea.
Jacobsen has used AChE-Is to improve memory in over 80 patients with unipolar or bipolar depression, aged 19-85. In a 2016 personal communication to the BNN, he indicated that doses of 5mg/day are typically enough to improve memory. Higher doses of 10mg/day may be more effective, but increase the risk of switching into mania for patients with bipolar depression. Some of Jacobsen’s patients have used AChE-I drugs for 10–15 years without the drugs losing effectiveness. For some patients, Jacobsen has switched from prescribing donezepil to prescribing rivastigmine (Exelon or Exelon patch), which he finds they can more easily tolerate.
We should also remind readers of the BNN of our previous report on memantine (Namenda) for bipolar depressed patients with cognitive impairment. We wrote, “In an abstract presented at the 67th Annual Meeting of the Society of Biological Psychiatry in 2012, Dan V. Iosifescu reported that in a randomized 12-week study in which the anti-Alzheimer’s drug memantine was given to 72 euthymic bipolar subjects experiencing cognitive deficits, the drug was associated with improvement in spatial and working memory, verbal and episodic memory, and other indices that included measurements of attention and language skills. In conjunction with this treatment, a subgroup of subjects had increases in left hippocampal NAA (a measure of neuronal viability) and increases in choline in the right hippocampus. The initial improvements in these neuropsychological test results remained over 12 weeks of open follow-up.”
In an earlier proof-of-concept study published in the journal CNS Neuroscience and Therapeutics in 2009, Iosifescu had also reported that among nineteen subjects with bipolar disorder that was in remission, but who had residual cognitive deficits, open-label treatment with the AChE-I galantamine (extended release) at doses of 8–24 mg/day led to improvement in those cognitive symptoms after 4 months.
Doctors have known for some time that treatment with high-intensity light (7,000–10,000 Lux) can improve seasonal depression. In an 8-week study published in the journal JAMA Psychiatry in 2015, researcher Raymond Lam compared four different treatment options for non-seasonal major unipolar depression: bright light therapy for 30 minutes per day first thing in the morning, 20 mg of the antidepressant fluoxetine per day, combined bright light therapy and fluoxetine, and a placebo device paired with a placebo pill.
The combination of bright light therapy and fluoxetine produced remission in 58.6% of the participants who received it, compared to remission rates of 43.8% for bright light alone, 19.4% for fluoxetine alone, and 30% for placebo. It is notable that the effects of fluoxetine did not exceed those of placebo, but the effects of light alone did. There were few side effects in any group.
These data provide convincing evidence of the efficacy of light therapy in the treatment of non-seasonal unipolar depression. Use of light therapy for non-seasonal depression should now be more routinely considered, particularly when combined with antidepressant treatment.
Patients who had previously failed to respond to two or more antidepressants and patients with bipolar depression were excluded from the study. Bright light therapy administered in the morning can sometimes bring about mixed states in people with bipolar disorder. A 2007 case study by D. Sit and colleagues in the journal Bipolar Disorders found that midday light led to more improvement and less risk of mixed states than morning light among women with bipolar disorder.
Raising body temperature by a few degrees may produce antidepressant effects as the body’s cooling mechanisms kick in. At the US Psychiatric and Mental Health Congress in 2015, researcher Charles Raison described a study comparing the effects of exposing participants to a special heating coil in a tent that retained the heat until their body temperatures increased by a few degrees to those of a sham procedure that did not raise body temperature. Those participants whose body temperature was increased had a lower body temperature the following day, and their depression improved as their bodies cooled. These improvements lasted six weeks or more.
Depressed patients tend to have elevated body temperatures. Raison suggests that raising body temperatures even more prompts the body’s cooling mechanisms to compensate, bringing cooling activity to normal levels from the skin to the brain and improving depression.
A 2015 study by Rene L. Olvera and colleagues in the Journal of Clinical Psychiatry indicated that among 1,768 Mexican-Americans living along the border from 2004–2010, 30% were currently depressed, 14% had severe depression, and 52% were obese. Women were more likely to be depressed, and more likely to have severe depression. Other factors making depression more likely included low education, obesity, low levels of “good” cholesterol, and larger waist circumference. Low education and extreme obesity were also linked to severe depression.
In a commentary on the article in the same issue, researcher Susan L. McElroy wrote that “the medical field needs to firmly accept that obesity is a risk factor for depression and, conversely, that depression is a risk factor of obesity.” She suggested that people with obesity, those who carry excess weight around their middles, and those who have related metabolic symptoms such as poor cholesterol should all be evaluated for depression. Likewise, those with depression should have their weight and body measures monitored. People with both obesity and depression should be evaluated for disordered eating.