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Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT2A binding kinetics (Bmax and KD) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher Bmax in all subjects (F=3.53, df=2,211; p=0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F=7.56, df=2,60, p=0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. Bmax was not related to a diagnosis of mood disorders. The TT genotype appears associated with higher platelet 5-HT2A Bmax in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.

The 5-HT(1B) receptor has been implicated in several psychopathologies, including pathological aggression, alcoholism and suicide. To test these and related potential genetic relationships in a single population, the human 5-HT(1B) receptor (h5-HTR(1B)) genotype for the G861C polymorphism was determined in 394 psychiatric patients and 96 healthy volunteers. Structured clinical interviews generated DSM III-R diagnoses. No significant association of the genotype or allele frequencies of the h5-HTR(1B) G861C locus was observed with diagnoses of alcoholism, bipolar disorder, schizophrenia or a history of a suicide attempt. Exploratory analyses indicated an association of the genotype and allele frequencies of the h5-HTR(1B) G861C locus with a history of substance abuse disorder (chi(2) = 9.51, df = 2, p = 0.009; chi(2) = 7.31, df = 1, p = 0.007, respectively) and with a diagnosis of a major depressive episode (chi(2) = 6.83, df = 2, p = 0.033; chi(2) = 5.81, df = 1, p = 0.016, respectively). Significant gene dose effects on the risk for substance abuse disorder and a major depressive episode were observed with the 861C allele (Armitage linearity tendency test: chi(2) = 7.20, df = 1, p = 0.008; chi(2) = 6.80, df = 1, p = 0.009, respectively). Substance abuse disorder and major depression appear to be associated with the h5-HTR(1B) G861C locus in the patient population, but other psychopathologies such as bipolar disorder, schizophrenia, alcoholism, and suicide attempts were not found to be associated with this polymorphism. This preliminary result will need replication, given the limitations of association studies.

Analysis of an extensive database of human platelet 5-HT2A receptor binding assays has been conducted in order to identify factors that may affect the assay results. Despite anecdotal reports that storage of frozen platelet pellets may affect 5-HT2A binding affinity and capacity, no quantitative study has been reported in the literature. Analysis of binding data for 373 frozen samples with a storage time up to three years is presented in this paper. It is shown that prolonged storage significantly decreases binding. The loss of binding capacity begins in the first six month of storage. Bmax declines by half after 17 month. The impact of storage time on the binding affinity is much smaller. There is only about 20% increase in the value of affinity KD during the half-life of Bmax. Differences in sample storage time may partly explain discrepancies in results between different research groups. Nonspecific binding due to binding to filter material diminishes accuracy and reliability of the binding assays as a result of a decrease in the ratio of specific to nonspecific ratio. A data analysis based on our suggested mathematical model shows that this effect depends on tissue concentration in test tube and becomes pronounced when the concentration is below 0.1 mg protein ml (at 0.2 nM of ligand). Above 0.1 mg protein ml , percentage of specific to total binding exceeds 65%, which is an acceptable level for the ratio. The majority of the binding studies reported in the literature employed a tissue concentration more than 0.5 mg ml , well above the minimal limit sufficient for a reliable assay. However, development of microassays to conserve precious tissue must take the limit into consideration.

Magnetohydrodynamic (MHD) buoyancy‐driven instability has much in common with gravity‐driven natural convection instability in thermally stratified fluids, in that account must be taken of the temperature dependence of conductivity in the former case and of density in the latter case. Employing the Monin–Obukhov theory of mixed convection in a stratified atmosphere, temperature and velocity profiles in MHD turbulent shear flow are obtained. The problem of the boundary‐layer development is solved, and the heat and momentum fluxes are found. It is shown that the buoyancy force effects drastically change the fluxes when the Stuart number exceeds unity. Anode–cathode asymmetry observed experimentally on MHD devices is explained.

This study explores the possibility of localizing the excitation centers of electrical waves inside the heart wall using voltage-sensitive dyes (fluorescent or absorptive). In the present study, we propose a method for the 3-D localization of excitation centers from pairs of 2-D images obtained in two modes of observation: reflection and transillumination. Such images can be obtained using high-speed charge-coupled device (CCD) cameras and photodiode arrays with time resolution up to 0.5 ms. To test the method, we simulate optical signals produced by point sources and propagating ellipsoidal waves in 1-cm-thick slabs of myocardial tissue. Solutions of the optical diffusion equation are constructed by employing the method of images with Robin boundary conditions. The coordinates of point sources as well as of the centers of expanding waves can be accurately determined using the proposed algorithm. The method can be extended to depth estimations of the outer boundaries of the expanding wave. The depth estimates are based on ratios of spatially integrated images. The method shows high tolerance to noise and can give accurate results even at relatively low signal-to-noise ratios. In conclusion, we propose a novel and efficient algorithm for the localization of excitation centers in 3-D cardiac tissue.

