The aim of the present study was to evaluate the psychometric properties and dimensionality of the instrument Quality in Psychiatric Care-Forensic In-Patient Staff (QPC-FIPS) and to describe the perceived quality of p...The aim of the present study was to evaluate the psychometric properties and dimensionality of the instrument Quality in Psychiatric Care-Forensic In-Patient Staff (QPC-FIPS) and to describe the perceived quality of psychiatric care among forensic inpatient service staff. A sample of 348 forensic inpatient staff from 18 forensic wards in Sweden participated in the study. A confirmatory factor analysis revealed a seven-factor structure with item loadings > 0.50 on expected factors, indicating adequate psychometric properties. The staff’s ratings of quality of care were high, 94% being positive. The highest ratings were found for the secluded-environment dimension and the lowest for the secure-environment dimension. Several factors influenced the ratings of quality of care, for instance, staff’s time to perform their duties and staff’s age. It is concluded that the QPC-FIPS can give valuable information about staff’s perceptions of the quality of care provided at inpatient forensic psychiatric care services, which can be used to identify areas for quality improvement. Use of the QPC-FIPS is an easy and inexpensive way to evaluate quality in forensic inpatient care, preferably in conjunction with the QPC-FIP instrument developed for forensic inpatients and covering the same items and dimensions.展开更多
There is a need for an internationally standardized and psychometrically tested instrument to measure the perceptions of staff members on the quality of forensic inpatient care provided. The aim of the present study w...There is a need for an internationally standardized and psychometrically tested instrument to measure the perceptions of staff members on the quality of forensic inpatient care provided. The aim of the present study was to adapt the Swedish instrument Quality of Psychiatric Care-Forensic In-Patient Staff (QPC-FIPS) to the Danish context and to evaluate its psychometric properties and factor structure in this context. All permanently employed staff members at all 27 forensic inpatient wards in Denmark were invited to answer the Danish version of the QPC-FIPS. In total, 641 staff members participated, resulting in a response rate of 80%. The Danish version of the QPC-FIPS showed adequate psychometric properties and excellent goodness of fit of the hypothesised factor structure. Hence, the Danish QPC-FIPS is an excellent instrument for evaluating quality of forensic inpatient care both in clinical practice and in cross-cultural research. The members of staff generally reported that the care provided to patients was of high quality. The quality of the forensic-specific dimension was rated the highest, followed by the support, secluded environment, encounter, discharge and participation. The quality of the secure environment dimension was perceived to be the worst. The QPC-FIPS includes important aspects of staff members’ assessments of quality of care and offers a simple and inexpensive way to evaluate psychiatric forensic inpatient care. The QPC-FIPS can be used together with the Quality of Psychiatric Care-Forensic In-Patient (QPC-FIP) instrument, which covers the same items and dimensions as the QPC-FIPS, to identify patients’ and staff members’ views on quality of care and to improve the quality of forensic psychiatric care and benchmarking.展开更多
Aim: This study was aimed to determine the relationship between sleep quality and mental health of veterans in comparison with that of their spouses and a control group. Methods: Thirty-seven chemical veterans with mo...Aim: This study was aimed to determine the relationship between sleep quality and mental health of veterans in comparison with that of their spouses and a control group. Methods: Thirty-seven chemical veterans with moderate to severe injury based on the standards of Foundation of Martyrs and Veterans Affairs were selected from Mazandaran province. Then, the spouses of 31 of them were selected and 15 of their close relatives also enrolled in the study as the control group. The three groups were evaluated by GHQ for their mental health and Pittsburg Sleep Quality Index (PSQI) for sleep quality. Collected data were analyzed using SPSS software 16 and descriptive and analytic statistical methods. Results: The mean score of mental health in veterans, their spouses and close relatives were 44.13 ± 14.4, 34.19 ± 15.2 and 21.73 ± 17.32, respectively. The mean scores of PSQI test in veterans, their spouses, and their close relatives were 10.94 ± 5.6, 8.7 ± 5.5 and 4.27 ± 1 that the difference was statistically significant among the three groups (P ≤ 0.0001). A positive relationship was seen between mental health and sleep quality in veterans and their spouses respectively (r = 0.4, P = 0.02) and (r = 0.83, P < 0.0001). Conclusion: Poor sleep quality in chemical veterans compared to their spouses and close relatives could be due to mental health, rather than chemical effects and chronic lung disease. Therefore, treatment of mental health might be an important step to improve the sleep quality of veterans.展开更多
Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternu...Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.展开更多
Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the deg...Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1 to better understand the mechanisms underlying the effects of eCB system modulation on cortical visual processing.Methods:Using Western blots and immunohistochemistry,we investigated the laminar and cellular expression patterns of CB1R,NAPE-PLD,and FAAH across the rostrocaudal axis of the vervet monkey(Chlorocebus sabaeus)primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in V1 throughout the rostrocaudal axis.CB1R showed very low staining in layer(L)4,with higher expression in all other layers,especially L1,followed by L2 and L3.NAPE-PLD and FAAH expression patterns were similar,but not quite as low in L4.CB1R,NAPE-PLD,and FAAH were localized in vGlut2-positive cells,representing glutamatergic projection neurons,and in somatostatin(SST)-positive cells,a class of GABAergic interneurons.Conclusions:The low level of CB1R in L4 indicates less direct endocannabinoid modulation of V1 afferents from the dLGN,but that greater modulation may occur via the higher expression of CB1R in L2 and L3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in these layers.Expression in vGlut2-positive and SST-positive cells represents a role at both glutamatergic and GABAergic neurons.These data indicate that CB1R may influence the network of activity patterns in the visual streams after the visual information has reached V1,and thus may influence visual perception.展开更多
Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN)...Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.展开更多
Background:Exposure to ethanol in utero leads to several brain development disorders including retinal abnormalities whose underlying cellular pathogenesis remains elusive.We have previously reported changes in electr...Background:Exposure to ethanol in utero leads to several brain development disorders including retinal abnormalities whose underlying cellular pathogenesis remains elusive.We have previously reported changes in electroretinogram recordings in moderate fetal alcohol exposure(MFAE)vervet monkeys.The goal of this study is to characterize the anatomical effects of moderate MFAE during the third trimester in the vervet monkey retina.Methods:Using immunohistochemistry and Western blots,we analyzed changes in the expression of cell-type specific proteins that may occur in the MFAE retina compared to the normal retina.We also compared the basic retinal anatomy across groups by examining retinal layering and thickness.Results:Our main result indicates that GFAP(a potent marker of astrocytes)immunoreactivity was increased in the MFAE retina indicating strong astrogliosis.There was no obvious change in the overall anatomy in the MFAE retina and no significant differences in the mean thickness of each retinal layer.Furthermore,no significant changes in the morphology of the photoreceptors,horizontal cells,bipolar cells,and amacrines cells was observed.Conclusions:These data indicate that astrogliosis is a consequence of prenatal alcohol exposure and might explain the reported changes in the electroretinographic responses.展开更多
In relationship between the affective disorders and Parkinson’s disease (PD) it was found that comorbidity was higher than expected in the majority of the studies. Patients with PD are at increased risk of developing...In relationship between the affective disorders and Parkinson’s disease (PD) it was found that comorbidity was higher than expected in the majority of the studies. Patients with PD are at increased risk of developing depression and, conversely, recent studies have shown that patients with depressive disorders have increased risk of incident PD. However, the temporal associations between the disorders are not fully elucidated. From this review it could be learned that the temporal aspects strongly suggest that a neurobiological association exists between affective disorder and PD. This is illustrated with hitherto unpublished data. Some of these issues may be investigated in case register studies, e.g. by linkage of registers of somatic and psychiatric illness, and suggestions for future research are given. For GP’s, psychiatrists, geriatricians, and neurologists these new findings will lead to a better understanding and better treatment for patients with complicated comorbid conditions. Here timing is important!展开更多
Hypoxia is increasingly recognized as an important physiological driving force.A specific transcriptional program,induced by a decrease in oxygen(O2)availability,for example,inspiratory hypoxia at high altitude,allows...Hypoxia is increasingly recognized as an important physiological driving force.A specific transcriptional program,induced by a decrease in oxygen(O2)availability,for example,inspiratory hypoxia at high altitude,allows cells to adapt to lower O2 and limited energy metabolism.This transcriptional program is partly controlled by and partly independent of hypoxia-inducible factors.Remarkably,this same transcriptional program is stimulated in the brain by extensive motor-cognitive exercise,leading to a relative decrease in O2 supply,compared to the acutely augmented O2 requirement.We have coined the term“functional hypoxia”for this important demand-responsive,relative reduction in O2 availability.Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial“brain hardware upgrade,”underlying advanced performance.Hypoxia-induced erythropoietin expression in the brain likely plays a decisive role in these processes,which can be imitated by recombinant human erythropoietin treatment.This article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain function.It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease.Finally,it sketches a planned multistep pilot study in healthy volunteers and first patients,about to start,aiming at improved performance upon motor-cognitive training under inspiratory hypoxia.展开更多
