- Email: [email protected]
The effect of neuroleptic drugs on olfactory sensitivity in schizophrenia
P.3 Psychotic disorders and antipsychotics
S4-114
impairment in recognition either brotizolam or midazolam was applied, while recall (recent memory) correlated with drug half-lives that meant that results with midazolam were better in comparison with brotizolam, but not significantly. References
Lezak M.D. (1976) Neuropsychological assessment. OxfordUniversityPress, New York. Roth, T. and Roehrs, A. T. (1994) Benzodiazepine agonists in insomnia: efficacy and safety, Neuropsychopharmacology-VollO, No 35/Part 1, 8618.
IP.3.03S! Pramipexole as an adjunct to haloperidol in schizophrenia
C. Bamas I, A. Heiden I, H.P.Yolz2, G. Laakmann ' , H. Zeit 4 • H. Pfolz 5 , S. Kasper I. I Department of Clinical Psychiatry, University of Vienna, Wiihringer Giirtel 18-20, A-/090 Vienna, Austria; 2 Department of Psychiatry, University of lena, Germany; 3 Department of Psychiatry, University of Munich, Germany; 4 Psychiatric Hospital, Evangelical Hospital Gelsenkirchen, Germany; 5 Psychiatric Hospital Baumgartner Hohe, Vienna, Austria Pramipexole is a dopamine D2ID3 receptor agonist. It is supposed to exert its activity with a net outcome of stimulation of the presynaptic D2 autoreceptors when the synapse is in good order. This leads to inhibition of the synthesis and release of dopamine and thus to a decreased firing rate of the dopaminergic neuron. In the case of a presynaptic degeneration with subsequent postsynaptic hypersensitivity pramipexole can exert its postsynaptic D2 agonist activity. Previous pilot studies have shown that pramipexole might have a therapeutic effect on negative symptoms of schizophrenia, whereas it seemed to lack efficacy against positive symptomswhen used as a monotherapy. The aim of the present study was the evaluation of the efficacy and safety of pramipexole (up to 10.25 mg/day) when added to a maintenance therapy with haloperidol for the treatment of residual positiveand negative symptoms of patients with a chronic or subchronic course of schizophrenia as diagnosed by DSM-IV. Fifteen patients (4 females, 11 males; mean age ± SD = 31.7 ± 10.0years) were recruited to participate. They all, while under haloperidol medication (5-2 0 mg/day or depot medication), showed a stable clinical course with a minimum PANSS score of 60 at the time of inclusion. The concept of the study was to reach the maximum tolerated dose of pramipexole (up to 10.25 mg) after a fast dose escalation on day 14 and a stable dose from day 14 to day 28. During the whole study the haloperidol medication remainedunchanged. Psychopathology was documentedwith the PANSSand the CGL Eleven of the fifteen patients completed the study. Three dropped out due to a worsening of positive schizophrenic symptoms, one because of administrative reasons. All patients who completed the study showed an amelioration in the PANSS score: the mean decrease in the positive subscale was 9.7%. in the negative subscale 24.2%, and in the general psychopathology subscale J 1.9%. The total score showed a decrease of 16%.Insomnia was the most frequently reportedside-effect (4 cases). No clinically relevantECG and laboratory changes were reponed. The study supports the safety of the treatment of schizophrenia with pramipexole and haloperidol as a combination therapy. However. further clinical studies are required to support these preliminary findings.