Voltage-sensitive dyes have become an important tool in visualizing electrical activity in cardiac tissue. However, there are no established methods for assessing the contribution of intramural electrical excitation to recorded optical signals. Here, we develop algorithms to calculate voltage-dependent optical signals from three-dimensional distributions of transmembrane voltage inside the myocardial wall (the forward problem). Optical diffusion theory is applied for different imaging modes including subsurface imaging or epi-illumination, transillumination and coaxial scanning. We use the solutions of the forward problem to assess these imaging methods with respect to their effectiveness in visualizing two types of 3D cardiac activity: electrical point sources and intramural scroll waves initiated at various depths. Simulations were performed both for fluorescent and absorptive voltage-sensitive dyes. In the case of point sources, we focus on the lateral optical resolution, as a function of the source depth. We find that, among the studied methods, fluorescent coaxial scanning yields the best optical resolution (

Background Major depression is often treated with medications in doses that are too low or too short in duration. We published an early version of the Antidepressant Treatment History Form (ATHF) that rates the adequacy of antidepressant treatment. The updated ATHF presented here includes newer medications and a computer algorithm to automate the evaluation of the adequacy of pharmacotherapy or electroconvulsive therapy for depression. Method The computer algorithm was written in MS-DOS Q-BASIC and in Visual Basic 5.0. Treatment data from 47 depressed (Structured Clinical Interview for DSM-III-R) patients were scored by the computer algorithm and assigned a number from 0 to 5 for the adequacy of antidepressant treatment. A psychiatrist blinded to the computer ratings manually rated the treatment using the ATHF. Results The computer algorithm, based on an updated version of the ATHF, estimates the adequacy of treatment of unipolar and bipolar depression. Computer algorithm results agreed with those generated by a clinician completing the form manually (kappa = 0.88 to 1.00). Conclusion The computer algorithm can be used to analyze large databases and may help reduce the morbidity and mortality associated with major depression by improving the assessment of adequacy of pharmacologic treatments for research and quality assurance purposes. The availability of the updated ATHF on the Internet for downloading allows for modifications according to the user's purposes.

Background : Seasonal variations in onset of mood disorders and in serotonergic function are reported, but their relationship is unclear. Methods : Circannual variation in platelet 5-HT 2A binding was measured in 68 healthy subjects and 121 patients with a major depressive episode. In 73 patients the current episode began during Spring or Fall. Results : Significant, but different, circannual variations were found in patients compared with controls. Controls had two peaks of B max , one in Spring and another in Fall. Fall and Winter K D was 41% lower compared with Spring and Summer K D . Patients had a peak of B max in early Spring and a lesser one in late Fall. B max during Spring and Fall was 12% higher compared with Winter and Summer. K D was higher during October through February compared with the rest of the year. B max in patients was higher compared with controls in March. The opposite difference was observed in September–December. These differences from controls were mostly due to patients with an onset of the current major depressive episode during Spring or Fall. Conclusions : Patients with a major depressive episode differed from controls in circannual variation of platelet 5-HT 2A binding. This may reflect a vulnerability to seasonal effects in patients with mood disorders.

To reevaluate platelet serotonin (5-HT) levels in autism, measuring and controlling for effects of race and puberty. The specificity of hyperserotonemia for autism versus cognitive impairment is also assessed.Platelet 5-HT levels were measured in 77 individuals, aged 2 through 37 years, with autistic disorder; 65 normal controls; and 22 mentally retarded or otherwise cognitively impaired (MR/CI) prepubertal children. Effects of diagnosis, race, and pubertal status were evaluated by analysis of variance in separate pre- and postpubertal groups. 5-HT levels were expressed as ng/mL blood and ng/microL platelet volume.Among prepubertal children, significant effects of diagnosis (ng/mL; F2,109 = 5.9, p = .004) and race (F2,109 = 14.7, p.0005) were found. Autistic youngsters had significantly higher 5-HT concentrations than controls, although the elevation (25%) was less than typically reported; MR/CI children had levels very similar to those of controls. White children had significantly lower 5-HT levels than black or Latino youngsters, regardless of diagnosis. Diagnosis and race effects were nonsignificant in the postpubertal group. Postpubertal subjects had lower 5-HT concentrations than prepubertal subjects (ng/mL; F1,114 = 28.5, p.0005).The data underscore the importance of matching for race and pubertal status in neuropsychiatric research and suggest that the prevalence of hyperserotonemia in autistic individuals may have been overestimated because of a failure to control for both variables. Hyperserotonemia was not found in MR/CI youngsters without autistic features.