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P.2.h. Affective disorders and antidepressants − Other (basic)
SNP of the single marker analysis showed a gene-dose dependent effect on the improved cortisol response (AUC) to the dex/CRH test prior to discharge (P=.038, between-subjects analysis of GLM; age and sex as covariates). Applying a hierarchical multiple regression model, this effect could be shown to be independent of the response status at the time of testing. Neither in the single marker analysis nor in the haplotype study, the NTRK2 gene associations withstood correction for multiple testing. Conclusions: These findings provide evidence for an involvement of genetic variations in the BDNF gene in the antidepressant treatment response and point to a possible role of BDNF in the normalization of an impaired stress hormone regulation. Disclosure statement: Menke, Holsboer inventors: Means and methods for diagnosing predisposition for treatment emergent suicidal ideation (TESI). European application number: 08016477.5 International application number: PCT/EP2009/061575. Hennings, Kohli, Heck, Roeske, Horstmann, Br¨uckl, Klengel, M¨ullerMyhsok, Ising, Lucae: Nothing to disclose. Florian Holsboer is founder and share holder of Affectis Pharmaceuticals. The study was supported in part by a research grant from the German Federal Ministry for Education and Research (BMBF, 01ES0811). P.2.h.002 Chronic stress induces changes in neuronal plasticity and inhibitory neurotransmission in the amygdala of adult mice J. Gilabert-Juan1 ° , E. Castillo-Gomez2 , M.D. Molt´o3 , J. N`acher2 . 1 Universitat de Val` encia. CIBERSAM, Department of Cell Biology, Burjassot (Valencia), Spain; 2 Universitat de Val`encia, Department of Cell Biology, Burjassot (Valencia), Spain; 3 Universitat de Val` encia. CIBERSAM, Department of Genetics, Burjassot (Valencia), Spain Several lines of evidence point to chronic stress as a major precipitating factor of some mental disorders, such as major depression, schizophrenia, bipolar disorder or posttraumatic stress disorder. However, the neural mechanisms by which the effects of stress contribute to the development of these clinical pathologies are still not well understood and controversial in some cases. Different studies have demonstrated that the structure and function of the amygdala is affected in patients suffering stress-related disorders. Similar results have been obtained in experimental animals, specially in rats, where chronic stress induces neuronal structural remodeling. Plasticity-related molecules, such as the polysialylated form of the neural cell adhesion molecule (PSANCAM) are involved in this remodeling. This molecule is expressed by mature interneurons in the adult cerebral cortex and amygdala. However, this structural plasticity has been studied only in principal neurons and little is known about how inhibitory neurons in the amygdala respond to chronic stress. We have subjected 2 groups of adult mice to chronic restraint stress and 2 groups of adult mice in control conditions for 21 days in order to know whether the stress response in the amygdala of these animals is similar to that described in rats, and to analyze in detail changes in the expression of PSA-NCAM, its synthesizing enzymes (polysialyltransferases II and IV) and that of proteins related to general (synaptophysin) or inhibitory synapses (glutamic acid decarboxylase isoform 67, GAD67 and glutamic acid decarboxylase isoform 65, GAD65), using qRT-PCR and immunohistochemistry. We remove the total amygdala of first control/ stress groups for quantitative PCR, after the mRNA isolation and the cDNA conversion. Primers for NCAM, polysialyltransferase II
(St8SiaII), polysialyltransferase IV (St8SiaIV), GAD65, GAD67 and synaptophysin (SYN) were designed to find the differences in gene expression between stressed and control mice. Antibodies against GAD67, SYN and PSA-NCAM were used in the immunohistochemistry brain slices of the second control/stress groups of mice in the study to determine the alterations in protein expression in three amygdala nuclei, central, medial and basolateral. We have observed a significant decrease in mRNA expression of GAD67 and polysialyltransferase II in total amygdala (p = 0.042; 0.0242 respectively), a no significant reduction of GAD65, St8siaIV and a no significant increase of NCAM and SYN genes. These changes are accompanied by specific reductions in PSA-NCAM expression in the central nucleus of the amygdala (p = 0.0041) and in GAD67 and SYN in the medial nucleus (p = 0.021; 0.012 respectively). All the protein markers tend to a reduction in the three nuclei in stressed mice. The present results indicate that the remodeling of amygdaloid inhibitory circuits is important in the response to chronic stress and confirm and expand previous results on the involvement of PSA-NCAM in this plasticity process. Disclosure statement: This study was financially supported by the following grants: Spanish Ministry of Education (BFU2006–07313/BFI), Generalitat Valenciana (ACOMP2009– 271 and AP127−09), Spanish Ministry of Science and Innovation (BFU2009–112284/BFI) and CIBERSAM. C-G E. and G-J J. have FPU predoctoral fellowships from the Spanish Ministry of Education (AP2006–0195 and AP2008–00937). P.2.h.003 Suicide attempts in a mental health unit of Galicia B. Portela Traba1 ° , M. P´erez Garc´ıa1 , A. Mozos Ansorena2 . 