Comorbid Migraine in Major Depressive Disorder Suggests a Subgroup Related to Bipolar Disorder

Aims: Previous small-scale studies suggest presence of migraine in major depressive disorder (MDD) is associated with specific clinical characteristics that may overlap with those of bipolar disorder. We aimed to compare a broad range of characteristics in participants who have MDD with and without migraine, and to explore possible similarities between those characteristics associated with the presence of migraine in MDD and those in bipolar disorder in a large UK sample. Methods: Lifetime and episodic clinical characteristics and affective temperaments in DSM-IV MDD with (n=134) and without (n=218) migraine were compared. Characteristics associated with the presence of migraine were then compared with a sample of participants with DSM-IV bipolar disorder (n=407). All participants were recruited into the Bipolar Disorder Research Network (www.bdrn.org). Results: The presence of migraine in MDD was associated with female gender (76.9% vs 56.9%, p<0.001), younger age of onset (23 vs 27 years, p=0.002), history of attempted suicide (38.3% vs 22.7%, p=0.002), and more panic/agoraphobia symptomatology (6 vs 4, p<0.001). Female gender (OR=2.44, p=0.006) and younger age of onset (OR=0.97, p=0.013) remained significant in a multivariate model. These clinical characteristics were not significantly different to those of our participants with bipolar disorder. Conclusions: The presence of migraine in MDD delineates a subgroup of individuals with a more severe illness course. The clinical presentation of this subgroup more closely resembles that of bipolar disorder than that of MDD without migraine. The presence of migraine in major depression may be a marker of a specific subgroup that could be useful in future research.

Polygenic Interactions with Environmental Adversity in the Aetiology of Major Depressive Disorder

Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD. The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them. PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples. CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.