RESUMO
BACKGROUND: The physical activity counseling for in-patients with major depression (PACINPAT) randomized controlled trial was launched to tackle physical inactivity for in-patients with major depressive disorder. Evidence shows that despite potential treatment effects, physical inactivity is prevalent in this population. To contribute to the assessment of how this in-person and remote, theory-based, individually tailored intervention was designed, received and effected behavior, the aim of this study was to evaluate its implementation. METHODS: This implementation evaluation was conducted within a multi-center randomized controlled trial according to the Process Evaluation Framework by the Medical Research Council including the analysis of reach, dose, fidelity and adaptation. Data were collected from the implementers and the participants randomized to the intervention group of the trial. RESULTS: The study sample comprised 95 physically inactive in-patients (mean age: 42 years, 53% women) with diagnosed major depressive disorder. The intervention reached the intended population (N = 95 in-patients enrolled in the study). The intervention dose varied between early dropouts (counseling sessions, M = 1.67) and study completers with some participants receiving a low dose (counseling sessions, M = 10.05) and high dose (counseling sessions, M = 25.37). Differences in the attendance groups were recognizable in the first two counseling sessions (duration of counseling session about 45 min in early dropouts versus 60 min for study completers). Fidelity of the in-person counseling content was partly achieved and adapted, whereas that of the remote counseling content was well achieved. Participants (86% at follow up) reported satisfaction with the implementers of the intervention. Adaptations were made to content, delivery mode and dose. CONCLUSION: The PACINPAT trial was implemented in the intended population, in varying doses and with adaptations made to in-person counseling content and remote counseling dose. These findings are key to understanding outcome analyses within the PACINPAT trial, further developing interventions and contributing to implementation research among in-patients with depressive disorders. TRIAL REGISTRATION: ISRCTN, ISRCTN10469580 , registered on 3rd September 2018.
Assuntos
Transtorno Depressivo Maior , Humanos , Feminino , Adulto , Masculino , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Aconselhamento , Exercício Físico , Comportamento SedentárioRESUMO
BACKGROUND: In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression. METHODS: This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention. RESULTS: We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes. LIMITATIONS: The modest sample size resulting from our exclusion of low-compliant cases should be considered. CONCLUSION: Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02957591.
Assuntos
Transtorno Depressivo Maior , Probióticos , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/complicações , Fator Neurotrófico Derivado do Encéfalo , Depressão , Cognição/fisiologia , Probióticos/uso terapêutico , Suplementos Nutricionais , EncéfaloRESUMO
BACKGROUND: Probiotics are suggested to improve depressive symptoms via the microbiota-gut-brain axis. We have recently shown a beneficial clinical effect of probiotic supplementation in patients with depression. Their underlying neural mechanisms remain unknown. METHODS: A multimodal neuroimaging approach including diffusion tensor imaging, resting-state functional MRI, and arterial spin labeling was used to investigate the effects of a four-weeks probiotic supplementation on fronto-limbic brain structure, function, and perfusion and whether these effects were related to symptom changes. RESULTS: Thirty-two patients completed both imaging assessments (18 placebo and 14 probiotics group). Probiotics maintained mean diffusivity in the left uncinate fasciculus, stabilized it in the right uncinate fasciculus, and altered resting-state functional connectivity (rsFC) between limbic structures and the temporal pole to a cluster in the precuneus. Moreover, a cluster in the left superior parietal lobule showed altered rsFC to the subcallosal cortex, the left orbitofrontal cortex, and limbic structures after probiotics. In the probiotics group, structural and functional changes were partly related to decreases in depressive symptoms. LIMITATIONS: This study has a rather small sample size. An additional follow-up MRI session would be interesting for seeing clearer changes in the relevant brain regions as clinical effects were strongest in the follow-up. CONCLUSION: Probiotic supplementation is suggested to prevent neuronal degeneration along the uncinate fasciculus and alter fronto-limbic rsFC, effects that are partly related to the improvement of depressive symptoms. Elucidating the neural mechanisms underlying probiotics' clinical effects on depression provide potential targets for the development of more precise probiotic treatments.
Assuntos
Imagem de Tensor de Difusão , Probióticos , Humanos , Depressão/diagnóstico por imagem , Depressão/terapia , Encéfalo/diagnóstico por imagem , Neuroimagem , PerfusãoRESUMO
A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.
