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Prediction relapse in melancholic out-patients
250S
Poster session IV
BlOL. PSYCHIATRY 1997;42: IS-297S
stress and vUlnerability hypothesis of affective disorders and suggest that a genetic factor is of greater Importance than a stress factor for earty onset of the disease. These data should be considered In the design of prophylactic studies.
190-81
I The early course of Illness among adolescent children of parents with bipolar disorder
A. Duffy, M. Aida, C. Fusee, S. Kutcher, P. Grot. University of Ottawa and Dalhousie University, Canada Aim: The purpose of this study was to describe the Initial symptoms and syndromes onsetting in adolescents at risk for affective disorders. Method: The primary author conducted blind KSADS interviews with 36 adolescent children of 22 bipolar patients diagnosed according to ROC criteria. The proband parents were divided on the basis of response to lithium prophylaxis, a clinical marker of a more genetlcelly based subgroup. Offspring were diagnosed according to DSM-IV criteria on a consensus basis blind to proband parent affiliation. Results: The offspring of lithium responders tended to manifest psy• chopathology within the affective domain, while offspring of lithium non• responders manifested a more diverse range of psychopathology. Moreover, of those children with affective diagnoses, the offspring of lithium responders tended to have an episodic course, while the offspring of lithium non-respon• ders tended to have chronic nonremittlng courses. Conclusions: These findings suggest that in some cases earty onset bipolar Illness follows a typical episodic course. It appears that clinical course may be highly Important for characterizing subtypes of affective Illness and for a rational treatment approach.
190-821
needs further study and a longitudinal approach so to allow appropriate observations of the effects of puberty, pregnancy, menstrual cycle and menopause in the course of bipolar affective illness.
190-841
Chronic mania: Clinical features and course
C. Quilici, L. Rossi, D. Madaro, A. Paiano, C. Socci, E. De Soricellis, L Musettl. Institute of Psychiatry. University of Piss. Italy The aim of this study is to define the epidemiological and clinical features of Chronic Mania and to compare them with those of more brief manic episodes. We evaluated 155 patients who met DSM-III-R criteria for Manic Episode by means of Hopkins Symptoms Check·Ust (HSCL·90), The Comprehensive Psycopathologlcal Rating scale (CPRS), Structured Interview for Mood Disorders (SIMD), Scale for the Assessment of Positive Symptoms (SAPS). One out of every 8 patients had a chronic course. Most demographic and clinical features and family histories showed no significant differences be• tween these patients and subjects with a more brief Manic Episode. Chronic Mania patients were more Impaired In social functioning and had a more severe course. In these patients psychotic features were more cornmon, especially mood-congruent or incongruent delusions. There was no corre• sponding Increased impairment as regards mood disturbance, psychomotor agitation and neurovegetative symptoms. Depressive Temperament was less frequent In subjects with a chronic course. Considering the severity of this clinical picture, future research should aim towards a better diagnostic definition especially with regards to more efficient therapeutic strategies.
190-851 Prediction relapse In melancholic out-patients
Mood-stabilizing drugs regulate serotonin transporter expression
R. Catalan, J. Vallejo, C. Gast6, A. Otero. ClGomera SIN Sant Cugat. Barcelona, Spain
A. Heils, R. Moessner, D. Bengel, K.P. Lesch. Department of Psychiatry, University of WOrzburg. Germany
The aim of the prospective study Is to evaluate the rate and the factors for relapse with different treatment periods of Imipramine (26 or 204 weeks). Methods: Eight-four out-patients aged between 18 and 70 years, who met DSMIII-Rcriteria for Major Depressive Disorder with melancholia, with• out psychotic symptoms, and in tum exhibited> = 6 points on the Newcastle scale. We collected data corresponding to: 1. Soclodemographic, clinical and personality variables; 2. Family antecedents; 3. Serial bimonsly dexametha• sone suppression test (DST); 4. Ufe events and social support. A relapse was considered to have taken place when the patient attained a scoring of> 16 points on the Hamilton Depression Rating scale (HDRS) alter a clinical recovery (HDRS < 6) of 8 weeks. Cumulative and Instantaneos probabilities of relapse were estlmed using the Kaplan-Meier method and the Cox proportional hazard model was used to ascertain the prognostic variables. Results: The strongest predictors of earty relapse were: 1) The mainte• nance treatment with Imipramine over 2 years; 2) High Initial neuroticism; 3) The presence In two or more Instance of NON-suppression In the serial DST previously to relapse (Ukelihood ratio x for overall model. 26, 67, dl =6, P < 0.001).
