Increased Asymmetric Perfusion of the Cerebral Cortices and Thalamus Indicates Individuals at Risk for Bipolar Disorder: A Family Cohort Single Photon Emission Computed Tomography Neuroimaging Study

Abstract

Bipolar disorder is a significant mental illness affecting over 4 million people in North America and approximately 46 million worldwide. While the onset of bipolar disorder is typically in late adolescence and early adulthood, the correct diagnosis can be delayed for several years. This delay can result in inappropriate pharmaceutical interventions, loss of career or productivity, suicide, family hardship, and unnecessary expense. Moreover, prolonged untreated or inappropriately treated bipolar disorder may cause damage to the brain. Early diagnosis is a critical need to circumvent the damage, suffering, and expense caused by the current delay. Brain perfusion single photon emission computed tomography (SPECT) neuroimaging reveals visual correlates of brain function. Herein, a family cohort all with bipolar disorder is described and their symptoms correlated with findings on the individual SPECT brain scans. The family consisted of two parents and three children (one female). The scans were interpreted by a panel of experts. Then a post hoc region-of-interest (ROI) analysis was conducted on SPECT data normalized to the cerebellum maximum with comparison to similarly normalized data from a normative sample. These findings support two distinct patterns of SPECT perfusion scan changes that can be found in individuals with bipolar disorder. In addition, these findings indicate that SPECT scan findings may be predictive of individual risk for progressing to symptomatic bipolar disorder. While preliminary, the findings in this cohort support the need for larger, diverse cohort studies of bipolar and control subjects to assess the predictive value of these particular SPECT perfusion findings in bipolar disorder.

Aberrant brain network topology in youth with a familial risk for bipolar disorder: a task‐based fMRI connectome study

“…Youth with a family history of BD often have symptoms of anxiety and mood disorders that may increase their risk for subsequently developing BD. These prodromal symptoms may represent early manifestations of psychopathology that frequently take onset during childhood or adolescence (McLean, Henderson, Pavel, & Cohen, 2022; Singh et al., 2007). The neurobiological characteristics of these youth have been only sparingly described, which may complicate early identification and clinical decision‐making about who benefits from treatment or preventive interventions.…”

“…In prospective follow‐up studies, most relatives do not appear go on to develop BD, so early neurodevelopmental patterns may represent either adaptations or compensatory mechanisms or true risk markers, which may be missed in small sample studies. Multifinality can be partially addressed by studying symptomatic rather than healthy youth at risk for BD (Fischer et al., 2022; McLean et al., 2022). In addition, as image analyses continue to be refined, a network model approach to investigate brain differences in the functional connectome rather than exploratory pair‐wise analyses of functional connectivities in individual brain regions may help (Menon, 2011).…”