T-helper-1 and T-helper-2 Responses in Psychiatric Disorders

Schwarz, Markus J.; Chiang, Sonnig Sue Whei; Müller, Norbert; Ackenheil, Manfred

doi:10.1006/brbi.2001.0647

Cited by 207 publications

(121 citation statements)

References 238 publications

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“…The larger symptom amelioration we observed in those patients with the lowest T H 1/T H 2 ratio was in accordance with our expectation and supports the hypothesis on the pathophysiologic role of dysbalance in pro-and antiinflammation in schizophrenia. 6 The role of inflammatory cytokines was further suggested in a recent case-control study in which several intronic haplotypes and missense variants in cytokine receptors were found to be associated with schizophrenia. 37 Nevertheless, aspirin may also reduce symptoms through other mechanisms, eg, by antagonizing dysfunction of the NMDA receptor.…”

Section: Discussionmentioning

confidence: 98%

“…First, an evolving body of evidence points to altered immune function, in particular helper T cell (T H ) changes with a relative shift to anti-inflammatory T H 2 cell activity over proinflammatory T H 1 cell activity. 5,6 Nonsteroidal anti-inflammatory drugs may restore this balance by inhibition of prostaglandin E 2 synthesis and regulating anti-inflammatory cytokine production, thereby increasing the T H 1/T H 2 cytokine ratio. [6][7][8] Second, NSAIDs may ameliorate symptoms through antagonizing dysfunction of the n-methyl-d-aspartate (NMDA) receptor, a key feature of a well-established neurochemical model of schizophrenia.…”

mentioning

confidence: 99%

“…5,6 Nonsteroidal anti-inflammatory drugs may restore this balance by inhibition of prostaglandin E 2 synthesis and regulating anti-inflammatory cytokine production, thereby increasing the T H 1/T H 2 cytokine ratio. [6][7][8] Second, NSAIDs may ameliorate symptoms through antagonizing dysfunction of the n-methyl-d-aspartate (NMDA) receptor, a key feature of a well-established neurochemical model of schizophrenia. 9,10 This action is possible because prostaglandins are intermediates in the postsynaptic signal transduction cascade of cells with NMDA-type glutamate receptors, and prostaglandins inhibit astrocytic reuptake of glutamate.…”

mentioning

confidence: 99%

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Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders

Laan¹,

Grobbee²,

Selten³

et al. 2010

J. Clin. Psychiatry

243

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders

Laan¹,

Grobbee²,

Selten³

et al. 2010

J. Clin. Psychiatry

243

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“…One hypothesized possibility is that endogenous IFN-α may be correspondingly involved in the etiology of primary MDD [9][10][11][12][13][14][15][16][17]. Examining the variable 'psychiatric effects triggered by exogenous IFN-α treatment' may therefore offer a way to prospectively explore variable vulnerability to MDD.…”

Section: Introductionmentioning

confidence: 99%

Depression following pegylated interferon-alpha: Characteristics and vulnerability

Lotrich

Rabinovitz

Gironda

et al. 2007

Journal of Psychosomatic Research

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Objective: Interferon-α2 (IFN-α) injections may be capable of triggering depression in some individuals. The first objective was to further characterize this depression, and secondly to examine whether pre-treatment temperament was correlated with subsequent vulnerability to IFN-α.Methods: Twenty-three initially euthymic adults undergoing year-long PEG-IFN-α treatment for hepatitis C were evaluated at baseline and then prospectively monitored using both the Structured Clinical Interview for DSM-IV (SCID) and self-report questionnaires.Results: A major depressive episode developed within three months in 39%. Principal component analysis of the change in self-report scores after one month of treatment demonstrated three orthogonal factors: (i) a specific increase in depression as manifested in the Beck Depression Inventory (BDI) and Hospital Anxiety and Depression Scale (HADS), (ii) an increase in hostility and anxiety, (iii) and a generalized combination of worse symptoms including somatic symptoms on the Symptom Check List (SCL-90). BDI at one month was predicted by baseline BDI (r=0.76, p=0.004). Hostility at one month was predicted by low baseline agreeableness (r=0.75, p=0.01). Controlling for baseline BDI scores, categorical major depression was predicted by combined high baseline neuroticism and low agreeableness (combined r=0.66, p=0.03). Conclusion:These initial results (i) support the depressogenic nature of IFN-α treatment in a subset of vulnerable individuals, (ii) indicate that some individuals are also independently vulnerable to worsened hostility, and (iii) suggest that it may be possible to clinically predict these vulnerabilities in initially euthymic subjects.

