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 After ten days of this, the female mice were socially withdrawn, had lost interest in drinking sucrose, and gave up more easily during a physical challenge.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.
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
The hormone oxytocin, best known for creating feelings of love and bonding, may help treat post-traumatic stress disorder, since it also reduces anxiety. A study by Saskia B.J. Koch and colleagues that will soon be published in the journal Neuropsychopharmacology reports that a single intranasal administration of oxytocin (at a dose of 40 IU) reduced anxiety and nervousness more than did placebo among police officers with PTSD.
Oxytocin also improved abnormalities in connectivity of the amygdala. Male participants with PTSD showed reduced connectivity between the right centromedial amygdala and the left ventromedial prefrontal cortex compared to other male participants who had also experienced trauma but did not have PTSD. This deficit was corrected in the men with PTSD after they received a dose of oxytocin. Female participants with PTSD showed greater connectivity between the right basolateral amygdala and the bilateral dorsal anterior cingulate cortex than female participants who had experienced trauma but did not have PTSD. This was also restored to normal following a dose of oxytocin.
These findings suggest that oxytocin can not only reduce subjective feelings of anxiety in people with PTSD, but may also normalize the way fear is expressed in the amygdala.
At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Charles Popper reviewed the literature to date about broad-spectrum micro-nutrient treatments for psychiatric disorders in young people, concluding that these formulations of vitamins and minerals can reduce symptoms of aggressive and disordered conduct, attention deficit hyperactivity disorder, mood disorders, anxiety, and stress. Four randomized controlled trials showed that micronutrient formulas reduced violence and major misconduct in children.
Popper warned that while these micronutrients can be helpful in treating children who have never been prescribed psychiatric medication, they can interact dangerously with psychiatric medications in children who do take them.
At the same meeting, researcher Bonnie Kaplan reported that six randomized controlled trials of broad-spectrum micro-nutrients and B-complex vitamins in adults with and without psychiatric disorders showed that both of the formulas reduced anxiety and stress following natural disasters (which are associated with the development of post-traumatic stress disorder (PTSD)).
Exercise isn’t just good for the body—new research suggests it can improve cognition and normalize brain activity.
At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Benjamin I. Goldstein reported that 20 minutes of vigorous exercise on a bike improved cognition and decreased hyperactivity in the medial prefrontal cortex in adolescents with and without bipolar disorder.
At the same meeting, researcher Danella M. Hafeman reported that offspring of parents with bipolar disorder who exercised more had lower levels of anxiety.
A plenary address by James J. Hudziak also suggested that exercise, practicing music, and mindfulness training all lead to improvements in brain function and should be an integral part of treatment for children at high risk for bipolar disorder and could be beneficial for all children.
Editor’s Note: Recognizing and responding to mood symptoms is key to the prevention and treatment of bipolar disorder in children and adolescents at high risk for the illness. For these young people, exercise, a nutritious diet, good sleep habits, and family psychoeducation about bipolar disorder symptoms may be a good place to start. Joining our Child Network may also be helpful.
At the 2015 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Jeffrey R. Strawn reported that among children at high risk for bipolar disorder (because of a family history of the disorder) who are prescribed antidepressants for depression and anxiety, adverse reactions are common. These reactions include irritability, aggression, impulsivity, and hyperactivity, and often lead to discontinuation of the antidepressant treatment.
Younger patients at risk for bipolar disorder were more likely to have an adverse reaction to antidepressants. Risk of an adverse reaction decreased 27% with each year of age.
A new longitudinal study of 391 youth at risk for bipolar disorder revealed some predictors of the disorder. The study by Danella M. Hafeman and colleagues was presented at the 2015 meeting of the Society of Biological Psychiatry. The participants were aged 6–18 and each had a parent with bipolar disorder. Over the course of the study, 40 developed an illness on the bipolar spectrum, including 21 who developed bipolar I or II. The participants were assessed for various descriptive characteristics and those who developed bipolar disorder were compared to those who developed major depressive disorder.
The most important predictors of bipolar disorder were parental assessment of internalizing symptoms of anxiety or depression, self-assessment of mood changeability, and self-assessment of hostility. A diagnosis of bipolar disorder not otherwise specified (BP-NOS) was the only predictor of a later diagnosis of bipolar I or II.
