Drug treatment for major depression can produce remission in 35–50% or patients. The others may need additional interventions, and some mind-body techniques have been successful. A recent randomized study by Anup Sharma and colleagues found that Sudarshan Kriya Yoga (SKY) decreased depression at one and two months when added to participants’ regular treatments. Participants who received the yoga treatment also showed reductions in inflammation in the blood, including lower levels of the inflammatory proteins TNF-alpha, IL-10, and CRP.
A recent study clarified how cognitive behavioral therapy improves symptoms of depression and post-traumatic stress disorder (PTSD). The participants were 62 adult women. One group had depression, one had PTSD, and the third was made up of healthy volunteers. None were taking medication at the time of the study. The researchers, led by Yvette Shelive, used functional magnetic resonance imaging (fMRI) to analyze participants’ amygdala connectivity.
At the start of the study, participants with depression or PTSD showed diminished connectivity between the amygdala and brain areas related to cognitive control, the process by which the brain can vary behavior and how it processes information in the moment based on current goals. The lack of connectivity reflected the severity of the participants’ depression. Twelve weeks of cognitive behavioral therapy improved mood and connectivity between the amygdala and these control regions, including the dorsolateral prefrontal cortex and the inferior frontal cortex. These regions also allow for executive functioning, which includes planning, implementation, and focus.
Children of parents with bipolar disorder are prone to anxiety and emotional dysregulation, but treating these symptoms with antidepressants can provoke symptoms of mania. Thus, non-pharmacological treatements for anxiety and depression are needed. A recent study by Melissa DelBello found that twelve weeks of mindfulness-based cognitive therapy improved symptoms of anxiety and mood dysregulation in 20 youth with a bipolar parent. DelBello used functional magnetic resonance imaging (fMRI) to observe that the therapy increased activation of brain structures related to emotion and sensing. Amygdala activation differed between those with anxiety and those with mood dysregulation, suggesting that the therapy’s effect was on regions that modulate the amygdala, including prefrontal and insular regions, rather than on the amygdala itself.
Stress is a risk factor for depression and other mental health disorders. Researchers are currently working to clarify how stress leads to depression, anxiety, and post-traumatic stress disorder, and why trauma early in life has lasting consequences.
Two recent studies in mice examined whether just witnessing a stressful event leads to depression-like behaviors. In one, adult female mice watched a male mouse as it was repeatedly attacked by a larger mouse. After ten days of this, the female mice were socially withdrawn, had lost interest in drinking sucrose, and gave up more easily during a physical challenge. They also lost weight and showed higher levels of the stress hormone corticosterone in their blood. The researchers, led by Sergio Iniguez, believe their study clarifies how witnessing traumatic events can lead to stress-induced mood disorders.
In the other study, by Carlos Bolanos-Guzman, adolescent male mice witnessed another mouse being attacked. Both the mice that went through the physical stress of being attacked and the mice that went through the emotional stress of watching the attacks occur showed similar depressive behaviors to the mice in the previous study—social withdrawal, loss of interest in sucrose, decreased food intake and exploration of the environment, and decreased motivation in physical challenges. These behaviors persisted into adulthood. Both groups of mice also had increased levels of corticosterone and reduced expression of a particular protein in the ventral tegmental area, a part of the brain linked to stress response. Bolanos-Guzman suggests that both physical and emotional stress have lifelong consequences in mice.
The studies were presented at a scientific meeting in December.
Many studies have found links between levels of inflammatory molecules in the blood and depression or depressive symptoms. There has been less research about inflammation in the brain and its possible role in depressive illness. Improvements in positron emission topography (PET) scan technology now allow for better brain imaging that can reveal when microglia are activated. (Microglia serve as the main immune responders in the central nervous system.)
A study by researcher Jeffrey Meyer found evidence of microglial activation in several brain regions (including the prefrontal cortex, the anterior cingulate cortex, and the insula) in people in an episode of depression who were not receiving any treatments. Participants with more microglial activation in the anterior cingulate cortex and insula had more severe depression and lower body mass indexes.
