Geochemical provenance of an Indo-Arabian stone anchor from Manikapatna highlights the medieval maritime trade of India.

India is one of the oldest maritime nations in the world, and the overseas contacts date back to the third millennium BCE. Besides several archaeological vestiges, numerous stone anchors of various types have been documented during maritime archaeological explorations along the Indian littoral. During a recent maritime archaeological exploration, a broken Indo-Arabian stone anchor, of the Medieval period, was discovered along the Manikapatna coast of Odisha, Indian eastern littoral.

Distribution, contamination status and bioavailability of trace metals in surface sediments along the southwest coast of India.

This study investigates the influence of upwelling induced seasonal hypoxia in the sediment-water interface on the distribution, bioavailability and geochemical partitioning of selected trace metals in surficial sediments along the southwest coast of India based on two successive cruises. The first cruise was during the southwest monsoon (SWM) season when coastal waters exhibited intermittent bottom hypoxia due to upwelling. The second cruise during the northeast monsoon (NEM) season was characterised by a uniformly warm and well-oxygenated water column in the study region.

Ethnogeographic prevalence and implications of the 677C>T and 1298A>C polymorphisms in US primary care populations.

Variants of the gene have been associated with a wide range of diseases. The present study analyzed data from clinical genotyping of and in 1405 patients in urban primary care settings. Striking differences in ethnogeographic frequencies of polymorphisms were observed.

VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study.

Vascular endothelial growth factor A (VEGFA) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of VEGFA gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different VEGFA gene variants influence psychosis risk, symptom severity, cognition, and brain volume.

Complications of Psychotropic and Pain Medications in an Ultrarapid Metabolizer Patient at the Upper 1% of Cytochrome P450 (CYP450) Function Quantified by Combinatorial CYP450 Genotyping.

A 44-year-old Caucasian woman presented with a history of empirical treatment with 20 pain and psychotropic medications, as well as dual comorbidity of intractable pain and depression. A multiple gain-of-function profile in the CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was discovered. The patient was a homozygote of suprafunctional alleles for both CYP2D6 (35/35) and CYP2C19 (17/17) genes and functional alleles for CYP2C9 (1/1), which account for aggregate drug metabolism function at the upper 1% of the population.

Novel gene-brain structure relationships in psychotic disorder revealed using parallel independent component analyses.

Background: Schizophrenia, schizoaffective disorder, and psychotic bipolar disorder overlap with regard to symptoms, structural and functional brain abnormalities, and genetic risk factors. Neurobiological pathways connecting genes to clinical phenotypes across the spectrum from schizophrenia to psychotic bipolar disorder remain largely unknown.

Methods: We examined the relationship between structural brain changes and risk alleles across the psychosis spectrum in the multi-site Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) cohort.

Practical interpretation of CYP2D6 haplotypes: Comparison and integration of automated and expert calling.

We describe a population genetic approach to compare samples interpreted with expert calling (EC) versus automated calling (AC) for CYP2D6 haplotyping. The analysis represents 4812 haplotype calls based on signal data generated by the Luminex xMap analyzers from 2406 patients referred to a high-complexity molecular diagnostics laboratory for CYP450 testing. DNA was extracted from buccal swabs.

Multivariate Genetic Correlates of the Auditory Paired Stimuli-Based P2 Event-Related Potential in the Psychosis Dimension From the BSNIP Study.

Objective: The complex molecular etiology of psychosis in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is not well defined, presumably due to their multifactorial genetic architecture. Neurobiological correlates of psychosis can be identified through genetic associations of intermediate phenotypes such as event-related potential (ERP) from auditory paired stimulus processing (APSP). Various ERP components of APSP are heritable and aberrant in SZ, PBP and their relatives, but their multivariate genetic factors are less explored.

Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study.

Schizophrenia (SZ) and psychotic bipolar disorder (PBP) are disabling psychiatric illnesses with complex and unclear etiologies. Electroencephalogram (EEG) oscillatory abnormalities in SZ and PBP probands are heritable and expressed in their relatives, but the neurobiology and genetic factors mediating these abnormalities in the psychosis dimension of either disorder are less explored. We examined the polygenic architecture of eyes-open resting state EEG frequency activity (intrinsic frequency) from 64 channels in 105 SZ, 145 PBP probands and 56 healthy controls (HCs) from the multisite BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study.

Genetic Sources of Subcomponents of Event-Related Potential in the Dimension of Psychosis Analyzed From the B-SNIP Study.

Objective: Biological risk factors underlying psychosis are poorly understood. Biological underpinnings of the dimension of psychosis can be derived using genetic associations with intermediate phenotypes such as subcomponents of auditory event-related potentials (ERPs). Various ERP subcomponent abnormalities in schizophrenia and psychotic bipolar disorder are heritable and are expressed in unaffected relatives, although studies investigating genetic contributions to ERP abnormalities are limited.

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia.

The brain's default mode network (DMN) is highly heritable and is compromised in a variety of psychiatric disorders. However, genetic control over the DMN in schizophrenia (SZ) and psychotic bipolar disorder (PBP) is largely unknown. Study subjects (n = 1,305) underwent a resting-state functional MRI scan and were analyzed by a two-stage approach.

Relation of mitochondrial oxygen consumption in peripheral blood mononuclear cells to vascular function in type 2 diabetes mellitus.

