European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Oct 2015
Associations of hippocampal metabolism and regional brain grey matter in neuroleptic-naïve ultra-high-risk subjects and first-episode schizophrenia.
Hippocampal pathology has been shown to be central to the pathophysiology of schizophrenia and a putative risk marker for developing psychosis. We applied both (1)H MRS (proton magnetic resonance spectroscopy) at 3Tesla and voxel-based morphometry (VBM) of high-resolution brain structural images in order to study the association of the metabolites glutamate (Glu) and N-acetyl-aspartate (NAA) in the hippocampus with whole-brain morphometry in 31 persons at ultra-high-risk for psychosis (UHR), 18 first-episode schizophrenia patients (Sz), and 42 healthy controls (all subjects being neuroleptic-naïve). ⋯ For NAA, we observed different associations for left prefrontal and caudate clusters bilaterally for both high-risk and first-episode schizophrenia subjects, diverging from the pattern seen in healthy subjects. Our results suggest that associations of hippocampal metabolites in key areas of schizophrenia might vary due to liability to or onset of the disorder.
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Eur Neuropsychopharmacol · Oct 2015
Benzodiazepines and risk of death: Results from two large cohort studies in France and UK.
Benzodiazepines are widely prescribed for the treatment of anxiety or insomnia, but their impact on mortality is still debated. This study investigated the impact of benzodiazepine use on short term mortality. Exposed-unexposed cohorts were constructed with the Clinical Practice Research Datalink (CPRD) in the UK and with the General Sample of Beneficiaries (EGB) in France. ⋯ When considering benzodiazepine use as a time-dependent covariate, adjusted HR for current use at 12 months was 1.03 (0.74-1.44). Using two nationally representative databases, we found a significant while moderate increase in all-cause mortality in relation to benzodiazepines, in a population of incident and mostly occasional users. This issue need to be monitored given the extensive use of these drugs.
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Eur Neuropsychopharmacol · Aug 2015
Anti-depressant therapy and cancer risk: a nested case-control study.
Previous studies demonstrated a possible association between anti-depressant therapy with selective serotonin reuptake inhibitors (SSRI) and tricyclic anti-depressants (TCA), several genetic and hormonal pathways and cancer risk, with inconsistent results. Exposure to serotonin-norepinephrine reuptake inhibitors (SNRI) was not studied extensively. We sought to evaluate the association between exposure to SSRIs, TCAs and SNRIs and the five most common solid tumors. We conducted nested case-control studies using a large UK population-representative database. Cases were those with any medical code for the specific malignancy. For every case, four controls matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence-density sampling. Exposure of interest was SSRI, SNRI or TCA therapy before index date. Odds ratios (ORs) and 95% CIs were estimated for each anti-depressant class using conditional logistic-regression analysis, adjusted for potential confounders, such as obesity, smoking history and alcohol consumption. ⋯ Treatment with SSRI and TCA might be associated with increased lung cancer risk. SSRI therapy might be associated with modest increase in breast cancer risk.
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Eur Neuropsychopharmacol · Aug 2015
Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice.
There is evidence to suggest that a dysregulation of endocannabinoid signaling may contribute to the etiology and pathophysiology of migraine. Thus, patients suffering from chronic migraine or medication overuse headache showed alterations in the activity of the arachidonoylethanolamide (AEA) degrading enzyme fatty acid amide hydrolase (FAAH) and a specific AEA membrane transporter, alongside with changes in AEA levels. The precise role of different endocannabinoid system components is, however, not clear. ⋯ Both inhibitors also dose-dependently blocked nitroglycerin-induced hyperalgesia and the activation of trigeminal neurons. The effects of the genetic deletion of pharmacological blockade of FAAH are mediated by CB1 receptors, because they were completely disrupted with the CB1 antagonist rimonabant. These results identify FAAH as a target for migraine pharmacotherapy.
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Eur Neuropsychopharmacol · Aug 2015
Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis.
Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. ⋯ Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis.