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P.1.b.004 Mismatch negativity in depressed patients under selective noradrenergic and serotonergic antidepressants
P.1.b. Basic and clinical neuroscience − Neuroanatomy and neurophysiology Results: In cortical neurons, it has been found that c-FOS immune staining is (−) in the control group while it is (++++) in SAH group and (+) in SAH-agmatine group. Caspase-3 immune staining is hardly seen in the control group, increased in SAH distinctly and regressed substantially with agmatine therapy. nNOS immunohistochemical staining is found (−) in the control group, (+++) in SAH group and (+) in SAH-agmatine group. In astrocytes, anti-GFAP immune staining is slightly seen in the control group, increased in SAH group but it regresses back to the values of the control group in SAH-agmatine group. In addition, staining of astrocytes extensions neighboring cortical veins are noticed to be regressed considerably in SAH-agmatine group compared to the SAH group. Conclusion: The results of this study have shown that agmatine can inhibit the cortical damage after SAH significantly. Consequently, it is thought that agmatine has protective effects at least in these two brain regions.
P.1.b.003 Stereological estimation of the substantia nigra neurons in 6-ODHA-lesioned rats receiving L-DOPA and the nitric oxide donor molsidomine A. Czarnecka1 ° , H. Domin2 , T. Lenda1 , J. Konieczny1 , M. Zapala1 , E. Lorenc-Koci1 . 1 Institute of Pharmacology Polish Academy of Sciences, Department of Neuro-Psychopharmacology, Krakow, Poland; 2 Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland Background: Nitric oxide (NO) is a short-lived bioactive molecule that acts as a neurotransmitter or a neuromodulator when synthesized by the neuronal isoform of the enzyme nitric oxide synthase. nNOS and its associated reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity are distributed throughout selective neuronal populations of the central and peripheral nervous system. Parkinsonian brains were found to contain decrease numbers of NADPH-d positive neurons in the caudate-putamen [1] and reduced nitrate level in the cerebrospinal fluid [2]. Moreover, chronic treatment with L-DOPA led to hypertrophy of the medial globus pallidus and substantia nigra (SN) pars reticulata in 6-hydroxydopamine (6-ODHA)-lesioned rats which is probably connected with L-DOPA induced dyskinesia in Parkinson’s disease [3]. Purpose: We aimed to investigate the effect of 6-ODHA lesion and L-DOPA treatment, alone or in combination with the nitric oxide donor, molsidomine, on stereological parameters of the SN such as the number of tyrosine hydroxylase-immunoreactive (THir), nNOS-ir and cresyl violet (CV)-stained neurons as well as on the volume of the structure. Additionally, the relationship between nNOS and NADPH-d expression was analyzed. Methods: Male Wistar rats were stereotactically injected with 6-ODHA (8 mg/4 ml) into the left medial forebrain bundle. Two weeks after surgery, animals were tested for rotational behavior induced by apomorphine (0.25 mg/kg s.c.). Rats exhibiting more than 100 contralateral turns per 1h were treated with solvent or drugs: molsidomine (2 mg/kg i.p.) and L-DOPA (25 mg/kg i.p.), alone or in combination, once daily for 14 days. The animals were killed 1h after the last injection of drug or solvent. The dissected brains were used for histological analysis of TH-ir and nNOS-ir neurons as well as CV- and NADPH-d stained neurons in the SN. An unbiased stereological technique was used for cell counting
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throughout the entire SNr. The data were analyzed using a oneway ANOVA, followed by a Tukey’s test for post hoc comparisons or T-test for dependent samples. Results: Stereological analysis of TH-ir neurons in the SN of 6-ODHA-lesioned rats demonstrated their almost 97% loss on the ipsilateral side. Regarding nNOS-ir neurons in that structure, the stereological analysis revealed a 25% decrease in their number on the ipsilateral side. Treatment with L-DOPA alone or in combination with molsidomine did not change these effects. Estimation of the whole quantity of CV-stained neurons in the rat SN indicated that nNOS positive neurons comprised about 70% of all SN neurons. However, only few of SN neurons were NADPH-d positive in all examined groups of rats. Chronic L-DOPA treatment led to a significant increase in the total volume of the SN on the lesioned side (p < 0.001 vs. intact side). The addition of the NO donor, molsidomine prevented the L-DOPA-induced hypertrophy of the lesioned side. Conclusions: Our findings substantiate the conclusion that NADPH-d histochemistry is not always overlapping with NOSimmunohistochemistry and provide evidence for the existence of a large population of nNOS containing neurons in the SN. It also confirms that chronic L-DOPA treatment is connected with hypertrophy of the SN and NO may be able to reverse this effect. References [1] Bockelmann R., Wolf G., Ransmayr G., Riederer P. 1994 NADPHdiaphorase/nitric oxide synthase containing neurons in normal and Parkinson’s disease putamen. J Neural Transm [P-D Sect] 7:115–121. [2] Kuiper M.A., Visser J.J., Bergmans P.L., Scheltens P., Wolters E.C., 1994 Decreased cerebrospinal fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients. J Neurol Sci, 121, 46−49. [3] Tomiyama M., Mori F., Kimura T., Ichinohe N., Wakabayashi K., Matsunaga M., Baba M. 2004 Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6-hydroxydopaminelesioned rats treated with L-DOPA: Implication for L-DOPA-induced dyskinesia in Parkinson’s disease Neuropathology; 24, 290–295. Disclosure statement: This study was supported by Grant N 066/B/P01/2008/35 from the Ministry of Science and Higher Education
P.1.b.004 Mismatch negativity in depressed patients under selective noradrenergic and serotonergic antidepressants C. Norra1 ° , A. Peddersen2 , G. Juckel1 , S. Waniek2 . 1 Ruhr University Bochum, Psychiatry, Bochum, Germany; 2 Westphalian Wilhelms University, Psychiatry, M¨unster, Germany Background: Mismatch negativity (MMN) is an auditory evoked potential that has consistently detected neural pre-attentive information processing deficits mainly in schizophrenia. The MMN potential is calculated as the difference wave between a sequence of repeated similar stimuli and rare unexpected deviants with slight physical changes for example in frequency (FD) or duration (DD). Neurochemically the glutamatergic neurotransmitter system has been identified as crucial for the origin of deficits in MMN [1]. There is also some evidence for monoaminergic modulation of MMN under tryptophan depletion [2] or SSRIs [3]. With regard to patients with depressive disorders there are only a few small and rather heterogeneous studies of MMN, so far. Yet, the MMN paradigm requires no task, thus it is not contaminated by motivational factors relevant for depression making it even more suitable as a non-invasive tool in clinical studies. Purpose: The aim of the study was first a comparison of MMN between unmedicated patients with major depression and
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P.1.b. Basic and clinical neuroscience − Neuroanatomy and neurophysiology
a healthy control group with the assumption of an attenuation of MMN, and second, a longitudinal examination of the patient group to investigate differential monoaminergic treatment effects of antidepressants on MMN. Methods: Auditory MMN was recorded using multi-channel EEG in 17 unmedicated inpatients with an acute depressive episode and age-matched healthy controls. Patients received a follow-up MMN after four weeks of randomized antidepressant treatment with a selective serotonergic or noradrenergic re-uptake inhibitor respectively citalopram or reboxetine. In parallel, depressed symptoms were documented (BDI, HAMD) on a weekly basis. Summary of results: MMN amplitudes of scalp derived potentials were impaired (all deviants), with different alterations in the latencies pointing to deficits of MMN generation in depressed patients as opposed to healthy controls. More sophisticated brain source analysis (BESA) located the largest MMN impairment left frontally (DD t = −2.680; p = 0.017, FD t = −2.224; p = 0.041) with increased latency (DD t = 2.700; p = 0.016). However, despite full psychopathological response patients showed no significant change of MMN after antidepressive pharmacotherapy, irrespective of the selective nature of the monoaminergic drug. Conclusion: Our findings point to deficits of the auditory information processing in MMN in patients with depressive disorder, too. However, the absence of any normalization of the MMN in the post-acute phase regardless of the pharmacological profile of monoaminergic antidepressants might refer to the trait character of underlying pathophysiological mechanisms in depression. Further longitudinal studies are warranted to investigate the potential serotonergic modulation of MMN and its clinical impact. References [1] Heekeren, K., Daumann, J., Neukirch, A., Stock, C., Kawohl, W., Norra, C., Waberski, T. D. Gouzoulis-Mayfrank, E., 2008 Mismatch negativity generation in the human 5HT-2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl.) 199, 77−88. [2] Ahveninen, J., K¨ahk¨onen, S., Pennanen, S., Liesivuori, J., Ilmoniemi, R. J. Jaaskelainen, I. P., 2002 EEG und MEG measurements after tryptophan depletion suggest serotonergic modulation of auditory involuntary attention. Neuroimage 16, 1052–1061. [3] Oranje, B., Jensen, K., Wienberg, M, Glenthoj, B.Y., 2008 Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention. Int J Neuropsychopharmacol 11, 453– 463.
