- Email: [email protected]
243. Dopaminergic function and HPA axis activity in psychotic depression
74S
Friday Abstracts
BIOL PSYCHIATRY 2000;47:1S–173S
242. THYROID AXIS ACTIVITY IN DEPRESSED INPATIENTS F. Duval (1,2), M.-C. Mokrani (2), P.E. Bailey (2), M.-A. Crocq (1,2), T.-S. Diep (1), J.-P. Macher (1,2) (1) Centre Hospitalier, Rouffach, France; (2) Research Center for Applied Neuroscience in Psychiatry (FORENAP), Rouffach, France Dysfunction of the thyroid axis is one of the most consistent findings in neuroendocrine studies of major depression. We have reported that, owing to chronobiological influences, the thyrotropin (TSH) response to protirelin (TRH) challenge at 11 PM is more sensitive than at 8 AM and that the difference in TSH response between 11 PM and 8 AM TRH tests (⌬⌬TSH) is an even more sensitive measure. We evaluated the serum levels of TSH, free thyroxine (FT4), and free triiodothyronine (FT3) before and after 8 AM and 11 PM TRH challenges (200 g IV), on the same day, in 108 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. Compared with controls, depressed patients showed lower basal levels of TSH (at 8 AM: p ⬍ 0.006; at 11 PM: p ⬍ 0.000001); lower ⌬TSH values (at 8 AM: p ⬍ 0.0002; at 11 PM: p ⬍ 0.000001); lower ⌬⌬TSH values (p ⬍ 0.000001); higher basal levels of FT4 (at 8 AM: p ⬍ 0.01; at 11 PM: p ⬍ 0.004) and higher basal levels of FT3 (at 8 AM: p ⬍ 0.08; at 11 PM: p ⬍ 0.01). Eighty six patients (80%) had a blunted ⌬⌬TSH test (i.e. ⬍2.5 U/ml). ⌬⌬TSH values were correlated 1) positively with basal levels of TSH (at 8 AM: r ⫽ 0.40; p ⬍ 0.000001; at 11 PM: r ⫽ 0.47; p ⬍ 0.000001) and ⌬TSH values (at 8 AM: r ⫽ 0.25; p ⬍ 0.002; at 11 PM: r ⫽ 0.66; p ⬍ 0.000001), and 2) negatively with FT4 (at 8 AM: r ⫽ 0.24; p ⬍ 0.006; at 11 PM: r ⫽ 0.25; p ⬍ 0.003) and FT3 (at 8 AM: r ⫽ 0.29; p ⬍ 0.0007; at 11 PM: r ⫽ 0.31; p ⬍ 0.0003). However, FT4, FT3 and TSH values (basal and after TRH) were not correlated with post-DST cortisol levels. These data indicate that ⌬⌬TSH, which is independent of HPA axis activity, is a chronobiological index and may be the first sign of thyroid axis dysfunction in depression. Moreover, the thyroid hormone negative feedback to the pituitary is preserved in depression and is a significant factor in the blunting of TSH response to TRH.
243. DOPAMINERGIC FUNCTION AND HPA AXIS ACTIVITY IN PSYCHOTIC DEPRESSION
effect—there were no differences in adrenocorticotropic hormone (ACTH), prolactin (PRL), and growth hormone (GH) responses to APO between SDPs and SDs and HCs. Moreover, in the total sample and in each diagnostic group, DST suppressors and DST non-suppressors showed no differences in hormonal responses to APO. Therefore, our study indicates that dopaminergic function, as assessed by the APO test, does not differ between psychotic and nonpsychotic depressed patients, although HPA disinhibition occurs more frequently in psychotic depressed patients. These results suggest that there is no causal link between HPA axis hyperactivity and dopamine dysfunction at the hypothalamic-pituitary level in psychotic depressed patients.
244. NEUROPSYCHOLOGICAL FUNCTION IN DRUG-FREE DEPRESSIVES A.H. Young, P. Gallagher, R.J. Porter Stanley Foundation Bipolar Research Centre, Department of Psychiatry, University of Newcastle upon Tyne, UK Neuropsychological impairment has been widely reported in major depressive disorder. To clarify if this is secondary to the effects of psychotropics or hypercortisolaemia, we examined 43 patients meeting DSM-IV criteria for major depression, who were free of psychotropic medication for at least 6 weeks and matched controls. All subjects completed a comprehensive neuropsychology test battery and salivary cortisol measures. Depressed subjects demonstrated a clear deficit in psychomotor performance, compared with control subjects, with increased response latencies across a variety of measures, and slowing on the digit symbol substitution test (unpaired t-test; t(72) ⫽ 2.50, p ⫽ 0.016). On the Tower of London task, depressed subjects exhibited slowed initial (MANOVA group effect; F(1,57) ⫽ 4.54, p ⫽ 0.037) and subsequent (MANOVA group effect; F(1,57) ⫽ 5.62, p ⫽ 0.021) thinking times, particularly for more difficult problems, but accuracy was preserved. Depressed subjects were also impaired on both accuracy and strategy measures on the Spatial Working Memory test. However, there were no significant difference from controls on accuracy of short-term visual recognition memory and conditional associative learning. Salivary cortisol levels of depressed patients did not differ from controls at any of the time points measured (MANOVA group effect; F(1,50) ⫽ 0.226, p ⫽ .637; group by time interaction F(3,150) ⫽ 0.126, p ⫽ 0.945). This study demonstrates neuropsychological impairment, primarily involving psychomotor slowing and impaired working memory in a large group of drug-free, depressed patients. The effects of drugs or hypercortisolaemia do not explain these deficits.
