- Email: [email protected]
Do WML contribute to the subsequent development of dementia in patients with mild cognitive impairment?
s179
Pl Affective disorders and antidepressants
1F?1.123)Synthetic pathways of 3a-reduced steroids in major depression recovery
neuroactive and after clinical
A. Strchle, E. Romeo’, B. Hermann, F. Holsboer, R. Rupprecht. Max Planck Institute of Psychiatry, Kraepelinstr 10, 80804 Munich, Germany I Unioersitci degli Studi di Roma Tor Vergata, Department of Experimentul Medicine, via Alberic,o Ii, n. 35, 00193 Rome, Italy There is preclinical and clinical evidence that concentrations of 3a,5atetrahydroprogesterone (3a,Sa-THP), a neuroactive steroid that is a positive allosteric modulator of the GABA* receptor, are altered in depression and normalize as a result of antidepressant treatment (Romeo et al. in press). However, no data are available on the concentrations of 3a,5atetrahydrodeoxycorticosterone (3a,Sa-THDOC), another GABAAergic neuroactive steroid, in depression. We studied nine depressed patients before and after treatment with various antidepressants and compared them to healthy matched control subjects. Blood samples were quantified by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of 3a,Sa-THDOC and its precursor 5a-dihydrodeoxycorticosterone (5aDHDOC) were increased in depressed patients and were not significantly influenced by antidepressant treatment. However, 3a,Sa-THP concentrations were decreased in depression and clinically effective antidepressant treatment was accompanied by an increase of 3a,Sa-THP concentrations in these patients. Our results provide the first evidence for a differential alteration in the biosynthesis of fa-reduced neuroactive steroids in major depression, which is only partially reversed by successful antidepressant treatment. References [l] Romeo E., Strtihle A., di Michele F., Spaletta G., Hermann B., Holsboer F., Pasini A. and Rupprecht R. (in press) Effects of antidepressant treatment on mumactive steroids in major depression. Am. J. Psychiatry.
[ml
Do WML contribute to the subsequent development of dementia in patients with mild cognitive impairment?
H. Wolf’, G. Ecke, M. Grunwald, S. Angerhiifer, D. Zedlick, H.-J. Gertz. lJnioer.sity of Leipzig, Department of Psychiatry, Emilienstr, 14, D-04107 Leipzig, e-mail: [email protected], Germany Background: In recent years, white matter changes on CT or MRI have been widely and controversially discussed with regard to their potential impact on the development and course of AD. Little is known about the prognostic significance of such changes in cognitively impaired individuals who are at risk for subsequent development of dementia. Our present study aims at investigating the impact of white matter changes seen on CT (white matter lucencies = WML) on the course of mild cognitive impairment (MCI). Patients: We report on 27 cognitively impaired patients attending a memory clinic with no evidence of symptomatic cerebrovascular disease or dementia at initial presentation (to). Subjects were consecutively included into the study (baseline, to) and were re-examined after an average interval of 2.7 years (tl) (mean age at to 72 years * 4.03, range 67-84). Methods: At to, all patients underwent cognitive screening tests (MMSE, SIDAM) and CT. White matter lucencies on CT were visually classified, using a 4-point grading scale (O-none, l-mild, 2-moderate, 3-severe changes). Bilateral scores of three different areas (frontal, occipital, paraventricular) were added to obtain a composite score. At tl , the patients were reassessed neuropsychologically and clinically. The diagnosis of dementia was established according to ICD- 10. Results: In the whole group, CT lucencies at b were seen in 13 cases (48.1%). At tl, 8 patients had developed dementia and met the clinical criteria for probable AD. In all but one of those who subsequently developed dementia, WML had been observed on the initial CT scan
(87.5% vs. 31.6% in the stable group p = 0.009). Retrospective analysis regarding the severity of WML at TVrevealed significantly more severe changes in patients who progressed to dementia as compared to those who remained cognitively stable (5.6 vs. 1.2; p = 0.0013). Discussion: WML on CT are a common finding in elderly patients with mild cognitive impairment. Our results suggest that, in some cases, they might contribute to the subsequent development of dementia in patients with MCI. Further investigations are necessary to examine whether or not WML represent a causal pathogenetic mechanism in AD. Nevertheless, white matter changes on CT or MRI should be included in prospective studies as potential predictor variables. (Supported by BMBF, lnterdisziplinlres Zentrum fiir klinische Forschung, IZKF, Projekt C8) )p.1.125]
Central serotonin transporter density in symptomatic depressed SAD patients and healthy controls