Recent studies have shown mitochondrial dysfunction and increased production of reactive oxygen species in peripheral blood mononuclear cells (PBMCs) and endothelial cells from patients with diabetes mellitus. Mitochondria oxygen consumption is coupled to adenosine triphosphate (ATP) production and also occurs in an uncoupled fashion during formation of reactive oxygen species by components of the electron transport chain and other enzymatic sites. We therefore hypothesized that diabetes would be associated with higher total and uncoupled oxygen consumption in PBMCs that would correlate with endothelial dysfunction.

Length of psychiatric hospitalization is correlated with CYP2D6 functional status in inpatients with major depressive disorder.

Aim: This study aimed to determine the effect of the CYP2D6 genotype on the length of hospitalization stay for patients treated for major depressive disorder.

Methods: A total of 149 inpatients with a diagnosis of major depressive disorder at the Institute of Living, Hartford Hospital (CT, USA), were genotyped to detect altered alleles in the CYP2D6 gene. Prospectively defined drug metabolism indices (metabolic reserve, metabolic alteration and allele alteration) were determined quantitatively and assessed for their relationship to length of hospitalization stay.

Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients.

Aim: This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy.

Patients & Methods: A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors.

Results: The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better 'ideal dose' estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day.

Prediction of warfarin dose reductions in Puerto Rican patients, based on combinatorial CYP2C9 and VKORC1 genotypes.

Background: The influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients.

Objective: To test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm.

Methods: A retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed.

Guidance of pharmacotherapy in a complex psychiatric case by CYP450 DNA typing.

Purpose: To illustrate the utility of CYP450 genotyping to guide clinical psychopharmacological treatment decisions and minimize or avoid harmful and costly adverse drug reactions (ADRs).

Data Sources: DNA was extracted from a whole blood sample from the case study subject and tested for CYP450 gene polymorphisms in the CLIA certified Laboratory of Personalized Health at Genomas, Inc. Clinical data were obtained from patient records and clinician observations.

Mechanisms of statin-induced myalgia assessed by physiogenomic associations.

Objective: We investigated genetic variants predictive of muscular side effects in patients treated with statins. We utilized a physiogenomic approach to prototype a multi-gene panel correlated with statin-induced myalgia.

Background: Statin-induced myalgia occurs in ∼10% of lipid clinic outpatients.

Physiogenomic analysis of CYP450 drug metabolism correlates dyslipidemia with pharmacogenetic functional status in psychiatric patients.

Aims: To investigate associations between novel human cytochrome P450 (CYP450) combinatory (multigene) and substrate-specific drug metabolism indices, and elements of metabolic syndrome, such as low density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), triglycerides and BMI, using physiogenomic analysis.

Methods: CYP2C9, CYP2C19 and CYP2D6 genotypes and clinical data were obtained for 150 consecutive, consenting hospital admissions with a diagnosis of major depressive disorder and who were treated with psychotropic medications. Data analysis compared clinical measures of LDLc, HDLc, triglyceride and BMI with novel combinatory and substrate-specific CYP450 drug metabolism indices.

Novel drug metabolism indices for pharmacogenetic functional status based on combinatory genotyping of CYP2C9, CYP2C19 and CYP2D6 genes.

Aims: We aim to demonstrate clinical relevance and utility of four novel drug-metabolism indices derived from a combinatory (multigene) approach to CYP2C9, CYP2C19 and CYP2D6 allele scoring. Each index considers all three genes as complementary components of a liver enzyme drug metabolism system and uniquely benchmarks innate hepatic drug metabolism reserve or alteration through CYP450 combinatory genotype scores.

Methods: A total of 1199 psychiatric referrals were genotyped for polymorphisms in the CYP2C9, CYP2C19 and CYP2D6 gene loci and were scored on each of the four indices.

Validation of candidate genes associated with cardiovascular risk factors in psychiatric patients.

The purpose of this study was to identify genetic variants predictive of cardiovascular risk factors in a psychiatric population treated with second generation antipsychotics (SGA). 924 patients undergoing treatment for severe mental illness at four US hospitals were genotyped at 1.2 million single nucleotide polymorphisms.

Exposure to non-therapeutic INR in a high risk cardiovascular patient: potential hazard reduction with genotype-guided warfarin (Coumadin) dosing.

A case to illustrate the utility of genetic screening in warfarin (Coumadin) management is reported. A 45 year-old woman of Puerto Rican ancestry was admitted to the emergency room twice within one month with chest pain. She was diagnosed with congestive heart failure, which was stabilized both times.

Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol?

Aim: Administered at maximal dosages, the most common statins--atorvastatin, simvastatin and rosuvastatin--lower low-density lipoprotein cholesterol (LDLC) by an average of 37-57% in patients with primary hypercholesterolemia. We hypothesized novel genetic underpinnings for variation in LDLC levels in the context of statin therapy.

Materials & Methods: Genotyping of 384 SNPs in 202 volunteers from a lipid outpatient clinic was accomplished and LDLC levels obtained from chart records.

CYP2C9 and VKORC1 genotypes in Puerto Ricans: A case for admixture-matching in clinical pharmacogenetic studies.

Backgrounds: Admixture is of great relevance to the clinical application of pharmacogenetics and personalized medicine, but unfortunately these studies have been scarce in Puerto Ricans. Besides, allele frequencies for clinically relevant genetic markers in warfarin response (i.e.

Prevalence of combinatorial CYP2C9 and VKORC1 genotypes in Puerto Ricans: implications for warfarin management in Hispanics.

Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. We determined the frequencies of alleles, single carriers, and double carriers of single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes in a Puerto Rican cohort and gauged the impact of these polymorphisms on warfarin dosage using a published algorithm. A total of 92 DNA samples were genotyped using Luminex x-MAP technology.