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

In the last two decades brain imaging studies, specifically with magnetic resonance imaging (MRI), have tried to elucidate the underlying neurobiology of bipolar disorder, which is a severe and heritable illness (Salvatore et al., 2007). There is evidence that an extensive fronto-limbic circuitry in brain areas, including prefrontal cortex (i.e. anterior cingulate, orbitofrontal and dorsolateral prefrontal cortex), striatum, hippocampus, and amygdala, as well as fronto-temporal and inter-hemispheric connectivity may sustain the pathophysiology 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 or accompanying the onset of the illness as a result of mal-development. In this special issue of International Review of Psychiatry the most consistent imaging and cognitive findings and latest research methods in bipolar disorder are debated by top-notch groups in four main sections. Also, an overview of the interface of imaging, diagnosis and treatment are discussed, with particular focus on intermediate endophenotypes. Section one is denominated ‘The pathophysiology of bipolar disorder’ and will describe the structural, functional and metabolic anatomy of the disease. In the second section, entitled ‘Cognitive endophenotypes of bipolar disorder’ neural systems underlying emotion regulation and neuropsychological deficits in subjects suffering from this illness will be debated. In the third section, ‘White matter communication in bipolar disorder’, the role of intra- and inter-hemispheric connectivity and of deep white matter and subcortical hyperintensities for the pathophysiology of the disorder will be discussed. Finally, the fourth and last section, entitled ‘Mood stabilizers and imaging studies in bipolar disorder’ is dedicated to the potential neuroprotective and neurotrophic properties of lithium and valproate, particularly focusing on the brain metabolic effects.

In conclusion, neuroimaging and cognitive studies have greatly contributed to map the neural circuitries involved in the pathophysiology of bipolar disorder. However, most of the research is biased by the recruitment of small and often chronic samples, by heterogeneous techniques and by cross-sectional designs (Joseph et al., 2008; Kempton et al., 2008). In this perspective, future studies should enrol and longitudinally follow large populations, including high risk subjects, unaffected relatives and paediatric patients by combing imaging, neuropsychological and cognitive investigations. This will be instrumental to disentangle the role of trait versus state mechanisms, the genetic versus environmental effects, as well as to further elucidate the contribution of treatment and illness progression on brain over time (Vieta & Phillips, 2007). Potentially, the detection of developmental imaging and cognitive markers of bipolar disorder will be crucial to develop strategies of early intervention or prevention.