M. Willeit’, N.N. Praschak-Rieder’, W. Pirke?, A. Neumeister’, J. Stasmy’,E. Hilger’, S. Asenbaum’, T. Briicke2, S. Kasper’. ‘Dept. of General Psychiahy; ‘Dept. of Neurology, Vienna Uniuersify, Austria Several lines of evidence suggest an important role for serotonergic mechanisms in the pathogenesis of seasonal affective disorder (SAD). A crucial step in the regulation of serotonergic neurotransmission is reuptake via the serotonin transporter (S-HTT). Therefore. platelet 5HTT as a model for central nervous neurotransmission has been studied extensively without conclusive results. We examined for the first time the central nervous 5-HTT density in symptomatic depressed SAD patients (fall-winter pattern) and healthy controls using [1231]-fi-ClT single photon emission computer tomography (SPECT). Seventeen drug free symptomatic depressed SAD patients and 17 healthy controls matched for age, season and gender were investigated with SPECT 4 hours post injection of 3.5 f 0.5 mCi [1231]-~-ClT. Examinations were performed between October and February, matched paires were studied within 3 weeks. All patients and controls were rated psychopathologically on the SPECT examination day by one and the same rater using the Structured Interview Guide for Hamilton Depression Rating Scale, SAD version (SIGH-SAD). Regions of interest (ROls) comprising thalamushypothalamus and mesencephalon-pons were hand drawn by one and the same examiner blind to the subjects condition. A ratio was calculated between mean counts in the target ROl’s and the cerebellum serving as reference region (ratio-l). [‘231]-fi-ClT SPECT revealed no difference in 5-HTT density between symptomatic depressed patients and healthy controls in the thalamus-hypothalamus (1.67 f 0.25 vs. 1.67 f 0.26; ratio-l : Mann-Whitney-U-test: ns.) and the mesencephalon-pons (0.98 f 1.7 vs. 0.9 1 f 0.10; ratio-l ; Mann-Whitney-U-test: n.s.). A positive correlation between 5-HTT density in the aforementioned ROls and severity of depression measured by the SIGH-SAD was found in the patient group (thalamus-hypothalamus: r = 0.61; 2-tailed p = 0.01; mesencephalonpons: r = 0.53; 2-tailed p = 0.03). These results suggest that the occurrence of depression in SAD is not associated with alterations in 5HTT density in thalamus-hypothalamus and the mesencephalon-pens. However, [‘231]-~-ClT binding correlates positively with the severity of depression. Thus, serotonin reuptake in thalamus-hypothalamus and mesencephalon-pons could influence the severity of depressive symptoms by modulating a third, yet unknown factor. Ip.1.1261
The contribution of ovarian steroids to early postnatal depression
K. Love& A. Wieck, L. Appleby. Department of Manchester: UK
@Psychiat~,
Universit?,
Background: It has been suggested that early postnatal depression is triggered by the effects of ovarian hormone “withdrawal” after childbirth on central neurotransmitter systems. If this is the case then women with a large posmatal drop should be likely to become depressed postnatally. This hypothesis was tested in this study.
Pl Affective disorders and antidepressants
1F?1.123)Synthetic pathways of 3a-reduced steroids in major depression recovery
neuroactive and after clinical
A. Strchle, E. Romeo’, B. Hermann, F. Holsboer, R. Rupprecht. Max Planck Institute of Psychiatry, Kraepelinstr 10, 80804 Munich, Germany I Unioersitci degli Studi di Roma Tor Vergata, Department of Experimentul Medicine, via Alberic,o Ii, n. 35, 00193 Rome, Italy There is preclinical and clinical evidence that concentrations of 3a,5atetrahydroprogesterone (3a,Sa-THP), a neuroactive steroid that is a positive allosteric modulator of the GABA* receptor, are altered in depression and normalize as a result of antidepressant treatment (Romeo et al. in press). However, no data are available on the concentrations of 3a,5atetrahydrodeoxycorticosterone (3a,Sa-THDOC), another GABAAergic neuroactive steroid, in depression. We studied nine depressed patients before and after treatment with various antidepressants and compared them to healthy matched control subjects. Blood samples were quantified by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of 3a,Sa-THDOC and its precursor 5a-dihydrodeoxycorticosterone (5aDHDOC) were increased in depressed patients and were not significantly influenced by antidepressant treatment. However, 3a,Sa-THP concentrations were decreased in depression and clinically effective antidepressant treatment was accompanied by an increase of 3a,Sa-THP concentrations in these patients. Our results provide the first evidence for a differential alteration in the biosynthesis of fa-reduced neuroactive steroids in major depression, which is only partially reversed by successful antidepressant treatment. References [l] Romeo E., Strtihle A., di Michele F., Spaletta G., Hermann B., Holsboer F., Pasini A. and Rupprecht R. (in press) Effects of antidepressant treatment on mumactive steroids in major depression. Am. J. Psychiatry.
[ml
Do WML contribute to the subsequent development of dementia in patients with mild cognitive impairment?
