Examining the Comorbidity Between Attention Deficit Hyperactivity Disorder and Bipolar I Disorder: A Meta-Analysis of Family Genetic Studies

Harvard University, Cambridge, Massachusetts, United States
American Journal of Psychiatry (Impact Factor: 12.3). 12/2012; 169(12):1256-66. DOI: 10.1176/appi.ajp.2012.12010087
Source: PubMed


The existence of comorbidity between attention deficit hyperactivity disorder (ADHD) and bipolar I disorder has been documented in clinical and epidemiological studies, in studies of children and adults, and in diagnosed ADHD and bipolar I patient samples. Yet questions remain about the validity of diagnosing bipolar I disorder in ADHD youth. The authors aim to clarify these issues by reviewing family genetic studies of ADHD and bipolar I disorder.

The authors applied random-effects meta-analysis to family genetic studies of ADHD and bipolar I disorder. Twenty bipolar proband studies provided 37 estimates of the prevalence of ADHD in 4,301 relatives of bipolar probands and 1,937 relatives of comparison probands. Seven ADHD proband studies provided 12 estimates of the prevalence of bipolar I disorder in 1,877 relatives of ADHD probands and 1,601 relatives of comparison probands.

These studies found a significantly higher prevalence of ADHD among relatives of bipolar probands and a significantly higher prevalence of bipolar I disorder among relatives of ADHD probands. These results could not be accounted for by publication biases, unusual results from any one observation, sample characteristics, or study design features. The authors found no evidence of heterogeneity in the ADHD or bipolar family studies.

The results suggest that ADHD plus bipolar comorbidity cannot be accounted for by misdiagnoses, but additional research is needed to rule out artifactual sources of comorbidity. More research is also needed to determine whether comorbidity of ADHD and bipolar I disorder constitutes a familial subtype distinct from its constituent disorders, which if confirmed would have implications for diagnostic nosology and genetic studies.

Full-text preview

Available from:
  • Source
    • "Family studies can contribute to elucidate the question of a real comorbidity of both diseases : Faraone et al . ( 2012 ) conducted a meta - analysis of family genetic studies of ADHD and bipolar I patients . The authors found a signif - icantly higher prevalence of bipolar I among relatives of ADHD patients , and a significantly higher prevalence of ADHD among relatives of bipolar I patients . Most impor - tantly , the relative risk for bipolar disorder"
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoarousal as indicated by skin conductance and electroencephalography (EEG) has been discussed as a pathogenetic factor in attention-deficit/hyperactivity disorder (ADHD). The aim of this paper was to review these arousal-related pathogenetic concepts and to present the more recently proposed vigilance regulation model of affective disorders and ADHD. The latter builds on methodological advances in classifying short EEG segments into vigilance stages (Vigilance Algorithm Leipzig, VIGALL), indicating different states of global brain function ("brain arousal"). VIGALL allows the objective assessment of vigilance regulation under defined conditions, e.g. how fast vigilance declines to lower vigilance stages associated with drowsiness during 15-20-min EEG recordings under resting conditions with eyes closed. According to the vigilance regulation model, the hyperactivity and sensation seeking observed in overtired children, ADHD and mania may be interpreted as an autoregulatory attempt to create a stimulating environment in order to stabilize vigilance. The unstable regulation of vigilance observed in both mania and ADHD may thus explain the attention deficits, which become especially prominent in monotonous sustained attention tasks. Among the arguments supporting the vigilance regulation model are the facts that destabilizing vigilance (e.g. via sleep deprivation) can trigger or exacerbate symptoms of ADHD or mania, whereas stabilizing vigilance (e.g. via psychostimulants, reducing sleep deficits) alleviates these symptoms. The potential antimanic effects of methylphenidate are presently being studied in an international randomized controlled trial. We propose vigilance regulation as a converging biomarker, which could be useful for identifying treatment responders to psychostimulants and forming pathophysiologically more homogeneous ADHD subgroups for research purposes.
    Full-text · Article · Sep 2014 · ADHD Attention Deficit and Hyperactivity Disorders
  • Source
    • "Dr Andreas Reif ( University Clinic of Würzburg , Germany ) described findings from the PGC cross - disorder GWAS focusing on BPD and ADHD samples . These disorders are comorbid , coheritable ( Faraone et al . , 2012 ) , and may share some similar phenotypes ( e . g . impulsivity ) . No genome - wide significant hits were identified in the previous GWAS of BPD and ADHD from the PGC , although there was an increased burden of BPD risk genes in ADHD samples . In an additional analysis of 5800 BPD cases and 6000 ADHD cases , more genes were concordant "
    [Show abstract] [Hide abstract]
    ABSTRACT: The XXI World Congress of Psychiatric Genetics (WCPG), sponsored by the International Society of Psychiatric Genetics (ISPG), took place in Boston, Massachusetts, on 17-21 October 2013. Approximately 900 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by student travel awardees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported.
    Full-text · Article · Jun 2014 · Psychiatric Genetics
  • Source
    • "A GWAS of major depression and meta-analyses have also demonstrated association with GRM7 [Sullivan et al., 2009; Muglia et al., 2010; Shi et al., 2011; Shyn et al., 2011]. Comorbidity between bipolar I disorder and ADHD has been well documented previously [Faraone et al., 2012]. A Korean study reported association between the GRM7 polymorphism rs37952452 and attention-deficit hyperactivity disorder (ADHD) using the transmission disequilibrium method in trios [Park et al., 2013]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic markers at the GRM7 gene have shown allelic association with bipolar disorder (BP) in several case–control samples including our own sample. In this report, we present results of resequencing the GRM7 gene in 32 bipolar samples and 32 random controls selected from 553 bipolar cases and 547 control samples (UCL1). Novel and potential etiological base pair changes discovered by resequencing were genotyped in the entire UCL case–control sample. We also report on the association between GRM7 and BP in a second sample of 593 patients and 642 controls (UCL2). The three most significantly associated SNPs in the original UCL1 BP GWAS sample were genotyped in the UCL2 sample, of which none were associated. After combining the genotype data for the two samples only two (rs1508724 and rs6769814) of the original three SNP markers remained significantly associated with BP. DNA sequencing revealed mutations in three cases which were absent in control subjects. A 3′-UTR SNP rs56173829 was found to be significantly associated with BP in the whole UCL sample (P = 0.035; OR = 0.482), the rare allele being less common in cases compared to controls. Bioinformatic analyses predicted a change in the centroid secondary structure of RNA and alterations in the miRNA binding sites for the mutated base of rs56173829. We also validated two deletions and a duplication within GRM7 using quantitative-PCR which provides further support for the pre-existing evidence that copy number variants at GRM7 may have a role in the etiology of BP. © 2014 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Published by Wiley Periodicals, Inc.
    Full-text · Article · Jun 2014 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
Show more