Neuroprotective agents in schizophrenia and affective disorders

Krebs, Michaël; Leopold, Karolina; Hinzpeter, Axel; Schaefer, Martin

doi:10.1517/14656566.7.7.837

Cited by 22 publications

(7 citation statements)

References 97 publications

(65 reference statements)

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“…Individuals suffering from schizophrenia may have hypofunction of NMDA receptors which may exaggerate the neuro-toxic effects of ROS. NMDA receptor antagonism induces the rapid release of glutamate with hypothesized subsequent excito-toxic effects on neurons secondary to the excessive influx of calcium (Kegeles et al, 2012;Krebs et al, 2006). Genetic variations in the calcium channel gene CACNA1C are demonstrated in schizophrenia, which impacts on glutamate transmission (Bray et al, 2010;Moosmang et al, 2005; Schizophrenia Psychiatric Genome-Wide Association Study Collaborators, 2011).…”

Section: Nmda Receptor Hypofunctionmentioning

confidence: 99%

Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries

Davis

Moylan

Harvey

et al. 2014

Aust N Z J Psychiatry

146

107

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Outside of the dopaminergic model, the potential pathogenesis of schizophrenia has yet to be fully elucidated, but common themes include neuropil shrinkage, the development of abnormal neuronal circuitry, and a chronic inflammatory state which further disrupts neuronal function. Whilst some early non-dopaminergic treatments show promise, none have yet to be fully studied in appropriately structured randomized controlled trials and they remain little more than potential attractive targets.

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Section: Nmda Receptor Hypofunctionmentioning

confidence: 99%

Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries

Davis

Moylan

Harvey

et al. 2014

Aust N Z J Psychiatry

146

107

View full text Add to dashboard Cite

show abstract

“…This is relevant in the context of the reported decrease in transition rates and the increased interest in using the lowest risk interventions possible. Table 5 summarizes agents with preclinical or clinical evidence that they might have neuroprotective properties, making them potential candidates forPRS intervention studies (Krebs et al 2006; Berger et al 2007). …”

Section: Interventionsmentioning

confidence: 99%

Research in people with psychosis risk syndrome: a review of the current evidence and future directions

Correll

Hauser

Auther

et al. 2010

Child Psychology Psychiatry

175

134

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After decades of research, schizophrenia and related psychotic disorders are still among the most debilitating disorders in medicine. The chronic illness course in most individuals, greater treatment responsiveness during the first episode, progressive grey matter decline during early disease stages, and retrospective accounts of "prodromal" or early illness signs and symptoms formed the basis for research on the psychosis risk syndrome,, known variably as "clinical high risk"(CHR), or "ultra-high risk" (UHR), or "prodromal". The pioneering era of research on the psychosis risk syndrome focused on the development and validation of specific assessment tools and the delineation of high risk criteria. This was followed by the examination of conversion rates in psychosis risk cohorts followed naturalistically, identification of predictors of conversion to psychosis, and investigation of interventions able to abort or delay the development of full psychosis. Despite initially encouraging results concerning the predictive validity of the psychosis risk syndrome criteria, recent findings of declining conversion rates demonstrate the need for further investigations. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioral therapy, are encouraging, but are currently still insufficient to make treatment recommendations for this early, relatively non-specific illness phase. The next phase of research on the psychosis risk syndrome just now beginning, has moved to larger, "multi-site" projects to increase generalizability and to ensure that sufficiently large samples at true risk for psychosis are included. Emphasis in these emerging studies is on: 1) identification of biomarkers for conversion to psychosis; 2) examination of non-antipsychotic, neuroprotective and low-risk pharmacologic and non-pharmacologic interventions; 3) testing of potentially phase-specific interventions; 4) examination of the relationship between treatment response during yhre of psychosis risk syundrome and prognosis for the course of illness; 5) follow-up of patients who developed schizophrenia despite early interventions and comparison of illness trajectories with patients who did not receive early interventions; 6) characterization of individuals with outcomes other than schizophrenia spectrum disorders, including bipolar disorder and remission from the psychosis risk syndrome, including false positive cases; 7) assessment of Corresponding Author: Christoph U. Correll, MD, The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, NY 11004, USA; telephone: 718-470-4812; fax: 718-343-1659; ccorrell@lij.edu. Financial Disclosure: Dr. Correll has been a consultant or Data Safety Monitoring Board member to or has received honoraria from Actelion, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GSK, Hoffman-La Roche, Lundbeck, OrthoMcNeill-Janssen/J&J, Medicure, Otsuka, Pfizer, Schering-Plough, Supernus and Vanda, and has served on the speaker's bureau of AstraZeneca, BristolMyers...

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“…Contemporary models regarding the pathophysiology of mood disorders posit that depressive syndromes are possibly toxic to neurons and glia via immuno-inflammatory dysregulation (McEwen 1999(McEwen , 2003Wood et al 2004;Krebs et al 2006;Lee et al 2002). Glial and neuronal cells are dynamic partners that actively participate in CNS metabolism, synaptic neurotransmission, and communication between neurons and are essential for the regulation of energy homeostasis, monoaminergic transmission, synaptic glutamate levels, and immuno-inflammatory function in the CNS (Wilson et al 2002;McNally et al 2008;Rajkowska and Miguel-Hidalgo 2007).…”

Section: Aberrant Microglial Activationmentioning

confidence: 99%

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

et al. 2010

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The aim of this review is to evaluate the evidentiary base supporting the hypothesis that the increased hazard for obesity in mood disorder populations (and vice versa) is a consequence of shared pathophysiological pathways. We conducted a PubMed search of all English-language articles with the following search terms: obesity, inflammation, hypothalamic-pituitary-adrenal axis, insulin, cognition, CNS, and neurotransmitters, cross-referenced with major depressive disorder and bipolar disorder. The frequent co-occurrence of mood disorders and obesity may be characterized by interconnected pathophysiology. Both conditions are marked by structural and functional abnormalities in multiple cortical and subcortical brain regions that subserve cognitive and/or affective processing. Abnormalities in several interacting biological networks (e.g. immuno-inflammatory, insulin signaling, and counterregulatory hormones) contribute to the co-occurence of mood disorders and obesity. Unequivocal evidence now indicates that obesity and mood disorders are chronic low-grade pro-inflammatory states that result in a gradual accumulation of allostatic load. Abnormalities in key effector proteins of the pro-inflammatory cascade include, but are not limited to, cytokines/adipokines such as adiponectin, leptin, and resistin as well as tumor necrosis factor alpha and interleukin-6. Taken together, the bidirectional relationship between obesity and mood disorders may represent an exophenotypic manifestation of aberrant neural and inflammatory networks. The clinical implications of these observations are that, practitioners should screen individuals with obesity for the presence of clinically significant depressive symptoms (and vice versa). This clinical recommendation is amplified in individuals presenting with biochemical indicators of insulin resistance and other concurrent conditions associated with abnormal inflammatory signaling (e.g. cardiovascular disease).

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Neuroprotective agents in schizophrenia and affective disorders

Cited by 22 publications

References 97 publications

Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries

Neuroprogression in schizophrenia: Pathways underpinning clinical staging and therapeutic corollaries

Research in people with psychosis risk syndrome: a review of the current evidence and future directions

Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus

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