Higher serotonin transporter availability in early‐onset obsessive–compulsive disorder patients undergoing escitalopram treatment: A [11C]DASB PET study

Objective

Early‐onset obsessive–compulsive disorder (EOCD) and late‐onset obsessive–compulsive disorder (LOCD) are distinct subtypes of obsessive–compulsive disorder (OCD). OCD patients are treated with serotonin reuptake inhibitors, but the difference in serotonin transporter (SERT) availability between medicated EOCD and LOCD is unexplored yet.

Methods

Six EOCD and 6 LOCD patients were enrolled. They underwent serial [¹¹C]DASB positron emission tomography scans during maintenance therapy with escitalopram, and their plasma concentration of escitalopram was measured simultaneously with the scan. Then, the drug‐free binding potential of SERT was calculated by pharmacokinetic–pharmacodynamic modelling.

Results

In comparison with LOCD patients, SERT availability was significantly higher in the putamen of EOCD patients (U = 4, p = .026), but not in the caudate nucleus (U = 14, p = .589), thalamus (U = 16, p = .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen showed a negative correlation (r = ?.580, p = .048) with age of onset of the disease, but not with the Yale–Brown Obsessive Compulsive Scale scores.

Conclusions

These findings indicate that the earlier the age of onset of OCD, the less serotonergic pathology there is and that this difference remains even after long‐term serotonin reuptake inhibitor treatment. Clinically, it might suggest that nonserotonergic treatments would be a better option for EOCD patients.     

Association between PLA2G12A polymorphism and patients with schizophrenia in a southern Chinese Han population

Background

Elevated phospholipase A2 (PLA2) activity is reported to be involved in the development of schizophrenia. Further study revealed an association between PLA2 groups XIIA (PLA2G12A) polymorphism and patients with schizophrenia in a northeast Chinese Han population.

Objective

This study will further examine whether PLA2G12A rs3087494 polymorphism is associated with patients with schizophrenia in a southern Chinese Han population.

Methods

This polymorphism was genotyped in 438 patients with schizophrenia (diagnosed according to Diagnostic and Statistical Manual of Mental Disorders‐IV) and 876 healthy controls using a case–control design. Demographic and clinical data were collected in all subjects.

Results

The allele and genotype frequencies of PLA2G12A rs3087494 polymorphism significantly differed between groups (both, p < .001). These differences still were significant by adjusting for sex and age. However, there was no difference in age at onset among 3 genotype groups in patients with schizophrenia by adjusting for the variables (F = 0.22, p = .80). Stepwise multivariate regression analysis showed that this polymorphism was not associated with age at onset in patients with schizophrenia (β = .008, t = .07, p = .94).

Conclusions

Our results indicated that even though PLA2G12A rs3087494 polymorphism did not influence age at onset in patients with schizophrenia, it may play an important role in the susceptibility to schizophrenia in a southern Chinese Han population.     

Short circuit: Disaggregation of adrenocorticotropic hormone and cortisol levels in HIV‐positive,methamphetamine‐using men who have sex with men

Objective

This study examined if methamphetamine use alone (METH + HIV?) and methamphetamine use in combination with HIV (METH + HIV+) were associated with hypothalamic‐pituitary‐adrenal (HPA) axis dysregulation as well as insulin resistance relative to a nonmethamphetamine‐using, HIV‐negative comparison group (METH‐HIV?).

Methods

Using an intact groups design, serum levels of HPA axis hormones in 46 METH + HIV? and 127 METH + HIV+ men who have sex with men (MSM) were compared to 136 METH‐HIV? men.

Results

There were no group differences in prevailing adrenocorticotropic hormone (ACTH) or cortisol levels, but the association between ACTH and cortisol was moderated by METH + HIV+ group (β = ?0.19, p < .05). Compared to METH‐HIV? men, METH + HIV+ MSM displayed 10% higher log₁₀ cortisol levels per standard deviation lower ACTH. Both groups of methamphetamine‐using MSM had lower insulin resistance and greater syndemic burden (i.e., sleep disturbance, severe depression, childhood trauma, and polysubstance use disorder) compared to METH‐HIV? men. However, the disaggregated functional relationship between ACTH and cortisol in METH + HIV+ MSM was independent of these factors.

Conclusions

Further research is needed to characterize the bio‐behavioral pathways that explain dysregulated HPA axis functioning in HIV‐positive, methamphetamine‐using MSM.     

Cytochrome P450 3A activity in mothers and their neonates as determined by plasma 4β-hydroxycholesterol

Purpose  

The purpose of this study was to determine the 4β-hydroxycholesterol to cholesterol ratio in mothers and neonates at the time of birth and 4 months post-partum.     

Antidepressant utilization patterns and mortality in Swedish men and women aged 20–34 years

Purpose  

To compare antidepressant utilization patterns and mortality in relation to antidepressant use in men and women aged 20–34 years.     

