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Mitochondrial respiration in bipolar affective disorder
S426
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)
data including that of thyroid function were all within normal limits. Suspecting the influence of Vitamin B12 deficiency we admitted her to our hospital. In the examination at hospitalization, electroencephalogram showed theta wave with the background of slow alpha wave and SPECT indicated nonspecific blood reduction of whole cerebral hemisphere. Considering all these findings we concluded that she met the criteria for delirium based on DSM-IVTR. Vitamin B12 (1000mg/day) was administered intravenously every day, On the other hand we didn’t use any psychotropic drug after hospitalization. On the seventh day of Vitamin B12 replacement therapy, serum vitamin B12 level achieved reference value. Her psychiatric symptoms and pancytopenia gradually improved. Actually instability of mood, incoherence of thought and euphoria remained while delirium seemed to disappear. Namely mania state became the main symptom then. After that, as we continued the treatment, mania state also improved. When she was discharged from hospital on the seventy-fourth day she had mild cognitive impairment without mania state. But SPECT showed no improvement in blood reduction of the cerebral hemisphere. After discharge therapy was continued with Vitamin B12 (1000 mg) intramuscular injections twice a week for a month and then monthly as maintenance treatment. One year after Vitamin B12 replacement started, she came to be able to score almost full points on MMSE and scored zero points on YMRS without delirium. Prior study have indicated that psychiatric symptoms secondary to Vitamin B12 deficiency had relationship with blood reduction of the cerebral hemisphere since it improved after the treatment [2]. This case was characteristic in terms that blood reduction of the cerebral hemisphere didn’t bring about any remarkable changes. This result reveals there is another factor which causes psychiatric symptoms secondary to Vitamin B12 deficiency. References [1] Lachner, C., Steinle, N.I., Regenold, W.T., 2012. The Neuropsychiatry of Vitamin B12 Deficiency in Elderly Patients. J Neuropsychiatry Clin Neurosci 24, 5−15. [2] Kashibayashi, T., Ishikawa, T., Komori, K., Fukuhara, R., Shimizu, H., Toyota, Y., Mori, T., Ueno, S-I., Tanimukai, S., 2009. Two Cases Showing psychotic symptoms, disturbance of consciousness and cognitive impairment which improved remarkably after intravenous hydroxocobalamin supplementation. Japanese J Geriatric Psychiatry 20, 1287– 1295.
P.2.d.010 Mitochondrial respiration in bipolar affective disorder J. Hroudov´a1 ° , Z. Fiˇsar1 , L. Kaliˇsov´a1 , E. Kitzlerov´a1 , M. Zvˇeˇrov´a1 , E. Sigitov´a1 , H. Hans´ıkov´a2 , J. Raboch1 1 First Faculty of Medicine- Charles University in Prague, Department of Psychiatry, Prague 2, Czech Republic; 2 First Faculty of Medicine- Charles University in Prague, Department of Pediatrics and Adolescent Medicine, Prague 2, Czech Republic Bipolar affective disorder (BAD) is a serious mental disorder manifested by recurrent episodes of mood swings, switching from depressive to manic mood. The predisposition to BAD is determined by genetic, psychosocial and biological factors; individual sensitivity to depressogenic effects during stressful life events is also a contributing factor. Recently, attention in the research of biological basis of BAD has been devoted to an overlapping set of molecular and cellular mechanisms of mood disorders, antidepressant response, neuroplasticity, and chronic stress [1], e.g. changes in neuroprogression, inflammatory and cell mediated
immune response, antioxidant capacity, oxidative and nitrosative stress, and mitochondrial functions [2]. Our research is focused on extension of knowledge related to pathophysiological processes of BAD. Changes in the activities of compounds of intracellular signaling pathways are studied with the aim of discovering new biological markers of mood disorders or predictors of response to pharmacotherapy, which can be easily examined in blood samples. The aim of our study is to find out association between changes in energy metabolism, different episodes of BAD and pathophysiological processes associated or provoking BAD. Selected mitochondrial parameters were measured in peripheral blood components. The analyses were examined in patients suffering from BAD in different states of the disease (in period of mania, depression and remission) and in healthy controls. Clinical evaluation of the BAD was provided by clinicians using wellestablished diagnostic scales and