P.1.b.005 Oxytocin and psychometric aspects in diabetes mellitus type 2 K. Kontoangelos1,3 ° , A.E. Raptis2 , C.C. Papageorgiou1,3 , G. Tsiotra2 , G.N. Papadimitriou1 , A.D. Rabavilas3 , 1 Eghinition Hospital, G. Dimitriadis2 , S.A. Raptis2,4 . 1st Department of Psychiatry, Athens, Greece; 2 Athens University Medical School Attikon University Hospital, 2nd Department of Internal Medicine–Propaedeutic-Research Institute and Diabetes Center, Athens, Greece; 3 University Mental Health Research Institute, Athens, Greece; 4 Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (H.N.D.C.), Athens, Greece Introduction: Oxytocin (OXT) is a neurohypophysial hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Few data suggest a link between OXT and neuropsychiatric disorders [1]. Regarding diabetes mellitus type 2, oxytocin is involved in glucose homeostasis by increasing glycogenolysis
as well as glyneogenesis [2,3]. The aim of this study is the exploration of this relation and the influence of diabetic profile in oxytocin and the psychometric factors. Method: The present study was conducted at the Attico Hospital and the sample was randomly selected from the Diabetic centre of the 2nd Department Internal Medicine-Propaedeutic of the University Hospital ‘Attico’. All the patients were suffering from diabetes mellitus type 2. The sample consisted of 131 diabetic patients, with mean age 64,8 years (S.D. = 10.17). The sample was divided in two groups, the group A which consisted of 86 (65.6%) controlled diabetic patients (Glycosylated Haemoglobin HbA1c <7) and the group B consisted of 45 (35.4%) uncontrolled diabetic patients (HbA1c 7). During the initial phase of the study (T0), blood samples were taken for measuring oxytocin. One year later (T1), the uncontrolled diabetic patients were re-evaluated with the use of the same psychometric instruments. From the initial sample of 45, finally 31 uncontrolled diabetic patients were re-assessed. Ten of these 31 uncontrolled patients had already managed to improve their metabolic profile (HbA1c <7) in the preceding year between Phase 1 (T0) and Phase 2 (T1) of the study. During the initial evaluation all the participants were assessed with the following two psychometric questionnaires: A. The Zung Self Rating Depression Scale (ZDRS). B. The Maudsley O-C Inventory Questionnaire (MOCI). C. The brief symptom inventory SCL-90, D. Hostility and Direction of Hostility Questionnaire (HDHQ), E. Eysenck Personality Questionnaire (EPQ). Oxytocin levels were measured in the serum of all the patients using reagent ELISA (Enzyme-linked immunosorbent assay) according to the instructions of the manufacturer (Phoenix Pharm. Europe GMBH, Karlsruhe, Germany). Result: During the First evaluation T0, in the uncontrolled diabetic patients there is a statistical significant positive relation between oxytocin and psychotism in the EPQ (rsp = 0.374, p = 0.013), which means that if the values of oxytocin increase will increase also the values of psychotism. Regarding the correlation between the SCL-90 and oxytocin there is a statistical significant correlation in the controlled diabetic patients between oxytocin and the subscales of somatization (rsp = −0.245, p = 0.030), and obsessive compulsive (rp = −0.228, p = 0.047. Among the correlation between oxytocin and Zung scale, the values of oxytocin increase as frequently the controlled diabetic patients have decreased libido (3.56±1.85 vs 4.68±2.58, p = 0.050). In the uncontrolled diabetic patients there is statistical significant relation between the psychomotor retardation and oxytocin. As frequently the uncontrolled diabetic patients show psychomotor retardation the values of oxytocin decrease (9.64±0.32 vs 4.20±2.25, p = 0.002). During the second evaluation the values of oxytocin decreased when the patients managed to control their metabolic profile. Although this result is not statistical significant. Conclusion: Oxytocin in diabetes mellitus type 2, I scorrelated with personality traits, somatization and depressive symptoms. Improvement of the metabolic profile influence the values of oxytocin. References [1] Marazziti D, Catena dell’ Osso M. 2008. The role of Oxytocin in Neuropsychiatric Disorders. Curr Med Chem 15, 698–704. [2] Neumann ID. Brain oxytocin. 2008. A key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 20, 858–865. [3] Bartz J, McInnes A., 2007. CD 38 regulates oxytocin secretion and complex social behaviour. Bio Essays 29, 837–841.
