Temporal and structural dynamics of anxiety sensitivity in predicting fearful responding to a 35% CO2 challenge

The current study assessed the incremental prediction of anxiety sensitivity (AS) in both taxonic (categorical) and dimensional representations at various time points before and after a single vital capacity inhalation of a 35% CO₂, 65% balanced O₂ gas mixture. Participants were 128 young adults screened for a history of panic attacks. By controlling for traitwise factors including state anxiety and testing both categorical and continuous conceptualizations of the AS construct at various timepoints, the present report was able to evaluate the temporal and structural dynamics of AS in relation to fearful responding to the challenge. Relevant variables were evaluated in a hierarchical linear regression framework, and it was found that a continuous conceptualization of AS provided incremental predictive validity above and beyond trait anxiety immediately post-challenge, while a categorical representation of AS was equivalent to a continuous model of AS at post-challenge but outperformed a continuous model at follow-up. These data provide basic but important evidence suggesting that AS is uniquely associated with anxious responding to a 35% CO₂ challenge, and that categorical representations of AS should be considered in biological challenge studies.     

Race/ethnicity,nativity, and lifetime risk of mental disorders in US adults

Social Psychiatry and Psychiatric Epidemiology - There has been no comprehensive examination of how race/ethnicity and nativity intersect in explaining differences in lifetime prevalence of mental...     

A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric illness with strong segregation data indicative of major genetic contributions. Association analyses of common functional variants of the serotonin transporter gene (SLC6A4), a long-standing OCD candidate, have so far been inconsistent. Here, we set out to investigate the role of additional functional SLC6A4 loci in OCD. We describe a common, functional C > T single nucleotide polymorphism, rs25532, located less than 150 nucleotides centromeric of the serotonin transporter-linked polymorphic region indel known as 5-HTTLPR. The minor allele of rs25532 significantly decreased luciferase reporter gene expression levels by 15-80%, depending on 5-HTTLPR allele background and cell type. Haplotype-based testing of rs25532 and all other known non-coding functional SLC6A4 variants revealed a highly significant omnibus association with OCD in a large case-control sample. Remarkably, the haplotype significantly overrepresented in probands contained the higher-expressing allele at each locus, supporting the notion of increased serotonin transporter functioning being pathogenetically involved in OCD. Conditional haplotype analyses with the software WHAP revealed that this association is primarily driven by 5-HTTLPR, rs25532 and rs16965628. Our results contribute to a better understanding of SLC6A4 expression genetics and provide a functional haplotype framework for future serotonin-related studies.     

Reversal of end stage renal failure with surgical revascularization in patients with atherosclerotic renal artery occlusion

A total of 9 patients with end stage renal failure caused by atherosclerotic renal artery occlusion underwent surgical revascularization with subsequent recovery of renal function. The duration of dialysis preoperatively ranged from 1 week to 13 months. In all cases renal viability was being maintained by collateral vascular supply. Postoperatively, renal function improved immediately and no patient required subsequent dialysis. Excellent over-all rehabilitation was achieved in all patients. Six patients currently are alive at a mean interval of 4.0 years postoperatively and with satisfactory renal function (mean serum creatinine 2.7 mg. per dl.). Three patients died at a mean interval of 6.8 years postoperatively and they all maintained satisfactory renal function (mean serum creatinine 3.0 mg. per dl.) until death. In some patients with end stage renal failure caused by atherosclerotic arterial occlusion surgical renal revascularization can yield extended survival with freedom from chronic dialysis.     

Metabolism of bis(2-chloroethyl)ether and bis(2-chloroisopropyl)ether in the rat

Male rats were given single peroral doses of bis(1-¹⁴C-2-chloroethyl)ether ([1-¹⁴C]BCEE) (40 mg/kg) and of bis(1-¹⁴C-2-chloroisopropyl)ether ([1-¹⁴C]BCIE) (90 mg/kg). Excretion of¹⁴CO₂ and urinary¹⁴C was followed for 48 hr. The time required to eliminate one half of the dose was 12 hr for [1-¹⁴C]BCEE and 19 hr for [1-¹⁴C]BCIE. In the case of [1-¹⁴C]BCEE, expired¹⁴CO₂ accounted for 11.5 ± 5.6(SD) % of the dose, urinary¹⁴C accounted for 64.7 ± 14.8%, and 2.4 ± 1.3% was found in the feces. The figures for [1-¹⁴C]BCIE were 20.3 ± 9.4% expired as¹⁴CO₂, 47.5 ± 8.1% as urinary¹⁴C, and 3.8 ± 0.3% as fecal¹⁴C. Thiodiglycolic acid (TDGA) accounted for roughly 75% of the total urinary¹⁴C collected after the [1-¹⁴C]BCEE dose. Lesser metabolites of BCEE were 2-chloroethoxyacetic acid (CEAA) (5%), and N-acetyl-S-[2-(2-chloroethoxy)ethyl]-L-cysteine (ACEEC) (7%). Metabolites of [1-¹⁴C]BCIE identified in rat urine were 2-(2-chloro-1-methylethoxy)propanoic acid (CMEPA), roughly 36% of the total urinary¹⁴C, and N-acetyl-S-(2-hydroxypropyl)-L-cysteine (AHPC) at 19%.     

Carbachol- and norepinephrine-stimulated phosphoinositide metabolism in rat brain: effect of chronic cholinesterase inhibition

Activation of cholinergic muscarinic receptors leads to several biochemical events including an increased turnover of phosphoinositides. In this study we have investigated whether repeated administration of the organophosphorus insecticide disulfoton, known to cause the development of tolerance to this compound, would affect phosphoinositide metabolism in rat brain. Basal and carbachol-stimulated phosphoinositide metabolism were measured in cerebral cortex slices, by measuring the accumulation of inositol phosphates (InsPs) in the presence of lithium. In control animals carbachol caused a 600% increase in InsPs accumulation with an EC50 of 100 microM. Maximal effect occurred with a LiCl concentration of 7.5 mM and required the presence of calcium. Administration of disulfoton for 10 days (2 mg/kg/day by gavage), decreased the number of muscarinic receptors in cortex from 1.1 to 0.7 pmol/mg of protein without changing the affinity of the receptors (both measured by binding of [3H]quinuclidinyl benzilate). Acetylcholinesterase was inhibited by 85%. Basal InsPs accumulation was unchanged in disulfoton-treated rats, whereas carbachol-stimulated InsPs accumulation decreased by 18%. No changes of norepinephrine-stimulated InsPs formation and of alpha-1 adrenoceptors were present in cortices from disulfoton-treated rats. Recovery of muscarinic receptor binding and carbachol-stimulated InsPs accumulation occurred at a similar rate and was completed 2 to 3 weeks after the end of the treatment, whereas acetylcholinesterase activity was still 38% inhibited 3 weeks later. These results support the hypothesis that a functional adaptation of muscarinic receptors is involved in the development of tolerance to organophosphates.