Prevention of Pediatric Bipolar Disorder

Abstract

Bipolar disorder (BD) is a prevalent condition in the United States that typically begins before the age of 18 years and is being increasingly recognized in children and adolescents. Despite great efforts in discovering more effective treatments for BD, it remains a difficult-to-treat condition with high morbidity and mortality. Therefore, it appears prudent to focus energies into developing interventions designed to prevent individuals from ever fully developing BD. Such interventions early in the development of the illness might prevent inappropriate interventions that may worsen or hasten development of BD, delay the onset of first manic episode, and/or prevent development of full BD. Studies of populations at high-risk for BD development have indicated that children with strong family histories of BD, who are themselves experiencing symptoms of attention-deficit/hyperactive disorder (ADHD) and/or depression or have early mood dysregulation, may be experiencing prodromal states of BD. Understanding the neurobiological and genetic underpinnings that create risk for BD development would help with more accurate identification of this prodromal population, which could then lead to suitable preventative interventions. Such interventions could be pharmacologic or psychosocial in nature. Reductions in stress and increases in coping abilities through psychosocial interventions could decrease the chance of a future manic episode. Similarly, psychotropic medications may decrease negative sequelae of stress and have potential for neuroprotective and neurogenic effects that may contribute to prevention of fully expressed BD. Further research into the biologic and environmental mechanisms of BD development as well as controlled early intervention studies are needed to ameliorate this significant public health problem.

Prevention of bipolar disorder in at-risk children: Theoretical assumptions and empirical foundations

“…Neurovegetative symptoms, including changes in sleep, appetite, and energy, associated with BD are hypothesized to result from the effects of dysregulated anterior limbic network activity on hypothalamic nuclei (Strakowski, Delbello, & Adler, 2005). This model of BD development is supported by neuroimaging studies in pediatric BD, which find abnormalities in subcortical-limbic brain regions, especially in the amygdala and basal ganglia (Caetano et al, 2005;Chang et al, 2006;Karchemskiy et al, under review). Whereas studies in adults with BD have reported increased, decreased, or unchanged amygdalar volume, studies in pediatric BD have been more consistent in finding relatively decreased amygdalar volume .…”

“…Therefore, future use of genetic or biological markers will be dependent on understanding the relative degree of contribution from many different biological risk processes. Based on prior research, these may include amygdalar size, prefrontal activation in response to affective stress, and the short-allele of the 5-HTTLPR gene (Chang, Howe, Gallelli, & Miklowitz, 2006). Understanding the cumulative effects and interactions among different neuropathophsiological factors may help us to tailor preventative interventions.…”

“…In turn, poor emotional self-regulation may be associated with increased cycling and greater resistance to pharmacologic interventions. Thus, preventive interventions (i.e., those administered before the first fully syndromal manic episode) that alleviate early symptoms, enhance the ability to cope with dependent and independent stressors, and restore healthy prefrontal neural circuitry should reduce the likelihood of adverse outcomes of the disorder (Chang et al, 2006). With these assumptions, the researcher or clinician planning interventions could intervene at the level of biological markers (e.g., brain-derived neurotrophic growth factor), environmental stressors (e.g., aversive family interactions), or subsyndromal mood or ADHD symptoms.…”

“…For example, certain abnormalities in the limbic system -such as altered amygdalar structure and functionality -could exist early in childhood in at-risk individuals, whether inborn or due to excessive neuronal pruning/apoptosis during childhood and adolescence (Blumberg et al, 2004;Chang et al, 2006;Karchemskiy et al, under review). Further disruptions in the network, particularly in prefrontal regions, may develop with continuing mood episodes, stress, and or exogenous substances such as alcohol.…”

correlates of high expressed emotion attitudes among parents of bipolar adolescents

“…Perhaps the presence of comorbid ADHD in boys led to psychiatric evaluation and a bipolar diagnosis at a younger age. Chang, Howe, Gallelli, & Miklowitz (2006) hypothesized that, among children with a family history of bipolar disorder, ADHD is the first prodromal sign of a developing bipolar illness. Alternatively, early psychostimulant use for ADHD may elicit manic symptoms in children who are genetically at risk for bipolar disorder (Reichart & Nolen, 2004).…”