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“…Production of IgG1 and IgG2b are typically caused by antiinflammatory Th2 cytokine signaling, whereas IgG2a typically results from proinflammatory Th1 signaling (35). The Th2 cytokine profile is likely favorable for inducing antibody production and thus A␤ clearance without the overt proinflammatory (i.e., possibly contributing to autoimmune responses) Th1-type activation that typifies cellular immune responses (19,36,37). Accordingly, to circumvent meningoencephalitic reactions, many studies investigating vaccination methods for reducing cerebral amyloidosis in AD have attempted to bias Th cell responses toward Th2 profiles by using various strategies (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous β-amyloid immunization reduces cerebral β-amyloid deposits without T cell infiltration and microhemorrhage

Nikolic¹,

Bai²,

Obregon³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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This therapeutic approach is clearly highly efficacious; however, the safety of this strategy has become an important concern. In a recent clinical trial, patients were administered a synthetic A␤ peptide (AN-1792) plus adjuvant, and Ϸ6% of these patients developed aseptic meningoencephalitis, most likely mediated by braininfiltrating activated T cells (3,4). This serious side effect led to suspension of the clinical trial. Furthermore, passive transfer of A␤ antibodies to transgenic AD mice results in cerebral microhemorrhage, a potentially adverse side effect (5, 6). Uncovering of these adverse events has redirected A␤ vaccination strategies toward the goal of developing an approach that is both safe and effective.Studies examining the brains of A␤-vaccinated patients developing meningoencephalitis implicate A␤-reactive T cell subsets as major components of this deleterious response to active A␤ vaccination (7, 8). To subvert possible meningoencephalitis resulting from A␤ vaccination, various strategies have been attempted. Interestingly, recent works suggest that A␤-derived peptides delivered intranasally (with adjuvant) to mucosal epithelial tissues results in effective clearance of A␤ plaques and improvement of cognitive function in animal models of AD. Moreover, T cell reactivity appeared to be considerably reduced compared with other active immunization strategies. In other studies, differential T cell responses depended on the epitope/fragment of A␤ peptide used for vaccination. Specifically, portions of the A␤ peptide seemed to stimulate different T cell responses, resulting in either proinflammatory T helper (Th) cell type 1 (Th1) responses or antiinflammatory Th cell type 2 (Th2) responses (9, 10). Such findings imply that A␤ vaccination is not only efficacious, but may also prove to be safe and therefore a feasible strategy for AD therapy depending on a number of factors, including route of delivery, adjuvant choice, and A␤ epitope administered.The skin is a well established effective route for vaccination, including delivery of peptide-based vaccines (11-13). Strong humoral and cellular immune responses have been elicited after transcutaneous (t.c.) vaccination (14), largely owing to the diverse populations of resident antigen-presenting cells (APCs) and other immune cells in the various dermal layers. Subsets of dermalresident Langerhans cell (LC) precursors, known as migratory CD14 ϩ LC precursors, are important immune regulators that demonstrate ''professional'' APC capability, including reducing T cell stimulatory function by producing antiinflammatory cytokines (15). Also, skin-resident keratinocytes release the antiinflammatory cytokine IL-10 in response to certain stimuli. Keratinocytederived IL-10 serves to buffer harmful proinflammatory immune activation and thereby preserves skin barrier integrity (16).Taken together, these lines of evidence led us to hypothesize that targeting A␤ immunotherapy to skin tissue might provide an immunotherapeutic approach that is both efficacious and safe. In...

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T-helper-1 and T-helper-2 Responses in Psychiatric Disorders

Cited by 207 publications

References 238 publications

Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders

Adjuvant Aspirin Therapy Reduces Symptoms of Schizophrenia Spectrum Disorders

Depression following pegylated interferon-alpha: Characteristics and vulnerability

Transcutaneous β-amyloid immunization reduces cerebral β-amyloid deposits without T cell infiltration and microhemorrhage

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