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P.2.d.025 White matter microstructure in bipolar disorder changes after antidepressant treatment with total sleep deprivation
P.2.d. Mood disorders and treatment − Bipolar disorders (clinical) 2015. Lithium and GSK-3b promoter gene variants influence cortical gray matter volumes in bipolar disorder. Psychopharmacology (Berl) 232(7), 1325–1336. [5] Chen, G., Rajkowska, G., Du, F., Seraji-Bozorgzad, N., Manji, H.K., 2000. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 75(4), 1729–1734.
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of the effect is in agreement with a suggested dominant role of the right hemisphere in mood regulation. The observed effect is likely driven by subjects responders to treatment but future studies in larger samples are needed to further clarify this issue. References
P.2.d.025 White matter microstructure in bipolar disorder changes after antidepressant treatment with total sleep deprivation S. Poletti1 ° , I. Bollettini1 , E. Melloni1 , S. Dallaspezia1 , F. Benedetti1 1 Scientific Institute and University Vita-Salute San Raffaele, Deptartment of Clinical Neurosciences, Milan, Italy Background and Purpose of the study: Bipolar disorder (BD) is characterised by changes of white matter (WM) microstructure [1] and by a disruption of circadian rhythms. Sleep deprivation is the most widely documented rapid-onset antidepressant therapy, targeting the broadly defined depressive syndrome. The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) not only can acutely reverse depressive symptoms in approximately 60% of patients, but it also reduces the high percentage of relapses seen after the recovery night [2]. Specific effects of sleep deprivation on the brain have been found by different brain imaging studies showing an association with functional and metabolic changes in specific brain areas of the corticolimbic circuit. Following this line of reasoning the aim of the study is to investigate the effect of chronoterapeutic treatment on WM microstructure in BD. Methods: Twenty-four patients affected by a major depressive episode without psychotic features, with a diagnosis of BD type I were administered one week of chronotherapeutic treatment through TSD+LT. On a 3.0 Tesla scanner (Gyroscan Intera, Philips, Netherlands) using a 6 channels SENSE head coil scanner were acquired diffusion tensor images (DTI) with 35 gradient directions, b-value: 900 s/mm2, EPI sequence, FOV: (231.43x126.5x240) mm3, slice thickness: 2.3 mm. Voxelwise DTI analyses were performed using Tract-Based Spatial Statistics using TFCE correction (p = 0.05). A paired t-test on DTI measures of WM integrity (axial, radial, and mean diffusivity, and fractional anisotropy) was performed between patients at baseline and after one week of TSD+LT treatment. Results: Seventeen out of 24 patients successfully responded to TSD+LT. After chronotherapeutic treatment patients showed increased axial diffusivity (AD) and mean diffusivity (MD) in corpus callosum, corona radiata, superior longitudinal fasciculus, corticospinal tract and anterior thalamic radiation. All tracts were localized in the right hemisphere. Discussion: The chronotherapeutic treatment is associated to increased AD and MD in several fibre tracts contributing to the functional integrity of the brain. The increase of MD was likely driven by the increase of AD, given that radial diffusivity was not significantly affected. AD represents the water diffusivity parallel to the axonal fibers, reflecting the greater freedom of water to diffuse along the principal fiber axis rather than to travel across the surrounding myelin sheaths thus reflecting the integrity of axons and myelin sheaths. We suggest that chronotherapeutic treatment could counteract part of the detrimental influences of BD on WM structure, with specific benefits resulting for the patients from effects on WM tracts previously associated to BD and involving inter-hemispheric, and frontal connections. The right lateralization
[1] Benedetti, F., Yeh, P.H., Bellani, M., Radaelli, D., Nicoletti, M.A., Poletti, S., Falini, A., Dallaspezia, S., Colombo, C., Scotti, G., Smeraldi, E., Soares, J.C., Brambilla, P., 2011. Disruption of white matter integrity in bipolar depression as a possible structural marker of illness. Biol Psychiatry 69(4), 309–317. [2] Dallaspezia, S., Benedetti, F., 2014. Sleep Deprivation Therapy for Depression. Curr Top Behav Neurosci [Epub ahead of print].
