What are the perspectives of human brain mapping in the field of bipolar disorder?

Abstract

In the last two decades brain imaging studies,specifically with magnetic resonance imaging(MRI), have tried to elucidate the underlyingneurobiology of bipolar disorder, which is a severeand heritable illness (Salvatore et al., 2007). Thereis evidence that an extensive fronto-limbic circuitryin brain areas, including prefrontal cortex (i.e.anterior cingulate, orbitofrontal and dorsolateralprefrontal cortex), striatum, hippocampus, andamygdala, as well as fronto-temporal and inter-hemispheric connectivity may sustain the pathophy-siology of bipolar disorder (Bellani et al., 2009;Brambilla et al., 2005; Strakowski et al., 2005).However, it is still unclear whether these brain‘features’ represent early markers preceding oraccompanying the onset of the illness as a resultof mal-development. In this special issue ofInternational Review of Psychiatry the most consistentimaging and cognitive findings and latest researchmethods in bipolar disorder are debated by top-notch groups in four main sections. Also, an over-view of the interface of imaging, diagnosis andtreatment are discussed, with particular focuson intermediate endophenotypes. Section one isdenominated ‘The pathophysiology of bipolar dis-order’ and will describe the structural, functionaland metabolic anatomy of the disease. In the secondsection, entitled ‘Cognitive endophenotypes of bipo-lar disorder’ neural systems underlying emotionregulation and neuropsychological deficits in subjectssuffering from this illness will be debated. In the thirdsection, ‘White matter communication in bipolardisorder’, the role of intra- and inter-hemisphericconnectivity and of deep white matter andsubcortical hyperintensities for the pathophysiologyof the disorder will be discussed. Finally, the fourthand last section, entitled ‘Mood stabilizersand imaging studies in bipolar disorder’ is dedicatedto the potential neuroprotective and neurotrophicproperties of lithium and valproate, particularlyfocusing on the brain metabolic effects.In conclusion, neuroimaging and cognitive studieshave greatly contributed to map the neural circuitriesinvolved in the pathophysiology of bipolar disorder.However, most of the research is biased by therecruitment of small and often chronic samples, byheterogeneous techniques and by cross-sectionaldesigns (Joseph et al., 2008; Kempton et al., 2008).In this perspective, future studies should enrol andlongitudinally follow large populations, includinghigh risk subjects, unaffected relatives and paediatricpatients by combing imaging, neuropsychologicaland cognitive investigations. This will be instrumen-tal to disentangle the role of trait versus statemechanisms, the genetic versus environmentaleffects, as well as to further elucidate the contributionof treatment and illness progression on brain overtime (Vieta & Phillips, 2007). Potentially, the detec-tion of developmental imaging and cognitive markersof bipolar disorder will be crucial to developstrategies of early intervention or prevention.References