Hypoxia is more and more perceived as pivotal physiological driving force,allowing cells in the brain and elsewhere to acclimate to lowered oxygen(O_(2)),and abridged metabolism.The mediating transcription program is ...Hypoxia is more and more perceived as pivotal physiological driving force,allowing cells in the brain and elsewhere to acclimate to lowered oxygen(O_(2)),and abridged metabolism.The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor-cognitive tasks,provoking a relative decrease in O_(2) in relation to the acutely augmented requirement.We termed this fundamental,demand-dependent drop in O_(2) availability"functional hypoxia."Major players in the hypoxia response are hypoxia-inducible factors(HIFs)and associated prolyl-hydroxylases.HIFs are transcription factors,stabilized by low O_(2) accessibility,and control expression of a multitude of genes.Changes in oxygen,however,can also be sensed via other pathways,among them the thiol-oxidase(2-aminoethanethiol)dioxygenase.Considering the far-reaching biological response to hypoxia,hitherto mostly observed in rodents,we initiated a translational project,combining mild to moderate inspiratory with functional hypoxia.We had identified this combination earlier to benefit motor-cognitive attainment in mice.A total of 20 subjects were included:13 healthy individuals and 7 patients with depression and/or autism spectrum disorder.Here,we show that motor-cognitive training under inspiratory hypoxia(12%O_(2))for 3.5 h daily over 3 weeks is optimally tolerated.We present first signals of beneficial effects on general well-being,cognitive performance,physical fitness and psychopathology.Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia.To obtain reliable information regarding the"add-on"value of inspiratory on top of functional hypoxia,induced by motor-cognitive training,a single-blind study—with versus without inspiratory hypoxia—is essential and outlined here.展开更多
文摘The aim of the present study was to evaluate the psychometric properties and dimensionality of the instrument Quality in Psychiatric Care-Forensic In-Patient Staff (QPC-FIPS) and to describe the perceived quality of psychiatric care among forensic inpatient service staff. A sample of 348 forensic inpatient staff from 18 forensic wards in Sweden participated in the study. A confirmatory factor analysis revealed a seven-factor structure with item loadings > 0.50 on expected factors, indicating adequate psychometric properties. The staff’s ratings of quality of care were high, 94% being positive. The highest ratings were found for the secluded-environment dimension and the lowest for the secure-environment dimension. Several factors influenced the ratings of quality of care, for instance, staff’s time to perform their duties and staff’s age. It is concluded that the QPC-FIPS can give valuable information about staff’s perceptions of the quality of care provided at inpatient forensic psychiatric care services, which can be used to identify areas for quality improvement. Use of the QPC-FIPS is an easy and inexpensive way to evaluate quality in forensic inpatient care, preferably in conjunction with the QPC-FIP instrument developed for forensic inpatients and covering the same items and dimensions.
文摘There is a need for an internationally standardized and psychometrically tested instrument to measure the perceptions of staff members on the quality of forensic inpatient care provided. The aim of the present study was to adapt the Swedish instrument Quality of Psychiatric Care-Forensic In-Patient Staff (QPC-FIPS) to the Danish context and to evaluate its psychometric properties and factor structure in this context. All permanently employed staff members at all 27 forensic inpatient wards in Denmark were invited to answer the Danish version of the QPC-FIPS. In total, 641 staff members participated, resulting in a response rate of 80%. The Danish version of the QPC-FIPS showed adequate psychometric properties and excellent goodness of fit of the hypothesised factor structure. Hence, the Danish QPC-FIPS is an excellent instrument for evaluating quality of forensic inpatient care both in clinical practice and in cross-cultural research. The members of staff generally reported that the care provided to patients was of high quality. The quality of the forensic-specific dimension was rated the highest, followed by the support, secluded environment, encounter, discharge and participation. The quality of the secure environment dimension was perceived to be the worst. The QPC-FIPS includes important aspects of staff members’ assessments of quality of care and offers a simple and inexpensive way to evaluate psychiatric forensic inpatient care. The QPC-FIPS can be used together with the Quality of Psychiatric Care-Forensic In-Patient (QPC-FIP) instrument, which covers the same items and dimensions as the QPC-FIPS, to identify patients’ and staff members’ views on quality of care and to improve the quality of forensic psychiatric care and benchmarking.