IP.3.037I Antibodies to human heat shock protein in
patients with schizophrenia and major depression
p. Sirota I, D. Mazeh I. A. Novogrotsky 2. 1 AbarbanelMental Health Center; Bat Yam, and Sackler Faculty of Medicine, Tel Aviv University, RamatAviv, Israel; 2 Felsenstien Institute for Medical Research, Beilinson Medical Center; Petah. Tiqwa; andSacklerFaculty of Medicine, Tel Aviv University, RamatAviv, Israel Different immunological abnormalities were reported in schizophrenia and major depression. Heat shock proteins are producedin everycelltype in reaction to different stressors. They are found in cells in normal conditions in minor quantities. In autoimmune diseases they were found in large quantities, Kilidries et al. reported an increase of hsp 60 antibodies
in the serumof patientswith schizophrenia. The serum of 26 patients with schizophrenia, 8 patients with major depression and 22 normal subjects, were tested for the presence of hsp antibodies. The serum samples were testedfor antibodybindingto protein extracts0fI.M.R.-32 neuroblastoma cell lineon Western blots. In Westernblots IgG in the serum of all patients but one and of normal subjects, reacted with a protein of 60 kDa. The intensity of each band in the 60 kDa region was quantified in a scale of four groups. No significant differences were found among the three groups.On the other hand, IgG of 8 patients with schizophrenia(30.71%) formed a band in the region of 85 kDa. This band was not formed with the serum of other groups. HSp 60 kDa is an antigen of many pathogens and antibodies againstit can be a result of an infectionand can thus not be a good indicator of an autoimmune process. The presence of antibodies againstHsp 90 kDa might be a much more specifieindicator.
IP.3.03SI Theeffect of neuroleptic drugs on olfactory sensitivity In schizophrenia
Pinkhas Sirota, Israel Ben-David, Keren Luca-Haimovici, Joseph Zohar, Ruth Gross-Isseroff. Abarbanel Mental Health Center; Bat-Yam. Israel; Division of Psychiatry, Chaim ShebaMedical Center; TelHashomet; Israel; Sackler FacultyofMedicine, Tel Aviv University, RamatAviv, lsrael; Department of Membrane Research and Biophysics. Weizmann Institute of Science, Rehovot, Israel Olfactory sensitivity to two odorants, iso-amylacetate and androstenone, was assessed in 19 schizophrenic patients and 10 non-schizophrenic controlsubjects(5 healthysubjects,4 OCD patients, and 1 MDD patient). Tests were performed during a drug free period and three weeks after initiation of neuroleptic drug therapy. The two main findings were: 1) a significantly reducedolfactorysensitivity to iso-amyl acetate in drug free schizophrenic patients as compared to non-schizophrenic controls and 2) a significant reduction in olfactorysensitivityinduced by commonlyused neuroleptic treatment. Is the reduced olfactorysensitivitydue to previous long-term exposure to neuroleptic drugs. or is it due to an inborn defect associated with the pathophysiology of the disorder?Further studies with drug-naive schizophrenic patients arc needed to elucidate this question.
IP.3.039I eNS Regulation of AP·' transcription complex in the byantipsychotics P. Rogue, A.N. Malviya, G. Vincendon. LN.M.1.C., CNRSCenterfor Neurochemistry, 5 rue BlaisePascal, Strasbourg 67084, France A single injection 1.P. of haloperidol (2 mglkg) produces a transient increase in c-fos and jWI B mRNA in the dorsal and vantral striatum of the rat. Using gel-shift assays, we studied the effect of haloperidol on the AP-l bindingactivity of nuclearextractsfrom the striatum.A single acute injection (2 mglkg) rapidly determines a significantand specific increase of AP-l binding activityin both the dorsal and the ventral striatum. The therapeutic effects of antipsychotic drugs are delayed. Upon prolonged haloperidol administration (2 mglkg for 15 days), both c-fos and jun B induction in the dorsal and v central striatum were significantly dessensitized, though not completely abolished. Despite this down-regulation, AP-l binding activity remainedelevated at levelscomparable to those seen after acute haloperidol administration for at least 5 days following the last haloperidol injection. Supershiftassays confirmed that the compositionof the AP-l transcription factorcomplex is modified upon prolongedneuroleptic administration. Resultswith clozapine and in other brain regions will be discussed. References [I] Rogue Pel aI. Brain Res Bull 1992, 9,469-472 (2) Rogue P et al, NeuroRepon 1994.5,501-504
S4-114
impairment in recognition either brotizolam or midazolam was applied, while recall (recent memory) correlated with drug half-lives that meant that results with midazolam were better in comparison with brotizolam, but not significantly. References
Lezak M.D. (1976) Neuropsychological assessment. OxfordUniversityPress, New York. Roth, T. and Roehrs, A. T. (1994) Benzodiazepine agonists in insomnia: efficacy and safety, Neuropsychopharmacology-VollO, No 35/Part 1, 8618.
