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Relationship between polymorphism of serotonin transporter and human personality
139-91
Poster session n
BIOL. PSYCHIATRY
1065
1997;42:15-2975
I Relationship between polymorphism of serotonin
139-941
transporter and human personality
S. Katsuragl, J. Akiyoshi, M. Furuta, Y. Kohno, Y. Yamamoto, T. Tsutsuml, K. lsogawa, I. FujII. Dept. Neuropsychiatry. Oita Medical University. Hasama-Machi. Oita. Japan This study examined the relationship between polymorphism of serotonin transporter (5-HTT) and personality Inventory. Method: One hundred normal volunteers were registered. We examined allelic variation In 5-HTT and tridimensional of the personality questionnaire (TPQ).
Results: We found a polymorphism of serotonin transporter (5-HTT). It showed length variations of the repetitive sequence containing GC-rich. The result relationship between polymorphism of serotonin transporter (5-HTT) and personality inventory will be reported on that day.
139-921
ImpUlsivity and platelet serotonin content In adolescents
F. Askenazy. A. lordache. Y. Lecrubier, M. Myquel, G. Darcourt. Child and Adolescent Psychiatry Dpt. Fondation Lenval, Nice. France
We studied the correlation between Impulsivity (measured With a clinical scale) and platelet serotonin concentration chosen as a possible peripherical marker of central serotonin function In impulsive adolescents. Methods: Therefore Inclusion was dimensionally based on the presence of Impulsivity Irrespective to diagnosis. All measures were performed every week during six weeks for all patients. Results: A total of eight impulsive adolescent Inpatients across diagnosis was recruted. Platelet serotonin contents were positively correlated with the severity of Impulsivity In the study group and all. This study provided further evidence for an association between serotonin system and impulsivity across diagnosis. The patients sample size was rather small. however the correlation observed was not only present for the group but for each individual patients which gives strength to the evidence. However, this study needs replication.
139-931
Potasslum-evoked neuronal release of serotonin In experimental chronic hepatic encephalopathy
P.B.F. Bergqvist, S. Hjorth " G. Apelqvist, F. Bengtsson. Department of Clinical Pharmacology. Lund University. Lund. Sweden, 1 Department of Pharmacology. University of Gothenburg, Gothenburg, Sweden Hepatic encephalopathy (HE) Is a neuropsychiatric syndrome associated with an increased brain neuronal tumover of serotonin (5-HT). Despite the Increased 5-HT metabolism, the brain 5-HT release In rats with chronic HE (portacaval shunt; PCS) seems to be unaltered. Although this may Indicate that the overall5-HT output is unaltered In HE, lt is also possible that the 5-HT release pattem may be altered in some way. In the present microdialysis study, the potasslum-evoked frontal neocortical release of 5-HT was studied In experimental chronic HE. KCI (60 mM) produced marked increases in the 5-HT output compared with basal values both in PCS and sham rats. Simultaneously, the KCI challenge resulted in significant elevations In the 5-HT release of PCS compared with sham. In ca2+·free medium, the difference between PCS and sham rats in the KCI-evoked release of 5-HT was abolished. In the presence of TTX (1 /oLM), both groups displayed Increases In neocortical extracellular 5-HT levels. Again, a difference with higher amplitude of the 5-HT release In PCS compared with sham was evidenced. It Is concluded that an augmented neocortical 5-HT release compared with the normal in vivo situation Is available upon depolarization In chronic experimental HE. Observations like these may be Important to the rational design of Mure pharmacological intervention strategies In this chronic neuropsychiatric syndrome that include the symptomatology displayed within core psychiatric conditions such as affective and psychotic disorders. Thus, the present observations may clearty contribute also to better outline the actions of 5-HT-psychoactive drugs when used from a broader clinical perspective In. for example, patients with liver dysfunction and pending HE.
