Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder

Attwells, Sophia; Setiawan, Elaine; Wilson, Alan A.; Rusjan, Pablo; Mizrahi, Romina; Miler, Laura; Xu, Cynthia; Richter, Margaret A.; Kahn, Alan R.; Kish, Stephen J.; Houle, Sylvain; Ravindran, Lakshmi N.; Meyer, Jeffrey H.

doi:10.1001/jamapsychiatry.2017.1567

Cited by 156 publications

(96 citation statements)

References 58 publications

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“…27,28 Ribonucleic acid transcriptomes from the basal ganglia of patients with Tourette syndrome demonstrate upregulation in immunerelated genes consistent with microglial activation, and neuroimaging studies demonstrate microglial activation in adults with OCD, and children with Tourette syndrome and paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. [29][30][31] However, these studies have limitations, and further studies are required to explore this hypothesis. 11 We acknowledge that the case series is selected and therefore open to bias, or coincidental association.…”

Section: Discussionmentioning

confidence: 99%

Maternal thyroid autoimmunity associated with acute‐onset neuropsychiatric disorders and global regression in offspring

Jones

Sharma

et al. 2019

Develop Med Child Neuro

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Epidemiological studies, animal models, and case–control studies indicate maternal immune activation may be an important factor involved in disease expression of autism spectrum disorder (ASD), Tourette syndrome, and obsessive–compulsive disorder (OCD). We report eight children (mean age 6y 6mo [range 4–15y]; six males and two females) referred over a 2‐year period with at least one of these neurodevelopmental disorders plus a maternal history of thyroid autoimmunity. Seven of eight children presented with an abrupt onset of neuropsychiatric symptoms (OCD [n=6], tics [n=5], and/or psychosis [n=1]), associated with an autistic or global regression. Four children had a pre‐existing diagnosis of ASD. Six presentations were preceded by infection, and symptoms followed a relapsing‐remitting course in seven children. All children responded to immunomodulatory treatment as indicated by a reduction in psychiatric symptoms, and seven children were also managed with conventional treatment with additional improvement. We propose that maternal autoimmunity can activate fetal microglia or alter transcription of neurodevelopmental vulnerability and/or immune genes in utero, and is an environmental factor that increases the expression and severity of neurodevelopmental problems, and susceptibility to deteriorations after infectious or stress stimuli. What this paper adds Maternal thyroid autoimmunity may represent a risk factor for neuropsychiatric disorders in offspring. Atypical neuropsychiatric features in these children may be due to maternal immune activation in utero.

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Section: Discussionmentioning

confidence: 99%

Maternal thyroid autoimmunity associated with acute‐onset neuropsychiatric disorders and global regression in offspring

Jones

Sharma

et al. 2019

Develop Med Child Neuro

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“…Indeed, recent studies showed the presence of inflammation in the cortico-striatal-thalamo-cortical circuit (Attwells et al, 2017) and the presence of greater plasma levels of IL-2, IL-4, IL-6, IL-10 and TNF-α levels in adult OCD patients compared to controls (Rao et al, 2015), as well as higher rates of anti-basal ganglia antibodies (Pearlman et al, 2014, Nicholson et al, 2012. Systemic autoimmune diseases are reported to be associated with an increased risk of OCD (Wang et al, 2018).…”

Section: Immunological Factors and Early Interventionmentioning

confidence: 99%

Early intervention for obsessive compulsive disorder: An expert consensus statement

Fineberg

Dell’Osso

Albert

et al. 2019

European Neuropsychopharmacology

110

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“…Evidence from human studies suggests that microglia are dysfunctional in at least a subset of individuals with neuropsychiatric disorders, as well as in neurodegenerative disorders such as Alzheimer's disease and chronic pain 17 . The range of neuropsychiatric disorders associated with at least some evidence of microglia dysfunction is broad and the list includes: Autism Spectrum Disorder (ASD), schizophrenia, bipolar disorder, major depression, OCD, and Tourette syndrome (TS) [17][18][19][20][21] . For example, postmortem studies of brain tissue from a small number of individuals with ASD have documented altered numbers of microglia in the dorsolateral prefrontal cortex [22][23][24] .…”

Section: Microglia and The Role Of The Immune System In Normal Brainmentioning

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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Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder

Cited by 156 publications

References 58 publications

Maternal thyroid autoimmunity associated with acute‐onset neuropsychiatric disorders and global regression in offspring

Maternal thyroid autoimmunity associated with acute‐onset neuropsychiatric disorders and global regression in offspring

Early intervention for obsessive compulsive disorder: An expert consensus statement

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

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