Influence of Genes and Environment on Brain Volumes in Twin Pairs Concordant and Discordant for Bipolar Disorder

Abstract

Focusing on genes controlling white matter integrity may be a fruitful strategy in the quest to discover genes implicated in bipolar disorder. Elucidating the mechanism by which lithium attenuates brain matter loss may lead to the development of neuroprotective drugs.

Using structural MRI to identify individuals at genetic risk for bipolar disorders: a 2-cohort, machine learning study

“…There is replicated evidence suggesting that repeated episodes of illness, 8,9 comorbid conditions, 13,14 or exposure to medications [10][11][12] introduce heterogeneity, which may mask/overcome the primary changes indicative of the risk for BD. 16,18,19 The findings emphasize the need to control for clinical heterogeneity, for example by recruiting unaffected participants at high genetic risk for the illness.…”

“…The biomarkers that could be used diagnostically (i.e., the brain changes that reflect the susceptibility for BD) are typically small. [15][16][17] They may be underrepresented in convenience samples, which include patients with long chronic illness, polypharmacy and medical and psychiatric comorbid conditions. 18 In such samples, neuroimaging may primarily detect the consequences of the illness, medication exposure or signatures of comorbid conditions, which may mask or override the diagnostically relevant biomarkers.…”

“…18 In such samples, neuroimaging may primarily detect the consequences of the illness, medication exposure or signatures of comorbid conditions, which may mask or override the diagnostically relevant biomarkers. 8,12,16,18,19 Consequently, the identification of brain changes with diagnostic potential requires research designs that attempt to minimize or completely eliminate the secondary brain changes and thus increase sensitivity for detection of the primary alterations/ biological risk factors. This can be achieved by studying the unaffected offspring of parents with BD, who are at high genetic risk for the illness but do not show any consequences of the illness -a so-called genetic high risk (HR) design.…”

Neuroimaging Data in Bipolar Disorder: An Updated View

“…There are many heterogeneous data (Table 1) revealing a variety of structural alterations in bipolar patients (Dougherty et al, 2004). It must be considered, moreover, that some of these differences may be referred to the effects of medications (Van der Schot, 2009). For instance, chronic lithium treatment may prevent volume loss in treated patients because of its neuroprotective action www.intechopen.com (Manji et al, 2000).…”

“…Furthermore, genetic and/or environmental factors involved in BD may influence some brain abnormalities. In this perspective, decreases in white matter have been associated with the genetic risk of developing BD, whereas important environmental correlations have been found in relation to cortical gray matter volume (Van der Schot, 2009). Brain abnormalities reported by fMRI studies in patients with BD include changes in cortical volumes, cerebral white matter, cortical and prefrontal gray matter.…”