Projects & Collaborations 4 foundShow per page10 10 20 50 A randomized add-on pilot trial of D-serine for depression Research Project | 3 Project MembersThe glutamate system is emerging as target for the development of novel antidepressant medication, in particular compounds modulating the NMDA receptor. While the NMDA receptor antagonist ketamine is an effective option for many treatment-restistan patients, it is also accompanied by dissociative and cognitive effects and also bears the risk to develop addiction, side effects that are significantly restricting its clinical utility. There is now compelling evidence of the antidepressant potential of D-serine, a NMDAR co-agonist. Compared to ketamine, D-serine goes along without any psychotomimetic effects or other side effects and thus might be a promising novel antidepressant. This study represents the first randomized control trial to test the efficacy of D-serine as an adjuvant therapy in patients with depression and thereby adds to recent efforts to establish novel glutamatergic antidepressants. Behavioural addiction or affective disorder? Clinical classification and neural substrates of excessive physical training Research Project | 6 Project MembersNo Description available Lifestyle physical activity counselling in in-patients with major depressive disorders (PACINPAT): Randomized controlled trial on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers Research Project | 4 Project MembersMajor depressive disorder (MDD) is an extremely wide-spread and burdensome condition. MDD is associated with the second greatest number of life years lost due to premature death or disability (DALY) and will most likely be the leading cause in 2030. Physical activity counselling may increase lifestyle physical activity and cardiorespiratory fitness in a particularly vulnerable population which often suffers from a mix of mental and physical health problems.Goal and specific objectives: This study will examine the effectiveness of lifestyle physical activity counselling intervention among in-patients diagnosed with MDD compared to (placebo) controls. Secondary purposes are to examine the acceptability and perceived usefulness of the intervention among the patients, to compare baseline values with an age- and gender-matched group of healthy controls, and to find out whether the effectiveness of the intervention is moderated by genetic factors.Methods: The study is designed as a multi-centric two-arm randomized clinical trial including an intervention and placebo control group, allocation concealment, double-blinding, and intention-to-treat analysis. Participants (N=334) will be continuously recruited from four clinics specialized in the treatment of MDD. The intervention builds on a standardized, theory-based, low cost lifestyle physical activity counselling program, which was specifically designed for an in-patient rehabilitation setting. The placebo control condition consists of general instructions about health-enhancing physical activity. Data assessment will take place 2-3 weeks after admission to in-patient treatment (baseline), six weeks (post) and 12 months (follow-up) after discharge from in-patient treatment. Primary outcome is objectively assessed physical activity at follow-up. Secondary outcomes are self-reported physical activity, cardiorespireatory fitness, autonomic function, cognitive and social determinants of exercise, depression severity, self-perceived physical and psychological health, insomnia symtpoms, cognitive function, cardiovascular health risk markers (blood pressure, heart rate variability, BMI, percentage body fat, total/LDL/HDL cholesterol, triglycerides, HbA1c), and biomarkers of MDD (cortisol awakening response, brain-derived neurotrophic factor, tumor necrosis factor-alpha, and insulin-like growth factor). Moreover, the serotonin transporter (5-HTT) polymorphic promoter region (5-HTTLPR) will be assessed as a potential moderator of intervention effects.Expected results: Because regular physical activity has proved to be an important predictor of long-term response and remission in patients with major depression, we believe that our planned study may lay important groundwork by showing how individually-tailored lifestyle physical activity counselling can be integrated into given clinical structures. Our primary hypothesis is that compared to treatment as usual, individually-tailored physical activity counselling in patients with MDD will lead to clinically relevant increases in physical activity and CRF, and that these outcomes will persist beyond clinical discharge. The planned study is innovative for several reasons. For instance, we will test for the first time the potential of individually-tailored physical activity counselling in psychiatric in-patients, (b) focus on patients with low physical activity levels, and (c) assess physical activity objectively via accelerometry. Significance and feasibility: Improving physical activity and cardiorespiratory fitness may have important implications for tackling metabolic and cardiovascular disease and increasing cognitive functioning in this at-risk population, hence, reducing the future burden of multiple chronic conditions. Increased physical activity and cardiorespiratory fitness may also reduce the likelihood of future depressive episodes. By moving toward the primary prevention of chronic physical conditions, much can be done to enhance the quality and quantity of life of people with MDD. These findings will strengthen the evidence for "exercise as medicine" as a holistic care option in routine clinical practice for people with MDD, by helping patients to adopt and maintain physically active lifestyles after the end of their hospital stay. The study can show feasible ways to achieve long-term behaviour change by integrating lifestyle physical activity counselling into given clinical structures. Moreover, the study will show whether such an approach is acceptable for in-patients treated for MDD, and how much financial resources are needed to implement lifestyle physical activity counselling. Brain derived neurotrophic factor as a biomarker of insomnia Research Project | 4 Project MembersBrain-derived