A substantial and bi-directional overlap has been documented between attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) in adults (Sachs et al. 2000) and children (Biederman et al. 2003). In adults, BPD comorbid with ADHD has an early age of onset in childhood and adolescence (Sachs et al. 2000). Family studies suggested that BPD comorbid with ADHD might be an early onset, familially distinct subtype of BPD (Faraone et al. 2003), given that co-segregation between BPD and ADHD has been demonstrated.
Although ADHD and bipolar disorder co-occur frequently and represent a particularly morbid clinical form of both disorders (Biederman et al. 2005) neuroimaging research addressing this co-morbidity is scarce, and no studies have used measures of cortical thickness. In a previous volumetric MRI study of the current sample we found that BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, and that this pattern was also found in comorbid subjects with ADHD+BPD (Biederman et al. 2008). Likewise, ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex, and less cerebellar gray matter, as was comorbid ADHD+BPD (Biederman et al. 2008). These results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. Yet, whether these results will extend to cortical thickness alterations remains unknown.
Given the architectonic nature of cortical and subcortical connections with respect to cortical lamination, cortical thickness could be an indicator of integrity of cytoarchitecture in the cortex and thus an indirect assessment of cortical connectivity (Makris et al. 2006). Recent neuroimaging studies of cortical thickness in ADHD, including our own, have shown consistent abnormalities in prefrontal and parietal regions associated with corticostriatal, attention and executive neural networks (Sowell et al. 2003; Makris et al. 2007; Shaw et al. 2007; Almeida et al. 2010; Batty et al. 2010). In contrast, in BPD, cortical thinning was shown in left rostral paracingulate and right dorsal paracingulate regions in one study (Fornito et al. 2008), whereas other studies of cortical thickness have found BPD-related thinning in left dorsal-anterior and posterior cingulate regions, left occipital region, left precentral area, right medial frontal, frontopolar and frontoorbital cortex (FOC), right postcentral and angular regions, right lateral occipital areas as well as right and left middle frontal areas (Lyoo et al. 2006; Fornito et al. 2008). To date, none of these studies evaluated individuals with combined ADHD+BPD.
The main aim of this study was to identify a network of MRI measures of cortical thickness in adults with ADHD comorbid with bipolar disorder (ADHD+BPD), and the independent contribution of each disorder to this network of alterations. Based on the existing, limited neuroimaging literature on comorbidity, we expected that each contributing disorder would be associated with disorder specific findings. Specifically, ADHD will be associated with abnormalities in the supervisory networks involved in generalized control of multiple cognitive functions involved in attentional and executive processing (e.g., prefrontal, inferior parietal lobule and anterior cingulate cortices (Strange et al. 2001; Seidman 2006; Burgess et al. 2007)). We also expected that BPD will be associated with abnormalities in the limbic and paralimbic cortices involved in emotion processing including anterior cingulate, and anterior insula, as well as the ventral PFC regions including FOC. To the best of our knowledge, this represents the first examination of cortical thickness measurements in adults with ADHD and BPD attending to the issue of the comorbidity.