1Orphanet J Rare Dis 2014 -1 9: 65
TitleDiagnostic and treatment implications of psychosis secondary to treatable metabolic disorders in adults: a systematic review.
AbstractIt is imPORtant for psychiatrists to be aware of certain inborn errors of metabolism (IEMs) as these rare disorders can present as psychosis, and because definitive treatments may be available for treating the underlying metabolic cause. A systematic review was conducted to examine IEMs that often present with schizophrenia-like symptoms.
Published literature on MEDLINE was assessed regarding diseases of homocysteine metabolism (DHM; cystathionine beta-synthase deficiency [CbS-D] and homocysteinemia due to methyltetrahydrofolate reductase deficiency [MTHFR-D]), urea cycle disorders (UCD), acute PORphyria (POR), Wilson disease (WD), cerebrotendinous-xanthomatosis (CTX) and Niemann-Pick disease type C (NP-C).
Case rePORts, case series or reviews with original data regarding psychiatric manifestations and cognitive impairment published between January 1967 and June 2012 were included based on a standardized four-step selection process.
All selected articles were evaluated for descriptions of psychiatric signs (type, severity, natural history and treatment) in addition to key disease features.
A total of 611 records were identified. Information from CbS-D (n?=?2), MTHFR-D (n?=?3), UCD (n?=?8), POR (n?=?12), WD (n?=?11), CTX (n?=?14) and NP-C publications (n?=?9) were evaluated. Six non-systematic literature review publications were also included. In general, published rePORts did not provide explicit descriptions of psychiatric symptoms. The literature search findings are presented with a didactic perspective, showing key features for each disease and psychiatric signs that should trigger psychiatrists to suspect that psychotic symptoms may be secondary to an IEM.
IEMs with a psychiatric presentation and a lack of, or sub-clinical, neurological signs are rare, but should be considered in patients with atypical psychiatric symptoms.
SCZ Keywordsschizophrenia, schizophrenic
2Ther Drug Monit 2015 Apr 37: 152-60
TitleCYP1A2*1D and *1F polymorphisms have a significant impact on olanzapine serum concentrations.
AbstractAlthough several polymorphisms in olanzapine-metabolizing enzymes have been identified, the clear role and benefit for pharmacotherapy remain uncertain. The aim of the study was to investigate the potential influence of polymorphisms in the CYP1A2 gene (*1D,*1F), in the UGT1A4 gene (*3), and in the POR gene (rs2302429) on olanzapine serum concentrations and the clinical outcome.
Ninety-eight white inpatients who received olanzapine as part of their treatment for at least 4 weeks were included in the retrospective investigation. Moreover, a sample of 209 inpatients receiving olanzapine or clozapine was built to investigate the influence of the relevant polymorphisms CYP1A2*1F, *1D, and CYP1A2 inducers on the clinical outcome.
Carriers of the delT-allele (*1D) developed significantly higher dose-corrected olanzapine serum concentrations (analysis of covariance; P < 0.001, delT + delTdelT: 3.1, TT: 1.6 ng·mL·mg, adjusted model including the confounding factors age, sex, baseline weight, CYP1A2*1F genotype, and concomitant CYP1A2 inducers). Moreover, the CYP1A2*1F (AA) genotype also revealed a significant impact on olanzapine serum concentrations according to the analysis of covariance model (P = 0.028; CC + CA: 2.05, AA: 1.44 ng·mL·mg). The other polymorphisms studied revealed no significant influence. Regarding response and adverse effects, a higher increase of weight could be observed in schizophrenic Paranoid Depressive Scale (responder: +5.7 vs nonresponder: +1.8 kg; P = 0.007) and Clinical Global Impression responders (4.6 vs 1.8 kg; P = 0.017). No direct correlation between olanzapine serum concentrations and response or weight gain could be detected. Patients with at least 2 factors promoting higher serum concentrations (no CYP1A2 inducer, *1D deltT-allele, or *1F C-allele) showed a better response according to the Paranoid Depressive Scale (P = 0.002) and a significant correlation with the Clinical Global Impression Scale-2 after 4 weeks (n = 193, r = -0.177; P = 0.005).
We, for the first time, identified a significant influence of polymorphisms in CYP1A2 in combination with CYP1A2 inducer status on the clinical outcome. Therefore, genotyping for CYP1A2*1D and *1F may be a useful tool for dose optimization and identification of high-risk patients. Further and larger studies are needed before genotype-based dosage recommendations can help patients treated with CYP1A2 metabolized drugs.
SCZ Keywordsschizophrenia, schizophrenic