P.2.d.026 A model to uncover bipolarity in recurrent depressive episodes P. Marinova1 , L. Hranov2 ° 1 University Hospital “Aleksandrovska”, Department of Psychiatry, Sofia, Bulgaria; 2 University Hospital “St. Naum”, Second Psychiatric Clinic, Sofia, Bulgaria Background: Precise differentiation between unipolar and bipolar depression is of high clinical importance due to the different therapeutic options. We have already presented a model to predict bipolarity from the first depressive episode [1]. Here, we present a model for recurrent depressive episodes, based on the same sample of patients. Aims: To find factors indicating bipolar disorder among depressed patients seeking help late in the course of their disorder. Methods: A cross-sectional non-intervention study of at least moderately depressed patients (DSM-IV-TR; CGI-S>4): 31 patients with recurrent unipolar depression (RUD), and 44 patients with bipolar depression (BD) (20 with BD1 and 24 with BD2). After obtaining informed consent, patients were interviewed with M.I.N.I. 6.0 (Mini International Neuropsychiatric Interview) [2] and BISS (Bipolar Inventory Symptom Scale) [3]. A comprehensive chart containing a multitude of demographic and course specific parameters was also filled in. A regression statistical analysis was performed with SPSS 16.0. Results: Several factors distinguished significantly the two groups of patients. The regression analysis demonstrated the prognostic value of five variables (Table). The median of the frequency of depressive episodes was 0.25 episodes/year (0.05–1.11) for RUD and 0.60 (0.12–2.00) for BD (p < 0.001). In 29.5% of the BD patients and only 6.5% of the RUD patients (p = 0.014) the onset of the illness was before the age of 25 years. Evening brightening was reported by 56.8% of the BD patients and 12.9% of the RUD patients (p < 0.001). Patietnts with BD had lower average scores on the somatic anxiety item (BISS 15) (1.75; SD = 1.38) than the RUD patients (2.68; SD = 1.19) (p = 0.004) and higher average scores on the impaired concentration item (BISS 21) (2.14; SD = 0.90 vs 1.52; SD = 0.93) (p = 0.005). ODDS = exp(−5.79 + 4.12·X1 + 6.72·X2 + 2.5·X3 −0.79·X4 + 1.61·X5) Age of onset before 25 years (OR = 61.8) X1 : Frequency of depressive episodes (OR = 825.8) X2 : Evening brightnening (OR = 12.2) X3 : Somatic anxiety (BISS 15) (OR = 0.456) X4 : Lack of concentration (BISS 21) (OR = 5.0) X5 :
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of the effect is in agreement with a suggested dominant role of the right hemisphere in mood regulation. The observed effect is likely driven by subjects responders to treatment but future studies in larger samples are needed to further clarify this issue. References
P.2.d.025 White matter microstructure in bipolar disorder changes after antidepressant treatment with total sleep deprivation S. Poletti1 ° , I. Bollettini1 , E. Melloni1 , S. Dallaspezia1 , F. Benedetti1 1 Scientific Institute and University Vita-Salute San Raffaele, Deptartment of Clinical Neurosciences, Milan, Italy Background and Purpose of the study: Bipolar disorder (BD) is characterised by changes of white matter (WM) microstructure [1] and by a disruption of circadian rhythms. Sleep deprivation is the most widely documented rapid-onset antidepressant therapy, targeting the broadly defined depressive syndrome. The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) not only can acutely reverse depressive symptoms in approximately 60% of patients, but it also reduces the high percentage of relapses seen after the recovery night [2]. Specific effects of sleep deprivation on the brain have been found by different brain imaging studies showing an association with functional and metabolic changes in specific brain areas of the corticolimbic circuit. Following this line of reasoning the aim of the study is to investigate the effect of chronoterapeutic treatment on WM microstructure in BD. Methods: Twenty-four patients affected by a major depressive episode without psychotic features, with a diagnosis of BD type I were administered one week of chronotherapeutic treatment through TSD+LT. On a 3.0 Tesla scanner (Gyroscan Intera, Philips, Netherlands) using a 6 channels SENSE head coil scanner were acquired diffusion tensor images (DTI) with 35 gradient directions, b-value: 900 s/mm2, EPI sequence, FOV: (231.43x126.5x240) mm3, slice