F. Duval (1,2), M.-C. Mokrani (2), P.E. Bailey (2), M.-A. Crocq (1,2), T.-S. Diep (1), J.-P. Macher (1,2) (1) Centre Hospitalier, Rouffach, France; (2) Research Center for Applied Neuroscience in Psychiatry (FORENAP), Rouffach, France It has been hypothesized that psychotic symptoms in depression may be due to increased dopamine activity secondary to hypothalamic-pituitaryadrenal (HPA) axis overactivity. To test this hypothesis we examined the cortisol response to dexamethasone suppression test (DST, 1 mg orally) and multihormonal responses to apomorphine (APO, 0.75 mg SC)—a dopamine agonist—in 123 drug-free DSM-IV severely-depressed inpatients: 81 without psychotic features (SD; 35M/46F; mean age ⫾ SD, 38.1 ⫾ 10.6 years) and 42 with psychotic features (SDP; 19M/23F; mean age 39.1 ⫾ 9.7 years); and 36 hospitalized controls (HC; 15M/21F; mean age 35.8 ⫾ 9.1 years). SDPs showed increased activity of the HPA system (i.e. higher post-DST cortisol levels) than HCs (p ⬍ 0.00001) and SDs (p ⬍ 0.00002). Although APO-induced cortisol stimulation was lower in SDPs than in HCs (p ⬍ 0.04)— owing to a baseline cortisol
245. REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION—EVIDENCE FOR ANTIDEPRESSANT-LIKE AND NEUROPROTECTIVE EFFECTS M.E. Keck, M.B. Mu¨ller, I. Sillaber, T. Welt, N. Toschi, R. Landgraf, M. Engelmann, F. Holsboer, A. Post Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany The effects of rTMS on selected brain functions were investigated in three different breeding lines of Wistar rats. Results obtained in com-
Friday Abstracts
BIOL PSYCHIATRY 2000;47:1S–173S
242. THYROID AXIS ACTIVITY IN DEPRESSED INPATIENTS F. Duval (1,2), M.-C. Mokrani (2), P.E. Bailey (2), M.-A. Crocq (1,2), T.-S. Diep (1), J.-P. Macher (1,2) (1) Centre Hospitalier, Rouffach, France; (2) Research Center for Applied Neuroscience in Psychiatry (FORENAP), Rouffach, France Dysfunction of the thyroid axis is one of the most consistent findings in neuroendocrine studies of major depression. We have reported that, owing to chronobiological influences, the thyrotropin (TSH) response to protirelin (TRH) challenge at 11 PM is more sensitive than at 8 AM and that the difference in TSH response between 11 PM and 8 AM TRH tests (⌬⌬TSH) is an even more sensitive measure. We evaluated the serum levels of TSH, free thyroxine (FT4), and free triiodothyronine (FT3) before and after 8 AM and 11 PM TRH challenges (200 g IV), on the same day, in 108 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. Compared with controls, depressed patients showed lower basal levels of TSH (at 8 AM: p ⬍ 0.006; at 11 PM: p ⬍ 0.000001); lower ⌬TSH values (at 8 AM: p ⬍ 0.0002; at 11 PM: p ⬍ 0.000001); lower ⌬⌬TSH values (p ⬍ 0.000001); higher basal levels of FT4 (at 8 AM: p ⬍ 0.01; at 11 PM: p ⬍ 0.004) and higher basal levels of FT3 (at 8 AM: p ⬍ 0.08; at 11 PM: p ⬍ 0.01). Eighty six patients (80%) had a blunted ⌬⌬TSH test (i.e. ⬍2.5 U/ml). ⌬⌬TSH values were correlated 1) positively with basal levels of TSH (at 8 AM: r ⫽ 0.40; p ⬍ 0.000001; at 11 PM: r ⫽ 0.47; p ⬍ 0.000001) and ⌬TSH values (at 8 AM: r ⫽ 0.25; p ⬍ 0.002; at 11 PM: r ⫽ 0.66; p ⬍ 0.000001), and 2) negatively with FT4 (at 8 AM: r ⫽ 0.24; p ⬍ 0.006; at 11 PM: r ⫽ 0.25; p ⬍ 0.003) and FT3 (at 8 AM: r ⫽ 0.29; p ⬍ 0.0007; at 11 PM: r ⫽ 0.31; p ⬍ 0.0003). However, FT4, FT3 and TSH values (basal and after TRH) were not correlated with post-DST cortisol levels. These data indicate that ⌬⌬TSH, which is independent of HPA axis activity, is a chronobiological index and may be the first sign of thyroid axis dysfunction in depression. Moreover, the thyroid hormone negative feedback to the pituitary is preserved in depression and is a significant factor in the blunting of TSH response to TRH.