H. Wolf’, G. Ecke, M. Grunwald, S. Angerhiifer, D. Zedlick, H.-J. Gertz. lJnioer.sity of Leipzig, Department of Psychiatry, Emilienstr, 14, D-04107 Leipzig, e-mail: [email protected], Germany Background: In recent years, white matter changes on CT or MRI have been widely and controversially discussed with regard to their potential impact on the development and course of AD. Little is known about the prognostic significance of such changes in cognitively impaired individuals who are at risk for subsequent development of dementia. Our present study aims at investigating the impact of white matter changes seen on CT (white matter lucencies = WML) on the course of mild cognitive impairment (MCI). Patients: We report on 27 cognitively impaired patients attending a memory clinic with no evidence of symptomatic cerebrovascular disease or dementia at initial presentation (to). Subjects were consecutively included into the study (baseline, to) and were re-examined after an average interval of 2.7 years (tl) (mean age at to 72 years * 4.03, range 67-84). Methods: At to, all patients underwent cognitive screening tests (MMSE, SIDAM) and CT. White matter lucencies on CT were visually classified, using a 4-point grading scale (O-none, l-mild, 2-moderate, 3-severe changes). Bilateral scores of three different areas (frontal, occipital, paraventricular) were added to obtain a composite score. At tl , the patients were reassessed neuropsychologically and clinically. The diagnosis of dementia was established according to ICD- 10. Results: In the whole group, CT lucencies at b were seen in 13 cases (48.1%). At tl, 8 patients had developed dementia and met the clinical criteria for probable AD. In all but one of those who subsequently developed dementia, WML had been observed on the initial CT scan
(87.5% vs. 31.6% in the stable group p = 0.009). Retrospective analysis regarding the severity of WML at TVrevealed significantly more severe changes in patients who progressed to dementia as compared to those who remained cognitively stable (5.6 vs. 1.2; p = 0.0013). Discussion: WML on CT are a common finding in elderly patients with mild cognitive impairment. Our results suggest that, in some cases, they might contribute to the subsequent development of dementia in patients with MCI. Further investigations are necessary to examine whether or not WML represent a causal pathogenetic mechanism in AD. Nevertheless, white matter changes on CT or MRI should be included in prospective studies as potential predictor variables. (Supported by BMBF, lnterdisziplinlres Zentrum fiir klinische Forschung, IZKF, Projekt C8) )p.1.125]
Central serotonin transporter density in symptomatic depressed SAD patients and healthy controls
M. Willeit’, N.N. Praschak-Rieder’, W. Pirke?, A. Neumeister’, J. Stasmy’,E. Hilger’, S. Asenbaum’, T. Briicke2, S. Kasper’. ‘Dept. of General Psychiahy; ‘Dept. of Neurology, Vienna Uniuersify, Austria Several lines of evidence suggest an important role for serotonergic mechanisms in the pathogenesis of seasonal affective disorder (SAD). A crucial step in the regulation of serotonergic neurotransmission is reuptake via the serotonin transporter (S-HTT). Therefore. platelet 5HTT as a model for central nervous neurotransmission has been studied extensively without conclusive results. We examined for the first time the central nervous 5-HTT density in symptomatic depressed SAD patients (fall-winter pattern) and healthy controls using [1231]-fi-ClT single photon emission computer tomography (SPECT). Seventeen drug free symptomatic depressed SAD patients and 17 healthy controls matched for age, season and gender were investigated with SPECT 4 hours post injection of 3.5 f 0.5 mCi [1231]-~-ClT. Examinations were performed between October and February, matched paires were studied within 3 weeks. All patients and controls were rated psychopathologically on the SPECT examination day by one and the same rater using the Structured Interview Guide for Hamilton Depression Rating Scale, SAD version (SIGH-SAD). Regions of interest (ROls) comprising thalamushypothalamus and mesencephalon-pons were hand drawn by one and the same examiner blind to the subjects condition. A ratio was calculated between mean counts in the target ROl’s and the cerebellum serving as reference region (ratio-l). [‘231]-fi-ClT SPECT revealed no difference in 5-HTT density between symptomatic depressed patients and healthy controls in the thalamus-hypothalamus (1.67 f 0.25 vs. 1.67 f 0.26; ratio-l : Mann-Whitney-U-test: ns.) and the mesencephalon-pons (0.98 f 1.7 vs. 0.9 1 f 0.10; ratio-l ; Mann-Whitney-U-test: n.s.). A positive correlation between 5-HTT density in the aforementioned ROls and severity of depression measured by the SIGH-SAD was found in the patient group (thalamus-hypothalamus: r = 0.61; 2-tailed p = 0.01; mesencephalonpons: r = 0.53; 2-tailed p = 0.03). These results suggest that the occurrence of depression in SAD is not associated with alterations in 5HTT density in thalamus-hypothalamus and the mesencephalon-pens. However, [‘231]-~-ClT binding correlates positively with the severity of depression. Thus, serotonin reuptake in thalamus-hypothalamus and mesencephalon-pons could influence the severity of depressive symptoms by modulating a third, yet unknown factor. Ip.1.1261
The contribution of ovarian steroids to early postnatal depression
K. Love& A. Wieck, L. Appleby. Department of Manchester: UK
@Psychiat~,
Universit?,
Background: It has been suggested that early postnatal depression is triggered by the effects of ovarian hormone “withdrawal” after childbirth on central neurotransmitter systems. If this is the case then women with a large posmatal drop should be likely to become depressed postnatally. This hypothesis was tested in this study.