neurotrophic factor (BDNF) is a member of a family of growth factors located in the brain and peripheral tissues and plays an essential role in the neuronal cell differentiation, growth and survival. In the last decade, BDNF has become increasingly accepted as a central mediator of the effects of stress on neuronal plasticity. In a recent pilot study, our research group was the first to show that patients suffering from insomnia showed significantly decreased serum BDNF levels compared to sleep healthy controls. In the proposed project, we aim at assessing, whether BDNF may serve as a biomarker for insomnia on a larger scale across different diagnostic entities of sleep disorders and sleep healthy controls to verify the results of our exploratory investigation (Giese at al. 2013) and to elucidate the underlying mechanisms more closely. Moreover, given the relationship between sleep and cognitive performance, our research is also aimed in a second line, to extend our knowledge on the relationship between sleep and cognitive disturbances with reference to potential mediators. For that purpose, 62 male and female patients aged between 18 and 65 years suffering from insomnia according to DMS-IV criteria as well as a control group of 62 healthy, age and gender-matched controls will be enrolled in a prospective sleep center study performed at the Psychiatric University Clinics in Basel. Our main working hypothesis is that higher severity of insomnia is related to lower BDNF serum levels in patients suffering from insomnia (primary study outcome). As secondary objectives, the relationship between serum BDNF levels and objective sleep EEG parameters of sleep continuity (sleep onset latency, sleep duration, number of awakenings, wakefulness after sleep onset and sleep efficiency) and sleep EEG parameters of sleep architecture (stage 1 and 2, slow wave sleep and REM sleep), BDNF serum levels, BDNF signalling and cognition will be investigated in an explorative approach. Thus, we expect the following secondary outcomes: i.) Objective EEG sleep parameters indicating abnormalities of sleep continuity and sleep architecture are related to lower serum BDNF levels. ii.) Higher severity of insomnia is associated with decreased cognitive performance in attentional as well as memory-related cognitive performance. iii.) Lower BDNF serum levels are associated with lower cognitive performance in the cognitive test battery. iv.) Lower BDNF serum levels are associated with reduced pattern separation ability, thus indicating a hippocampal-dependent memory dysfunction. v.) Lower BDNF serum levels are associated with disturbed BDNF signalling pathways. If we can substantiate the role of BDNF as a marker of insomnia in a larger group of patients and across different diagnostic entities this has important implications for our understanding of the pathophysiology of insomnia. Once validated as a reliable marker of insomnia BDNF may serve as a research and diagnostic tool for a dimensional approach to insomnia that better reflects the underlying neurobiological mechanisms than mere categorical diagnostic attributions. 1 1
A randomized add-on pilot trial of D-serine for depression Research Project | 3 Project MembersThe glutamate system is emerging as target for the development of novel antidepressant medication, in particular compounds modulating the NMDA receptor. While the NMDA receptor antagonist ketamine is an effective option for many treatment-restistan patients, it is also accompanied by dissociative and cognitive effects and also bears the risk to develop addiction, side effects that are significantly restricting its clinical utility. There is now compelling evidence of the antidepressant potential of D-serine, a NMDAR co-agonist. Compared to ketamine, D-serine goes along without any psychotomimetic effects or other side effects and thus might be a promising novel antidepressant. This study represents the first randomized control trial to test the efficacy of D-serine as an adjuvant therapy in patients with depression and thereby adds to recent efforts to establish novel glutamatergic antidepressants.
Behavioural addiction or affective disorder? Clinical classification and neural substrates of excessive physical training Research Project | 6 Project MembersNo Description available
Lifestyle physical activity counselling in in-patients with major depressive disorders (PACINPAT): Randomized controlled trial on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers Research Project | 4 Project MembersMajor depressive disorder (MDD) is an extremely wide-spread and burdensome condition. MDD is associated with the second greatest number of life years lost due to premature death or disability (DALY) and will most likely be the leading cause in 2030. Physical activity counselling may increase lifestyle physical activity and cardiorespiratory fitness in a particularly vulnerable population which often suffers from a mix of mental and physical health problems.Goal and specific objectives: This study will examine the effectiveness of lifestyle physical activity counselling intervention among in-patients diagnosed with MDD compared to (placebo) controls. Secondary purposes are to examine the acceptability and perceived usefulness of the intervention among the patients, to compare baseline values with an age- and gender-matched group of healthy controls, and to find out whether the effectiveness of the intervention is moderated by genetic factors.Methods: The study is designed as a multi-centric two-arm randomized clinical trial including an intervention and placebo control group, allocation concealment, double-blinding, and intention-to-treat analysis. Participants (N=334) will be continuously recruited from four clinics specialized in the treatment of MDD. The intervention builds on a standardized, theory-based, low cost lifestyle physical activity counselling program, which was specifically designed for an in-patient rehabilitation setting. The placebo control condition consists of general instructions about health-enhancing physical activity. Data assessment will take place 2-3 weeks after admission to in-patient treatment (baseline), six weeks (post) and 