P.1.b.003 Stereological estimation of the substantia nigra neurons in 6-ODHA-lesioned rats receiving L-DOPA and the nitric oxide donor molsidomine A. Czarnecka1 ° , H. Domin2 , T. Lenda1 , J. Konieczny1 , M. Zapala1 , E. Lorenc-Koci1 . 1 Institute of Pharmacology Polish Academy of Sciences, Department of Neuro-Psychopharmacology, Krakow, Poland; 2 Institute of Pharmacology Polish Academy of Sciences, Department of Neurobiology, Krakow, Poland Background: Nitric oxide (NO) is a short-lived bioactive molecule that acts as a neurotransmitter or a neuromodulator when synthesized by the neuronal isoform of the enzyme nitric oxide synthase. nNOS and its associated reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity are distributed throughout selective neuronal populations of the central and peripheral nervous system. Parkinsonian brains were found to contain decrease numbers of NADPH-d positive neurons in the caudate-putamen [1] and reduced nitrate level in the cerebrospinal fluid [2]. Moreover, chronic treatment with L-DOPA led to hypertrophy of the medial globus pallidus and substantia nigra (SN) pars reticulata in 6-hydroxydopamine (6-ODHA)-lesioned rats which is probably connected with L-DOPA induced dyskinesia in Parkinson’s disease [3]. Purpose: We aimed to investigate the effect of 6-ODHA lesion and L-DOPA treatment, alone or in combination with the nitric oxide donor, molsidomine, on stereological parameters of the SN such as the number of tyrosine hydroxylase-immunoreactive (THir), nNOS-ir and cresyl violet (CV)-stained neurons as well as on the volume of the structure. Additionally, the relationship between nNOS and NADPH-d expression was analyzed. Methods: Male Wistar rats were stereotactically injected with 6-ODHA (8 mg/4 ml) into the left medial forebrain bundle. Two weeks after surgery, animals were tested for rotational behavior induced by apomorphine (0.25 mg/kg s.c.). Rats exhibiting more than 100 contralateral turns per 1h were treated with solvent or drugs: molsidomine (2 mg/kg i.p.) and L-DOPA (25 mg/kg i.p.), alone or in combination, once daily for 14 days. The animals were killed 1h after the last injection of drug or solvent. The dissected brains were used for histological analysis of TH-ir and nNOS-ir neurons as well as CV- and NADPH-d stained neurons in the SN. An unbiased stereological technique was used for cell counting
S251
throughout the entire SNr. The data were analyzed using a oneway ANOVA, followed by a Tukey’s test for post hoc comparisons or T-test for dependent samples. Results: Stereological analysis of TH-ir neurons in the SN of 6-ODHA-lesioned rats demonstrated their almost 97% loss on the ipsilateral side. Regarding nNOS-ir neurons in that structure, the stereological analysis revealed a 25% decrease in their number on the ipsilateral side. Treatment with L-DOPA alone or in combination with molsidomine did not change these effects. Estimation of the whole quantity of CV-stained neurons in the rat SN indicated that nNOS positive neurons comprised about 70% of all SN neurons. However, only few of SN neurons were NADPH-d positive in all examined groups of rats. Chronic L-DOPA treatment led to a significant increase in the total volume of the SN on the lesioned side (p < 0.001 vs. intact side). The addition of the NO donor, molsidomine prevented the L-DOPA-induced hypertrophy of the lesioned side. Conclusions: Our findings substantiate the conclusion that NADPH-d histochemistry is not always overlapping with NOSimmunohistochemistry and provide evidence for the existence of a large population of nNOS containing neurons in the SN. It also confirms that chronic L-DOPA treatment is connected with hypertrophy of the SN and NO may be able to reverse this effect. References [1] Bockelmann R., Wolf G., Ransmayr G., Riederer P. 1994 NADPHdiaphorase/nitric oxide synthase containing neurons in normal and Parkinson’s disease putamen. J Neural Transm [P-D Sect] 7:115–121. [2] Kuiper M.A., Visser J.J., Bergmans P.L., Scheltens P., Wolters E.C., 1994 Decreased cerebrospinal fluid nitrate levels in Parkinson’s disease, Alzheimer’s disease and multiple system atrophy patients. J Neurol Sci, 121, 46−49. [3] Tomiyama M., Mori F., Kimura T., Ichinohe N., Wakabayashi K., Matsunaga M., Baba M. 2004 Hypertrophy of medial globus pallidus and substantia nigra reticulata in 6-hydroxydopaminelesioned rats treated with L-DOPA: Implication for L-DOPA-induced dyskinesia in Parkinson’s disease Neuropathology; 24, 290–295. Disclosure statement: This study was supported by Grant N 066/B/P01/2008/35 from the Ministry of Science and Higher Education