1 Unidad de Salud Mental VI, Psiquiatr´ıa, Santiago de Compostela, Spain; 2 Unidad de Hospitalizaci´on de Conxo, Psiquiatr´ıa, Santiago de Compostela, Spain INTRODUCTION:Suicide attempts are a major problem in public health y many studies have been realized to study them in specific population groups, as well as, the attended ones in different devices, including Mental Health Unit, in order to plan a suitable treatment and to realize a prevention of the suicidal behavior, by a general education about suicide, early detection, taking actions on high risk groups, among other measures. OBJETIVES:Establish the sociodemographic profile of subjects who come as first consultation to the Mental Health Unit VI and within these, the subgroup of patients with a history of suicide attempts (SA). Identify mental disorders most frequently associated with suicide attempts. To determine the methods most commonly used in attempts. Study the relationship between repetition of suicidal behavior and severity of suicide attempt. MATERIAL AND METHODS:Retrospective and descriptive study of clinical and epidemiological characteristics of patients who come as a first consultation to a Mental Health Unit of the Galician coast (n = 288) for a period of 6 months. We designed a specific protocol and the diagnoses made by clinical interview following ICD-10 criteria. RESULTS:In 13.2% of the total sample was collected history of suicide attempts, corresponding to the women 10.1%.42.1% of SA patients is in the age group between 25 and 44 years. In the SA group 76.3% are women. The most common diagnoses among the SA patients belong to the mood disorders (F30−39) and neurotic, stress-related and somatoform disorders (F40−48), although over 50% of patients who are in the group of disorders
P.3.a. Psychotic disorders and antipsychotics − Psychotic disorders (clinical) of adult personality and behaviour (F60−69), have a history of suicide attempts (p < 0.05). Taking into account the last attempt by SA women, was mild in 58.6% of cases, moderate in 31% and severe in 10.3%. While the SA men, the percentages are distributed equitably in all three types (33.3%). In all age groups are more frequent attempts mild, with the exception of the group under the age of 25 years, in which are more frequent the moderate but contains no serious, unlike the observed in other groups. Emphasize that 50% of the patients whose last suicide attempt has been serious, had a history of 2 or more previous attempts. In the SA group only can find intent/planning suicide in 15.8%, belong all of these patients to diagnostic groups F30−39 (66.7%) and F60−69 (33.3%). Although most of the patients in these two groups have no suicide intention. Suicide attempts with the possibility of rescue are the most frecuently, in both men and women. 80% of the SA that have made 3 or more attempts, belong to the diagnostic groups F30−39 and F60−69. CONCLUSIONS:Profile of the patient who comes as a first consultation to our Mental Health Unit with a history of suicide attempt/s:woman,45-year-old, married/with partner, who lives with own family, with primary studies, casual employment, sent from primary care, with personal and family psychiatric history, with a diagnosis compatible with disorder included in the group F30−39. She makes a single suicide attempt by drug overeating, without prior planning, with the possibility of “rescue” and whose initial medical care has been limited to first aid. References [1] Bugar´ın Gonz´alez, R.; Gallego Feal, P.; Balo Junquera, F.; Canedo Santos, M.; Cornes Iglesias, J.M; Castreo Calvo, R. La ingesti´on de f´armacos como causa de suicidios y tentativas de suicidios en Galicia. Rev. Psiquiatr´ıa Fac Med Barna 2000; 27(1): 22−25. [2] Scocco P, Toffol E, Pilotto E, Riccardo P, Pavan L. How the psychiatrists of a mental health department managed their patients before an attempted suicide. Psychiatry Clin Neuroscience. 2009 Dec;63(6):706−14. [3] Posada-Villa J, Camacho JC, Valenzuela JI, Arguello A, Cendales JG, Fajardo R. Prevalence of suicide risk factors and suicide-related outcomes in the National Mental Health Study, Colombia. Suicide Life Threat Behav. 2009 Aug;39(4):408−24.
