Suchergebnisse

Background: Clozapine and lithium increase neurosteroids in rodents, and both drugs demonstrate antisuicidal actions. We therefore hypothesized that neurosteroid levels may be reduced in patients with schizophrenia or bipolar disorder who completed suicide. Aims: To investigate neurosteroid levels in the parietal cortex and posterior cingulate in schizophrenia and bipolar patients who died by suicide, and compare them with patients with these disorders who died of other causes. Method: Neurosteroid levels were quantified by gas chromatography/mass spectrometry in the parietal cortex and posterior cingulate. Mann–Whitney analyses were conducted in exploratory post hoc analyses to investigate neurosteroids as possible biomarker candidates for suicide. Results: The study showed that pregnenolone was significantly decreased in the parietal cortex in the combined group of patients with schizophrenia or bipolar disorder who died by suicide (n = 13) compared with patients with these disorders who died of other causes (n = 17, p = .02). Pregnenolone levels were also lower in the parietal cortex in the individual group of schizophrenia patients who died by suicide (n = 4) compared with schizophrenia patients who died of other causes (n = 11) p = .04). Conclusion: Pregnenolone alterations may be relevant to the neurobiology of suicide in schizophrenia and bipolar disorder.

IMPORTANCE: In response to the national opioid public health crisis, there is an urgent need to develop nonopioid solutions for effective pain management. Neurosteroids are endogenous molecules with pleotropic actions that show promise for safe and effective treatment of chronic low back pain. OBJECTIVE: To determine whether adjunctive pregnenolone has therapeutic utility for the treatment of chronic low back pain in Iraq- and Afghanistan-era US military veterans. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trial that enrolled for 42 months, from September 2013 to April 2017. Participants were Iraq- and Afghanistan-era veterans aged 18 to 65 years with chronic low back pain who received treatment in the Durham VA Health Care System in Durham, North Carolina, over 6 weeks. Data analysis began in 2018 and was finalized in March, 2019. INTERVENTIONS: Following a 1-week placebo lead-in, participants were randomized to pregnenolone or placebo for 4 weeks. Pregnenolone and placebo were administered at fixed, escalating doses of 100 mg for 1 week, 300 mg for 1 week, and 500 mg for 2 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in mean pain intensity ratings from a daily pain diary (numerical rating scale, 0-10) between visit 3 (baseline) and visit 6. Secondary outcomes included pain interference scores (Brief Pain Inventory, Short Form). Preintervention and postintervention neurosteroid levels were quantified by gas chromatography with tandem mass spectrometry. Hypotheses tested were formulated prior to data collection. RESULTS: A total of 94 participants (84 [89.4%] male; mean [SD] age, 37.5 [9.8] years; 53 [56.4%] of self-reported Caucasian race and 31 [33.0%] of self-reported African American race) were included. Forty-eight participants were randomized to pregnenolone and 52 to placebo, of whom 45 and 49, respectively, were included in baseline demographic characteristics secondary to noncompliance with medications as per protocol. ...