Clavulanic Acid-Mediated Increases in Anterior Cingulate Glutamate Levels are Associated With Decreased Cocaine Craving and Brain Network Functional Connectivity Changes.

Background: There is an urgent need for pharmacological treatment for cocaine (COC) use disorder (CUD). Glutamatergic transmission in the prefrontal cortex is affected by addictive behaviors. Clavulanic acid (CLAV), a glutamate transporter GLT-1 (excitatory amino acid transporter) activator, is a clinical-stage medication that has potential for treating CUD.

Clavulanic Acid Decreases Cocaine Cue Reactivity in Addiction-Related Brain Areas, a Randomized fMRI Pilot Study.

Background: Preclinical studies show that clavulanic acid (CLAV) inhibits cocaine self-administration. This study investigates the effect of CLAV on regions of brain activation in response to cocaine cues during functional magnetic resonance imaging (fMRI) in participants with cocaine use disorder (CUD).

Methods: A double-masked, placebo-controlled clinical trial with thirteen individuals with severe CUD who were randomized to treatment with CLAV (N = 10, 9 completers) 500 mg/day or matched placebo (PBO) (N = 3) for 3 days.

Association Among Chronic Obstructive Pulmonary Disease Severity, Exacerbation Risk, and Anxiety and Depression Symptoms in the SPIROMICS Cohort.

Background: Chronic obstructive pulmonary disease (COPD) is a common, progressive lung disease that often manifests with psychiatric symptoms. Despite this, patients with COPD are not routinely screened for anxiety and depression, which substantially contribute to COPD-related morbidity.

Objective: To determine the relationship among COPD symptom severity, exacerbation risk, and clinically significant anxiety and depression symptoms in ever smokers with COPD.

The GLT-1 enhancer clavulanic acid suppresses cocaine place preference behavior and reduces GCPII activity and protein levels in the rat nucleus accumbens.

The β-lactam antibiotic ceftriaxone (CTX) is a glutamate transporter subtype 1 (GLT-1) enhancer that reduces cocaine reinforcing efficacy and relapse in rats, but pharmacokinetic liabilities limit translational utility. An attractive alternative is clavulanic acid (CLAV), a structurally related β-lactamase inhibitor and component of FDA-approved Augmentin. CLAV retains the GLT-1 enhancing effects of CTX but displays greater oral bioavailability, brain penetrability and negligible antibacterial activity.

Double-blind, placebo-controlled, proof-of-concept trial of a kappa-selective opioid receptor antagonist augmentation in treatment-resistant depression.

Background: Kappa-opioid antagonism may possess antidepressant properties. We assessed, in a proof-of-concept pilot trial among patients with major depressive disorder with inadequate response to antidepressants, the efficacy of adjunctive CERC-501 (formerly LY2456302), a kappaselective opioid receptor antagonist.

Methods: In a Sequential Parallel Comparison Design study, patients were pre-randomized to: a) 10 mg/d of CERC-501 for 6 days, b) 20 mg/d of CERC-501 for 6 days, c) placebo for 3 days followed by 10 mg/d of CERC- 501 for 3 days, d) placebo for 3 days followed by 20 mg/d of CERC-501 for 3 days, or e) placebo for 6 days.

Depression and its association with adverse childhood experiences in people with substance use disorders and comorbid medical illness recruited during medical hospitalization.

Aims: People who have experienced adverse childhood experiences (ACEs) are more susceptible to substance use disorder (SUD) and depression. The present study examined depression prevalence in hospitalized patients with SUD and examined the association of individual ACEs with major depression. Depression rates 3 months after discharge were also examined.

A New Single-Item Sleep Quality Scale: Results of Psychometric Evaluation in Patients With Chronic Primary Insomnia and Depression.

Study Objectives: A single-item sleep quality scale (SQS) was developed as a simple and practical sleep quality assessment and psychometrically evaluated.

Methods: SQS measurement characteristics were evaluated using the Pittsburgh Sleep Quality Index (PSQI) and morning questionnaire-insomnia (MQI) according to prespecified analysis plans in separate clinical studies of patients with insomnia and depression. Patients with insomnia (n = 70) received 4 weeks' usual care with an FDA-approved hypnotic agent; patients with depression (n = 651) received 8 weeks' active or experimental therapy.

How to study the impact of sex and gender in medical research: a review of resources.

