The functional neuroanatomy of bipolar disorder: a consensus model

Abstract

Objectives Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants’ work as well as that of others. Methods Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. Results Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity, prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially amygdala. This developmental failure to establish healthy ventral prefrontal–limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. Conclusions This model provides a potential substrate to guide future investigations and areas needing additional focus are identified.

Neuropsychological and Brain Functional Changes Across the Different Phases of Schizoaffective Disorder

“…However, there is now a consensus that the disorder is broadly characterized by reduced activity in prefrontal and other cortical regions coupled with increased activity in limbic regions (Strakowski et al, 2012). This view is supported by the findings of two meta-analyses (Chen et al, 2011, Kupferschmidt andZakzanis, 2011).…”

“…Using a verbal fluency task, also found failure of de-activation in the posterior cingulate and retrosplenial cortex in euthymic patients, which is in the posterior midline node of the DMN, supporting the concept of a 'trait' DMN dysfunction. There is a consensus that bipolar disorder is associated with other functional imaging abnormalities which have been broadly characterized as overactivity in subcortical structures such as the amygdala, hippocampus and basal ganglia, coupled with reduced activity in prefrontal and some other cortical regions (Green et al, 2007, Savitz and Drevets, 2009, Strakowski et al, 2012, Strakowski et al, 2005. Recent meta-analyses suggest that this pattern is seen both at rest and in studies using task activation (Kupferschmidt and Zakzanis, 2011), although the pattern differs to some extent depending on whether cognitive or emotional tasks (typically facial emotion processing) are used .…”

Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis

“…We performed an immunohistochemical survey of the intact adult mouse brain and determined that CRMP2 is highly expressed in neurons of the hippocampus (e.g., CA1 pyramidal neurons) (Fig. 6A), cerebral cortex, olfactory bulb, and cerebellum (Purkinje neurons), regions postulated to be involved in BPD (31). We verified that, as was seen in BPD hiPSC-derived neurons in vitro, lithium administration to mice increases the inactive form of GSK3β (GSK3β-p-S9) and lowers CRMP2-p-T514 in vivo (Fig.…”

Neurobiological underpinnings of bipolar disorder focusing on findings of diffusion tensor imaging: a systematic review

“…[16][17][18] Changes in brain structure have been widely reported in BD patients. 19 Over the past decade, substantial effort has been made in neuroimaging research to understand the neural system abnormalities that underlie BD, and significant progress has been made in identifying regional brain differences that could contribute to the symptoms of acute episodes. 20 Morphometric studies have demonstrated that patients with BD exhibit enlargement of the third and lateral ventricles; a reduction in the gray matter volumes of the orbital and medial prefrontal cortex, ventral striatum, and mesotemporal cortex; and enlargement of the amygdala.…”