Assuntos
Transtorno Depressivo Maior , Microbioma Gastrointestinal , Probióticos , Transtorno Depressivo Maior/tratamento farmacológico , Suplementos Nutricionais , Humanos , Probióticos/farmacologia , Probióticos/uso terapêuticoRESUMO
BACKGROUND: Patients with major depressive disorder (MDD) often experience relapses despite regular treatment with pharmacotherapy and psychotherapy. Further, long waiting lists and more demand than treatment capacity characterize ambulatory settings. Mindfulness-based interventions proved to be effective in relapse prevention in MDD. Next, mindfulness-based interventions in the form of free mobile applications can be an effective augmentation of the treatment as usual and can fill a gap in ambulatory care. OBJECTIVE: Given this background, the aim of this randomized controlled study is to assess the effectiveness of additional MBI via a mobile app on the symptom severity and stress levels, compared to treatment as usual. METHODS: A total of 140 individuals with MDD will be randomly allocated to the intervention or control condition. The intervention consists of the daily use of the mindfulness mobile application Headspace for thirty days (up to 10 minutes a day). The control condition will be treatment as usual. At baseline and four weeks later, the following key outcome dimensions will be assessed: self-rated (Beck Depression Inventory) and experts' rated symptoms of MDD (Hamilton Depression Rating Scale); secondary outcome variables will be blood pressure, heart rate, and respiratory rate and changes in tobacco and alcohol consumption and medication as a proxy of perceived stress. RESULTS: This study was funded in February 2021 and approved by the institutional review board on April 15, 2021, and it started in May 2021. As of December 2021, we enrolled 30 participants. The findings are expected to be published in spring 2023. CONCLUSIONS: We hypothesize that compared to the control conditions, individuals with MDD of the mobile app-condition will have both lower self- and experts' rated symptoms of MDD and more favorable stress-related levels. While the risk for medical events is low, the immediate benefit for participants could be a decrease in symptom severity and reduction of the stress level. TRIAL REGISTRATION: Clinical Trials.gov NCT05060393; https://clinicaltrials.gov/ct2/show/NCT05060393. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33423.
RESUMO
Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment.
RESUMO
Introduction: A physical activity counseling intervention based on a motivation-volition model was developed and delivered to in-patients with Major Depressive Disorders with the aim of increasing lifestyle physical activity. The aim of this study is to evaluate the short-term outcomes of this intervention. Methods: A multi-center randomized controlled trial was conducted in four Swiss psychiatric clinics. Adults who were initially insufficiently physically active and were diagnosed with Major Depressive Disorder according to ICD-10 were recruited. The sample consisted of 113 participants in the intervention group (M age = 42 years, 56% women) and 107 in the control group (M age = 40 years, 49% women). Motivation and volition determinants of physical activity were assessed with questionnaires. Implicit attitudes were assessed with an Implicit Association Test. Physical activity was self-reported and measured with hip-worn accelerometers over 7 consecutive days starting on the day following the data collection. Results: According to accelerometer measures, step count decreased on average 1,323 steps less per day (95% CI = -2,215 to -431, p < 0.01) over time in the intervention group compared to the control group. A trend was recognized indicating that moderate-to-vigorous physical activity decreased on average 8.37 min less per day (95% CI = -16.98 to 0.23, p < 0.06) over time in the intervention group compared to the control group. The initial phase of the intervention does not seem to have affected motivational and volitional determinants of and implicit attitudes toward physical activity. Conclusion: Physical activity counseling may be considered an important factor in the transition from in-patient treatment. Methods to optimize the intervention during this period could be further explored to fulfill the potential of this opportunity. Clinical trial registration: https://www.isrctn.com/ISRCTN10469580, identifier ISRCTN10469580.