文摘Aim: This study was aimed to determine the relationship between sleep quality and mental health of veterans in comparison with that of their spouses and a control group. Methods: Thirty-seven chemical veterans with moderate to severe injury based on the standards of Foundation of Martyrs and Veterans Affairs were selected from Mazandaran province. Then, the spouses of 31 of them were selected and 15 of their close relatives also enrolled in the study as the control group. The three groups were evaluated by GHQ for their mental health and Pittsburg Sleep Quality Index (PSQI) for sleep quality. Collected data were analyzed using SPSS software 16 and descriptive and analytic statistical methods. Results: The mean score of mental health in veterans, their spouses and close relatives were 44.13 ± 14.4, 34.19 ± 15.2 and 21.73 ± 17.32, respectively. The mean scores of PSQI test in veterans, their spouses, and their close relatives were 10.94 ± 5.6, 8.7 ± 5.5 and 4.27 ± 1 that the difference was statistically significant among the three groups (P ≤ 0.0001). A positive relationship was seen between mental health and sleep quality in veterans and their spouses respectively (r = 0.4, P = 0.02) and (r = 0.83, P < 0.0001). Conclusion: Poor sleep quality in chemical veterans compared to their spouses and close relatives could be due to mental health, rather than chemical effects and chronic lung disease. Therefore, treatment of mental health might be an important step to improve the sleep quality of veterans.
文摘Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.
文摘Background:The goal of this study is to determine the expression and localization of the cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1 to better understand the mechanisms underlying the effects of eCB system modulation on cortical visual processing.Methods:Using Western blots and immunohistochemistry,we investigated the laminar and cellular expression patterns of CB1R,NAPE-PLD,and FAAH across the rostrocaudal axis of the vervet monkey(Chlorocebus sabaeus)primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in V1 throughout the rostrocaudal axis.CB1R showed very low staining in layer(L)4,with higher expression in all other layers,especially L1,followed by L2 and L3.NAPE-PLD and FAAH expression patterns were similar,but not quite as low in L4.CB1R,NAPE-PLD,and FAAH were localized in vGlut2-positive cells,representing glutamatergic projection neurons,and in somatostatin(SST)-positive cells,a class of GABAergic interneurons.Conclusions:The low level of CB1R in L4 indicates less direct endocannabinoid modulation of V1 afferents from the dLGN,but that greater modulation may occur via the higher expression of CB1R in L2 and L3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in these layers.Expression in vGlut2-positive and SST-positive cells represents a role at both glutamatergic and GABAergic neurons.These data indicate that CB1R may influence the network of activity patterns in the visual streams after the visual information has reached V1,and thus may influence visual perception.
文摘Background:The expression,localization,and function of the endocannabinoid system has been well characterized in recent years in the monkey retina and in the primary thalamic relay,the lateral geniculate nucleus(dLGN).Few data are available on cortical recipients’structures of the dLGN,namely the primary visual cortex(V1).The goal of this study is to characterize the expression and localization of the metabotropic cannabinoid receptor type 1(CB1R),the synthesizing enzyme N-acyl phosphatidyl-ethanolamine phospholipase D(NAPE-PLD),and the degradation enzyme fatty acid amide hydrolase(FAAH)in the vervet monkey area V1.Methods:Using Western blots and immunohistochemistry,we investigated the expression patterns of CB1R,NAPE-PLD,and FAAH in the vervet monkey primary visual cortex.Results:CB1R,NAPE-PLD,and FAAH were expressed in the primary visual cortex throughout the rostro-caudal axis.CB1R showed very low levels of staining in cortical layer 4,with higher expressions in all other cortical layers,especially layer 1.NAPE-PLD and FAAH expressions were highest in layers 1,2 and 3,and lowest in layer 4.Conclusions:Interestingly enough,CB1R was very low in layer 4 of V1 in comparison to the other cortical layers.The visual information coming from the dLGN and entering layer 4Calpha(magno cells)and 4Cbeta(parvo cells)may be therefore modulated by the higher expression levels of CB1R in cortical layers 2 and 3 on the way to the dorsal and ventral visual streams.This is further supported by the higher expression of NAPE-PLD and FAAH in the outer cortical layers.These data indicate that CB1R system can influence the network of activity patterns in the visual stream after the visual information has reached area V1.These novel results provide insights for understanding the role of the endocannabinoids in the modulation of cortical visual inputs,and hence,visual perception.