thickness: 2.3 mm. Voxelwise DTI analyses were performed using Tract-Based Spatial Statistics using TFCE correction (p = 0.05). A paired t-test on DTI measures of WM integrity (axial, radial, and mean diffusivity, and fractional anisotropy) was performed between patients at baseline and after one week of TSD+LT treatment. Results: Seventeen out of 24 patients successfully responded to TSD+LT. After chronotherapeutic treatment patients showed increased axial diffusivity (AD) and mean diffusivity (MD) in corpus callosum, corona radiata, superior longitudinal fasciculus, corticospinal tract and anterior thalamic radiation. All tracts were localized in the right hemisphere. Discussion: The chronotherapeutic treatment is associated to increased AD and MD in several fibre tracts contributing to the functional integrity of the brain. The increase of MD was likely driven by the increase of AD, given that radial diffusivity was not significantly affected. AD represents the water diffusivity parallel to the axonal fibers, reflecting the greater freedom of water to diffuse along the principal fiber axis rather than to travel across the surrounding myelin sheaths thus reflecting the integrity of axons and myelin sheaths. We suggest that chronotherapeutic treatment could counteract part of the detrimental influences of BD on WM structure, with specific benefits resulting for the patients from effects on WM tracts previously associated to BD and involving inter-hemispheric, and frontal connections. The right lateralization
[1] Benedetti, F., Yeh, P.H., Bellani, M., Radaelli, D., Nicoletti, M.A., Poletti, S., Falini, A., Dallaspezia, S., Colombo, C., Scotti, G., Smeraldi, E., Soares, J.C., Brambilla, P., 2011. Disruption of white matter integrity in bipolar depression as a possible structural marker of illness. Biol Psychiatry 69(4), 309–317. [2] Dallaspezia, S., Benedetti, F., 2014. Sleep Deprivation Therapy for Depression. Curr Top Behav Neurosci [Epub ahead of print].
P.2.d.026 A model to uncover bipolarity in recurrent depressive episodes P. Marinova1 , L. Hranov2 ° 1 University Hospital “Aleksandrovska”, Department of Psychiatry, Sofia, Bulgaria; 2 University Hospital “St. Naum”, Second Psychiatric Clinic, Sofia, Bulgaria Background: Precise differentiation between unipolar and bipolar depression is of high clinical importance due to the different therapeutic options. We have already presented a model to predict bipolarity from the first depressive episode [1]. Here, we present a model for recurrent depressive episodes, based on the same sample of patients. Aims: To find factors indicating bipolar disorder among depressed patients seeking help late in the course of their disorder. Methods: A cross-sectional non-intervention study of at least moderately depressed patients (DSM-IV-TR; CGI-S>4): 31 patients with recurrent unipolar depression (RUD), and 44 patients with bipolar depression (BD) (20 with BD1 and 24 with BD2). After obtaining informed consent, patients were interviewed with M.I.N.I. 6.0 (Mini International Neuropsychiatric Interview) [2] and BISS (Bipolar Inventory Symptom Scale) [3]. A comprehensive chart containing a multitude of demographic and course specific parameters was also filled in. A regression statistical analysis was performed with SPSS 16.0. Results: Several factors distinguished significantly the two groups of patients. The regression analysis demonstrated the prognostic value of five variables (Table). The median of the frequency of depressive episodes was 0.25 episodes/year (0.05–1.11) for RUD and 0.60 (0.12–2.00) for BD (p < 0.001). In 29.5% of the BD patients and only 6.5% of the RUD patients (p = 0.014) the onset of the illness was before the age of 25 years. Evening brightening was reported by 56.8% of the BD patients and 12.9% of the RUD patients (p < 0.001). Patietnts with BD had lower average scores on the somatic anxiety item (BISS 15) (1.75; SD = 1.38) than the RUD patients (2.68; SD = 1.19) (p = 0.004) and higher average scores on the impaired concentration item (BISS 21) (2.14; SD = 0.90 vs 1.52; SD = 0.93) (p = 0.005). ODDS = exp(−5.79 + 4.12·X1 + 6.72·X2 + 2.5·X3 −0.79·X4 + 1.61·X5) Age of onset before 25 years (OR = 61.8) X1 : Frequency of depressive episodes (OR = 825.8) X2 : Evening brightnening (OR = 12.2) X3 : Somatic anxiety (BISS 15) (OR = 0.456) X4 : Lack of concentration (BISS 21) (OR = 5.0) X5 :