Mood-stabilizJng drugs like lithium, valproate. and carbamazepine, widely used In the therapy and prevention of recurrent affective and psychotic disorders, originate different described intracellular effects. Within this study we investigated the effects of these drugs on 5-HT transporter gene expression, a candidate gene, probably Involved In the pathogenesis of those psychotic and affective disorders. Methods: We applied a reporter gene assay studying the activity of the polymorphic human promoter region ligated Into the pGL3 luci/erase vector and expressed In JAR celis. A genotype related S-Iymphoblastold cell model, baslcly expressing the 5-HT transporter, revealed the data of pharmacologically stimulated trans• porter density and transport capacity. Results: Uthlum and valproate cause an significant Increase In 5-HT transporter gene promoter activity within a therapeutical concentration range, whereas carbamazeplne decreases promoter activity. Uthlum but not val• proate and carbamazeplne looses Its stimulatory capacity alter transfectlng deletional mutants of the reporter gene constructs. This loss depends on a deletion of the polymorphic repetitive promoter sequence, Indicating that this region might be a genomic target site of lithium's action. 5-HT transporter density within the B-Iymphoblastoid cell model reflects the reSUlts of the reporter gene study demonstrating that different cellular effects depend on pharmacologically modulated promoter activity. While the serotonin transporter gene is one of the first genes, described to be regulated by these substances, our findings don't reveal a common way of action. probably to be found In mood-stabilizing effects.
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190-831
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Gender differences In bipolar disorder
A. Palano, L Rossi, C. Quilici, C. Micheli, E. Simonlnl, M.T. Xuereb, L Musettl. Institute of Psychiatry. University of Pisa, Pisa, Italy Although the numerous clinical studies about bipolar affective illness have answered various questions, they seldom address how gender differences affect this disorder. In order to define more precisely sex differences In bipolar disorder course, 354 bipolar I patients were analysed with regard to clinical characteristics, demographic features, course of Illness and family history. On our sample, as in literature, depressive episodes and suicide attempts occur more frequenijy In bipolar women than In men. Moreover, when bipolar women develop depression, they are more olten affected by serious depressive episodes together with melancholic features In our stUdy. Other important gender differences In the course of bipolar disorder, partially confirmed by data of our study. Is the prevalence of rapid cycling in women. Higher rates of hypothyroidism, greater use of antidepressants, and gonadal steroids' fluctuations are possible explanations for the greater prevalence of rapid cycling among bipolar women. This field of research however
19 0-861
Urinary excretion of Indoleacetic acid In a group of psychiatric patients
G. V4zquez. M. Cetkovich-Bakmas, J. Ciprian-Dllivler. Centro de Pslqulatrfa Bioldglca. Buenos Aires, Argentina Indoleacetic Acid (IAA) Is the major metabolic derivative from Tryptamine one of the altemative methabolic pathways of Tryptophan. It Is well know~ that tryptamine posses a neuromodulatory effect over Indolamines neura• transmission, analogous to that of Phenylethylamlne on catecholamines neurotransmlssion. Previous reports showed abnormal levels of Indoleacetic Acld excretion In different psychiatric populations. In this paper we Investigated, In a very significative psychiatric sample, uri-
Poster session IV
BlOL. PSYCHIATRY 1997;42: IS-297S
stress and vUlnerability hypothesis of affective disorders and suggest that a genetic factor is of greater Importance than a stress factor for earty onset of the disease. These data should be considered In the design of prophylactic studies.
190-81
I The early course of Illness among adolescent children of parents with bipolar disorder
A. Duffy, M. Aida, C. Fusee, S. Kutcher, P. Grot. University of Ottawa and Dalhousie University, Canada Aim: The purpose of this study was to describe the Initial symptoms and syndromes onsetting in adolescents at risk for affective disorders. Method: The primary author conducted blind KSADS interviews with 36 adolescent children of 22 bipolar patients diagnosed according to ROC criteria. The proband parents were divided on the basis of response to lithium prophylaxis, a clinical marker of a more genetlcelly based subgroup. Offspring were diagnosed according to DSM-IV criteria on a consensus basis blind to proband parent affiliation. Results: The offspring of lithium responders tended to manifest psy• chopathology within the affective domain, while offspring of lithium non• responders manifested a more diverse range of psychopathology. Moreover, of those children with affective diagnoses, the offspring of lithium responders tended to have an episodic course, while the offspring of lithium non-respon• ders tended to have chronic nonremittlng courses. Conclusions: These findings suggest that in some cases earty onset bipolar Illness follows a typical episodic course. It appears that clinical course may be highly Important for characterizing subtypes of affective Illness and for a rational treatment approach.
190-821
needs further study and a longitudinal approach so to allow appropriate observations of the effects of puberty, pregnancy, menstrual cycle and menopause in the course of bipolar affective illness.
190-841
Chronic mania: Clinical features and course
C. Quilici, L. Rossi, D. Madaro, A. Paiano, C. Socci, E. De Soricellis, L Musettl. Institute of Psychiatry. University of Piss. Italy The aim of this study is to define the epidemiological and clinical features of Chronic Mania and to compare them with those of more brief manic episodes. We evaluated 155 patients who met DSM-III-R criteria for Manic Episode by means of Hopkins Symptoms Check·Ust (HSCL·90), The Comprehensive Psycopathologlcal Rating scale (CPRS), Structured Interview for Mood Disorders (SIMD), Scale for the Assessment of Positive Symptoms (SAPS). One out of every 8 patients had a chronic course. Most demographic and clinical features and family histories showed no significant differences be• tween these patients and subjects with a more brief Manic Episode. Chronic Mania patients were more Impaired In social functioning and had a more severe course. In these patients psychotic features were more cornmon, especially mood-congruent or incongruent delusions. There was no corre• sponding Increased impairment as regards mood disturbance, psychomotor agitation and neurovegetative symptoms. Depressive Temperament was less frequent In subjects with a chronic course. Considering the severity of this clinical picture, future research should aim towards a better diagnostic definition especially with regards to more efficient therapeutic strategies.
