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Toward Biomarker-Guided Treatment in Psychosis

Toward Biomarker-Guided Treatment in Psychosis

  • Is oxidative stress a therapeutic target in schizophrenia?

  • • All FDA-approved antipsychotics for schizophrenia antagonize dopamine D2 receptors

    • Identification of novel treatment targets in schizophrenia is needed

    • Recent studies suggest that oxidative stress (an imbalance of free radicals), particularly deficits in the glutathione (GSH) system, plays a role in the pathophysiology of schizophrenia

  • • Two randomized controlled trial (RCTs) found that adjunctive N-acetylcysteine (NAC), an antioxidant and GSH precursor, improved (particularly negative) symptoms in schizophrenia with modest effect sizes[1,2]

    • Evidence from developmental rodent models of schizophrenia suggests that the adverse effects of oxidative stress may occur early in the illness trajectory

    • Conus and colleagues[3] performed an RCT of adjunctive NAC in early psychosis

  • The aims of the present study were to determine the effect of adjunctive NAC on:

    • Negative symptoms in early psychosis

    • Positive and cognitive symptoms in early psychosis

    • Brain GSH parameters, and whether response to NAC is associated with peripheral blood GSH-related biomarkers

  • • The authors performed a 6-month, double-blind, placebo-controlled, 2-center RCT of add-on NAC vs placebo in early psychosis from 2009-2014

    • Inclusion criteria were age 18-40, psychotic disorder diagnosis (based on the Comprehensive Assessment of At Risk Mental States scale), < 12 months of treatment for psychosis, and sufficient clinical stability

  • • Subjects were randomized 1:1 to 2700 mg/d NAC (1800 mg qAM + 900 mg qPM) or placebo for 6 months

    • Subjects were seen monthly for 6 months, and then at 1 month post-discontinuation, and assessed for psychopathology, cognition, psychosocial functioning, and medication adverse effects

    • Blood GSH system markers and brain medial prefrontal cortex GSH (via 1H-MRS) were measured at multiple time points during the study

  • • 302 patients were screened, and 63 were randomized (32 to NAC and 31 to placebo)

    • There were no significant between-group differences regarding baseline clinical and demographic characteristics

    • Mean subject age was 25, 77% were male, and the majority of subjects were Caucasian

  • • There were no significant differences between groups on change in psychopathology or functional outcome

    • NAC improved cognitive processing speed (verbal fluency and trail making test)

    • Improved cognitive processing speed was correlated with decreased negative symptoms in NAC-treated patients

  • • NAC treatment was associated with a mean 19% increase in blood GSH levels, and a mean 23% increase in medial prefrontal cortex GSH levels

    • High baseline blood GSH peroxidase activity was a predictor of decrease in PANSS positive subscale scores with NAC treatment

    • Treatment with NAC was not associated with significant adverse effects

  • The authors concluded that in patients with early psychosis:

    • The addition of NAC to standard treatment did not improve symptoms or functioning

    • Oral NAC increased brain GSH levels and improved cognition (processing speed)

    • Peripheral blood GSH peroxidase identified a response to NAC in terms of positive symptoms

  • • NAC administration modified peripheral blood markers of oxidative stress/redox status, which paralleled clinical improvement

    • These peripheral blood markers also allowed identification of a subgroup of patients who benefited from NAC

    • Findings represent an important step toward biomarker-guided treatment in psychosis

Comments

I click on the box -- nothing happens

Dileep @

can not open

RITIKA @

can not open

RITIKA @

I've been using NAC in the treatment of OCD and irritability features in autism with very good results with little known risk. FYI, it is also helpful to help prevent/treat hangover from a few too many.

amy @

It does not work either in Safari

Guillemain @

does not open.

jorge @

Can’t access the article, only the title...

ADRIANA @

It's in the little boxes that you click on. A number of the articles are in this format. Find the blue box and click on it and the little boxes are like slide shows.

Anne @

I click on the box and it still goes nowhere

Austin @

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