Effect of lithium on phosphoinositide metabolism in human brain: a proton decoupled (31)P magnetic resonance spectroscopy study.

BACKGROUND: The objective of our study was to evaluate whether lithium increases brain phosphomonoester (PME) levels in human subjects. METHODS: Proton decoupled (31)P magnetic resonance spectra were obtained from eight healthy volunteers before and after the administration of lithium carbonate, 450 mg b.i.d., for 7 and 14 days. RESULTS: Pairwise comparisons of the mole percent PME revealed a significant increase from baseline at day 7 and day 14 of lithium administration. CONCLUSIONS: An increase in PME concentration with 7 and 14 days of lithium administration in the human brain in vivo was observed. Because the inositol-1-monophosphate contributes to the PME peak, this result suggests that some of the initial actions of lithium may occur through a reduction of myo-inositol, which in turn may initiate a cascade of secondary changes at different levels of signal transduction process and gene expression in brain, effects that are ultimately responsible for the therapeutic benefits of lithium.

Additional findings on the association between anxiety sensitivity and hypochondriacal concerns: examination of patients with major depression.

Hypochondriacal concerns ranging from disease phobias to bodily preoccupations are common among patients with panic disorder. In a previous study of patients with panic disorder, we found that, of a number of symptom dimensions examined, anxiety sensitivity was the strongest predictor of hypochondriacal concerns. This finding has been the topic of subsequent debate in the anxiety literature, with concerns raised whether true hypochondriacal concerns were confounded with typical panic-related concerns. To clarify this issue, we now report on the association between anxiety sensitivity and hypochondriacal concerns in 100 patients with major depression and no history of panic disorder. Consistent with our previous study, we found that of the symptoms examined--anxiety sensitivity, depressed mood, anxious mood, somatic symptoms, and anger/hostility--anxiety sensitivity was the strongest predictor of hypochondriacal concerns. Findings are discussed in relation to the role of catastrophic interpretations of somatic symptoms in depression, panic disorder, and hypochondriasis.

"Specific" [(3)H]8-OH-DPAT binding to glass fiber filter paper: Implications for the analysis of serotonin binding site subtypes.

The effect of buffer constituents on [(3)H]8-OH-DPAT binding to glass fiber filter paper was examined. Apparent "specific" [(3)H]8-OH-DPAT binding to glass fiber filter paper can be demonstrated when the radioligand binding assay is performed in the absence of 0.1% ascorbate. This artifactual "specific" binding is time dependent and appears to saturate. In addition, drug competition studies reveal complex interactions with [(3)H]8-OH-DPAT binding to glass fiber filter paper in the absence of ascorbate. Both 5-HT and chlorimipramine appear to "complete" for the sites labeled by [(3)H]8-OH-DPAT while both d-LSD and methysergide cause an increase in the [(3)H]8-OH-DPAT binding to glass fiber filter paper at micromolar concentrations. These data indicate that [(3)H]8-OH-DPAT binding to glass fiber filter paper may lead to misinterpretation of radioligand data obtained using brain homogenates in the absence of ascorbate.

Linkage disequilibrium and evolutionary relationships of DNA variants (restriction enzyme fragment length polymorphisms) at the serum albumin locus.

Four additional DNA variants (restriction enzyme fragment length polymorphisms) making a total of eight polymorphic sites at the human albumin locus have been identified. These eight sites were found after screening 689 of 20,000 nucleotides by using cDNA probes for albumin with 27 different restriction enzymes. One in 85 nucleotides was therefore potentially polymorphic. The average nucleotide diversity between any two randomly chosen chromosomes was calculated to be 1/500. We observed marked linkage disequilibrium between the eight variants. Only 7 haplotypes among 256 possible combinations were observed in 160 chromosomes from Caucasoids, Blacks, and Asians. Two haplotypes were found in all three human races, indicating that their origin predated human racial divergence. The three rarest haplotypes appear to represent recombinational events between the more common haplotypes. All crossovers occurred in the same general region. Studies of several nonhuman primates indicated that the origin of one haplotype predated the human-African ape divergence. Although it is not possible to rule out maintenance of this tight linkage by selection or fixation, it is suggested that the limited number of haplotypes at the chromosomal site of the albumin gene near the centromere of chromosome 4 may be the result of decreased recombination.

Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia.

By using cDNA probes for the human albumin gene, four restriction enzyme fragment length polymorphisms (RFLPs) were discovered that were transmitted by codominant autosomal inheritance. Among Caucasians, the gene frequencies were 0.04/0.96 for Msp I/5', 0.43/0.57 for Hae III/3', 0.44/0.56 for Hae III/5', and 0.04/0.42/0.54 for Pst I/5'. These common variants provide a marker for chromosome 4 (q11-q13). A calculation of the extent of DNA variation at the albumin locus revealed that 1/95 nucleotide sites was affected by a RFLP, a figure similar to that found in the globin system. Restriction enzyme fragment study of the DNA of a human analbuminemic individual revealed no gross structural rearrangements of the albumin locus. The exact nature of abnormality will require more study.