文摘Background:Exposure to ethanol in utero leads to several brain development disorders including retinal abnormalities whose underlying cellular pathogenesis remains elusive.We have previously reported changes in electroretinogram recordings in moderate fetal alcohol exposure(MFAE)vervet monkeys.The goal of this study is to characterize the anatomical effects of moderate MFAE during the third trimester in the vervet monkey retina.Methods:Using immunohistochemistry and Western blots,we analyzed changes in the expression of cell-type specific proteins that may occur in the MFAE retina compared to the normal retina.We also compared the basic retinal anatomy across groups by examining retinal layering and thickness.Results:Our main result indicates that GFAP(a potent marker of astrocytes)immunoreactivity was increased in the MFAE retina indicating strong astrogliosis.There was no obvious change in the overall anatomy in the MFAE retina and no significant differences in the mean thickness of each retinal layer.Furthermore,no significant changes in the morphology of the photoreceptors,horizontal cells,bipolar cells,and amacrines cells was observed.Conclusions:These data indicate that astrogliosis is a consequence of prenatal alcohol exposure and might explain the reported changes in the electroretinographic responses.
基金The Theodore Foundation (USA) Vada Stanley Foundation (USA)
文摘In relationship between the affective disorders and Parkinson’s disease (PD) it was found that comorbidity was higher than expected in the majority of the studies. Patients with PD are at increased risk of developing depression and, conversely, recent studies have shown that patients with depressive disorders have increased risk of incident PD. However, the temporal associations between the disorders are not fully elucidated. From this review it could be learned that the temporal aspects strongly suggest that a neurobiological association exists between affective disorder and PD. This is illustrated with hitherto unpublished data. Some of these issues may be investigated in case register studies, e.g. by linkage of registers of somatic and psychiatric illness, and suggestions for future research are given. For GP’s, psychiatrists, geriatricians, and neurologists these new findings will lead to a better understanding and better treatment for patients with complicated comorbid conditions. Here timing is important!
基金supported by the Max Planck Society,the Max Planck Förderstiftung,the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation),via DFG-Center for Nanoscale Microscopy&Molecular Physiology of the Brain(CNMPB)and DFG-TRR 274/12020–408885537.
文摘Hypoxia is increasingly recognized as an important physiological driving force.A specific transcriptional program,induced by a decrease in oxygen(O2)availability,for example,inspiratory hypoxia at high altitude,allows cells to adapt to lower O2 and limited energy metabolism.This transcriptional program is partly controlled by and partly independent of hypoxia-inducible factors.Remarkably,this same transcriptional program is stimulated in the brain by extensive motor-cognitive exercise,leading to a relative decrease in O2 supply,compared to the acutely augmented O2 requirement.We have coined the term“functional hypoxia”for this important demand-responsive,relative reduction in O2 availability.Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial“brain hardware upgrade,”underlying advanced performance.Hypoxia-induced erythropoietin expression in the brain likely plays a decisive role in these processes,which can be imitated by recombinant human erythropoietin treatment.This article review presents hints of how inspiratory O2 manipulations can potentially contribute to enhanced brain function.It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease.Finally,it sketches a planned multistep pilot study in healthy volunteers and first patients,about to start,aiming at improved performance upon motor-cognitive training under inspiratory hypoxia.
基金ERC Advanced Grant acronym BREPOCI,Grant/Award Number:101054369ALTIBRAIN,Grant/Award Number:101043416DFG,Grant/Award Number:TRR-274/12020-408885537。
文摘Hypoxia is more and more perceived as pivotal physiological driving force,allowing cells in the brain and elsewhere to acclimate to lowered oxygen(O_(2)),and abridged metabolism.The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor-cognitive tasks,provoking a relative decrease in O_(2) in relation to the acutely augmented requirement.We termed this fundamental,demand-dependent drop in O_(2) availability"functional hypoxia."Major players in the hypoxia response are hypoxia-inducible factors(HIFs)and associated prolyl-hydroxylases.HIFs are transcription factors,stabilized by low O_(2) accessibility,and control expression of a multitude of genes.Changes in oxygen,however,can also be sensed via other pathways,among them the thiol-oxidase(2-aminoethanethiol)dioxygenase.Considering the far-reaching biological response to hypoxia,hitherto mostly observed in rodents,we initiated a translational project,combining mild to moderate inspiratory with functional hypoxia.We had identified this combination earlier to benefit motor-cognitive attainment in mice.A total of 20 subjects were included:13 healthy individuals and 7 patients with depression and/or autism spectrum disorder.Here,we show that motor-cognitive training under inspiratory hypoxia(12%O_(2))for 3.5 h daily over 3 weeks is optimally tolerated.We present first signals of beneficial effects on general well-being,cognitive performance,physical fitness and psychopathology.Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia.To obtain reliable information regarding the"add-on"value of inspiratory on top of functional hypoxia,induced by motor-cognitive training,a single-blind study—with versus without inspiratory hypoxia—is essential and outlined here.