New Fluorescent Probes Targeting the Mitochondrial-Located Translocator Protein 18 kDa (TSPO) as Activated Microglia Imaging Agents

Purpose  

To evaluate the utility of new Translocator protein 18 kDa (TSPO)-targeted fluorescent probes for in vivo molecular imaging of activated microglia.     

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

Rationale  

There has been little investigation of the possible lasting adverse effects of γ-hydroxybutyrate (GHB).     

Development of Lidocaine-Coated Microneedle Product for Rapid, Safe, and Prolonged Local Analgesic Action

Purpose  

To demonstrate rapid (~1 min) lidocaine delivery using 3M’s solid microstructured transdermal system (sMTS) for prolonged, local analgesic action.     

Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population

   

This study provides the first analysis of the TPMT mutant allele frequency in a sample of the Jordanian population and indicates that TPMT*3A is the most common allele in Jordanian subjects.     

Lack of a pharmacokinetic interaction between steady-state tipranavir/ritonavir and single-dose valacyclovir in healthy volunteers

Objective  

This study assessed the single-dose pharmacokinetics of the herpes antiviral acyclovir (administered as the pro-drug valacyclovir) alone and in combination with twice-daily 200 mg ritonavir-boosted tipranavir (500 mg) at steady state.     

Comparative risk of serious hypoglycemia with oral antidiabetic monotherapy: A retrospective cohort study

Purpose

To examine and compare risks of serious hypoglycemia among antidiabetic monotherapy‐treated adults receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione.

Methods

We performed a retrospective cohort study of apparently new users of monotherapy with metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide within a dataset of Medicaid beneficiaries from California, Florida, New York, Ohio, and Pennsylvania. We did not include users of dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 agonists, or sodium‐glucose co‐transporter 2 inhibitors. We identified serious hypoglycemia outcomes within 180 days following new use using a validated, diagnosis‐based algorithm. We calculated age‐ and sex‐standardized outcome occurrence rates for each drug and generated propensity score–adjusted hazard ratios vs metformin using Cox proportional hazards regression.

Results

The ranking of standardized occurrence rates of serious hypoglycemia was glyburide > glimepiride > glipizide > repaglinide > nateglinide > rosiglitazone > pioglitazone > metformin. Rates were increased for all study drugs at higher average daily doses. Adjusted hazard ratios (95% confidence intervals) vs metformin were 3.95 (3.66‐4.26) for glyburide, 3.28 (2.98‐3.62) for glimepiride, 2.57 (2.38‐2.78) for glipizide, 2.03 (1.64‐2.52) for repaglinide, 1.21 (0.89‐1.66) for nateglinide, 0.90 (0.75‐1.07) for rosiglitazone, and 0.80 (0.68‐0.93) for pioglitazone.

Conclusions

Sulfonylureas were associated with the highest rates of serious hypoglycemia. Among all study drugs, the highest rate was seen with glyburide. Pioglitazone was associated with a lower adjusted hazard for serious hypoglycemia vs metformin, while rosiglitazone and nateglinide had hazards similar to that of metformin.     

Mitochondrial Antioxidants Alleviate Oxidative and Nitrosative Stress in a Cellular Model of Sepsis

Purpose  

Mitochondrial dysfunction plays a key role in sepsis.     

Efficacy and safety of the novel α<Subscript>4</Subscript>β<Subscript>2</Subscript> neuronal nicotinic receptor partial agonist ABT-089 in adults with attention-deficit/hyperactivity disorder: a randomized,double-blind,placebo-controlled crossover study

Rationale  

α₄β₂ Neuronal nicotinic receptors (NNRs) are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD).     

Emergence of anti-conflict effects of zolpidem in rhesus monkeys following extended post-injection intervals

Rationale  

Zolpidem is a hypnotic drug that binds to γ-aminobutyric acid type A receptors but lacks consistently demonstrable anxiolytic efficacy.     

Clinical trials during pregnancy: what has been done

Objective  

We describe clinical trials conducted in pregnant women.     

Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT

Rationale  

Pharmacokinetics of melatonin in children might differ from that in adults.     

Impact of better adherence to statin agents in the primary prevention of coronary artery disease

Background  

Statins reduce cardiovascular morbidity and mortality after continuous treatment. Studies have shown that less than 50% of patients take 80% or more of prescribed doses 1 year after starting therapy.     

One-year prospective follow-up of pharmacological treatment in children with attention-deficit/hyperactivity disorder

Objectives  

To delineate the safety and tolerability profile of methylphenidate and atomoxetine in children and adolescents with attention deficit hyperactivity disorder (ADHD) monitored for more than 1 year.     

Improvement of Cerebral Metabolism Mediated by Ro5-4864 is Associated with Relief of Intracranial Pressure and Mitochondrial Protective Effect in Experimental Brain Injury

Purpose  

To investigate the possible impact of reduction of mitochondrial membrane permeabilization by modulation of the 18 kDa translocator protein mediated by Ro5-4864 over post-traumatic cerebral edema and metabolic crisis.