RESUMO
Introduction: Major depression is a psychiatric disease associated with physical inactivity, which in turn affects mental and physical health. A randomized controlled trial is being implemented to facilitate physical activity in people with major depression. In March 2020, Swiss state authorities temporarily legislated a lockdown to contain the Coronavirus disease-19 (COVID-19), which influenced health, behavior and research. The aim of this study was to find out whether data gathered before and during/after the lockdown among in-patients with major depression differ with regard to psychosocial health, physical activity and related attitudes and to establish whether baseline data have been affected by the lockdown. Methods: This is a cross-sectional analysis within a randomized controlled trial. Physically inactive, adult in-patients diagnosed with major depression were recruited from four Swiss psychiatric clinics between January 2019 and December 2020. Psychosocial health was measured with questionnaires pertaining to stress, sleep and health-related quality of life. Physical activity was measured with the Simple Physical Activity Questionnaire. Explicit attitudes were measured with seven questionnaires pertaining to physical activity-related motivation and volition. Implicit attitudes toward physical activity were captured with a single target implicit association test. Results: The sample consisted of 165 participants (n = 119 before lockdown, n = 46 during/after lockdown). No statistically significant differences were found between in-patients with major depression assessed before and during/after the COVID-19 lockdown with regard to psychosocial health (stress, p = 0.51; sleep, p = 0.70; physical component of health-related quality of life, p = 0.55; mental component of health-related quality of life, p = 0.64), self-reported physical activity (p = 0.16) and explicit as well as implicit attitudes toward physical activity (p = 0.94). Hence, the COVID-19-induced lockdown seems not to have led to group differences. Conclusion: Baseline data gathered in in-patients suffering from major depression who are physically inactive upon admission to in-patient treatment in Switzerland seem to be unaffected by the COVID-19-induced lockdown. To assess changes in said population regarding psychosocial health and physical activity patterns over time, longitudinal data are needed.
RESUMO
Anhedonia has been associated with abnormal reward-related striatal dopamine functioning in patients with different psychiatric disorders. Here, we tested whether anhedonia expression mapped onto striatal volume across several psychiatric diagnoses. T1-weighted images from 313 participants including 89 healthy controls (HC), 22 patients with opioid use disorder (OUD), 50 patients with major depressive disorder (MDD), 45 patients with borderline personality disorder (BPD), 49 patients with first-episode psychosis (FEP), 43 patients with cocaine use disorder (CUD) and 15 patients with schizophrenia (SZ) were included. Anhedonia was assessed with subscores of the Beck Depression Inventory (BDI) and/or the Scale for the Assessment of Negative Symptoms (SANS). Voxel-based morphometry (VBM) was conducted for identifying dimensional symptom-structure associations using region of interest (ROI, dorsal and ventral striatum) and whole-brain analyses, as well as for group comparisons of striatal volume. ROI analyses revealed significant negative relationships between putamen volume and BDI and SANS anhedonia scores across OUD, MDD, BPD, CUD and SZ patients (n = 175) and MDD, FEP and SZ patients (n = 114), respectively. Whole-brain VBM analyses confirmed these associations and further showed negative relationships between anhedonia severity and volume of the bilateral cerebellum. There were group differences in right accumbens volume, which however were not related to anhedonia expression across the different diagnoses. Our findings indicate volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities.
Assuntos
Transtorno Depressivo Maior , Estriado Ventral , Anedonia , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
Background: Online or internet gaming disorder (IGD) is currently not recognized as a mental disorder in the actual Diagnostic and Statistical Manual of Mental Disorders (DSM-5), although it is an emerging disease. Non-substance-related addictions often have similarities with substance addictions. It is therefore important to have a good understanding of the client but also to have a good endurance. Due to the rise of e-sports, there is an anticipated and therefore possible trend to have many more patients with a non-substance addiction. There are many parallels, for instance tolerance, withdrawal and social problems, resulting from an increasing investment of time spent on the internet. Case presentation: To reduce possible inhibition in treating a patient with IGD, we present a case of a 19-year-old adolescent man who exhibited IGD and showed social problems associated with his addiction. Conclusions: This paper shows the importance and the effects of treating a non-substance addiction with cognitive behavioral therapy (CBT). After having successfully coped with an addiction, several shifts in addiction were often reported. In this case, no shifts were reported. The absence of such shifts makes our case a distinct and unique case. This is not a multimorbidity case, and that is the reason why we think this is an excellent example to show what we achieved, how we achieved it, and what we could establish. Of course, additional research and manuals are urgently needed.