There is a growing appreciation by the biomedical community that studying the impact of sex and gender on health, aging, and disease will lead to improvements in human health. Sex- and gender-based comparisons can inform research on disease mechanisms and the development of new therapeutics as well as enhance scientific rigor and reproducibility. This review will assist basic researchers, clinical investigators, as well as epidemiologists, population, and social scientists by providing an annotated bibliography of currently available resource tools on how to consider sex and gender as independent variables in research design and methodology.

Smoking and Cellular Telephone Use Among Pregnant Women Seeking Prenatal Care: Opportunities for Intervention.

Objectives: Although smoking during pregnancy is associated with poor pregnancy outcomes, many women continue to smoke throughout pregnancy. Behavioral interventions for smoking cessation yield modest benefits, particularly in lower socioeconomic groups. Pharmacotherapy, a first-line option for smoking cessation, has not shown clear benefits for pregnant smokers, partly due to limited adherence.

Higher DHEA-S (dehydroepiandrosterone sulfate) levels are associated with depressive symptoms during the menopausal transition: results from the PENN Ovarian Aging Study.

The influence of sex hormones on mood during the menopausal transition has been the subject of ongoing investigation. Because dehydroepiandrosterone sulfate (DHEA-S) has been associated with several indicators of healthy aging, we conducted a population-based study of midlife women to determine the relationship between DHEA-S levels and depressive symptoms and major depression during the transition through menopause. Unexpectedly, the original report revealed a positive correlation between DHEA-S levels and depressive symptoms at baseline.

Randomized, controlled, double-blind trial of taranabant for smoking cessation.

Rationale: It has been proposed that cannabinoid-1 receptor inverse agonists might be effective for smoking cessation. We evaluated this hypothesis with the cannabinoid-1 receptor inverse agonist taranabant.

Methods: Adults who smoked > or =10 cigarettes a day for >1 year and had an expired CO level of > or =10 ppm participated in a randomized, double-blind, 8-week, study of taranabant (N = 159) or placebo (N = 158).

Pilot study on the effect of estrogen replacement therapy on brain dopamine transporter availability in healthy, postmenopausal women.

Objective: Authors investigated the association between estrogen replacement therapy (ERT) and dopamine transporter (DAT) availability in women.

Methods: Thirteen postmenopausal women were administered ERT and underwent neuroimaging, using single-photon emission computed tomography (SPECT) and [99mTc]TRODAT-1, a radioligand that binds DAT. In this 6-week pilot study, subjects underwent SPECT before ERT, after 4 weeks of 0.

Comparative cardiac safety of low-dose thioridazine and low-dose haloperidol.

Aim: To compare the rate of ventricular arrhythmia, sudden death and unexplained or unattended death among users of thioridazine and haloperidol.

Methods: Observational cohort study of thioridazine and haloperidol users in the UK General Practice Research Database (GPRD) using data from 1987 through 29 June 2000. Patients were followed for 30 days following each study prescription.

Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial.

Background: Estrogen has been considered as a potential antidepressant in postmenopausal women. Our goal was to study whether estrogen therapy is effective in treating depressive disorders in older postmenopausal women and to determine whether progestins are associated with a deterioration of mood.

Methods: After 2 weeks of single-blind placebo treatment in 87 patients, 57 were randomly assigned to receive 8 weeks of treatment with estradiol (.

Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data.

Objective: To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls.

Design: Cohort study of outpatients using administrative data.

Setting: 3 US Medicaid programmes.

Depressive and anxiety disorders in women with HIV infection.

Objective: This study examined whether there were differences in the rate of depressive and anxiety disorders between HIV-infected women (N=93) and a comparison group of uninfected women (N=62). Secondary objectives were to examine correlates of depression in HIV-infected women-including HIV disease stage and protease inhibitor use-and the associations between symptoms of depression or anxiety and other potential predictor variables.

Method: Subjects underwent extensive semiannual clinical, psychiatric, neuropsychological, and immunological evaluations.

Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial.

Background: Many agents have been proposed as potential treatments for SSRI-associated sexual dysfunction, but few placebo-controlled trials have been reported.

Method: After a 1-month baseline evaluation, pre-menopausal women with moderate to severe sexual dysfunction associated with the institution of fluoxetine therapy were randomized to augmentation therapy with placebo (N=39), mirtazapine (N=36), yohimbine (N=35) or olanzapine (N=38) for a 6-week period. Outcomes were measured using a daily diary, a biweekly self-report assessment, and a computer assisted structured interview.