P.1.b.004 Mismatch negativity in depressed patients under selective noradrenergic and serotonergic antidepressants C. Norra1 ° , A. Peddersen2 , G. Juckel1 , S. Waniek2 . 1 Ruhr University Bochum, Psychiatry, Bochum, Germany; 2 Westphalian Wilhelms University, Psychiatry, M¨unster, Germany Background: Mismatch negativity (MMN) is an auditory evoked potential that has consistently detected neural pre-attentive information processing deficits mainly in schizophrenia. The MMN potential is calculated as the difference wave between a sequence of repeated similar stimuli and rare unexpected deviants with slight physical changes for example in frequency (FD) or duration (DD). Neurochemically the glutamatergic neurotransmitter system has been identified as crucial for the origin of deficits in MMN [1]. There is also some evidence for monoaminergic modulation of MMN under tryptophan depletion [2] or SSRIs [3]. With regard to patients with depressive disorders there are only a few small and rather heterogeneous studies of MMN, so far. Yet, the MMN paradigm requires no task, thus it is not contaminated by motivational factors relevant for depression making it even more suitable as a non-invasive tool in clinical studies. Purpose: The aim of the study was first a comparison of MMN between unmedicated patients with major depression and
S252
P.1.b. Basic and clinical neuroscience − Neuroanatomy and neurophysiology
a healthy control group with the assumption of an attenuation of MMN, and second, a longitudinal examination of the patient group to investigate differential monoaminergic treatment effects of antidepressants on MMN. Methods: Auditory MMN was recorded using multi-channel EEG in 17 unmedicated inpatients with an acute depressive episode and age-matched healthy controls. Patients received a follow-up MMN after four weeks of randomized antidepressant treatment with a selective serotonergic or noradrenergic re-uptake inhibitor respectively citalopram or reboxetine. In parallel, depressed symptoms were documented (BDI, HAMD) on a weekly basis. Summary of results: MMN amplitudes of scalp derived potentials were impaired (all deviants), with different alterations in the latencies pointing to deficits of MMN generation in depressed patients as opposed to healthy controls. More sophisticated brain source analysis (BESA) located the largest MMN impairment left frontally (DD t = −2.680; p = 0.017, FD t = −2.224; p = 0.041) with increased latency (DD t = 2.700; p = 0.016). However, despite full psychopathological response patients showed no significant change of MMN after antidepressive pharmacotherapy, irrespective of the selective nature of the monoaminergic drug. Conclusion: Our findings point to deficits of the auditory information processing in MMN in patients with depressive disorder, too. However, the absence of any normalization of the MMN in the post-acute phase regardless of the pharmacological profile of monoaminergic antidepressants might refer to the trait character of underlying pathophysiological mechanisms in depression. Further longitudinal studies are warranted to investigate the potential serotonergic modulation of MMN and its clinical impact. References [1] Heekeren, K., Daumann, J., Neukirch, A., Stock, C., Kawohl, W., Norra, C., Waberski, T. D. Gouzoulis-Mayfrank, E., 2008 Mismatch negativity generation in the human 5HT-2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl.) 199, 77−88. [2] Ahveninen, J., K¨ahk¨onen, S., Pennanen, S., Liesivuori, J., Ilmoniemi, R. J. Jaaskelainen, I. P., 2002 EEG und MEG measurements after tryptophan depletion suggest serotonergic modulation of auditory involuntary attention. Neuroimage 16, 1052–1061. [3] Oranje, B., Jensen, K., Wienberg, M, Glenthoj, B.Y., 2008 Divergent effects of increased serotonergic activity on psychophysiological parameters of human attention. Int J Neuropsychopharmacol 11, 453– 463.