Serotonin receptors In experimental hepatic encephalopathy - Regional changes In the brain
G. Apelqvist, P.B.F. Bergqvist, B. Larsson, M. Bugge, F. Bengtsson. Department of Clinical Pharmacology, Lund University, Lund, Sweden The pathogenesis of hepatic encephalopathy (HE) is unknown, but metabolic perturbations including profound hyperammonemla and a SUbstantially in• creased tumover of serotonin (5-Hydroxy-tryptamlne; 5-HT) in the brain are clearty identified in chronic hepatic encephalopathy (HE). However. a1ter• ations of 5-HT receptors in the brain in HE have still been only rudimentarily studied. We thus investigated the 5-HT,A. 5-HTIB and 5-HT2A receptor den• sities In 18 to 22 various brain regions of portacaval shunted (PCS) rats, a commonly used non-toxin animal model of HE. The 5-HT receptor densities were determined by means of autoradiography. The results revealed that the postsynaptic 5-HTIA receptor density was significantly decreased in substannigra, frontoparietal cortex, hippocampus (CAl, gyrus dentatus), sup colliculus, central gray, and septal nc (dorsal part). Significantly Increased 5-HT'A receptor density was shown in nc ace. subiculum and hypothalamus. No apparent changes of the somatodendritic 5-HTlI. receptor density were observed in the raphe region. The presy• naptic 5-HT B autoreceptor density was significantly increased in thaJamus (paracentric),' striatum. gyrus dentatus, tub olf, sup colliculus. Decreased 5-HT B receptor density was shown in CAl and frontoparietal cortex. The ' postsynaptic 5-HT2A receptor density was only significantiy increased In subiculum. In conclusion, major changes with a general decrease In the 5-HTtA and elevations In the 5-HT Band essentially unaltered 5-HT2A receptor densities were found in PCS as 'rats compared to controls. These findings further sug• gest that major perturbations in the central serotonergic neurotransmiSSion may be of Importance as a pathogenetic mechanism In chronic HE.
139-951
Prolonged tryptophan depletion and family history: Effects on mood and memory
H.M. van Praag, T. Klaassen, W. Riedel, A. Honig. Department of Psychiatry and Neuropsychology. Maastricht University. Maastricht, The Netherlands Aim of the study was to apply a prolonged (up to 24 hour) acute tryptophan depletion and measure effects on mood and memory. We hypothesised thai more symptoms of depression would occur after 24 hours of restriction than after 6 hours and that more symptoms would occur in first degree nelatives of depressed SUbjects. Methods: We applied an amino-acid mixture followed by a 24-hour die( free of tryptophan. Results: 27 normal subjects, 16 with and 11 without first degree depr&ssed family members completed the study. Tryptophan levels stayed low for at least 14 hours. A significant Increase of depressed mood was found after 6 hours, but not after 24 hours. Mood changes parallelled plasma tryptophan levels, which had risen again after 24 hours probably due to katabolic processes. Lowering of mood occurred In 8 first degree family members and In 1 control. Also, after 6 hours (again not after 24 hours), consolidation of new information was significantly diminished In the tryptophan depletion condition. Conclusion: We concluded that tryptophan depletion leads to mood lowering and cognitive defic~s In subjects with a certain vulnerability for depression and that symptoms parallel plasma tryptophan levels.
139-961
Altered Imipramine and 5-HT2 but not paroxetine binding sites In platelets from melancholic patients P. Rosell, P. Alvarez 2, B. Arranz 1,3, J. Vallejo 2, J.M. Mench6n 2.
M.A. Navarro '. 1 Hormone Unit, Hospital Princeps d'Espanya, Barcelona, Spain, 2 Department of Psychiatry, Hospital Princeps cl'Espanya, Barcelona. Spain, 3 Department of Psychiatry (IMIM), Barcelona, Spain The maximum binding (Bmax) and affinity (Kd) of [3H]imiPl'amine, [3H)paroxetine (5-HT uptake site) and [3H)ketanserine (postsynaptic 5-HT2) binding sites was simultaneously assessed in platelet membranes from 51 melancholic patients (DSM-III-R diagnosed) and 63 age and sex-rnatehed control subjects. Binding data was analyzed with the non-linear curve fitting program LIGAND. All three radioligands bound to brain membranes in • saturable high-affinity manner to a single population of binding Sites. A significant diminished number of imipramine binding sites was obse.....ed in melancholic patients in comparison to the control group (1198 :l:: 75 versus
Poster session n
BIOL. PSYCHIATRY
1065
1997;42:15-2975
I Relationship between polymorphism of serotonin
139-941
transporter and human personality
S. Katsuragl, J. Akiyoshi, M. Furuta, Y. Kohno, Y. Yamamoto, T. Tsutsuml, K. lsogawa, I. FujII. Dept. Neuropsychiatry. Oita Medical University. Hasama-Machi. Oita. Japan This study examined the relationship between polymorphism of serotonin transporter (5-HTT) and personality Inventory. Method: One hundred normal volunteers were registered. We examined allelic variation In 5-HTT and tridimensional of the personality questionnaire (TPQ).
