How Illness Progresses In The Recurrent Affective Disorders
This editor (RM Post) in collaboration with Jacqueline Fleming and Flavio Kapczinski published the article “Neurobiological mechanisms of illness progression in the recurrent affective disorders” in the Journal of Psychiatric Research this year. The article built on several themes about the progression of bipolar illness that had been explored in previous research.
These themes include:
- The likely acceleration of repeated episodes as a function of the number of prior episodes (episode sensitization)
- The increased responsivity of the illness to repeated stressors (stress sensitization)
- The increased behavioral reactivity to repeated use of psychomotor stimulants such as cocaine (stimulant-induced behavioral sensitization)
Not only are these observations well documented in the scientific literature, but recent observations also suggest that each type of sensitization can show cross-sensitization to the other two types. That is, individuals exposed to repeated stressors are more likely both to experience affective illness episodes and to adopt comorbid substance abuse. In a similar way, episodes of an affective disorder and stressors may also be associated with the relapse into drug administration in those who have been abstinent.
In addition to these mechanisms of illness progression in the recurrent affective disorders, the new article reviews the literature showing that the number of affective episodes or the duration of the illness appear to be associated with a variety of other clinical and neurobiological variables.
The number of affective episodes a patient experiences is associated with the degree of cognitive dysfunction present in their bipolar illness, and experiencing more than 4 episodes of unipolar or bipolar depression is a risk factor for dementia in late life. A relative lack of response to most treatments is also correlated with the number of prior episodes, and this holds true for response to naturalistic treatment in general. While most of these data are correlational and the direction of causality cannot be ascertained for certain, it is likely that the number of affective episodes and/or their duration could account for and drive difficulties with treatment and with cognitive function.
If this were the case, one would expect to see a variety of neurobiological correlates with the number of prior episodes or duration of illness, and in the article we summarize those that have been found in unipolar and bipolar disorder. Considerable data indicate that cortical volume and degrees of prefrontal cortical dysfunction can vary as a function of number of prior episodes. There is evidence that increased activity of the amygdala and the nucleus accumbens are also related to episodes or duration of illness. In those with unipolar depression, the volume of the hippocampus is decreased with longer duration of illness. Read more
Parental Nurturing Linked to Greater Hippocampal Volume in Young Children
An article published by Medscape reports that in a recent study by Dr. Joan Luby of Washington University School of Medicine in St. Louis, non-depressed preschool children whose parents showed more nurturing behaviors during a mildly stressful task were found to have hippocampal volume almost 10% greater than their peers whose parents showed fewer nurturing behaviors. The hippocampus affects cognitive functioning and emotion regulation.
Unfortunately, parental nurturing did not effect the hippocampal volume of children with early-onset depression.
Dr. Luby and colleagues think their findings could have “profound public health implications and suggest that greater public health emphasis on early parenting could be a very fruitful social investment.”
“The finding that early parenting support, a modifiable psychosocial factor, is directly related to healthy development of a key brain region known to impact cognitive functioning and emotion regulation opens an exciting opportunity to impact the development of children in a powerful and positive fashion”.
Exercise Good for Learning and Memory in Children and the Elderly
Another article in the Telegraph today suggests that aerobic exercise can increase the size of the hippocampus in elderly people and lead to improvements in memory, attention, and ability to multi-task. Children who were more fit were also better at multitasking. Art Kramer of the Beckman Institute for Advanced Science and Technology at the University of Illinois said,
“It is aerobic exercise that is important so by starting off doing just 15 minutes a day and working up to 45 minutes to an hour of continuous working we can see some real improvements in cognition after six months to a year.
“We have been able to do a lot of neuroimaging work alongside our studies in the elderly and show that brain networks and structures also change with exercise.
Schizophrenia v. Bipolar Disorder: Different Risk Factors
Robin Murray gave a plenary presentation at the 65th Annual Scientific Convention of the Society of Biological Psychiatry this year, in which he indicated that the genetic risk for schizophrenia and other major mental disorders may be overestimated. He suggested that even in identical twins there are considerable differences in incidence of major psychiatric illnesses, and sharing an environment could further inflate the appearance of genetic risk.
Evidence of some genetic vulnerability factors, such as neuregulin, disbindin, DISC-1, zinc finger transcription factors, and neurexin, has been replicated. However, these genes appear to contribute only about 1% of the vulnerability to schizophrenia or bipolar illness. Copy number variations (CNVs, extra or missing copies of a gene, which may alter its activity) and gene micro-deletions (in which small bits of DNA are missing) have been found in about 5% of patients with schizophrenia, in some patients with autism and mental disabilities, but not in those with bipolar illness.
Murray emphasized the importance of psychosocial and neuromotor markers of neural development in determining risk of subsequent major psychiatric illness, rather than the relatively weak genetic effects. He cited the work of MacCabe (2009), who collected information from 907,000 individuals in Sweden. Their scholastic achievement at age 15?16 was rated, and hospitalizations for psychosis were recorded from age 17?31. Of the 315,000 followed for the long term, 493 developed schizophrenia and 208 developed bipolar disorder.
Predictors of cognitive and motor development in these two major psychiatric illnesses appeared to differ. In those who went on to develop schizophrenia, there was a slower rate of motor development, receptive language, and overall IQ in adolescence, while in those who went on to develop bipolar disorder, there was a faster rate of motor development, more language facility, and higher IQ in adolescence.
Inflammation and Oxidative Stress in Bipolar Disorder
A number of studies presented at the 4th Biennial Conference of the International Society for Bipolar Disorders conference in Sao Paulo, Brazil in March reported new data relevant to inflammation and oxidative stress. Both inflammation and oxidative stress increase risk of cardiovascular disorders, and patients with inadequately treated mood disorders lose 10 or more years of life expectancy from cardiovascular disorders compared to the general population. Inflammation and oxidative stress may also contribute to the symptoms, evolution, and progression of the mood disorders themselves.
It is possible that these two processes could become new targets for therapeutic intervention in addition to more traditional psychopharmacological drugs that primarily target the neurotransmitters dopamine, norepinephrine, serotonin, and the neurotrophic factor BDNF. Read more