questionnaires: mood disorder ˚ questionnaire (MDQ), Montgomery-Asberg Depression Rating Scale (MADRS) (depression), Young Mania Rating Scale (YMRS) (mania), clinical global impression − severity scale (CGI-S), brief psychiatric rating scale (BPRS). Mitochondrial respiration was examined in intact and permeabilized blood platelets using high resolution respirometry (Oxygraph-2k). It was evaluated by both respiratory rate and respiratory control ratios. Enzyme activities (citrate synthase, electron transport chain complexes − complex I, II+III, IV) were measured spectrophotometrically. Statistical analyses were performed using the STATISTICA data analysis software system (version 12, StatSoft, Inc., Tulsa, OK, USA). Activities of individual complexes were normalized to citrate synthase activity. Statistical significance was evaluated using the ANOVA and post-doc Scheff´e test. Our preliminary results showed increased physiological respiration in intact platelets from patients in the period of mania; complex-I linked respiration was found increased in patients in mania and in remission compared to healthy controls. Citrate synthase activity was not changed in BAD patients compared to controls. Decreased complex IV activity was observed in BAD patients suffering from depression in comparison to controls. Our results support the hypothesis that changes in the rate of oxygen consumption and electron transport chain complexes activities may participate in pathophysiology of BAD. In conclusion, better insight into molecular mechanisms of cellular respiration could lead to better understanding of pathophysiology of BAD. Mitochondrial dysfunctions in different episodes of BAD should be further studied. References [1] Pittenger, C., Duman, R.S., 2008. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33, 88–109. [2] Maes, M., Fiˇsar, Z., Medina, M., Scapagnini, G., Nowak, G., Berk, M., 2012. New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates − Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology 20, 127−50. Disclosure statement: Supported by Ministry of Health of the Czech Republic, grant nr. 15–28616A. All rights reserved.
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)
data including that of thyroid function were all within normal limits. Suspecting the influence of Vitamin B12 deficiency we admitted her to our hospital. In the examination at hospitalization, electroencephalogram showed theta wave with the background of slow alpha wave and SPECT indicated nonspecific blood reduction of whole cerebral hemisphere. Considering all these findings we concluded that she met the criteria for delirium based on DSM-IVTR. Vitamin B12 (1000mg/day) was administered intravenously every day, On the other hand we didn’t use any psychotropic drug after hospitalization. On the seventh day of Vitamin B12 replacement therapy, serum vitamin B12 level achieved reference value. Her psychiatric symptoms and pancytopenia gradually improved. Actually instability of mood, incoherence of thought and euphoria remained while delirium seemed to disappear. Namely mania state became the main symptom then. After that, as we continued the treatment, mania state also improved. When she was discharged from hospital on the seventy-fourth day she had mild cognitive impairment without mania state. But SPECT showed no improvement in blood reduction of the cerebral hemisphere. After discharge therapy was continued with Vitamin B12 (1000 mg) intramuscular injections twice a week for a month and then monthly as maintenance treatment. One year after Vitamin B12 replacement started, she came to be able to score almost full points on MMSE and scored zero points on YMRS without delirium. Prior study have indicated that psychiatric symptoms secondary to Vitamin B12 deficiency had relationship with blood reduction of the cerebral hemisphere since it improved after the treatment [2]. This case was characteristic in terms that blood reduction of the cerebral hemisphere didn’t bring about any remarkable changes. This result reveals there is another factor which causes psychiatric symptoms secondary to Vitamin B12 deficiency. References [1] Lachner, C., Steinle, N.I., Regenold, W.T., 2012. The Neuropsychiatry of Vitamin B12 Deficiency in Elderly Patients. J Neuropsychiatry Clin Neurosci 24, 5−15. [2] Kashibayashi, T., Ishikawa, T., Komori, K., Fukuhara, R., Shimizu, H., Toyota, Y., Mori, T., Ueno, S-I., Tanimukai, S., 2009. Two Cases Showing psychotic symptoms, disturbance of consciousness and cognitive impairment which improved remarkably after intravenous hydroxocobalamin supplementation. Japanese J Geriatric Psychiatry 20, 1287– 1295.
