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Polygenic Heterogeneity Across Obsessive-Compulsive Disorder Subgroups Defined by a Comorbid Diagnosis.

ABSTRACT: Among patients with obsessive-compulsive disorder (OCD), 65-85% manifest another psychiatric disorder concomitantly or at some other time point during their life. OCD is highly heritable, as are many of its comorbidities. A possible genetic heterogeneity of OCD in relation to its comorbid conditions, however, has not yet been exhaustively explored. We used a framework of different approaches to study the genetic relationship of OCD with three commonly observed comorbidities, namely major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). First, using publicly available summary statistics from large-scale genome-wide association studies, we compared genetic correlation patterns for OCD, MDD, ADHD, and ASD with 861 somatic and mental health phenotypes. Secondly, we examined how polygenic risk scores (PRS) of eight traits that showed heterogeneous correlation patterns with OCD, MDD, ADHD, and ASD partitioned across comorbid subgroups in OCD using independent unpublished data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The comorbid subgroups comprised of patients with only OCD (N = 366), OCD and MDD (N = 1,052), OCD and ADHD (N = 443), OCD and ASD (N = 388), and OCD with more than 1 comorbidity (N = 429). We found that PRS of all traits but BMI were significantly associated with OCD across all subgroups (neuroticism: p = 1.19 × 10^-32, bipolar disorder: p = 7.51 × 10^-8, anorexia nervosa: p = 3.52 × 10^-20, age at first birth: p = 9.38 × 10^-5, educational attainment: p = 1.56 × 10^-4, OCD: p = 1.87 × 10^-6, insomnia: p = 2.61 × 10^-5, BMI: p = 0.15). For age at first birth, educational attainment, and insomnia PRS estimates significantly differed across comorbid subgroups (p = 2.29 × 10^-4, p = 1.63 × 10^-4, and p = 0.045, respectively). Especially for anorexia nervosa, age at first birth, educational attainment, insomnia, and neuroticism the correlation patterns that emerged from genetic correlation analysis of OCD, MDD, ADHD, and ASD were mirrored in the PRS associations with the respective comorbid OCD groups. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across OCD comorbid subgroups.

SUBMITTER: Strom NI

PROVIDER: S-EPMC8438210 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Introduction: Attention deficit hyperactivity disorder (ADHD) is a common disease in childhood and adolescence. In about 60% of pediatric patients, the symptoms persist into adulthood. Treatment guidelines for adult ADHD patients suggest multimodal therapy consisting of psychostimulants and psychotherapy. Many adult ADHD patients also suffer from psychiatric comorbidities, among others obsessive-compulsive disorder (OCD). The treatment of the comorbidity of ADHD and OCD remains challenging as the literature is sparse. Moreover, the impact of psychostimulants on obsessive-compulsive symptoms is still unclear. Case Presentation: Here, we report on a 33-year-old patient with an OCD who was unable to achieve sufficient remission under long-term guideline-based treatment for OCD. The re-examination of the psychological symptoms revealed the presence of adult ADHD as a comorbid disorder. The patient has already been treated with paroxetine and quetiapine for the OCD. Due to the newly established diagnosis of ADHD, extended-release methylphenidate (ER MPH) was administered in addition to a serotonin reuptake inhibitor. After a dose of 30 mg ER MPH, the patient reported an improvement in both the ADHD and the obsessive-compulsive symptoms. After discharge, the patient reduced ER MPH without consultation with a physician due to subjectively described side effects. The discontinuation of medication led to a renewed increase in ADHD and obsessive-compulsive symptoms. The readjustment to ER MPH in combination with sertraline and quetiapine thereafter led to a significant improvement in the compulsive symptoms again. Conclusion: The present case shows that in ADHD and comorbid obsessive-compulsive disorder, treatment with psychostimulants can improve the obsessive-compulsive symptoms in addition to the ADHD-specific symptoms. To our knowledge, this is only the second case report describing a treatment with ER MPH for an adult patient with OCD and ADHD comorbidity in the literature. Further research, especially randomized controlled trials, is needed to standardize treatment options.

Project description:Background: While the Yale-Brown Obsessive-Compulsive Scale Second Edition (Y-BOCS-II) is the gold-standard for measurement of obsessive-compulsive (OC) symptom severity, its factor structure is still a matter of debate and, most importantly, criterion validity for diagnosis of OC disorder (OCD) has not been tested. This study aimed to clarify factor structure and criterion validity of the Y-BOCS-II. Methods: We first validated and quantified the psychometric properties of a culturally adapted Portuguese translation of the Y-BOCS-II (PY-BOCS-II). The PY-BOCS-II and other psychometric instruments, including the OCD subscale of the Structured Clinical Interview for the DSM-IV, used to define OCD diagnosis, were administered to 187 participants (52 patients with OCD, 18 with other mood and anxiety disorders and 117 healthy subjects). In a subsample of 20 OCD patients and the 18 patients with other diagnoses, PY-BOCS-II was applied by clinicians blinded to diagnosis. Results: PY-BOCS-II had excellent internal consistency (Cronbach's α = 0.96) and very good test-retest reliability (Pearson's r = 0.94). Exploratory factor analysis revealed a two-factor structure with loadings consistent with the Obsessions and Compulsions subscales, and there was good to acceptable convergent and divergent validity. Importantly, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve suggested elevated accuracy in discriminating between patients with OCD and control subjects (AUC = 0.96; 95% confidence interval [CI]: 0.92-0.99), that was retained in comparisons with age, gender and education matched controls (AUC = 0.95; 95% CI: 0.91-0.99), as well as with patients with other mood and anxiety disorders (AUC = 0.93; 95% CI: 0.84-1). Additionally, a cut-off score of 13 had optimal discriminatory ability for the diagnosis of OCD, with sensitivity ranging between 85 and 90%, and specificity between 94 and 97%, respectively when all samples or only the clinical samples were considered. Conclusion: The PY-BOCS-II has excellent psychometric properties to assess the severity of obsessive-compulsive symptoms, reflecting obsessive, and compulsive dimensions, compatible with currently defined subscales. Furthermore, we found that a cut-off of 13 for the Y-BOCS-II total score has good to excellent sensitivity and specificity for the diagnosis of OCD.

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Polygenic Heterogeneity Across Obsessive-Compulsive Disorder Subgroups Defined by a Comorbid Diagnosis.

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