The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia

Miller, Brian J.; Buckley, Peter F.

doi:10.1016/j.psc.2016.01.003

Cited by 32 publications

(16 citation statements)

References 44 publications

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“…The RNA-Seq profiling of 3-week-old female and male pigs, 2 months after viral infection during gestation, offered insights into MIA-associated neurodevelopmental diseases in humans such as ASD and SSD and potential effects in livestock health. The prevalent and sex-dependent dysregulation of genes in immune pathways was detected, supporting established immunotherapies to alleviate the pathophysiology of SSD, ASD, and AD (Busche et al, 2015;Miller and Buckley, 2016).…”

Section: Resultsmentioning

confidence: 59%

Lasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala

et al. 2020

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The prolonged and sex-dependent impact of maternal immune activation (MIA) during gestation on the molecular pathways of the amygdala, a brain region that influences social, emotional, and other behaviors, is only partially understood. To address this gap, we investigated the effects of viral-elicited MIA during gestation on the amygdala transcriptome of pigs, a species of high molecular and developmental homology to humans. Gene expression levels were measured using RNA-Seq on the amygdala for 3-week-old female and male offspring from MIA and control groups. Among the 403 genes that exhibited significant MIA effect, a prevalence of differentially expressed genes annotated to the neuroactive ligand-receptor pathway, glutamatergic functions, neuropeptide systems, and cilium morphogenesis were uncovered. Genes in these categories included corticotropin-releasing hormone receptor 2, glutamate metabotropic receptor 4, glycoprotein hormones, alpha polypeptide, parathyroid hormone 1 receptor, vasointestinal peptide receptor 2, neurotensin, proenkephalin, and gastrin-releasing peptide. These categories and genes have been associated with the MIA-related human neurodevelopmental disorders, including schizophrenia and autism spectrum disorders. Gene network reconstruction highlighted differential vulnerability to MIA effects between sexes. Our results advance the understanding necessary for the development of multifactorial therapies targeting immune modulation and neurochemical dysfunction that can ameliorate the effects of MIA on offspring behavior later in life.

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Section: Resultsmentioning

confidence: 59%

Lasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala

et al. 2020

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“…The often invasive nature and potential adverse effects of the treatments mean that trials need to be careful to select those patients that are most likely to benefit from this approach. However, there are case reports of people with psychosis who have received these immunosuppressive agents, for the treatment of concurrent illness, with improvement of their psychotic symptoms reported . One open label study to date, of patients with NSAb‐positive psychosis treated with steroids, plasma exchange and/or intravenous immunoglobulins, demonstrates that immunosuppression can be effective in treating psychosis .…”

Section: Effect Of Immunomodulatory Treatments On Schizophreniamentioning

confidence: 99%

Psychosis: an autoimmune disease?

et al. 2017

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Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B-cell markers CD19 and CD20 achieve genome-wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19 and reduced CD3 lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post-mortem studies have found CD3 and CD20 lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody-mediated (NSAb) central nervous system disease provides an antigen-specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo-controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis.

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“…There is now a broad understanding that immune dysregulation may form an important part of the pathophysiology of schizophrenia and a whole range of drugs targeting specific parts of the immune system are already available. Following up on the studies with various anti-inflammatory acting drugs that have already been conducted, the stage is set for a new phase of drug studies in schizophrenia (19).…”

Section: Introductionmentioning

confidence: 99%

Constructing the Immune Signature of Schizophrenia for Clinical Use and Research; An Integrative Review Translating Descriptives Into Diagnostics

et al. 2019

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Schizophrenia is considered a syndrome comprised by several disease phenotypes, covering a range of underlying pathologies. One of these disease mechanisms seems to involve immune dysregulation and neuroinflammation. While the current dopamine receptor-blocking antipsychotic drugs decrease psychotic symptoms and prevent relapse in the majority of patients with schizophrenia, there is a huge need to explore new treatment options that target other pathophysiological pathways. Such studies should aim at identifying robust biomarkers in order to diagnose and monitor the immune biophenotype in schizophrenia and develop better selection procedures for clinical trials with anti-inflammatory and immune-modulating drugs. In this focused review, we describe available methods to assess inflammatory status and immune disturbances in vivo. We also outline findings of immune disturbances and signs of inflammation at cellular, protein, and brain imaging levels in patients with schizophrenia. Furthermore, we summarize the results from studies with anti-inflammatory or other immune-modulating drugs, highlighting how such studies have dealt with participant selection. Finally, we propose a strategy to construct an immune signature that may be helpful in selecting and monitoring participants in studies with immune modulating drugs and also applicable in regular clinical work.

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The Case for Adjunctive Monoclonal Antibody Immunotherapy in Schizophrenia

Cited by 32 publications

References 44 publications

Lasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala

Lasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala

Psychosis: an autoimmune disease?

Constructing the Immune Signature of Schizophrenia for Clinical Use and Research; An Integrative Review Translating Descriptives Into Diagnostics

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