Assuntos
Comportamento Aditivo , Jogos de Vídeo , Adolescente , Adulto , Comportamento Aditivo/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Internet , Transtorno de Adição à Internet , Masculino , Prática Privada , Adulto JovemRESUMO
Background: Individuals suffering from major depressive disorder (MDD) often describe workplace-related stress as one of the main causes of their disorder. Here, we present the story of a 33 year old "Bob" (a pseudonym) who suffered from a moderate (Hamilton-21 = 18) major depressive episode. Workplace-related stress seemed to be the main stressor for Bob at the time. We were interested in long-lasting effects of a newly established group called "work-related interpersonal Psychotherapy, W-IPT". W-IPT consists of eight weekly 90 min sessions. The follow-ups were 12 weeks after the group-treatment and 18 months later. Bob was chosen because he agreed in advance to participate in a follow-up. We were interested if the group-treatment of W-IPT also has a persistent positive effect. Case presentation: We present the case of a 33-year-old man "Bob". He was included in our previous published pilot-study 2020 with diagnosed moderate MDD, and he attended the group treatment. This case report focuses on a follow-up period of 18 months. A structured clinical interview for DSM-IV was carried out in order to be included in the study, and no comorbid diagnoses were detected. Conclusions: However, the psychotherapeutic effects in this case seem enduring and prolonged. Of course, additional research to study the long-term effects of W-IPT is needed, and more patients need to be included.
Assuntos
Transtorno Depressivo Maior , Psicoterapia de Grupo , Adulto , Transtorno Depressivo Maior/terapia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Masculino , Projetos Piloto , Psicoterapia , Resultado do TratamentoRESUMO
OBJECTIVES: Individuals suffering from major depressive disorder (MDD) often report workplace-related stress as the major cause of their disorder. Accordingly, workplace-related stress was established as a fifth psychosocial problem area of Interpersonal Psychotherapy (workplace-related Interpersonal Psychotherapy, W-IPT). The aim of the study was to investigate the influence of W-IPT on depressive symptoms and on workplace-related issues in individuals with MDD compared to a treatment-as-usual (TAU) condition. METHODS: A total of 27 individuals with MDD (mean age = 43 years, 48% males) were randomly assigned either to eight weekly group sessions of W-IPT or to the TAU condition. At baseline, 8 weeks later at the end of the intervention, and 20 weeks later at follow-up, the Hamilton Rating Scale for Depression was conducted. In addition, the participants completed the Beck Depression Inventory, the Work Ability Index (WAI), the Return to Work Attitude (RTW-SE), and the Insomnia Severity Index (ISI). RESULTS: Symptoms of depression in experts' ratings as well as in self-rated ratings decreased over time, but more so in the W-IPT condition compared to the TAU condition [experts rating: large effect size (d = 1.25) and self-assessment: large effect sizes (d = 0.94)]. The subjective ability to work (WAI) [medium effect size (d = 0.68)], self-efficacy to returning to work RTW-SE [medium effect size (d = 0.57)], and subjective symptoms of insomnia (ISI) [large effect size (d = 1.15)] increased over time, but again more so in the W-IPT condition compared to the TAU condition. The effects of the intervention remained stable from the end of the intervention to follow-up. CONCLUSIONS: The pattern of results of this pilot study suggests that a newly established fifth IPT focus on workplace-related stress appeared to be particularly efficient in individuals with MDD due to work-related stress in reducing depressive symptoms and reducing sleep complaints as well as in improving occupational outcomes.
RESUMO
BACKGROUND: Major depressive disorder (MDD) is a widespread and burdensome psychiatric issue. Physical activity counselling may increase lifestyle physical activity and cardiorespiratory fitness in this specific and particularly vulnerable population, which often suffers from both mental and physical health problems. Therefore, this study will examine the impact of a lifestyle physical activity counselling intervention on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers among in-patients diagnosed with MDD compared to controls. Secondary purposes are to examine the acceptability and perceived usefulness of the intervention among these patients, to find out whether the effectiveness of the intervention is moderated by genetic factors, and to compare baseline values with an age- and gender-matched group of healthy controls. METHODS: The study is designed as a multi-centric two-arm randomized clinical trial including an intervention group and a placebo control group, allocation concealment, single-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 programme, which was specifically designed for an in-patient rehabilitation setting. The placebo control condition consists of general instructions about health-enhancing physical activity. Data assessments will take place 2-3 weeks after admission to in-patient treatment (baseline), and 6 weeks (post) and 12 months (follow-up) after discharge from in-patient treatment. The primary outcome is objectively assessed physical activity at follow-up. DISCUSSION: Because regular physical activity has proven 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. Improving physical activity may have important implications for tackling metabolic and cardiovascular disease and increasing mood and cognitive functioning in this at-risk population, hence limiting the future burden of multiple chronic conditions. Increased physical activity may also reduce the likelihood of future depressive episodes. By moving towards the primary prevention of chronic physical conditions, much can be done to enhance the quality and quantity of life of people with MDD. TRIAL REGISTRATION: ISRCTN, ISRCTN10469580 . Registered on 3 September 2018.