P.1.b.005 Oxytocin and psychometric aspects in diabetes mellitus type 2 K. Kontoangelos1,3 ° , A.E. Raptis2 , C.C. Papageorgiou1,3 , G. Tsiotra2 , G.N. Papadimitriou1 , A.D. Rabavilas3 , 1 Eghinition Hospital, G. Dimitriadis2 , S.A. Raptis2,4 . 1st Department of Psychiatry, Athens, Greece; 2 Athens University Medical School Attikon University Hospital, 2nd Department of Internal Medicine–Propaedeutic-Research Institute and Diabetes Center, Athens, Greece; 3 University Mental Health Research Institute, Athens, Greece; 4 Hellenic National Center for Research, Prevention and Treatment of Diabetes Mellitus and its Complications (H.N.D.C.), Athens, Greece Introduction: Oxytocin (OXT) is a neurohypophysial hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Few data suggest a link between OXT and neuropsychiatric disorders [1]. Regarding diabetes mellitus type 2, oxytocin is involved in glucose homeostasis by increasing glycogenolysis
as well as glyneogenesis [2,3]. The aim of this study is the exploration of this relation and the influence of diabetic profile in oxytocin and the psychometric factors. Method: The present study was conducted at the Attico Hospital and the sample was randomly selected from the Diabetic centre of the 2nd Department Internal Medicine-Propaedeutic of the University Hospital ‘Attico’. All the patients were suffering from diabetes mellitus type 2. The sample consisted of 131 diabetic patients, with mean age 64,8 years (S.D. = 10.17). The sample was divided in two groups, the group A which consisted of 86 (65.6%) controlled diabetic patients (Glycosylated Haemoglobin HbA1c <7) and the group B consisted of 45 (35.4%) uncontrolled diabetic patients (HbA1c 7). During the initial phase of the study (T0), blood samples were taken for measuring oxytocin. One year later (T1), the uncontrolled diabetic patients were re-evaluated with the use of the same psychometric instruments. From the initial sample of 45, finally 31 uncontrolled diabetic patients were re-assessed. Ten of these 31 uncontrolled patients had already managed to improve their metabolic profile (HbA1c <7) in the preceding year between Phase 1 (T0) and Phase 2 (T1) of the study. During the initial evaluation all the participants were assessed with the following two psychometric questionnaires: A. The Zung Self Rating Depression Scale (ZDRS). B. The Maudsley O-C Inventory Questionnaire (MOCI). C. The brief symptom inventory SCL-90, D. Hostility and Direction of Hostility Questionnaire (HDHQ), E. Eysenck Personality Questionnaire (EPQ). Oxytocin levels were measured in the serum of all the patients using reagent ELISA (Enzyme-linked immunosorbent assay) according to the instructions of the manufacturer (Phoenix Pharm. Europe GMBH, Karlsruhe, Germany). Result: During the First evaluation T0, in the uncontrolled diabetic patients there is a statistical significant positive relation between oxytocin and psychotism in the EPQ (rsp = 0.374, p = 0.013), which means that if the values of oxytocin increase will increase also the values of psychotism. Regarding the correlation between the SCL-90 and oxytocin there is a statistical significant correlation in the controlled diabetic patients between oxytocin and the subscales of somatization (rsp = −0.245, p = 0.030), and obsessive compulsive (rp = −0.228, p = 0.047. Among the correlation between oxytocin and Zung scale, the values of oxytocin increase as frequently the controlled diabetic patients have decreased libido (3.56±1.85 vs 4.68±2.58, p = 0.050). In the uncontrolled diabetic patients there is statistical significant relation between the psychomotor retardation and oxytocin. As frequently the uncontrolled diabetic patients show psychomotor retardation the values of oxytocin decrease (9.64±0.32 vs 4.20±2.25, p = 0.002). During the second evaluation the values of oxytocin decreased when the patients managed to control their metabolic profile. Although this result is not statistical significant. Conclusion: Oxytocin in diabetes mellitus type 2, I scorrelated with personality traits, somatization and depressive symptoms. Improvement of the metabolic profile influence the values of oxytocin. References [1] Marazziti D, Catena dell’ Osso M. 2008. The role of Oxytocin in Neuropsychiatric Disorders. Curr Med Chem 15, 698–704. [2] Neumann ID. Brain oxytocin. 2008. A key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 20, 858–865. [3] Bartz J, McInnes A., 2007. CD 38 regulates oxytocin secretion and complex social behaviour. Bio Essays 29, 837–841.