Bipolar Disorder Vulnerability
Perspectives from Pediatric and High-Risk Populations
Jair Soares,Consuelo Walss-Bass,Paolo Brambilla
- 288 pages
- English
- ePUB (mobile friendly)
- Available on iOS & Android
Bipolar Disorder Vulnerability
Perspectives from Pediatric and High-Risk Populations
Jair Soares,Consuelo Walss-Bass,Paolo Brambilla
About This Book
Bipolar Disorder Vulnerability: Perspectives from Pediatric and High-Risk Populations synthesizes our current understanding of high-risk and pediatric populations to aid readers in identifying markers of vulnerability for the development of bipolar disorder, with an ultimate goal of the development of drug targets and other therapies for early diagnosis and treatment. The book provides readers with an understanding of biological and environmental factors influencing disease manifestation that will aid them in defining discrete clinical stages and, importantly, establish an empirical basis for the application of novel therapeutics in a phase of illness during which specific treatments could more effectively alter disease course.
Whereas most of the literature available on the pathophysiological mechanisms of bipolar disorder focuses on chronically ill adult individuals, this represents the only book that specifically examines pediatric and high-risk populations. An estimated 30 to 60 percent of adult bipolar disorder patients have their disease onset during childhood, with early-onset cases representing a particularly severe and genetically loaded form of the illness.
- Highlights diverse translational methodologies, including functional and structural neuroimaging, neuropsychological testing and integrated genomics
- Examines molecular trajectories in youth with bipolar disorder and unaffected youth at high risk for developing bipolar disorder
- Explores the interaction between genomic and environmental influences that shape behavior
Frequently asked questions
Information
The bipolar prodrome
Abstract
Keywords
Introduction
Methods
Study Design: Challenges and Strategies
- ā¢ Family studies: There are several longitudinal studies of offspring of parents with bipolar disorder, which have well-characterized these at-risk offspring in childhood and adolescence, and prospectively followed them to assess new-onset disorders, including bipolar disorder (Birmaher, Axelson, Monk, et al., 2009; Duffy, Alda, Crawford, Milin, & Grof, 2007; Egeland et al., 2003; Hillegers et al., 2005). Because the onset of bipolar disorder is much more prevalent in individuals at familial risk, there are sufficient converters to evaluate clinical characteristics that might precede new-onset disorder. In addition, these individuals are at higher risk of other disorders as well, and have high levels of subsyndromal symptoms, so they also represent a clinically at-risk population that is important to characterize and better understand. There are some limitations to this approach, however. First, we donāt know that the course of the bipolar prodrome is similar in individuals with vs. without a first-degree relative with bipolar disorder, so it is unclear the degree to which these findings are generalizable to individuals without such family risk. Second, the prevalence of syndromal bipolar disorder (bipolar-I/II) in offspring is still fairly low (e.g., 8.4% in BIOS, though not all participants have passed the risk period), so large samples are required to have sufficient new-onset cases to make inference about predictors (Axelson et al., 2015). To handle this limitation, some groups have instead assessed less stringent outcomes, including bipolar spectrum disorder (which includes bipolar disorder, not otherwise specified) and āmood disorderā (which includes unipolar or bipolar depression). Another approach is to identify high-risk samples within the offspring of parents with bipolar disorder, based on the presence of mood, anxiety, and/or mood lability symptoms. Third, there is the important issue of comorbidity in the bipolar parents, and whether differences observed in offspring are related to the family history of bipolar disorder, per se, or a comorbidity. For example, in the Pittsburgh Bipolar Offspring Study, Attention-Deficit/Hyperactivity Disorder (ADHD) was higher in at-risk offspring than community controls. However, after adjusting for confounders (including nonbipolar psychopathology in both biological parents), this difference was no longer significant (Birmaher, Axelson, Monk, et al., 2009). Studies that recruit healthy controls (as opposed to including parents with nonbipolar psychiatric disorders) cannot necessarily conclude that a particular difference in at-risk vs offspring of healthy parents is due to the bipolar disorder (vs higher rates of ADHD, for example). Fourth, another critical issue when carrying out family risk studies is blinding. If the interviewer knows that a parent has bipolar disorder, ratings might be elevated due to expectations of worse outcomes. Most studies discussed here were blinded, except for the Dutch study, which only included offspring of parents with bipolar disorder (Mesman, Nolen, Reichart, Wals, & Hillegers, 2013). Fifth, when using parent report to assess a childās psychiatric symptoms, it is important to take into account the current mood state of the reporting parent, since this can impact symptom ratings (Maoz, Goldstein, Goldstein, et al., 2014). This is especially crucial in family risk studies where, by definition, at least one parent has bipolar disorder, and thus over-reporting of symptomatology could bias parent-report measures of child psychopathology. Sixth, depending on the age range, participants might not have reached the peak period of conversion to bipolar disorder; thus, there is the possibility that some of the nonconverters might still develop the disorder. These issues have been summarized in previous reviews (DelBello & Geller, 2001; Hauser & Correll, 2013; Hunt, Schwarz, Nye, & Frazier, 2016).
- ā¢ Unipolar depression studies: An episode of unipolar depression, particularly with earlier age of onset and psychotic features, sharply increases the risk of new-onset bipolar disorder (Akiskal, Maser, Zeller, et al., 1995; Kovacs, 1996; Strober & Carlson, 1982). Thus investigators have prospectively assessed depressed individuals, to determine symptom predictors of conversion from unipolar depression to bipolar disorder. The strengths of this approach are the fact that it is prospective, and using a select population with conversion rates that allow for adequate cases of new-onset bipolar disorder, at least over a long follow-up (e.g., 19.6% over a mean follow-up period of 17.5 years) (Fiedorowicz et al., 2011). However, there are also some limitations. First, the rate of conversion is still relatively low over shorter periods of follow-up, thus necessitating a longer follow-up period or larger sample for adequate converters. One way that investigators have handled this is to narrow the selection criteria to participants with depression with psychotic features, thus increasing the base rate for developing bipolar disorder; however, this also makes recruitment more difficult. Second, as with the family studies, there is also the possibility that participants who have not passed the peak age of conversion might be misclassified as nonconverting. Third, selection of a sample based on unipolar depression means that the results might be specific to individuals that debut with a major depressive episode, and not necessarily generalize to those who have a different presentation (e.g., cyclothymia or initial mania/hypomania).
- ā¢ Cyclothymia/bipolar disorder-not otherwise specified (BD-NOS) samples: One of the strongest predictors of new-onset bipolar disorder is subthreshold manic episodes (see below for specific findings), and thus several studies have assessed the clinical variables that predict progression from BD-NOS to BD-I/II (Akiskal, Djenderedjian, Rosenthal, & Khani, 1977; Alloy, UroÅ”eviÄ, et al., 2012; Axelson et al., 2011). Significant strengths of this approach are that conversion is high (30%ā50% in ...