Assuntos
Aptidão Cardiorrespiratória , Doenças Cardiovasculares/etiologia , Aconselhamento , Transtorno Depressivo Maior/fisiopatologia , Exercício Físico , Estilo de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/psicologia , Humanos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Risco , Método Simples-Cego , Adulto JovemRESUMO
Migration can be a stressful experience and may lead to poor health and behavioral changes. The immigrant population in Switzerland is disproportionately burdened by several negative health outcomes, chief among these is mental health issues. The aim of the study was to investigate whether sleep disturbances are more prevalent among immigrants compared to non-immigrants and whether emotional distress might explain sleep differences. Based on the Swiss Health Survey 2012 dataset, we analyzed the data of 17,968 people, of which 3406 respondents were immigrants. We examined variables including insomnia symptoms, emotional distress and clinical and socio-demographic data using unadjusted and adjusted generalized linear models. Compared to non-immigrants, immigrants suffer significantly more often from insomnia symptoms. Immigrants also endured higher levels of emotional distress. Higher values of emotional distress are related to other symptoms of sleep disorders. Immigrants with emotional distress were at significant risk of sleep disturbances. Sleep disparities between immigrants and non-immigrants may be influenced by emotional distress. Migration health care should address emotional distress, a more proximal and modifiable factor, as a possible cause of insomnia symptoms in immigrants.
Assuntos
Emigrantes e Imigrantes , Emoções , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Estresse Psicológico/psicologia , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Suíça/epidemiologia , Adulto JovemRESUMO
Background: People with mental disorders engage in sedentary behaviors more often than their healthy counterparts. In Switzerland, nearly all psychiatric hospitals offer structured exercise and sport therapy as part of their standard therapeutic treatment. However, little is known about the degree to which psychiatric patients make use of these treatment offers. The aim of this study is to examine, in a sample of psychiatric in-patients (a) how many participate in the structured exercise and sport therapy programs offered by the clinic, (b) how many engage in exercise and sport activities on an individual basis, and (c) how many meet recommended levels of health-enhancing physical activity during their stay at the clinic. Furthermore, we examine whether those who engage in exercise and sport activities are more likely to meet internationally accepted physical activity recommendations. Methods: 107 psychiatric in-patients (49% women, Mage = 39.9 years) were recruited at three psychiatric clinics in the German-speaking part of Switzerland. All participants were engaged in treatment and received usual care. Based on accelerometer data, participants were classified as either meeting or not meeting physical activity recommendations (≥150 min of moderate-to-vigorous physical activity per week). Participation in structured and individually performed exercise and sport activities was assessed with the Simple Physical Activity Questionnaire. Results: In total, 57% of all patients met physical activity recommendations. 55% participated in structured exercise and sport therapy activities, whereas only 22% of all patients engaged in exercise and sport activities independently. Psychiatric patients were significantly more likely to meet recommended levels of health-enhancing physical activity if they engaged in at least 60 min per week of structured exercise and sport therapy or in at least 30 min of individually performed exercise and sport activity. Conclusions: Given that prolonged immobilization and sedentary behavior have harmful effects on patients' physical and mental well-being, promoting exercise and sport activities is an important endeavor in psychiatric care. Clinics currently succeed in involving between 50 and 60% of all patients in sufficient physical activity. While this is encouraging, more systematic efforts are needed to ensure that all patients get enough physical activity.
RESUMO
OBJECTIVE: Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate release, or antagonising the action of glutamate at its receptors, may therefore represent viable treatment strategies. Several glutamatergic agents with regulatory approval for other indications are available and may be of potential benefit in the treatment of compulsivity/impulsivity in psychiatric disorders in paediatric patients. METHOD: This review was performed according to PRISMA guidelines and evaluates available scientific literature concerning the use of glutamatergic agents in these patients, in order to determine their reported effectiveness/efficacy and tolerability/safety. RESULTS: Out of a total of 1,426 publications, 21 trials examining six glutamatergic substances in patients with obsessive-compulsive disorder, autism spectrum disorders, and attention deficit/hyperactivity disorder were included. CONCLUSIONS: Trial designs as well as results were heterogeneous and thus comparability was limited. Available data support the hypothesis that glutamatergic agents are of potential value in the treatment of compulsivity/impulsivity in children and adolescents. Based on the data reviewed, memantine and N-acetylcysteine suggest the best risk-benefit profile for future trials. Riluzole should primarily be further investigated in adults. Clinical research of this nature is a key element of the TACTICS Consortium project funded by the European Union (FP7).