P.2.h.004 Antidepressant and antipsychotic-like effects of GABA-B receptor ligands in mGlu7 deficient mice J.M. Wieronska1 ° , P. Branski1 , T. Lech1 , M. Marciniak1 , A. Pilc1 . 1 Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland mGlu7 receptor is the unique member of the metabotropic glutamate receptor family, as it is the most conserved among mammalian species and its affinity to glutamate is the lowest. The selective ligand of this receptor, AMN 082, exerts antidepressant and anxiolytic-like activity in animals. Similar results were observed when mGlu7 deficient mice were undergone behavioral tests detecting antidepressant and anxiolytic activity in standard animal test such as forced swim test, stress-induced hyperthermia, plus-maze test etc. The results strongly support the idea that mGlu7 receptor is involved in the pathology and treatment of mood disorders. In contrast, there were no studies performed in the field of psychotic-like behavior of mGlu7 knockout animals and antipsychotic medication. Therefore, in the present study the mGlu7 KO mice were assessed in one of the mostly used animal test reflecting hallucinogenic-like behavior e.g DOI-induced head
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twitches (DIHT). DOI was administered in a dose of 2.5 mg/kg and the number of episodes was investigate thereafter. As the balance between two major amino acid systems was described to be important in psychiatric disorders, including depression and schizophrenia, the ligands of the receptors for both amino acids were widely investigated in many laboratories. The special attention was paid on the metabotropic receptors, as being more promising as potential novel therapy. Therefore, the metabotropic glutamate receptors (mGlu) and GABAB receptors ligands were shown to posses great therapeutic efficacy. In the study we focused on GABAergic system as the main inhibitory neurotransmission in the brain. The GABAB receptor ligands were shown to possess anxiolytic and/or antidepressant-like effects in animals. CGP 36742, novel antagonist of this receptor, was assessed in forced swim test and olfactory bulbectomy with positive results. In contrast, GS 39783, a positive allosteric modulator of the receptor, was shown to posses anxiolytic, but not antidepressant like effect in animals. The GABAB deficient mice were shown to be more anxious and more sensible in prepulse inhibition test. In contrast, antidepressant-like behavior was observed in those animals. In our previous study we showed that mGlu7 knockout animals have decreased level of GABAB receptors. Therefore, in the present study, we investigated the efficacy of GABAB ligands in mGlu7 deficient mice. The TST and DIHT were performed. GS 39783 (30 mg/kg) and CGP 36742 (15 mg/kg) were administered i.p, 30 min before tests. GS 39783 inhibited DOI-induced head twitches while was not active in TST test when measured in mGlu7 +/+ animals. In contrast, CGP 36742 was effective in TST and not in DIHT. mGlu7 deficient mice were less sensitive to DOI administration comparing to wild types, and the effect of GS 39783 was significant in those animals, too. CGP 36742 was not active in mGlu7 −/− animals in TST, which suggests the crucial role for mGlu7 receptor in antidepressant-like effect of the compound. The study was supported by the grant no N N401 009536 given to Joanna Wieronska.
P.3.a. Psychotic disorders and antipsychotics − Psychotic disorders (clinical) P.3.a.001 Evaluation of the effect of aripiprazole on quality of life in patients with schizophrenia C. Bervoets1 ° , E. Constant2 , B. Sabbe1 , M. Morrens1 , K. Vansteelandt3 , A. De Patoul4 , D. Pitzi4 , V. Halkin4 , 1 UAntwerp, Capri, Antwerp, J.Y. Loze5 , J. Peuskens6 . Belgium; 2 UCLouvain, cliniques universitaires, Louvain, Belgium; 3 KUleuven, UC Kortenberg, Kortenberg, Belgium; 5 Otsuka Pharmaceutical, Otsuka, Paris, France; 6 KULeuven, UC Kortenberg, Kortenberg, Belgium Background: Aripiprazole has been claimed to have a beneficial effect on cognition with an emphasis on verbal functioning in schizophrenic patients[1]. This study was set to evaluate the effect on quality of life, in relation to illness severity and cognitive functioning of a treatment with aripiprazole in schizophrenic patients. Methods: 363 patients with a diagnosis of schizophrenia, ranging from 18 to 65 years, who were treated with different typical and atypical antipsychotics or had no previous treatment, were