Associations between prefrontal γ-aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women

Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (−703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (−703 G/T) and rs2129575 (p≤0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (−703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.

Low single dose gabapentin does not affect prefrontal and occipital gamma-aminobutyric acid concentrations

The γ-aminobutyric acid (GABA) system has been proposed as a target for novel antidepressant and anxiolytic treatments. Emerging evidence suggests that gabapentin (GBP), an anticonvulsant drug that significantly increases brain GABA levels, is effective in the treatment of anxiety disorders. The current study was designed to measure prefrontal and occipital GABA levels in medication-free healthy subjects after taking 0 mg, 150 mg and 300 mg GBP. Subjects were scanned on a 3T scanner using a transmit-receive head coil that provided a relatively homogenous radiofrequency field to obtain spectroscopy measurement in the medial prefrontal (MPFC) and occipital cortex (OCC). There was no dose-dependent effect of GBP on GABA levels in the OCC or MPFC. There was also no effect on Glx, choline or N-acetyl-aspartate concentrations. The previously reported finding of increased GABA levels after GBP treatment is not evident for healthy subjects at the dose of 150 and 300 mg. As a result, if subjects are scanned on a 3T scanner, low dose GPB is not useful as an experimental challenge agent on the GABA system.

The International ADHD in Substance Use Disorders Prevalence (IASP) study: background, methods and study population

Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized comorbid condition in subjects with substance use disorders (SUDs). This paper describes the methods and study population of the International ADHD in Substance Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine the prevalence of ADHD in adult treatment seeking patients with SUD in different countries and SUD populations, determine the reliability and validity of the Adult ADHD Self-report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD populations, investigate the comorbidity profile of SUD patients with and without ADHD, compare risk factors and protective factors in SUD patients with and without a comorbid diagnosis of ADHD, and increase our knowledge about the relationship between ADHD and the onset and course of SUD. In this cross-sectional, multi-centre two stage study, subjects were screened for ADHD with the ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social personality disorder and borderline personality disorder. Three thousand five hundred and fifty-eight subjects from 10 countries were included. Of these 40.9% screened positive for ADHD. This is the largest international study on this population evaluating ADHD and comorbid disorders.

Sedimentary evolution and environmental history of Lake Van (Turkey) over the past 600,000 years

The lithostratigraphic framework of Lake Van, eastern Turkey, has been systematically analysed to document the sedimentary evolution and the environmental history of the lake during the past ca 600,000 years. The lithostratigraphy and chemostratigraphy of a 219 m long drill core from Lake Van serves to separate global climate oscillations from local factors caused by tectonic and volcanic activity. An age model was established based on the climatostratigraphic alignment of chemical and lithological signatures, validated by 40Ar/39Ar ages. The drilled sequence consists of ca 76% lacustrine carbonaceous clayey silt, ca 2% fluvial deposits, ca 17% volcaniclastic deposits and 5% gaps. Six lacustrine lithotypes were separated from the fluvial and event deposits, such as volcaniclastics (ca 300 layers) and graded beds (ca 375 layers), and their depositional environments are documented. These lithotypes are: (i) graded beds frequently intercalated with varved clayey silts reflect rising lake-levels during the terminations; (ii) varved clayey silts reflect strong seasonality and an intralake oxic–anoxic boundary, for example, lake-level highstands during interglacials/interstadials; (iii) CaCO3-rich banded sediments are representative of a lowering of the oxic-anoxic boundary, for example, lake-level decreases during glacial inceptions; (iv) CaCO3-poor banded and mottled clayey silts reflect an oxic–anoxic boundary close to the sediment-water interface, for example, lake-level low-stands during glacials/stadials; (v) diatomaceous muds were deposited during the early beginning of the lake as a fresh water system; and (vi) fluvial sands and gravels indicate the initial flooding of the lake basin. The recurrence of lithologies (i) to (iv) follows the past five glacial/interglacial cycles. A 20 m thick disturbed unit reflects an interval of major tectonic activity in Lake Van at ca 414 ka BP.

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study.

BACKGROUND Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE None.

Chronostratigraphy of the 600,000 year old continental record of Lake Van

Lake Van sediment cores from the Ahlat Ridge and Northern Basin drill sites of the ICDP project PALEOVAN contain a wealth of information about past environmental processes. The sedimentary sequence was dated using climatostratigraphic alignment, varve chronology, tephrostratigraphy, argon-argon single-crystal dating, radiocarbon dating, magnetostratigraphy, and cosmogenic nuclides. Based on the lithostratigraphic framework, the different age constraints are compiled and a robust and precise chronology of the 600,000 year-old Lake Van record is constructed. Proxy records of total organic carbon content and sediment color, together with the calcium/potassium-ratios and arboreal pollen percentages of the 174-meter-long Ahlat Ridge record, mimic the Greenland isotope stratotype (NGRIP). Therefore, the proxy records are systematically aligned to the onsets of interstadials reflected in the NGRIP or synthesized Greenland ice-core stratigraphy. The chronology is constructed using 27 age control points derived from visual synchronization with the GICC05 timescale, an absolutely-dated speleothem record (e.g., Hulu, Sanbao, Linzhu cave) and the Epica Dome C timescale. In addition, the uppermost part of the sequence is complemented with four ages from Holocene varve chronology and two calibrated radiocarbon ages. Furthermore, nine argon-argon ages and a comparison of the relative paleointensity record of the magnetic field with reference curve PISO-1500 confirm the accuracy of the age model. Also the identification of the Laschamp event via measurements of 10Be in the sediment confirms the presented age model. The chronology of the Ahlat Ridge record is transferred to the 79-meter-long event-corrected composite record from the Northern Basin and supplemented by additional radiocarbon dating on organic marco-remains. The basal age of the Northern Basin record is estimated at ~90 ka. The variations of the time series of total organic carbon content, the Ca/K ratio, and the arboreal pollen percentages illustrate that the presented chronology and paleoclimate data are suited for reconstructions and modeling of the Quaternary and Pleistocene climate evolution in the Near East at millennial timescales. Furthermore, the chronology of the last 250 kyr can be used to test other dating techniques.