Meyer, who presented this research at a scientific meeting in December, called it strong evidence for brain inflammation in depressive episodes, and suggested that treatments that target microglial activation would be promising for depression.
However, at the same meeting, researcher Erica Richards reported that she had not been able to replicate Meyer’s results. Her research, which included depressed participants both on and off medication and non-depressed participants, found that depressed participants did show more inflammation in the two brain regions she targeted, the anterior cingulate and the subgenual cortices, but this difference did not reach statistical significance, particularly when patients taking antidepressants were included in the calculations. Richards hopes that with a greater sample size, the data may show a significant difference in brain inflammation between depressed and non-depressed participants.
Studies have found that inflammatory molecules play a role in depression. A recent study by researcher Yu Sun and colleagues used data from clinical trials of anti-inflammatory drugs to show that these drugs also reduced depressive symptoms. The two drugs, which are administered either by a shot or injection into the skin, each consist of antibodies that target the inflammatory molecule IL-6. Sirukumab is being looked at as a possible treatment for rheumatoid arthritis, while siltuximab is a potential treatment for Castleman’s disease, an illness characterized by enlarged lymph nodes. As part of the clinical trials for these drugs, patients with these illnesses responded to survey questions that assessed symptoms of depression and fatigue.
Among patients who reported that they have at least one depressive symptom most of the time and another symptom at least part of the time, the anti-inflammatory drugs significantly improved depressive symptoms compared to placebo. Even when the patients’ inflammatory illnesses did not respond to the anti-inflammatory treatments, their depressive symptoms did improve (symptoms of fatigue did not). An improvement in depressive symptoms was observed after 6 weeks in patients with Castleman’s disease taking siltuximab, and after 12 weeks in patients with rheumatoid arthritis taking sirukumab.
In the sirukumab study, the level of the inflammatory molecule IL-6 in participants’ blood before the study was linked to the magnitude of improvement in their depressive symptoms during the study. IL-6 is elevated in many patients with unipolar and bipolar depression. It is possible that antibodies that target IL-6 could be used to treat primary depression (in the absence of other inflammatory disorders).
Stress increases the risk of psychiatric illnesses such as major depression and post-traumatic stress disorder. Not everyone who experiences stress goes on to develop these illnesses, though. Researchers are currently trying to find out why, exploring treatments that might increase resilience and prevent mental illnesses.
Animal research is often used to study depression. Mice exposed to certain stressors behave in ways that resemble human depression—like giving up faster when they’re forced to tread water, or withdrawing from activities they once enjoyed, like eating sucrose. In a recent study by researcher Christine Denny and colleagues, mice were injected with either saline or ketamine, a rapid-acting antidepressant, and one week later they were exposed to triggers that typically produce a depressive response. Mice who received the saline injection still got depressed when, for example, they were repeatedly forced to confront a dominant mouse. But mice who received ketamine injections did better, maintaining their motivation and not showing signs of depressive behavior following the stress. The researchers concluded that ketamine may have a protective effect against stress.
Editor’s Note: These results are remarkable because ketamine’s effects are typically short-lived.
Brain-derived neurotrophic factor (BDNF) is a protein that protects neurons and aids with learning and memory. BDNF levels are low in people with depression, and every type of antidepressant treatment increases BDNF, including different types of medications, electro-convulsive therapy, repeated transcranial magnetic stimulation (rTMS), exercise, atypical antipsychotic drugs used to treat bipolar depression, omega-3 fatty acids, and ketamine. New research shows that sleep deprivation, which is sometimes used to rapidly improve depression, also increases BDNF.
A study by researcher Anne Eckert and colleagues found that partial sleep deprivation (preventing sleep only during the second half of one night) increased BDNF levels in the blood the following day. Those participants who responded well to the sleep deprivation were found to have BDNF levels that fluctuated more throughout the day before the sleep deprivation compared to participants who did not respond well to the sleep deprivation, whose BDNF levels were relatively stable.
The research, which was presented at a scientific meeting in 2015, suggests that sleep deprivation in depressed patients increases BDNF, and that such increases are an important function of any antidepressant treatment.
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.