[Oxidative stress in psychosis: a new target for intervention?] / Oxidatieve stress bij psychotische stoornissen: een nieuw target voor interventie?

BACKGROUND: Oxidative stress is a state of imbalance between reactive oxidants and anti-oxidants. Oxidative stress and a disrupted redox regulation in the brain might contribute to the pathophysiology of psychotic disorders and could serve as interesting new targets for clinical intervention. Advanced glycation end products (AGEs) in the skin can be measured non-invasively and indicate cumulative oxidative stress. AIM: To investigate cross-sectional and longitudinal differences in AGE-levels in patients with recent onset psychosis (patients) and healthy controls (controls). To investigate association of AGE-levels and brain volume in psychosis. METHOD: An autofluorescence measurement of AGEs in the skin was performed in patients and controls. AGEs were compared in patients and controls. Furthermore, the association between AGEs and volumes of the amygdala, hippocampus and total cortical gray matter was investigated in patients. RESULTS: AGEs in the skin were elevated by 15% (or 0.66 standard deviations) in patients (n = 86) compared to controls (n = 135) (p < 0.001). An indication of a higher AGE-accumulation rate (p = 0.07) was found in patients (n = 66) compared to controls (n = 160). We found a negative association between AGEs in the skin and hippocampus volume (standardized beta= 0.27; p = 0.03) in patients (n = 46). CONCLUSION: Findings of a high level of AGEs in the skin indicate excessive oxidative stress in patients with recent onset psychosis.

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers.

BACKGROUND: Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. METHODS: We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb(2+)), manganese (Mn(2+)), cadmium (Cd(2+)), copper (Cu(2+)), magnesium (Mg(2+)), and zinc (Zn(2+)), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. RESULTS: We found higher early-life Pb(2+) exposure among patients with schizophrenia than controls. The differences in log Mn(2+) and log Cu(2+) changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb(2+) levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb(2+) levels and adult IQ. CONCLUSIONS: In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.

Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis.

OBJECTIVE: To perform a meta-analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was to analyze factors possibly moderating heterogeneity. METHOD: A systematic search was performed to identify studies into T. gondii infection for all major psychiatric disorders versus healthy controls. Methodological quality, publication bias, and possible moderators were assessed. RESULTS: A total of 2866 citations were retrieved and 50 studies finally included. Significant odds ratios (ORs) with IgG antibodies were found in schizophrenia (OR 1.81, P < 0.00001), bipolar disorder (OR 1.52, P = 0.02), obsessive-compulsive disorder (OR 3.4, P < 0.001), and addiction (OR 1.91, P < 0.00001), but not for major depression (OR 1.21, P = 0.28). Exploration of the association between T. gondii and schizophrenia yielded a significant effect of seropositivity before onset and serointensity, but not IgM antibodies or gender. The amplitude of the OR was influenced by region and general seroprevalence. Moderators together accounted for 56% of the observed variance in study effects. After controlling for publication bias, the adjusted OR (1.43) in schizophrenia remained significant. CONCLUSION: These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia reactivation of latent T. gondii infection may occur.

Treating prolactinoma and psychosis: medication and cognitive behavioural therapy.

The patient in this case report had two severe medical conditions that require oppositional treatment: prolactinoma and psychosis. A prolactinoma is a benign tumour of the pituitary gland that produces prolactin. Dopamine agonist medication is the first-line treatment in patients with prolactinoma. The psychotic symptoms started after a dosage increase of a dopamine D2-receptor agonist. Several antipsychotic medications were tried with and without the dopamine D2-receptor agonist, but severe command hallucinations remained. Cognitive behavioural therapy (CBT) was added which reduced the impact of the hallucinations to a great extent, indicating that CBT can have an additional positive effect in prolactinoma patients with psychosis that shows incomplete recovery after antipsychotic medication. Future research should be aimed at the severe and prolonged side effects of dopamine agonists in the treatment of prolactinoma patients with multiple risk factors for a psychotic decompensation.