Why have early investigational therapies of obsessive–compulsive disorder failed to materialise?

Marazziti, Donatella; Dell’Osso, Liliana

doi:10.1517/13543784.2015.1005735

Cited by 8 publications

(7 citation statements)

References 14 publications

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“…Activation of the immune response, especially inflammation, has been implicated in the pathophysiology of several psychiatric disorders in humans (e.g., Schizophrenia, ASD, Depression, Bipolar disorder, OCD, and Anxiety disorder; Hinze-Selch and Pollmacher, 2001 ; Wilson et al, 2002 ; Kaplin et al, 2005 ; Kerr et al, 2005 ; Leonard and Myint, 2006 ; Marazziti and Dell’Osso, 2015 ; Dell’Osso et al, 2016 ). Several inflammation cytokines, such as TNF and IL-6 in serum, have been considered as sensitive biomarkers in identifying a predisposition for psychiatric disorder or as a diagnosis of a psychiatric disorder ( Pape et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis

et al. 2021

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Motor stereotypic behaviors (MSBs) are common in captive rhesus macaques (Macaca mulatta) and human with psychiatric diseases. However, large gaps remain in our understanding of the molecular mechanisms that mediate this behavior and whether there are similarities between human and non-human primates that exhibit this behavior, especially at gene expression and gut microbiota levels. The present study combined behavior, blood transcriptome, and gut microbiota data of two groups of captive macaques to explore this issue (i.e., MSB macaques with high MSB exhibition and those with low: control macaques). Observation data showed that MSB macaques spent the most time on MSB (33.95%), while the CONTROL macaques allocated more time to active (30.99%) and general behavior (30.0%), and only 0.97% of their time for MSB. Blood transcriptome analysis revealed 382 differentially expressed genes between the two groups, with 339 upregulated genes significantly enriched in inflammation/immune response-related pathway. We also identified upregulated pro-inflammatory genes TNFRSF1A, IL1R1, and IL6R. Protein–protein interaction network analysis screened nine hub genes that were all related to innate immune response, and our transcriptomic results were highly similar to findings in human psychiatric disorders. We found that there were significant differences in the beta-diversity of gut microbiota between MSB and CONTROL macaques. Of which Phascolarctobacterium, the producer of short chain fatty acids (SCFAs), was less abundant in MSB macaques. Meanwhile, PICRUSTs predicted that SCFAs intermediates biosynthesis and metabolic pathways were significantly downregulated in MSB macaques. Together, our study revealed that the behavioral, gene expression levels, and gut microbiota composition in MSB macaques was different to controls, and MSB was closely linked with inflammation and immune response. This work provides valuable information for future in-depth investigation of MSB and human psychiatric diseases.

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Section: Discussionmentioning

confidence: 99%

Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis

et al. 2021

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“…Conversely, somatic obsessions seem to correlate with a worse prognosis. A possible hypothesis in this respect could be that these specific patients may show a lower insight and, therefore, a minor adherence to prescribed treatments (33).…”

Section: Discussionmentioning

confidence: 99%

Application of a staging model in patients with obsessive–compulsive disorder: cross-sectional and follow-up results

et al. 2020

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Introduction Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition with frequent chronic course. Staging models applied to psychiatric disorders seek to define their extent of progression at a particular time-point and differentiate early, milder clinical phenomena from those characterizing illness progression and chronicity. In OCD patients, a staging model has been recently proposed but not tested yet. This was the aim of the present study. Methods From an overall sample of 198 OCD patients, recruited across two psychiatric clinics in Northern Italy, 70 patients on stable treatment completed a follow-up assessment ranging from 12 to 24 months. At follow-up initiation, patients had been divided into four staging groups, according to the model proposed by Fontenelle and Yucel. At the end of the follow-up, patients were subdivided into three groups (no stage change, improved stage, or worsened stage) compared with statistical analyses. Results At the end of the follow-up, 67.1% patients showed no stage changes, 24.3% a stage improvement, and 8.6% a stage progression. Worsened patients showed higher rates of comorbid disorders and higher rates of unfavorable employment characteristics compared to the other subgroups (P < .05). Patients with worsened stage showed higher prevalence of somatic obsessions (P < .05), while patients with improved stage showed higher rates of magical thinking and violence/harm obsessions compared to other groups (P < .05). Discussion The present results provide epidemiologic and clinical correlates of the first application of a staging model in a sample of OCD patients, encouraging further studies to assess the utility of this approach in the field.

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“…OCD has been recognized as a distinct nosological entity, separated from anxiety disorders in the latest edition of the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5). 17 The pathophysiology of OCD is still unknown; however, two neurotransmitters systems have been largely supposed to play a major role, in particular, the serotonin (5-HT) and dopamine (DA) systems. 18 In any case, as the classical hypotheses cannot fully explain the complexity of this disorder, alternative possibilities have been put forward, such as those suggesting a possible implication of the immune system.…”

Section: Ocd and The Immune Systemmentioning

confidence: 99%

“…Therefore, there is a great need for novel treatments in OCD, which might involve other neurotransmitters besides the classical 5-HT and DA, such as the glutamate, or second messenger modulators, ie, inositol, or immune-modulator compounds. 17,117,118 As far as PANDAS is concerned, the difficulty in distinguishing it from other phenotypes of OCD or tics, and occasionally from SC, makes it difficult to establish practical treatment protocols. In spite of the fact that the pathophysiology of PANDAS has not yet been fully clarified, the current treatment for young patients fulfilling the PANDAS diagnostic criteria continues to be the standard-of-care practices for patients who suffer from OCD or Tourette's syndrome.…”

Section: Treatment Implicationsmentioning

confidence: 99%

The cytokine profile of OCD: pathophysiological insights

Marazziti¹,

Mucci²,

Lombardi³

et al. 2015

IJICMR

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Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by the presence of obsessions and/or compulsions, which has been commonly associated with alterations of some neurotransmitters systems, in particular, the serotonin and dopamine ones. However, it is now evident that these supposed disturbances cannot explain the development of this disorder, and so other possible mechanisms have been invoked, such as those involving the immune system that is attracting an increasing interest. According to the current literature, immune system alterations are reported in OCD of both children and adults. In children, it has been widely described as a clinical syndrome resulting from infections driven by group A β-hemolytic streptococci and characterized by rheumatic fever, OCD, and neurological symptoms called "pediatric autoimmune neuropsychiatric disorders associated with streptococcus". In adults, available findings are meager and controversial, although intriguing. Such preliminary findings underline the presence of OCD in a number of autoimmune disorders, as well as of alterations of different immune parameters in OCD patients. This paper aims at presenting an exhaustive review of the role of the immune system in the development of OCD, with a major focus on the possible pathophysiological role of cytokines that seems to open novel treatment options.

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Why have early investigational therapies of obsessive–compulsive disorder failed to materialise?

Cited by 8 publications

References 14 publications

Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis

Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis

Application of a staging model in patients with obsessive–compulsive disorder: cross-sectional and follow-up results

The cytokine profile of OCD: pathophysiological insights

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