Assuntos
Encéfalo/efeitos dos fármacos , Fármacos Atuantes sobre Aminoácidos Excitatórios/uso terapêutico , Transtorno Obsessivo-Compulsivo/tratamento farmacológico , Acetilcisteína/efeitos adversos , Acetilcisteína/uso terapêutico , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Corpo Estriado/efeitos dos fármacos , Fármacos Atuantes sobre Aminoácidos Excitatórios/efeitos adversos , Ácido Glutâmico/metabolismo , Humanos , Memantina/efeitos adversos , Memantina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Glutamato/efeitos dos fármacos , Medição de Risco , Resultado do TratamentoRESUMO
Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD). Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13), a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive-compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment of MDD from the US Food and Drug Administration, representing one of the most promising alternative antidepressants under current investigation.
RESUMO
BACKGROUND: The predictive therapeutic value of brain derived neurotrophic factor (BDNF) and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. METHODS: We examined serum BDNF (ELISA kit) in a sample of 76 (47 female and 29 male) depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA) was measured in the anterior cingulate cortex (ACC) with magnetic resonance spectroscopy (MRS). Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. RESULTS: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. LIMITATIONS: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. CONCLUSION: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction.
RESUMO
Several nutrition, food and dietary compounds have been suggested to be involved in the onset and maintenance of depressive disorders and in the severity of depressive symptoms. Nutritional compounds might modulate depression associated biomarkers and parallel the development of depression, obesity and diabetes. In this context, recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin, leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota) acting in gut brain circuits. In this context several healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat have been inversely associated with depression risk and even have been postulated to improve depressive symptoms. In contrast, unhealthy western dietary patterns including the consumption of sweetened beverage, refined food, fried food, processed meat, refined grain, and high fat diary, biscuits, snacking and pastries have been shown to be associated with an increased risk of depression in longitudinal studies. However, it is always difficult to conclude a real prospective causal relationship from these mostly retrospective studies as depressed individuals might also change their eating habits secondarily to their depression. Additionally specific selected nutritional compounds, e.g. calcium, chromium, folate, PUFAs, vitamin D, B12, zinc, magnesium and D-serine have been postulated to be used as ad-on strategies in antidepressant treatment. In this context, dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and treatment strategy for depression. At last, several medications (pioglitazone, metformin, exenatide, atorvastatin, gram-negative antibiotics), which have traditionally been used to treat metabolic disorders showed a certain potential to treat depression in first randomized controlled clinical trials.
Assuntos
Antidepressivos/uso terapêutico , Biomarcadores/metabolismo , Transtorno Depressivo/dietoterapia , Suplementos Nutricionais/análise , Terapia Combinada , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Transtorno Depressivo/psicologia , Ingestão de Energia , Comportamento Alimentar/psicologia , Comportamentos Relacionados com a Saúde , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Interleukin (IL)-2 regulates the immune response through the proliferation of activated T-cells and also exerts effects on the central nervous system (CNS). Alongside having marked neurobehavioral effects, IL-2 has been suggested to impact on various psychiatric disorders. The immune-CNS communication of IL-2 remains unclear, although, it is suggested that microglia are the source and target of IL-2. Here, we analyzed changes in brain metabolites following a peripheral IL-2 challenge and examined the contribution of microglia in mediating these effects. Rats were assessed by magnetic resonance spectroscopy (MRS) in a 9.4 T scanner for baseline metabolite levels in the prefrontal cortex (PFC) and the hippocampus. After 7 days animals were scanned again following a single injection of IL-2 (2.5 µg/kg) and then tested on the elevated plus-maze for the correlation of IL-2-induced brain metabolites and measures of anxiety. In another experiment CD25(+) microglia cells were determined. A separate group of rats was injected either with IL-2 or vehicle, and afterward the PFC and hippocampus were dissected and fluorescence activated cell sorting (FACS) analysis was performed. The MRS scans in the intra-individual study design showed a significant increase in myo-inositol in the analyzed regions. A significant correlation of anxiety-like measures and myo-inositol, a marker for microglia activity, was found in the hippocampus. The FACS analysis showed a significant increase in CD25(+) microglia in the hippocampus compared to controls. The results support the role of microglia as a mediator in the immune-CNS communication and the effects of peripheral IL-2.