Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder

Abstract

The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self‐reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource. We conducted genome‐wide association studies of manic symptom quantitative traits and symptom subgroups, derived from the MDQ items (N = 11,568–19,859). We calculated genetic correlations with bipolar disorder and other psychiatric and behavioral traits. The MDQ screener showed low positive predictive value (0.29) for self‐reported bipolar disorder. Neither concurrent nor lifetime manic symptoms were genetically correlated with bipolar disorder. Lifetime manic symptoms had a highest genetic correlation (rg = 1.0) with posttraumatic stress disorder although this was not confirmed by within‐cohort phenotypic correlations (rp = 0.41). Other significant genetic correlations included attention deficit hyperactivity disorder (rg = 0.69), insomnia (rg = 0.55), and major depressive disorder (rg = 0.42). Our study adds to existing literature questioning the MDQ's validity and suggests it may capture symptoms of general distress or psychopathology, rather than hypomania/mania specifically, in at‐risk populations.

Strong Genetic Overlaps Between Dimensional and Categorical Models of Bipolar Disorders in a Family Sample

“…The three-factor model performed slightly better in this sample. These findings align with similar three-factor models observed in Korean (Jon et al, 2009), Chinese (Yang et al, 2011), Hong Kong (Chung et al, 2009), and UK (Mundy et al, 2023) populations, suggesting a cross-cultural consistency in the underlying dimensions of the MDQ. While specific dimension labels may differ slightly, the overall three-factor model ( Figure 3 ) seems robust, consistent with core dimensions that capture typical constructs of mania.…”

“…Previous MDQ studies have shown that either a two factor (Carta et al, 2014; Chung et al, 2008; Ouali et al, 2020; Sanchez-Moreno et al, 2008) or three factor (Chung et al, 2009; Jon et al, 2009; Massidda et al, 2016; Mundy et al, 2023; Yang et al, 2011) best fit the data structure of the MDQ. We put this to the test by performing a PCA with varimax rotation on both a two-factor and a three-factor model, comparing the results to a PCA without varimax rotation.…”

“…To our knowledge only two previous studies have examined the relationship between dimensional and categorical models of BD. Bruce et al (2019) found that a quantitative measure of bipolar symptoms was significantly heritable and concluded that “bipolarity trait assessment may be used to supplement the diagnosis of BD in future genetic studies and could be especially useful for capturing subclinical genetic contributions to a BD phenotype.” Those results largely agree with the present study, even though we employed a different measure of “bipolarity.” Recently, Mundy et al (2023) conducted a genome-wide association study of MDQ scores on a sample of the UK population. The purpose of their study was to determine the validity of the MDQ as a screening tool for BD in at-risk populations.…”

Screening, Genetic Variants, and Bipolar Disorders: Can Useful Hypotheses Arise from the Sum of Partial Failures?

“…New evidence has recently been added to this controversy, favoring the poor validity of the MDQ since, according to the authors, the MDQ score does not correlate with a pattern that is closely linked to BD, such as genetic risk or the presence of genetic variants associated with BD. On the contrary, MDQ positivity was found to have a higher genetic correlation with post-traumatic stress disorder, attention deficit hyperactivity disorder, insomnia, and major depressive disorder [ 31 ]. The authors suggest that MDQ may capture symptoms of general distress or psychopathology rather than hypomania/mania, specifically in at-risk populations [ 31 ].…”

Does the Response to a Stressful Condition in Older Adults with Life Rhythm Dysregulations Provide Evidence of the Existence of the “Dysregulation of Mood, Energy, and Social Rhythms Syndrome”?

“…Using the MDQ, a survey in the United States found a lifetime prevalence of screening positivity of just under 4% [ 11 ]); the positivity is 4.3% in adults in South Korea overall [ 12 ]; in Italy, it was 3% [ 13 ]; and in France, it was 3.6% [ 13 ]. The MDQ has provided links to a disruption of rhythms; particularly, a notable correlation has been observed with sleep dysregulation, which is the primary element taken into consideration in the regulation of life rhythms [ 14 ].…”