12 months (follow-up) after discharge from in-patient treatment. Primary outcome is objectively assessed physical activity at follow-up. Secondary outcomes are self-reported physical activity, cardiorespireatory fitness, autonomic function, cognitive and social determinants of exercise, depression severity, self-perceived physical and psychological health, insomnia symtpoms, cognitive function, cardiovascular health risk markers (blood pressure, heart rate variability, BMI, percentage body fat, total/LDL/HDL cholesterol, triglycerides, HbA1c), and biomarkers of MDD (cortisol awakening response, brain-derived neurotrophic factor, tumor necrosis factor-alpha, and insulin-like growth factor). Moreover, the serotonin transporter (5-HTT) polymorphic promoter region (5-HTTLPR) will be assessed as a potential moderator of intervention effects.Expected results: Because regular physical activity has proved to be an important predictor of long-term response and remission in patients with major depression, we believe that our planned study may lay important groundwork by showing how individually-tailored lifestyle physical activity counselling can be integrated into given clinical structures. Our primary hypothesis is that compared to treatment as usual, individually-tailored physical activity counselling in patients with MDD will lead to clinically relevant increases in physical activity and CRF, and that these outcomes will persist beyond clinical discharge. The planned study is innovative for several reasons. For instance, we will test for the first time the potential of individually-tailored physical activity counselling in psychiatric in-patients, (b) focus on patients with low physical activity levels, and (c) assess physical activity objectively via accelerometry. Significance and feasibility: Improving physical activity and cardiorespiratory fitness may have important implications for tackling metabolic and cardiovascular disease and increasing cognitive functioning in this at-risk population, hence, reducing the future burden of multiple chronic conditions. Increased physical activity and cardiorespiratory fitness may also reduce the likelihood of future depressive episodes. By moving toward the primary prevention of chronic physical conditions, much can be done to enhance the quality and quantity of life of people with MDD. These findings will strengthen the evidence for "exercise as medicine" as a holistic care option in routine clinical practice for people with MDD, by helping patients to adopt and maintain physically active lifestyles after the end of their hospital stay. The study can show feasible ways to achieve long-term behaviour change by integrating lifestyle physical activity counselling into given clinical structures. Moreover, the study will show whether such an approach is acceptable for in-patients treated for MDD, and how much financial resources are needed to implement lifestyle physical activity counselling.
Brain derived neurotrophic factor as a biomarker of insomnia Research Project | 4 Project MembersBrain-derived neurotrophic factor (BDNF) is a member of a family of growth factors located in the brain and peripheral tissues and plays an essential role in the neuronal cell differentiation, growth and survival. In the last decade, BDNF has become increasingly accepted as a central mediator of the effects of stress on neuronal plasticity. In a recent pilot study, our research group was the first to show that patients suffering from insomnia showed significantly decreased serum BDNF levels compared to sleep healthy controls. In the proposed project, we aim at assessing, whether BDNF may serve as a biomarker for insomnia on a larger scale across different diagnostic entities of sleep disorders and sleep healthy controls to verify the results of our exploratory investigation (Giese at al. 2013) and to elucidate the underlying mechanisms more closely. Moreover, given the relationship between sleep and cognitive performance, our research is also aimed in a second line, to extend our knowledge on the relationship between sleep and cognitive disturbances with reference to potential mediators. For that purpose, 62 male and female patients aged between 18 and 65 years suffering from insomnia according to DMS-IV criteria as well as a control group of 62 healthy, age and gender-matched controls will be enrolled in a prospective sleep center study performed at the Psychiatric University Clinics in Basel. Our main working hypothesis is that higher severity of insomnia is related to lower BDNF serum levels in patients suffering from insomnia (primary study outcome). As secondary objectives, the relationship between serum BDNF levels and objective sleep EEG parameters of sleep continuity (sleep onset latency, sleep duration, number of awakenings, wakefulness after sleep onset and sleep efficiency) and sleep EEG parameters of sleep architecture (stage 1 and 2, slow wave sleep and REM sleep), BDNF serum levels, BDNF signalling and cognition will be investigated in an explorative approach. Thus, we expect the following secondary outcomes: i.) Objective EEG sleep parameters indicating abnormalities of sleep continuity and sleep architecture are related to lower serum BDNF levels. ii.) Higher severity of insomnia is associated with decreased cognitive performance in attentional as well as memory-related cognitive performance. iii.) Lower BDNF serum levels are associated with lower cognitive performance in the cognitive test battery. iv.) Lower BDNF serum levels are associated with reduced pattern separation ability, thus indicating a hippocampal-dependent memory dysfunction. v.) Lower BDNF serum levels are associated with disturbed BDNF signalling pathways. If we can substantiate the role of BDNF as a marker of insomnia in a larger group of patients and across different diagnostic entities this has important implications for our understanding of the pathophysiology of insomnia. Once validated as a reliable marker of insomnia BDNF may serve as a research and diagnostic tool for a dimensional approach to insomnia that better reflects the underlying neurobiological mechanisms than mere categorical diagnostic attributions.
