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Neuroendocrine correlates of antipsychotic response in schizophrenia
642
Abstracts
DlOL PSYCIIIATR'I' 1996;39:500 - 666
483. DETERMINATION OF SALIVARY CORTISOL BY NON-RADIOISOTOPIC IMMUNOASSAY 1.K. Yao l •2 , H.B. Moss 1, D.E. Sokulski ' , & G.P. Kirillova J ICEDAR Project. University of Pittsburgh Medical Cenler, WPJC, Pillsburgh. PA !5213; ~Depanment of Vetenms Affairs Medical Ccnter. Highland Drive, Pillsbuq;h, PA 15206 Salivary cortisol has been correlateu directly with the biologically aClive. non-protein-hounded plasma cortisol. Measuremenl of salivary cortisol may provide us an assessment of adrenal conical function in evaluation of neurocmlocrinc disturbances in patients Wilh psychiatric disorders. The method used to as.'>..y salivary cortisol requires II sensitive. but tedious radioimmunoassny (RI,\) because of its minute amounts «10% of those in plasma). The purpose of our study was to tesl whether otlter non-radioisotopic immuno:l.';say is suitable for salivary cortisol. The Dissociation-Enhanced Lanlhanidc FJuoroimmunoamly (DELFIA) is a solid phase lime-resolved FlA based on the competilive reaction between europium-labeled cortisol and sample cortisol for a limited nmount of binding sites on cortisol specific. biotinylated monoclonal antibodies. To adapt DElFIA for salivary conisol assay, we have modifjed procedures for sample preparation. Salivary sample was Iirst centrifuged to remove any insoluble substance. Cortisol was then extracted from 0,5 ml of c1earcd sample with cold dichloromethane and mconstituted with 0.1 mL of cortisol·free serum (CFS), Aliquols (25 j.l.L x 3) of cortisol cxtmct were assayed by DELFIA. The rcsultq obtl'ined from DELFIA were significantly correlated (0=31; r=0.85; p
484. NEUROENDOCRINE ABNORMALITIES IN PSYCHIATRIC PATIENTS: A MULTIVARIATE STUDY F. Duval l ,2, M.e. Mokrani 2 , M.A. Crocq l.2, P. Bailey:!, T.S Diepl, & J.P, Macher l ,2 'Centre HospilaJier, Rouffach. Fmllce; ~Research Center for Applied Neuroscience in Psychilltry FORENAP, Rouffach. Ff'Jnce We examined multihonnonal responses to a scries of neuroendocrine chlillenges including the apomorphine (APO) test. 8 AM llnd II PM protirelin (TRH) le~ts. and the tlexamelhasone suppression test (DST) in medication-free inplltients with DSM-IV major depressive disorder (MDE. n 93), schizophrenia (SCZ, n=36). or schizoaffective disorder (SAD, n=23). and in hospitalized heulthy controls (HC, 1'1=27). A factorial corrcspontlcnce lInalysis (FCA) separated the neuroendocrine pronles of Ihe HC, MOE and SCZ groups. The MDE group WIlS D
chal':lctcriled by chronobiological dysrcgulation of the thyroh.l axis (blunte() II PM·lnS~I: maximum increment in thyrotropin ITSHIllbove baseline after TRH. and blunte() L\6.TSH: ()iffercncc between II PM· ATSH and 8 AM·6.TSH). and normal homlonal responses to APO (prolactin [PRLI, growth honnone [GHI. adrenocorticotropic honnone and cortisol (COR», The SCZ group was characterized by a functional alteration of the hypolhaiamic·pituitary dopamine reccptors (blunted APO·induced GH and COR slimulation and PRL suppression), and nonnat thyroid axis activity. The SAD group showed abnonn:llilies found both in sez and in MDE groups. Neither the DST results nor the 8 AM TSH and PRL responses to TRH contributed to the diagnostic classilication. Further rCAs perfonned on the sez STOUp showed that abnonnal responses 10 APO c1mmclcri1.ed th~ psychotic dimension. whcfCas the disorganized dimension was associated with nomml responses to APO; depressive fe3lurcs were associated with ehronobiological tlysregulatiun of the thyroid axi~. These results suggeslthat multiple neumendocrine measures distinguish different diagnostic groups more clearly than single tests, However. the endocrine abnonnalities appear more linkcd to psychialIie syndrome Ihan to nosological entities.