190-851 Prediction relapse In melancholic out-patients
Mood-stabilizing drugs regulate serotonin transporter expression
R. Catalan, J. Vallejo, C. Gast6, A. Otero. ClGomera SIN Sant Cugat. Barcelona, Spain
A. Heils, R. Moessner, D. Bengel, K.P. Lesch. Department of Psychiatry, University of WOrzburg. Germany
The aim of the prospective study Is to evaluate the rate and the factors for relapse with different treatment periods of Imipramine (26 or 204 weeks). Methods: Eight-four out-patients aged between 18 and 70 years, who met DSMIII-Rcriteria for Major Depressive Disorder with melancholia, with• out psychotic symptoms, and in tum exhibited> = 6 points on the Newcastle scale. We collected data corresponding to: 1. Soclodemographic, clinical and personality variables; 2. Family antecedents; 3. Serial bimonsly dexametha• sone suppression test (DST); 4. Ufe events and social support. A relapse was considered to have taken place when the patient attained a scoring of> 16 points on the Hamilton Depression Rating scale (HDRS) alter a clinical recovery (HDRS < 6) of 8 weeks. Cumulative and Instantaneos probabilities of relapse were estlmed using the Kaplan-Meier method and the Cox proportional hazard model was used to ascertain the prognostic variables. Results: The strongest predictors of earty relapse were: 1) The mainte• nance treatment with Imipramine over 2 years; 2) High Initial neuroticism; 3) The presence In two or more Instance of NON-suppression In the serial DST previously to relapse (Ukelihood ratio x for overall model. 26, 67, dl =6, P < 0.001).
Mood-stabilizJng drugs like lithium, valproate. and carbamazepine, widely used In the therapy and prevention of recurrent affective and psychotic disorders, originate different described intracellular effects. Within this study we investigated the effects of these drugs on 5-HT transporter gene expression, a candidate gene, probably Involved In the pathogenesis of those psychotic and affective disorders. Methods: We applied a reporter gene assay studying the activity of the polymorphic human promoter region ligated Into the pGL3 luci/erase vector and expressed In JAR celis. A genotype related S-Iymphoblastold cell model, baslcly expressing the 5-HT transporter, revealed the data of pharmacologically stimulated trans• porter density and transport capacity. Results: Uthlum and valproate cause an significant Increase In 5-HT transporter gene promoter activity within a therapeutical concentration range, whereas carbamazeplne decreases promoter activity. Uthlum but not val• proate and carbamazeplne looses Its stimulatory capacity alter transfectlng deletional mutants of the reporter gene constructs. This loss depends on a deletion of the polymorphic repetitive promoter sequence, Indicating that this region might be a genomic target site of lithium's action. 5-HT transporter density within the B-Iymphoblastoid cell model reflects the reSUlts of the reporter gene study demonstrating that different cellular effects depend on pharmacologically modulated promoter activity. While the serotonin transporter gene is one of the first genes, described to be regulated by these substances, our findings don't reveal a common way of action. probably to be found In mood-stabilizing effects.
=
190-831
=
Gender differences In bipolar disorder
A. Palano, L Rossi, C. Quilici, C. Micheli, E. Simonlnl, M.T. Xuereb, L Musettl. Institute of Psychiatry. University of Pisa, Pisa, Italy Although the numerous clinical studies about bipolar affective illness have answered various questions, they seldom address how gender differences affect this disorder. In order to define more precisely sex differences In bipolar disorder course, 354 bipolar I patients were analysed with regard to clinical characteristics, demographic features, course of Illness and family history. On our sample, as in literature, depressive episodes and suicide attempts occur more frequenijy In bipolar women than In men. Moreover, when bipolar women develop depression, they are more olten affected by serious depressive episodes together with melancholic features In our stUdy. Other important gender differences In the course of bipolar disorder, partially confirmed by data of our study. Is the prevalence of rapid cycling in women. Higher rates of hypothyroidism, greater use of antidepressants, and gonadal steroids' fluctuations are possible explanations for the greater prevalence of rapid cycling among bipolar women. This field of research however
19 0-861
Urinary excretion of Indoleacetic acid In a group of psychiatric patients
G. V4zquez. M. Cetkovich-Bakmas, J. Ciprian-Dllivler. Centro de Pslqulatrfa Bioldglca. Buenos Aires, Argentina Indoleacetic Acid (IAA) Is the major metabolic derivative from Tryptamine one of the altemative methabolic pathways of Tryptophan. It Is well know~ that tryptamine posses a neuromodulatory effect over Indolamines neura• transmission, analogous to that of Phenylethylamlne on catecholamines neurotransmlssion. Previous reports showed abnormal levels of Indoleacetic Acld excretion In different psychiatric populations. In this paper we Investigated, In a very significative psychiatric sample, uri-