P.2.d.010 Mitochondrial respiration in bipolar affective disorder J. Hroudov´a1 ° , Z. Fiˇsar1 , L. Kaliˇsov´a1 , E. Kitzlerov´a1 , M. Zvˇeˇrov´a1 , E. Sigitov´a1 , H. Hans´ıkov´a2 , J. Raboch1 1 First Faculty of Medicine- Charles University in Prague, Department of Psychiatry, Prague 2, Czech Republic; 2 First Faculty of Medicine- Charles University in Prague, Department of Pediatrics and Adolescent Medicine, Prague 2, Czech Republic Bipolar affective disorder (BAD) is a serious mental disorder manifested by recurrent episodes of mood swings, switching from depressive to manic mood. The predisposition to BAD is determined by genetic, psychosocial and biological factors; individual sensitivity to depressogenic effects during stressful life events is also a contributing factor. Recently, attention in the research of biological basis of BAD has been devoted to an overlapping set of molecular and cellular mechanisms of mood disorders, antidepressant response, neuroplasticity, and chronic stress [1], e.g. changes in neuroprogression, inflammatory and cell mediated
immune response, antioxidant capacity, oxidative and nitrosative stress, and mitochondrial functions [2]. Our research is focused on extension of knowledge related to pathophysiological processes of BAD. Changes in the activities of compounds of intracellular signaling pathways are studied with the aim of discovering new biological markers of mood disorders or predictors of response to pharmacotherapy, which can be easily examined in blood samples. The aim of our study is to find out association between changes in energy metabolism, different episodes of BAD and pathophysiological processes associated or provoking BAD. Selected mitochondrial parameters were measured in peripheral blood components. The analyses were examined in patients suffering from BAD in different states of the disease (in period of mania, depression and remission) and in healthy controls. Clinical evaluation of the BAD was provided by clinicians using wellestablished diagnostic scales and questionnaires: mood disorder ˚ questionnaire (MDQ), Montgomery-Asberg Depression Rating Scale (MADRS) (depression), Young Mania Rating Scale (YMRS) (mania), clinical global impression − severity scale (CGI-S), brief psychiatric rating scale (BPRS). Mitochondrial respiration was examined in intact and permeabilized blood platelets using high resolution respirometry (Oxygraph-2k). It was evaluated by both respiratory rate and respiratory control ratios. Enzyme activities (citrate synthase, electron transport chain complexes − complex I, II+III, IV) were measured spectrophotometrically. Statistical analyses were performed using the STATISTICA data analysis software system (version 12, StatSoft, Inc., Tulsa, OK, USA). Activities of individual complexes were normalized to citrate synthase activity. Statistical significance was evaluated using the ANOVA and post-doc Scheff´e test. Our preliminary results showed increased physiological respiration in intact platelets from patients in the period of mania; complex-I linked respiration was found increased in patients in mania and in remission compared to healthy controls. Citrate synthase activity was not changed in BAD patients compared to controls. Decreased complex IV activity was observed in BAD patients suffering from depression in comparison to controls. Our results support the hypothesis that changes in the rate of oxygen consumption and electron transport chain complexes activities may participate in pathophysiology of BAD. In conclusion, better insight into molecular mechanisms of cellular respiration could lead to better understanding of pathophysiology of BAD. Mitochondrial dysfunctions in different episodes of BAD should be further studied. References [1] Pittenger, C., Duman, R.S., 2008. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33, 88–109. [2] Maes, M., Fiˇsar, Z., Medina, M., Scapagnini, G., Nowak, G., Berk, M., 2012. New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates − Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology 20, 127−50. Disclosure statement: Supported by Ministry of Health of the Czech Republic, grant nr. 15–28616A. All rights reserved.