485. NEUROENDOCRINE CORRELATES OF ANTIPSYCHOTIC RESPONSE IN SCHIZOPHRENIA F. Duval l •2 , M.e. Mokrani 2 , M.A. Crocq l_2, p, BaileY=\ T,S Diepl, & J.P, Macher l ,:! ICentre Hospilnlicr, Rouffach. Fmncc; 2Research Center for Applied Neuroscience in Psychiatry (FORENAI'), Rouffach, France Thirty.five medication-free DSM-IV schizophrcnic inpatients were treated for two monlhs with antipsychotic drugs and were then classified as respondcrs or non·n:sponders according to lheir BPRS anu COl scores, These IWO &roup~ were examined for differenec~ in prlltreatment m:urocndocrine varinbtes (llpomorphine [AI'O] lest, 8 AM and II PM protirelin ITRHI tests, and dexamethasone suppression lcst [DSTJ). When compared with responders (n=24), non-responders (n= II) showed lower basal thyrotropin (TSfI) levels both al 8 AM anti II PM (p<0.02 and p
Abstracts
DlOL PSYCIIIATR'I' 1996;39:500 - 666
483. DETERMINATION OF SALIVARY CORTISOL BY NON-RADIOISOTOPIC IMMUNOASSAY 1.K. Yao l •2 , H.B. Moss 1, D.E. Sokulski ' , & G.P. Kirillova J ICEDAR Project. University of Pittsburgh Medical Cenler, WPJC, Pillsburgh. PA !5213; ~Depanment of Vetenms Affairs Medical Ccnter. Highland Drive, Pillsbuq;h, PA 15206 Salivary cortisol has been correlateu directly with the biologically aClive. non-protein-hounded plasma cortisol. Measuremenl of salivary cortisol may provide us an assessment of adrenal conical function in evaluation of neurocmlocrinc disturbances in patients Wilh psychiatric disorders. The method used to as.'>..y salivary cortisol requires II sensitive. but tedious radioimmunoassny (RI,\) because of its minute amounts «10% of those in plasma). The purpose of our study was to tesl whether otlter non-radioisotopic immuno:l.';say is suitable for salivary cortisol. The Dissociation-Enhanced Lanlhanidc FJuoroimmunoamly (DELFIA) is a solid phase lime-resolved FlA based on the competilive reaction between europium-labeled cortisol and sample cortisol for a limited nmount of binding sites on cortisol specific. biotinylated monoclonal antibodies. To adapt DElFIA for salivary conisol assay, we have modifjed procedures for sample preparation. Salivary sample was Iirst centrifuged to remove any insoluble substance. Cortisol was then extracted from 0,5 ml of c1earcd sample with cold dichloromethane and mconstituted with 0.1 mL of cortisol·free serum (CFS), Aliquols (25 j.l.L x 3) of cortisol cxtmct were assayed by DELFIA. The rcsultq obtl'ined from DELFIA were significantly correlated (0=31; r=0.85; p
484. NEUROENDOCRINE ABNORMALITIES IN PSYCHIATRIC PATIENTS: A MULTIVARIATE STUDY F. Duval l ,2, M.e. Mokrani 2 , M.A. Crocq l.2, P. Bailey:!, T.S Diepl, & J.P, Macher l ,2 'Centre HospilaJier, Rouffach. Fmllce; ~Research Center for Applied Neuroscience in Psychilltry FORENAP, Rouffach. Ff'Jnce We examined multihonnonal responses to a scries of neuroendocrine chlillenges including the apomorphine (APO) test. 8 AM llnd II PM protirelin (TRH) le~ts. and the tlexamelhasone suppression test (DST) in medication-free inplltients with DSM-IV major depressive disorder (MDE. n 93), schizophrenia (SCZ, n=36). or schizoaffective disorder (SAD, n=23). and in hospitalized heulthy controls (HC, 1'1=27). A factorial corrcspontlcnce lInalysis (FCA) separated the neuroendocrine pronles of Ihe HC, MOE and SCZ groups. The MDE group WIlS D
chal':lctcriled by chronobiological dysrcgulation of the thyroh.l axis (blunte() II PM·lnS~I: maximum increment in thyrotropin ITSHIllbove baseline after TRH. and blunte() L\6.TSH: ()iffercncc between II PM· ATSH and 8 AM·6.TSH). and normal homlonal responses to APO (prolactin [PRLI, growth honnone [GHI. adrenocorticotropic honnone and cortisol (COR», The SCZ group was characterized by a functional alteration of the hypolhaiamic·pituitary dopamine reccptors (blunted APO·induced GH and COR slimulation and PRL suppression), and nonnat thyroid axis activity. The SAD group showed abnonn:llilies found both in sez and in MDE groups. Neither the DST results nor the 8 AM TSH and PRL responses to TRH contributed to the diagnostic classilication. Further rCAs perfonned on the sez STOUp showed that abnonnal responses 10 APO c1mmclcri1.ed th~ psychotic dimension. whcfCas the disorganized dimension was associated with nomml responses to APO; depressive fe3lurcs were associated with ehronobiological tlysregulatiun of the thyroid axi~. These results suggeslthat multiple neumendocrine measures distinguish different diagnostic groups more clearly than single tests, However. the endocrine abnonnalities appear more linkcd to psychialIie syndrome Ihan to nosological entities.
485. NEUROENDOCRINE CORRELATES OF ANTIPSYCHOTIC RESPONSE IN SCHIZOPHRENIA F. Duval l •2 , M.e. Mokrani 2 , M.A. Crocq l_2, p, BaileY=\ T,S Diepl, & J.P, Macher l ,:! ICentre Hospilnlicr, Rouffach. Fmncc; 2Research Center for Applied Neuroscience in Psychiatry (FORENAI'), Rouffach, France Thirty.five medication-free DSM-IV schizophrcnic inpatients were treated for two monlhs with antipsychotic drugs and were then classified as respondcrs or non·n:sponders according to lheir BPRS anu COl scores, These IWO &roup~ were examined for differenec~ in prlltreatment m:urocndocrine varinbtes (llpomorphine [AI'O] lest, 8 AM and II PM protirelin ITRHI tests, and dexamethasone suppression lcst [DSTJ). When compared with responders (n=24), non-responders (n= II) showed lower basal thyrotropin (TSfI) levels both al 8 AM anti II PM (p<0.02 and p