243. DOPAMINERGIC FUNCTION AND HPA AXIS ACTIVITY IN PSYCHOTIC DEPRESSION
effect—there were no differences in adrenocorticotropic hormone (ACTH), prolactin (PRL), and growth hormone (GH) responses to APO between SDPs and SDs and HCs. Moreover, in the total sample and in each diagnostic group, DST suppressors and DST non-suppressors showed no differences in hormonal responses to APO. Therefore, our study indicates that dopaminergic function, as assessed by the APO test, does not differ between psychotic and nonpsychotic depressed patients, although HPA disinhibition occurs more frequently in psychotic depressed patients. These results suggest that there is no causal link between HPA axis hyperactivity and dopamine dysfunction at the hypothalamic-pituitary level in psychotic depressed patients.
244. NEUROPSYCHOLOGICAL FUNCTION IN DRUG-FREE DEPRESSIVES A.H. Young, P. Gallagher, R.J. Porter Stanley Foundation Bipolar Research Centre, Department of Psychiatry, University of Newcastle upon Tyne, UK Neuropsychological impairment has been widely reported in major depressive disorder. To clarify if this is secondary to the effects of psychotropics or hypercortisolaemia, we examined 43 patients meeting DSM-IV criteria for major depression, who were free of psychotropic medication for at least 6 weeks and matched controls. All subjects completed a comprehensive neuropsychology test battery and salivary cortisol measures. Depressed subjects demonstrated a clear deficit in psychomotor performance, compared with control subjects, with increased response latencies across a variety of measures, and slowing on the digit symbol substitution test (unpaired t-test; t(72) ⫽ 2.50, p ⫽ 0.016). On the Tower of London task, depressed subjects exhibited slowed initial (MANOVA group effect; F(1,57) ⫽ 4.54, p ⫽ 0.037) and subsequent (MANOVA group effect; F(1,57) ⫽ 5.62, p ⫽ 0.021) thinking times, particularly for more difficult problems, but accuracy was preserved. Depressed subjects were also impaired on both accuracy and strategy measures on the Spatial Working Memory test. However, there were no significant difference from controls on accuracy of short-term visual recognition memory and conditional associative learning. Salivary cortisol levels of depressed patients did not differ from controls at any of the time points measured (MANOVA group effect; F(1,50) ⫽ 0.226, p ⫽ .637; group by time interaction F(3,150) ⫽ 0.126, p ⫽ 0.945). This study demonstrates neuropsychological impairment, primarily involving psychomotor slowing and impaired working memory in a large group of drug-free, depressed patients. The effects of drugs or hypercortisolaemia do not explain these deficits.
F. Duval (1,2), M.-C. Mokrani (2), P.E. Bailey (2), M.-A. Crocq (1,2), T.-S. Diep (1), J.-P. Macher (1,2) (1) Centre Hospitalier, Rouffach, France; (2) Research Center for Applied Neuroscience in Psychiatry (FORENAP), Rouffach, France It has been hypothesized that psychotic symptoms in depression may be due to increased dopamine activity secondary to hypothalamic-pituitaryadrenal (HPA) axis overactivity. To test this hypothesis we examined the cortisol response to dexamethasone suppression test (DST, 1 mg orally) and multihormonal responses to apomorphine (APO, 0.75 mg SC)—a dopamine agonist—in 123 drug-free DSM-IV severely-depressed inpatients: 81 without psychotic features (SD; 35M/46F; mean age ⫾ SD, 38.1 ⫾ 10.6 years) and 42 with psychotic features (SDP; 19M/23F; mean age 39.1 ⫾ 9.7 years); and 36 hospitalized controls (HC; 15M/21F; mean age 35.8 ⫾ 9.1 years). SDPs showed increased activity of the HPA system (i.e. higher post-DST cortisol levels) than HCs (p ⬍ 0.00001) and SDs (p ⬍ 0.00002). Although APO-induced cortisol stimulation was lower in SDPs than in HCs (p ⬍ 0.04)— owing to a baseline cortisol
245. REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION—EVIDENCE FOR ANTIDEPRESSANT-LIKE AND NEUROPROTECTIVE EFFECTS M.E. Keck, M.B. Mu¨ller, I. Sillaber, T. Welt, N. Toschi, R. Landgraf, M. Engelmann, F. Holsboer, A. Post Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804 Munich, Germany The effects of rTMS on selected brain functions were investigated in three different breeding lines of Wistar rats. Results obtained in com-