Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane.

BACKGROUND: The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however. METHOD: Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-na?ve, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD. RESULTS: Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder. CONCLUSIONS: These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD.     

Buspirone does not produce a 5-HT1A-mediated decrease in temperature in man

Summary Buspirone, a putative serotonin (5-HT)_1A partial agonist, did not produce hypothermia in 17 normal volunteers in a placebo controlled, single blind study. Thus, buspirone may be a weaker agonist at those 5-HT_1A receptors which mediate hypothermia compared to ipsapirone or gepirone, two other 5-HT_1A partial agonists which have been reported to produce hypothermia by a 5-HT_1A-mediated mechanism.     

CD4-positive/heat-stable antigen-positive thymocytes cause graft-versus-host disease across non-major histocompatibility complex incompatibilities

Single-positive thymocytes are the immediate precursors of peripheral recent thymic emigrants (RTE) which develop into mature peripheral T cells. The functional ability of RTE is unclear but their state of differentiation may be relevant to the development of tolerance to peripheral “self” antigens. Since RTE are difficult to analyze, precursor CD4⁺/8⁻ thymocytes were assessed in a model in vivo to determine their functional capability and their susceptibility to tolerance induction. The ability of both heat-stable antigen-positive (HSA⁺) (immature) and HSA⁻ (mature) single-positive thymocytes to cause graft-versus-host disease (GVHD) across non-major histocompatibility complex differences was examined. Both HSA⁻ and HSA⁺ CD4⁺/8⁻ thymocytes from C3H mice caused lethal GVHD in AKR recipients as did CD4⁺ peripheral T cells in controls. Further, neonatal C3H thymocytes also caused lethal GVHD in AKR recipients. Since CD4⁺/8⁻ thymocytes are the precursors of RTE, these results suggest that RTE are not susceptible to tolerance induction to “minor” antigens and may have a normal immune function in vivo. This would suggest that peripheral tolerance may be dependent upon the manner of antigen presentation rather than T cell maturity.     

SAS amplification in soft tissue sarcomas.

Gene amplification is an important mechanism of increased gene expression in a number of human solid tumors. We have recently identified and cloned sequences from a novel DNA amplification unit in malignant fibrous histiocytoma. The amplified sequences are derived from chromosome 12q13-14 and encode a gene designated SAS (sarcoma amplified sequence). In the present study, a series of soft tissue sarcomas was studied to characterize further the phenomenon of SAS amplification. Seven of 22 (32%) malignant fibrous histiocytomas and three liposarcomas contained SAS amplification. Strikingly, all of the tumors with SAS amplification occurred in central sites (i.e., in the abdominal or inguinal regions) rather than in the extremities (i.e., in the arms of legs). These observations demonstrate that SAS amplification occurs with a significant frequency in mesenchymal tumors and is particularly associated with abdominal disease.     

Dexamethasone suppression test abnormalities in multiple sclerosis: relation to ACTH therapy

We studied the 1-mg overnight dexamethasone suppression test (DST) in patients with MS. In about 50% of patients, serum cortisol did not fall below 5.0 micrograms/dl. This percentage was similar in patients with major depression, but contrasted to 11% in normal controls. MS nonsuppressors were not more depressed than suppressors; dexamethasone bioavailability may have contributed because nonsuppressors had lower serum dexamethasone levels than suppressors. Suppressors improved in the week following ACTH therapy; nonsuppressors did not. Furthermore, serum dexamethasone values correlated positively with clinical response to ACTH treatment. The DST may be a useful neuroendocrine test of glucocorticoid sensitivity in MS patients.     

Platelet MAO activity and the cortisol response to dexamethasone in major depression

Previous studies have sometimes found a positive relationship between platelet monoamine oxidase (MAO) activity and dexamethasone nonsuppression in depressed patients. To assess this relationship in more detail, we examined the association between these two biological variables in unmedicated depressed patients. A positive correlation between platelet MAO activity and 8:00 AM serum cortisol levels following an overnight dexamethasone test (1 mg) was observed. The relationship between high and low platelet MAO activity (median split) and suppression of serum cortisol levels was also significant. These relationships were stronger in bipolar patients. Multiple regression revealed that postdexamethasone 8:00 AM dexamethasone levels and platelet MAO activity were independent predictors of the 8:00 AM cortisol levels following dexamethasone. The possibility that platelet MAO activity may be a peripheral marker of brain serotonergic activity which in turn may affect various aspects of the hypothalamo-pituitary-adrenal axis activity, is discussed. We also found that all nine depressed patients studied greater than or equal to 15 days after admission were suppressors. Platelet MAO activity, but not 8:00 AM pre- or postdexamethasone serum cortisol, was related to the severity of depression.