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Journal ArticleDOI

Evidence for a Dysregulated Immune System in the Etiology of Psychiatric Disorders

Sinead M. Gibney, +1 more
- 05 May 2013 - 
- Vol. 8, Iss: 4, pp 900-920
TLDR
Support for a role of immune dysregulation in the pathophysiology of these psychiatric disorders comes from studies showing the immunomodulating effects of antipsychotics and antidepressants, and the mood altering effects of anti-inflammatory therapies.
Abstract
There is extensive bi-directional communication between the brain and the immune system in both health and disease. In recent years, the role of an altered immune system in the etiology of major psychiatric disorders has become more apparent. Studies have demonstrated that some patients with major psychiatric disorders exhibit characteristic signs of immune dysregulation and that this may be a common pathophysiological mechanism that underlies the development and progression of these disorders. Furthermore, many psychiatric disorders are also often accompanied by chronic medical conditions related to immune dysfunction such as autoimmune diseases, diabetes and atherosclerosis. One of the major psychiatric disorders that has been associated with an altered immune system is schizophrenia, with approximately one third of patients with this disorder showing immunological abnormalities such as an altered cytokine profile in serum and cerebrospinal fluid. An altered cytokine profile is also found in a proportion of patients with major depressive disorder and is thought to be potentially related to the pathophysiology of this disorder. Emerging evidence suggests that altered immune parameters may also be implicated in the neurobiological etiology of autism spectrum disorders. Further support for a role of immune dysregulation in the pathophysiology of these psychiatric disorders comes from studies showing the immunomodulating effects of antipsychotics and antidepressants, and the mood altering effects of anti-inflammatory therapies. This review will not attempt to discuss all of the psychiatric disorders that have been associated with an augmented immune system, but will instead focus on several key disorders where dysregulation of this system has been implicated in their pathophysiology including depression, schizophrenia and autism spectrum disorder.

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Citations
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Regulatory T Cells

TL;DR: Firm evidence is provided for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis.
Journal ArticleDOI

A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression.

TL;DR: Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction.
Journal ArticleDOI

The Bidirectional Relationship of Depression and Inflammation: Double Trouble.

TL;DR: How the immune system regulates mood and the potential causes of the dysregulated inflammatory responses in depressed patients are described, and inflammation is likely a critical disease modifier, promoting susceptibility to depression.
Journal ArticleDOI

C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.

TL;DR: Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.
Journal ArticleDOI

Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression

TL;DR: There is preliminary evidence for similarities in the pattern of CSF cytokine and tryptophan catabolite alterations across major psychiatric disorders, although findings must be interpreted with caution in light of small numbers of studies/subjects.
References
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Journal ArticleDOI

From inflammation to sickness and depression: when the immune system subjugates the brain

TL;DR: In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour, which can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals.
Journal ArticleDOI

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Shaun Purcell, +81 more
- 06 Aug 2009 - 
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Journal ArticleDOI

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TL;DR: A meta-analysis of studies measuring cytokine concentration in patients with major depression reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects, strengthening evidence that depression is accompanied by activation of the IRS.
Journal ArticleDOI

Depression, chronic diseases, and decrements in health: results from the World Health Surveys

TL;DR: Depression produces the greatest decrement in health compared with the chronic diseases angina, arthritis, asthma, and diabetes, and the urgency of addressing depression as a public-health priority is indicated to improve the overall health of populations.
Journal ArticleDOI

Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

TL;DR: Preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication.
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