Brain Imaging Finds Abnormalities that Appear Over the Course of Childhood-Onset Bipolar Illness
There is considerable evidence that children with bipolar disorder have smaller amygdalas, and the amygdala also appears to be hyper-reactive when these children perform facial emotion recognition tasks. A symposium on longitudinal imaging studies in pediatric bipolar disorder was held at the 2012 meeting of the American Academy of Child and Adolescent Psychiatry to shed light on other brain abnormalities in these children.
Researcher Nancy Aldeman reported that there is some evidence children with bipolar disorder have decreased gray matter volume in parts of the brain including the subgenual cingulate gyrus, the orbital frontal cortex, and the superior temporal gyrus, as well as the left dorsolateral prefrontal cortex and amygdala. At the same time there is evidence of increased size of the basal ganglia. These abnormalities do not appear to precede the onset of the illness.
Some changes occur over the course of the illness. The basal ganglia seem to increase in volume in patients with bipolar disorder, but decrease in volume in those with severe mood dysregulation and comorbid ADHD. Moreover, parietal cortex and precuneus cortex volumes appeared to increase in children with bipolar disorder while decreasing or staying the same in normal volunteer controls.
A meta-analysis of brain imaging studies indicated that in general, the size of the amygdala appears to increase from childhood to adulthood in bipolar patients, starting out smaller than that of similarly-aged normal volunteers, but becoming larger than that of adult normal volunteers as the patients age into adulthood.
Lithium treatment increases gray matter volume in a variety of cortical areas and in the hippocampus in multiple studies. In contrast, treatment with valproate for 6 weeks appears to decrease hippocampal volume.
The Impact of Obesity on Brain and Behavior
In an abstract presented at the 5th Biennial Conference of the International Society for Bipolar Disorders, K. Sim and colleagues discussed the impact of increased body mass index on the integrity of white matter in the brain during a first episode of mania. The researchers found significant abnormalities in white matter integrity in the temporal pole and occipital brain regions in overweight and obese patients compared to patients of normal weight. These data highlight the need to clarify the neural mechanisms that link obesity and poorer functional outcomes in bipolar disorder.
Other investigators have reported that bipolar patients with obesity have a less robust response to naturalistic treatment compared to those of normal weight. At least one study suggested that patients with overweight and obesity experience more cognitive difficulties.
Editor’s Note: The pathophysiological mechanisms involved in the relationship between weight and brain function are not yet clear, although one possibility is that in obese patients, some fat cells in the abdominal area become too big to survive and are scavenged by other cytokine-producing cells. These inflammatory cytokines are then able to cross the blood-brain barrier, enter the brain, and affect neuronal functioning. Whether a mechanism like this is at play in relation to these particular findings remains for further investigation.
Nonetheless, these data suggest the importance of good diet, exercise, and other means of maintaining a good body weight in order to attempt to avoid some of the adverse associations of obesity with deficits in cognition, white matter integrity, and treatment outcome.
Diet, Depression, Inflammation and the Brain
We’ve been posting recently about diet and about treatments that are weight-neutral. There is evidence that diet, inflammation and depression are all linked. Epidemiological studies by Joe Hiblen have shown that in countries whose populations eat more fish and thus have high levels of omega-3 fatty acids in their diet, there is lower incidence of depression, suicide, and cardiovascular disease such as heart attacks and strokes. This may be because the major omega-3 fatty acids, EPA and DHA, are anti-inflammatory, and inflammation has been linked to depression. EPA inhibits the enzymes phospholipase A2 and cyclo-oxygenase-2 (COX-2), and their subsequent inflammatory effects on cytokines. DHA inhibits the pro-inflammatory cytokine IL6.
Researcher John Davis recently reviewed relevant literature and found that diets high in anti-inflammatory omega-3 fatty acids are associated with lower incidence of depression, cardiovascular disease, and markers of inflammatory processes. Conversely, diets high in fat and in inflammatory omega-6 fatty acids are associated with obesity, depression, and cardiovascular disease.
Various studies have shown the links between inflammation and depression. For example, when patients are given alpha-interferon to treat viral hepatitis, there is a subsequent increase in inflammatory cytokines IL-1 and IL-6, and depression often follows. Also, depressed patients have an increased ratio of pro-inflammatory to anti-inflammatory cytokines in their blood.
Another sign of a link between bipolar illness and inflammation can be seen in biochemical analysis of brain specimens obtained at autopsy. Researcher Rapaka Rao in the laboratory of Stanley Rapoport at the National Institute on Aging at the National Institutes of Health in Bethesda, Maryland, has reported that increased markers of neuronal inflammation and excitotoxicity were found in the brains of people who had had bipolar disorder. Phospholipase A2 and COX-2 were significantly elevated in the brains of those with bipolar illness and those with schizophrenia compared with controls. Pro-inflammatory interleukin I was also significantly increased in the brains of those who had had either illness. Read more
