All aspects of the proposed work pertain to the thyroid axis,providing thematic unity. Operational cohesion is provided by the participation and leadership of the applicant, by his experience, and by his commitment to mentorship. Clinical studies are guided in part by the observation that changes in thyroid status,especially toward hypothyroidism, are common and by the notion that such changes, even when slight, may impair CNS function. Study One is addressed to patients with Graves' disease, who are assessed in several ways when hyperthyroid (from illness), when hypothyroid (from radioiodine treatment), and when euthyroid (from hormone replacement). In Study Two the notions are examined: that patients coming for ECT may have been inadvertently """"""""selected"""""""" for subclinical hypothyroidism; that ECT thus does them """"""""special"""""""" damage, because it, like hypothyroidism, impairs memory. Does administered thyroid hormone protect them? Study Three goes directly to the question of subclinical hypothyroidism. What is its prevalence? Do such patients profit from treatment with a thyroid hormone? Study Four seeks to assess the extent to which TRH will offset effects of common sedatives. In Study Five children with a learning disorder are assessed for the nature and severity of their disorder and for subtle changes in thyroid status. Four animal studies are proposed, each resonating with one or another clinical study. In Study One the role of thyroid hormones in regulating the uptake of calcium by brain neurons is measured. We have found that hypothyroidism reduces depolarization-induced calcium ptake. In Study Two the complex relationships in rats between alcohol intake and thyroid state are examined, including an analog of the now-classical clinical finding, TSH blunting in response to administered TRH. Study Three examines the effects of psychotropic drugs, including common sedatives, on TRH binding in brain. Study Four takes as its dependent variable the uptake by brain neurons of thyroid hormones (see uptake of calcium, above). How do drugs affect it? We have confirmed the finding of Dratman that desmethylimi- pramine reduces thyroxine uptake. Do antidepressants make the brain hypothyroid?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Award (K05)
Project #
2K05MH022536-21
Application #
3076051
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1990-09-15
Project End
1995-06-30
Budget Start
1990-09-15
Budget End
1991-06-30
Support Year
21
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Mason, G A; Walker, C H; Prange Jr, A J (1993) L-triiodothyronine: is this peripheral hormone a central neurotransmitter? Neuropsychopharmacology 8:253-8
Prange Jr, A J (1992) The manifold actions of neurotensin, a trophotropic agent. Ann N Y Acad Sci 668:298-306
Garbutt, J C; Mayo Jr, J P; Mason, G A et al. (1991) Interpretation of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH): implications of an improved TSH assay system. Biol Psychiatry 29:718-20
Hashimoto, H; Walker, C H; Prange Jr, A J et al. (1991) The effects of thyroid hormones on potassium-stimulated release of 3H-GABA by synaptosomes of rat cerebral cortex. Neuropsychopharmacology 5:49-54
Stern, R A; Nevels, C T; Shelhorse, M E et al. (1991) Antidepressant and memory effects of combined thyroid hormone treatment and electroconvulsive therapy: preliminary findings. Biol Psychiatry 30:623-7
Shimoda, K; Mason, G A; Walker, C H et al. (1991) Administration of chlordiazepoxide affects [3H][3-MeHis2]thyrotropin-releasing hormone binding in rat brain. Peptides 12:199-202
Mason, G A; Walker, C H; Prange Jr, A J (1990) Depolarization-dependent 45Ca uptake by synaptosomes of rat cerebral cortex is enhanced by L-triiodothyronine. Neuropsychopharmacology 3:291-5
Mason, G A; Stanley, D A; Walker, C H et al. (1988) Chronic alcohol ingestion decreases pituitary-thyroid axis measures in Fischer-344 rats. Alcohol Clin Exp Res 12:731-4
Pedersen, C A; Caldwell, J D; Drago, F et al. (1988) Grooming behavioral effects of oxytocin. Pharmacology, ontogeny, and comparisons with other nonapeptides. Ann N Y Acad Sci 525:245-56
Mason, G A; Bondy, S C; Nemeroff, C B et al. (1987) The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain. Psychoneuroendocrinology 12:261-70

Showing the most recent 10 out of 20 publications