Editors Note: These data resemble findings from a 2015 study by David Axelson and colleagues in the American Journal of Psychiatry that used the same cohort of participants. The Axelson study indicated that a categorical diagnosis of a major psychiatric disorder occurred in 74% of the offspring of a bipolar parent compared to about 50% in a control group from the community. Depression, anxiety, attention deficit hyperactivity disorder (ADHD), and oppositional disorders were even more common than bipolar disorder in the at-risk population.
The presence of a major psychiatric diagnosis in about three-quarters of the offspring of a parent with bipolar disorder suggests the importance of early vigilance. One way to track symptoms of depression, anxiety, ADHD, oppositional behavior, and bipolar disorder is to join the Child Network, a secure online platform for rating children’s moods, medications, and side effects. These weekly ratings can be collected longitudinally and printed out to help parents and clinicians assess mood difficulties in their children.
Studies of primates suggest that the amygdala plays an important role in the development of anxiety disorders. Researcher Ned Kalin suggested at the 2015 meeting of the Society of Biological Psychiatry that the pathology of anxiety begins early in life. When a child with anxiety faces uncertainty, the brain increases activity in the amygdala, the insula, and the prefrontal cortex. Children with an anxious temperament, who are sensitive to new social experiences, are at almost sevenfold risk of developing a social anxiety disorder, and later experiencing depression or substance abuse.
A study by Patrick H. Roseboom and colleagues presented at the meeting was based on the finding that corticotropin-releasing hormone (CRH) plays a role in stress and is found in the central nucleus of the amygdala (as well as in the hypothalamus). The researchers used viral vectors to increase CRH in the central nucleus of the amygdala in young rhesus monkeys, hoping to determine what impact increased CRH has on a young brain. Rhesus monkeys and humans share similar genetic and neural structures that allow for complex social and emotional functioning.
Roseboom and colleagues compared the temperaments of five monkeys who received injections increasing the CRH in their amygdala region to five monkeys who received control injections. As expected, the monkeys with increased CRH showed increases in anxious temperament. Brain scans also revealed increases in metabolism not only in the central nucleus of the amygdala, but also in other parts of the brain that have been linked to anxiety, including the orbitofrontal cortex, the hippocampus, and the brainstem, in the affected monkeys. The degree of increase in amygdala metabolism was directly proportional to the increase in anxious temperament in the monkeys, further linking CRH’s effects in the amygdala to anxiety.
Adolescence can be a time of vulnerability to illness. Anxiety disorders increase during this period, and three-quarters of adults with anxiety disorders trace the illness back to their childhood or adolescence. The most common treatments for anxiety disorder are based on the idea of fear extinction. A certain stimulus, like a social situation or seeing a spider, provokes a fear reaction in the brain. Through gradually increasing exposure to the stimulus and extinction training, the person becomes desensitized to the stimulus. New research on rodents presented by Francis S. Lee at the 2015 meeting of the Society for Biological Psychiatry suggests that the extinction process is diminished during adolescence.
At specific stages of maturation, neural circuits related to particular abilities can become flexible. Brain and behavior become sensitive to and are increasingly shaped by experience. Studies of rodents and humans have shown that adolescence is a time when the neural circuitry for fear extinction is in flux. In mice, this period falls around their 29th day of life. Lee reported that around this time, the mice begin to exhibit resistance to extinction of fear learning.
In adolescent rodents, there is a surge of contextual fear learning and retrieval that is mediated by hyper-connectivity of the ventral hippocampus and the amygdala to the prelimbic part of the prefrontal cortex. In contrast, the pathway from the amygdala to the infralimbic cortex mediates the extinction of this type of learning. Because the prelimbic pathway for fear learning is overactive, the infralimbic pathway for extinction learning is less effective.
Adolescent mice temporarily lose their ability to retrieve memories related to cue-dependent (as opposed to context-dependent) fear learning. Remarkably, when these animals proceed into adulthood, the fear learning associated with cues returns and becomes accessible again.
This could help explain how teenagers can lose fear conditioning to cues (for example, speeding through a red light) they learned in childhood. The fear is forgotten (or becomes inaccessible) in adolescence, but then what had been learned is again “remembered” (retrieved) in adulthood. Read more