IP.3.03S! Pramipexole as an adjunct to haloperidol in schizophrenia
C. Bamas I, A. Heiden I, H.P.Yolz2, G. Laakmann ' , H. Zeit 4 • H. Pfolz 5 , S. Kasper I. I Department of Clinical Psychiatry, University of Vienna, Wiihringer Giirtel 18-20, A-/090 Vienna, Austria; 2 Department of Psychiatry, University of lena, Germany; 3 Department of Psychiatry, University of Munich, Germany; 4 Psychiatric Hospital, Evangelical Hospital Gelsenkirchen, Germany; 5 Psychiatric Hospital Baumgartner Hohe, Vienna, Austria Pramipexole is a dopamine D2ID3 receptor agonist. It is supposed to exert its activity with a net outcome of stimulation of the presynaptic D2 autoreceptors when the synapse is in good order. This leads to inhibition of the synthesis and release of dopamine and thus to a decreased firing rate of the dopaminergic neuron. In the case of a presynaptic degeneration with subsequent postsynaptic hypersensitivity pramipexole can exert its postsynaptic D2 agonist activity. Previous pilot studies have shown that pramipexole might have a therapeutic effect on negative symptoms of schizophrenia, whereas it seemed to lack efficacy against positive symptomswhen used as a monotherapy. The aim of the present study was the evaluation of the efficacy and safety of pramipexole (up to 10.25 mg/day) when added to a maintenance therapy with haloperidol for the treatment of residual positiveand negative symptoms of patients with a chronic or subchronic course of schizophrenia as diagnosed by DSM-IV. Fifteen patients (4 females, 11 males; mean age ± SD = 31.7 ± 10.0years) were recruited to participate. They all, while under haloperidol medication (5-2 0 mg/day or depot medication), showed a stable clinical course with a minimum PANSS score of 60 at the time of inclusion. The concept of the study was to reach the maximum tolerated dose of pramipexole (up to 10.25 mg) after a fast dose escalation on day 14 and a stable dose from day 14 to day 28. During the whole study the haloperidol medication remainedunchanged. Psychopathology was documentedwith the PANSSand the CGL Eleven of the fifteen patients completed the study. Three dropped out due to a worsening of positive schizophrenic symptoms, one because of administrative reasons. All patients who completed the study showed an amelioration in the PANSS score: the mean decrease in the positive subscale was 9.7%. in the negative subscale 24.2%, and in the general psychopathology subscale J 1.9%. The total score showed a decrease of 16%.Insomnia was the most frequently reportedside-effect (4 cases). No clinically relevantECG and laboratory changes were reponed. The study supports the safety of the treatment of schizophrenia with pramipexole and haloperidol as a combination therapy. However. further clinical studies are required to support these preliminary findings.
