Obsessive–compulsive disorder, which genes? Which functions? Which pathways? An integrated holistic view regarding OCD and its complex genetic etiology

Bozorgmehr, Ali; Ghadirivasfi, Mohammad; Ananloo, Esmaeil Shahsavand

doi:10.1080/01677063.2017.1336236

Cited by 26 publications

(13 citation statements)

References 39 publications

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“…Compulsions are neutral habits that have been linked to reduced fear and thereby strengthened. 30 (C) Neurobiological factors: Hyperactivity in frontalsubcortical thalamic pathways is implicated in the pathogenesis of OCD, according to data from imaging, pharmacological, and behavioral research (Figure 2). 31 Based on this hypothesis, hyperactivity in these pathways causes excessive activity in the frontal-subcortical networks, resulting in the behavioral dysfunction seen in OCD.…”

Section: Etiology Of Ocdmentioning

confidence: 99%

Treatment Approaches Based on Neuroscientific Data in Patients With Obsessive-Compulsive Disorder

Asl

Asgari

Bakhti

2021

Int Clin Neurosci J

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Background: Obsessive-compulsive disorder (OCD) is a severe psychological disorder that can be very disabling. Recent increasing neuroscientific data about OCD has provided important evidence that has started to change our knowledge about treatment. This paper offers an applied perspective of neuroscience on diagnosis and treatment preparation for people with OCD disease. The main aim is to enhance clinician-researcher communication to promote the conversion of developments in neuroscience research into better treatment for patients with OCD. Methods: A PubMed search was performed using the keywords "obsessive-compulsive disorder", "neuroimaging methods", "neuroscience", and "neurological treatment". The search provided sufficient articles published in peer-reviewed journals from 1995 to 2021. The data were obtained from these various sources and were included in this review. Results: The advancement of neurotherapeutic techniques targeting the cortico-striatal-thalamo-cortical (CSTC) circuit is the subject of a circuit dysregulation system. Also, according to neuroimaging studies, reductions in D2 receptors (about -18%), GABAA receptors (-15%), and cingulate 5-HT1A receptors (-18%) in patients with OCD were reported compared with healthy controls. Conclusion: The result suggests that DA, 5-HT, and GABA have considerable roles in anxiety- and compulsion-related disorders such as OCD. For patients with OCD, these core neuroscience themes collectively guide formulation and clinical preparation.

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Section: Etiology Of Ocdmentioning

confidence: 99%

Treatment Approaches Based on Neuroscientific Data in Patients With Obsessive-Compulsive Disorder

Asl

Asgari

Bakhti

2021

Int Clin Neurosci J

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“…TS, OCD, and ADHD are also highly heritable conditions [53][54][55][56][57][58] . Despite evidence for a substantial genetic contribution to disease risk, the identification and replication of genetic variants associated with these related conditions has been challenging.…”

Section: Genetic Riskmentioning

confidence: 99%

What does immunology have to do with brain development and neuropsychiatric disorders?

Leckman¹,

Alvarenga²,

Ravagnani³

et al. 2019

Rev. Med. (São Paulo)

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Introduction: Neural development is an enormously complex and dynamic process. From very early in brain development ‘immune cells’ play a key role in a number of processes including the formation and refinement of neural circuits, as well as sexual differentiation. There is a growing body of evidence that the immune system also plays an important role in the pathobiology of several neurodevelopmental and neuropsychiatric disorders. Objective: The goal of this article is to review the currently available data concerning the role of the ‘immune system’ in normal brain development, as well as its role in the pathobiology of neurodevelopmental and neuropsychiatric disorders. Methodology: We conducted a traditional literature search using PubMed and recent special issues of journals to locate relevant review articles. Results: The cellular and molecular processes that make up our ‘immune system’ are crucial to normal brain development and the formation and maintenance of neural circuits. It is also increasingly evident that the immune system and neuroinflammation play important roles in the pathobiology of at least a subset of individuals with Autism Spectrum Disorder (ASD), schizophrenia, obsessive-compulsive disorder, Tourette syndrome and mood disorders, such as depression, as well as autoimmune and neurodegenerative disorders. Emerging evidence also points to the importance of the ‘gut-brain axis’ and an individual’s microbiome, which can impact an individual’s somatic and mental well-being. Conclusions: There are multidirectional interconnections across multiple biological systems in our brains and bodies that are mediated in part by the immune system. At present, however, the ‘promise’ of this field remains greater than the ‘deliverables.’ Time will tell whether novel interventions will be developed that will make a positive difference in the care of our patients. It is also possible that valid biomarkers will emerge that will guide a more personalized approach to treatment.

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“…Genome-wide association studies (GWAS) in OCD have found suggestive evidence for some single nucleotide polymorphisms (SNPs) and genes that are potentially involved in its pathogenesis (International Obsessive Compulsive Disorder Foundation Genetics, 2017 ). Yet, overall these findings remain rather inconclusive with no single genetic variant reliably replicating across individual studies (Sampaio et al, 2013 ; Bozorgmehr et al, 2017 ). These studies did, however, suggest that an increase in sample size will likely aid the identification of genome-wide significant loci, following the example of other psychiatric disorders like major depressive disorder (MDD) (Wray et al, 2018 ), attention-deficit hyperactivity-disorder (ADHD) (Demontis et al, 2019 ), or autism spectrum disorder (ASD) (Grove et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Obsessive–compulsive disorder, which genes? Which functions? Which pathways? An integrated holistic view regarding OCD and its complex genetic etiology

Cited by 26 publications

References 39 publications

Treatment Approaches Based on Neuroscientific Data in Patients With Obsessive-Compulsive Disorder

Treatment Approaches Based on Neuroscientific Data in Patients With Obsessive-Compulsive Disorder

What does immunology have to do with brain development and neuropsychiatric disorders?

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

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