Results: We found a polymorphism of serotonin transporter (5-HTT). It showed length variations of the repetitive sequence containing GC-rich. The result relationship between polymorphism of serotonin transporter (5-HTT) and personality inventory will be reported on that day.
139-921
ImpUlsivity and platelet serotonin content In adolescents
F. Askenazy. A. lordache. Y. Lecrubier, M. Myquel, G. Darcourt. Child and Adolescent Psychiatry Dpt. Fondation Lenval, Nice. France
We studied the correlation between Impulsivity (measured With a clinical scale) and platelet serotonin concentration chosen as a possible peripherical marker of central serotonin function In impulsive adolescents. Methods: Therefore Inclusion was dimensionally based on the presence of Impulsivity Irrespective to diagnosis. All measures were performed every week during six weeks for all patients. Results: A total of eight impulsive adolescent Inpatients across diagnosis was recruted. Platelet serotonin contents were positively correlated with the severity of Impulsivity In the study group and all. This study provided further evidence for an association between serotonin system and impulsivity across diagnosis. The patients sample size was rather small. however the correlation observed was not only present for the group but for each individual patients which gives strength to the evidence. However, this study needs replication.
139-931
Potasslum-evoked neuronal release of serotonin In experimental chronic hepatic encephalopathy
P.B.F. Bergqvist, S. Hjorth " G. Apelqvist, F. Bengtsson. Department of Clinical Pharmacology. Lund University. Lund. Sweden, 1 Department of Pharmacology. University of Gothenburg, Gothenburg, Sweden Hepatic encephalopathy (HE) Is a neuropsychiatric syndrome associated with an increased brain neuronal tumover of serotonin (5-HT). Despite the Increased 5-HT metabolism, the brain 5-HT release In rats with chronic HE (portacaval shunt; PCS) seems to be unaltered. Although this may Indicate that the overall5-HT output is unaltered In HE, lt is also possible that the 5-HT release pattem may be altered in some way. In the present microdialysis study, the potasslum-evoked frontal neocortical release of 5-HT was studied In experimental chronic HE. KCI (60 mM) produced marked increases in the 5-HT output compared with basal values both in PCS and sham rats. Simultaneously, the KCI challenge resulted in significant elevations In the 5-HT release of PCS compared with sham. In ca2+·free medium, the difference between PCS and sham rats in the KCI-evoked release of 5-HT was abolished. In the presence of TTX (1 /oLM), both groups displayed Increases In neocortical extracellular 5-HT levels. Again, a difference with higher amplitude of the 5-HT release In PCS compared with sham was evidenced. It Is concluded that an augmented neocortical 5-HT release compared with the normal in vivo situation Is available upon depolarization In chronic experimental HE. Observations like these may be Important to the rational design of Mure pharmacological intervention strategies In this chronic neuropsychiatric syndrome that include the symptomatology displayed within core psychiatric conditions such as affective and psychotic disorders. Thus, the present observations may clearty contribute also to better outline the actions of 5-HT-psychoactive drugs when used from a broader clinical perspective In. for example, patients with liver dysfunction and pending HE.
