Evidence is mounting that certain behaviors by parents can leave marks on their sperm or eggs that are passed on to their offspring in a process called epigenetics. In a recent study by researcher Mathieu Wimmer and colleagues, male rats that were exposed to cocaine for 60 days (the time it takes for sperm to develop fully) had male offspring who showed diminished short- and long-term spatial memory compared to the offspring of male rats that were not exposed to cocaine. Female offspring were not affected in this way.
The spatial tasks the offspring rats completed depended heavily on the hippocampus. Wimmer and colleagues believe that cocaine use in the fathers decreased the amount of a brain chemical called d-serine in the offspring. D-serine plays a role in memory formation and the brain’s ability to form synaptic connections. Injecting the offspring of rats who were exposed to cocaine with d-serine before the spatial memory tasks normalized the rats’ performance.
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.
Inflammation has been linked to both unipolar and bipolar depression. New research shows that anti-inflammatory treatments may reduce bipolar depression, for which few treatments exist.
Researchers led by Jonathan Savitz divided people with bipolar depression into four groups. One group received two placebos, another received minocycline (a drug with neuroprotective and immune-modulating properties) plus a placebo, the third received aspirin plus a placebo, and the final group received both minocycline and aspirin. Of the 64 participants, those who took both minocycline and aspirin were most likely to respond to treatment and to enter remission. In people with body mass indexes (BMIs) above the median of 30, a sign of greater inflammation, 100% of those who received both anti-inflammatory drugs responded to treatment, compared to 36% of those who received aspirin alone, 33% of those who received minocycline alone, and 25% of those who received two placebos.
Dosages of the drugs were 100mg twice a day for minocycline and 81mg twice a day for aspirin. Savitz and colleagues believe that aspirin and minocycline must work particularly well together, and are modifying their study to more directly compare use of the two anti-inflammatory drugs together to the absence of anti-inflammatory treatments.
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.
People with post-traumatic stress disorder (PTSD) often experience fearful memories of the trauma they witnessed. Researchers are working to determine the neurobiological basis for these persistent fear memories in order to better treat PTSD. Current treatments mainly target the central nervous system. Because many people with PTSD have elevated levels of pro-inflammatory immune molecules in their blood, there has been a recent push to determine whether targeting that inflammation may be another way of treating PTSD.
A recent study by researchers Matthew Young and Leonard Howell used an animal model to learn more about the link between trauma, inflammation, and fear memories. The researchers exposed mice to a trauma that produced both a persistent fear response and an increase in inflammatory molecules in the blood. Some of the mice were also given antibodies to neutralize the inflammatory immune response. When the mice were exposed to a cue meant to remind them of the trauma, levels of the inflammatory molecule IL-6 spiked again. When the mice were given antibodies to neutralize IL-6 just before being exposed to the cue, they produced less of a fear reaction.
The researchers, who presented their work at a scientific meeting in December, concluded that traumatic experiences produce not only persistent fearful memories, but also an immune reaction. They believe that the spike in IL-6 following trauma plays a role in the persistence of those memories, and that elevated IL-6 in the blood may explain symptoms of PTSD and other disorders that involve fear learning (such as phobias).
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).
Many psychiatric illnesses, including bipolar disorder, schizophrenia, autism, attention deficit hyperactivity disorder (ADHD), and anxiety disorders may stem from abnormalities in brain development that begin before birth. Researchers are trying to determine whether dietary supplements taken by pregnant mothers or infants can reduce the risk of such illnesses. At a recent scientific meeting, researcher Randal Ross and colleagues reported that compared to placebo, choline supplements reduced problems with a brain process called sensory gating in one-month-old infants and also improved the children’s attention span and social skills at age 3.
Sensory gating is the process by which the brain filters out unimportant information, to avoid flooding higher cortical centers with irrelevant stimuli. Deficits in the way the brain inhibits response to this type of irrelevant information are associated with mental illnesses such as schizophrenia.
In Ross’s study, healthy pregnant mothers received either a placebo or 6300 mg of choline, a nutrient found in liver, egg yolks, and meat. After delivery, the infants also received 700 mg of supplemental choline per day. In children who carried CHRNA7, a risk gene for schizophrenia discovered by Ross’s colleague Robert Freedman, choline reversed the associated risk of sensory gating problems and normalized their behavior at age 3.