IP.3.037I Antibodies to human heat shock protein in
patients with schizophrenia and major depression
p. Sirota I, D. Mazeh I. A. Novogrotsky 2. 1 AbarbanelMental Health Center; Bat Yam, and Sackler Faculty of Medicine, Tel Aviv University, RamatAviv, Israel; 2 Felsenstien Institute for Medical Research, Beilinson Medical Center; Petah. Tiqwa; andSacklerFaculty of Medicine, Tel Aviv University, RamatAviv, Israel Different immunological abnormalities were reported in schizophrenia and major depression. Heat shock proteins are producedin everycelltype in reaction to different stressors. They are found in cells in normal conditions in minor quantities. In autoimmune diseases they were found in large quantities, Kilidries et al. reported an increase of hsp 60 antibodies
in the serumof patientswith schizophrenia. The serum of 26 patients with schizophrenia, 8 patients with major depression and 22 normal subjects, were tested for the presence of hsp antibodies. The serum samples were testedfor antibodybindingto protein extracts0fI.M.R.-32 neuroblastoma cell lineon Western blots. In Westernblots IgG in the serum of all patients but one and of normal subjects, reacted with a protein of 60 kDa. The intensity of each band in the 60 kDa region was quantified in a scale of four groups. No significant differences were found among the three groups.On the other hand, IgG of 8 patients with schizophrenia(30.71%) formed a band in the region of 85 kDa. This band was not formed with the serum of other groups. HSp 60 kDa is an antigen of many pathogens and antibodies againstit can be a result of an infectionand can thus not be a good indicator of an autoimmune process. The presence of antibodies againstHsp 90 kDa might be a much more specifieindicator.
IP.3.03SI Theeffect of neuroleptic drugs on olfactory sensitivity In schizophrenia
Pinkhas Sirota, Israel Ben-David, Keren Luca-Haimovici, Joseph Zohar, Ruth Gross-Isseroff. Abarbanel Mental Health Center; Bat-Yam. Israel; Division of Psychiatry, Chaim ShebaMedical Center; TelHashomet; Israel; Sackler FacultyofMedicine, Tel Aviv University, RamatAviv, lsrael; Department of Membrane Research and Biophysics. Weizmann Institute of Science, Rehovot, Israel Olfactory sensitivity to two odorants, iso-amylacetate and androstenone, was assessed in 19 schizophrenic patients and 10 non-schizophrenic controlsubjects(5 healthysubjects,4 OCD patients, and 1 MDD patient). Tests were performed during a drug free period and three weeks after initiation of neuroleptic drug therapy. The two main findings were: 1) a significantly reducedolfactorysensitivity to iso-amyl acetate in drug free schizophrenic patients as compared to non-schizophrenic controls and 2) a significant reduction in olfactorysensitivityinduced by commonlyused neuroleptic treatment. Is the reduced olfactorysensitivitydue to previous long-term exposure to neuroleptic drugs. or is it due to an inborn defect associated with the pathophysiology of the disorder?Further studies with drug-naive schizophrenic patients arc needed to elucidate this question.
IP.3.039I eNS Regulation of AP·' transcription complex in the byantipsychotics P. Rogue, A.N. Malviya, G. Vincendon. LN.M.1.C., CNRSCenterfor Neurochemistry, 5 rue BlaisePascal, Strasbourg 67084, France A single injection 1.P. of haloperidol (2 mglkg) produces a transient increase in c-fos and jWI B mRNA in the dorsal and vantral striatum of the rat. Using gel-shift assays, we studied the effect of haloperidol on the AP-l bindingactivity of nuclearextractsfrom the striatum.A single acute injection (2 mglkg) rapidly determines a significantand specific increase of AP-l binding activityin both the dorsal and the ventral striatum. The therapeutic effects of antipsychotic drugs are delayed. Upon prolonged haloperidol administration (2 mglkg for 15 days), both c-fos and jun B induction in the dorsal and v central striatum were significantly dessensitized, though not completely abolished. Despite this down-regulation, AP-l binding activity remainedelevated at levelscomparable to those seen after acute haloperidol administration for at least 5 days following the last haloperidol injection. Supershiftassays confirmed that the compositionof the AP-l transcription factorcomplex is modified upon prolongedneuroleptic administration. Resultswith clozapine and in other brain regions will be discussed. References [I] Rogue Pel aI. Brain Res Bull 1992, 9,469-472 (2) Rogue P et al, NeuroRepon 1994.5,501-504