Serotonin receptors In experimental hepatic encephalopathy - Regional changes In the brain
G. Apelqvist, P.B.F. Bergqvist, B. Larsson, M. Bugge, F. Bengtsson. Department of Clinical Pharmacology, Lund University, Lund, Sweden The pathogenesis of hepatic encephalopathy (HE) is unknown, but metabolic perturbations including profound hyperammonemla and a SUbstantially in• creased tumover of serotonin (5-Hydroxy-tryptamlne; 5-HT) in the brain are clearty identified in chronic hepatic encephalopathy (HE). However. a1ter• ations of 5-HT receptors in the brain in HE have still been only rudimentarily studied. We thus investigated the 5-HT,A. 5-HTIB and 5-HT2A receptor den• sities In 18 to 22 various brain regions of portacaval shunted (PCS) rats, a commonly used non-toxin animal model of HE. The 5-HT receptor densities were determined by means of autoradiography. The results revealed that the postsynaptic 5-HTIA receptor density was significantly decreased in substannigra, frontoparietal cortex, hippocampus (CAl, gyrus dentatus), sup colliculus, central gray, and septal nc (dorsal part). Significantly Increased 5-HT'A receptor density was shown in nc ace. subiculum and hypothalamus. No apparent changes of the somatodendritic 5-HTlI. receptor density were observed in the raphe region. The presy• naptic 5-HT B autoreceptor density was significantly increased in thaJamus (paracentric),' striatum. gyrus dentatus, tub olf, sup colliculus. Decreased 5-HT B receptor density was shown in CAl and frontoparietal cortex. The ' postsynaptic 5-HT2A receptor density was only significantiy increased In subiculum. In conclusion, major changes with a general decrease In the 5-HTtA and elevations In the 5-HT Band essentially unaltered 5-HT2A receptor densities were found in PCS as 'rats compared to controls. These findings further sug• gest that major perturbations in the central serotonergic neurotransmiSSion may be of Importance as a pathogenetic mechanism In chronic HE.
139-951
Prolonged tryptophan depletion and family history: Effects on mood and memory
H.M. van Praag, T. Klaassen, W. Riedel, A. Honig. Department of Psychiatry and Neuropsychology. Maastricht University. Maastricht, The Netherlands Aim of the study was to apply a prolonged (up to 24 hour) acute tryptophan depletion and measure effects on mood and memory. We hypothesised thai more symptoms of depression would occur after 24 hours of restriction than after 6 hours and that more symptoms would occur in first degree nelatives of depressed SUbjects. Methods: We applied an amino-acid mixture followed by a 24-hour die( free of tryptophan. Results: 27 normal subjects, 16 with and 11 without first degree depr&ssed family members completed the study. Tryptophan levels stayed low for at least 14 hours. A significant Increase of depressed mood was found after 6 hours, but not after 24 hours. Mood changes parallelled plasma tryptophan levels, which had risen again after 24 hours probably due to katabolic processes. Lowering of mood occurred In 8 first degree family members and In 1 control. Also, after 6 hours (again not after 24 hours), consolidation of new information was significantly diminished In the tryptophan depletion condition. Conclusion: We concluded that tryptophan depletion leads to mood lowering and cognitive defic~s In subjects with a certain vulnerability for depression and that symptoms parallel plasma tryptophan levels.
139-961
Altered Imipramine and 5-HT2 but not paroxetine binding sites In platelets from melancholic patients P. Rosell, P. Alvarez 2, B. Arranz 1,3, J. Vallejo 2, J.M. Mench6n 2.
M.A. Navarro '. 1 Hormone Unit, Hospital Princeps d'Espanya, Barcelona, Spain, 2 Department of Psychiatry, Hospital Princeps cl'Espanya, Barcelona. Spain, 3 Department of Psychiatry (IMIM), Barcelona, Spain The maximum binding (Bmax) and affinity (Kd) of [3H]imiPl'amine, [3H)paroxetine (5-HT uptake site) and [3H)ketanserine (postsynaptic 5-HT2) binding sites was simultaneously assessed in platelet membranes from 51 melancholic patients (DSM-III-R diagnosed) and 63 age and sex-rnatehed control subjects. Binding data was analyzed with the non-linear curve fitting program LIGAND. All three radioligands bound to brain membranes in • saturable high-affinity manner to a single population of binding Sites. A significant diminished number of imipramine binding sites was obse.....ed in melancholic patients in comparison to the control group (1198 :l:: 75 versus