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Over 300 million individuals worldwide suffer from major depressive disorder (MDD). Individuals with MDD are less physically active than healthy people which results in lower cardiorespiratory fitness (CRF) and less favorable perceived fitness compared with healthy controls. Additionally, individuals with MDD may show autonomic system dysfunction. The purpose of the present study was to evaluate the CRF, perceived fitness and autonomic function in in-patients with MDD of different severity compared with healthy controls. We used data from 212 in-patients (age: 40.7 ± 12.6 y, 53% female) with MDD and from 141 healthy controls (age: 36.7 ± 12.7 y, 58% female). We assessed CRF with the Åstrand-Rhyming test, self-reported perceived fitness and autonomic function by heart rate variability (HRV). In specific, we used resting heart rate, time- and frequency-based parameters for HRV. In-patients completed the Beck Depression Inventory-II (BDI-II) to self-assess the subjectively rated severity of depression. Based on these scores, participants were grouped into mild, moderate and severe MDD. The main finding was an inverse association between depression severity and CRF as well as perceived fitness compared with healthy controls. Resting heart rate was elevated with increasing depression severity. The time-based but not the frequency-based autonomic function parameters showed an inverse association with depression severity. The pattern of results suggests that among in-patients with major depressive disorder, those with particularly high self-assessed severity scores show a lower CRF, less favorable perceived fitness and partial autonomic dysfunction compared to healthy controls. To counteract these conditions, physical activity interventions may be effective., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. The PACINPAT trial is funded by the Swiss National Science Foundation (grant number: 321003B-179353). The authors JB, MH, CI, UEL, SM, TM, AO, AR and NS supported the patient screening and recruitment processes on the four study sites. JNK and RC recruited the participants and collected the data. EHT, LD, AE, SB, LZ and MG offered thematic support. JNK and OF were responsible for conceptualizing the manuscript. JNK conducted the statistical analyses. JNK wrote the first draft of the manuscript with assistance of OF. All listed co-authors read, contributed to and approved the final manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (M age  = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (β = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580 ., (© 2024. The Author(s).)

Background and Objectives: Almost by default, people with major depression disorder (MDD) also report sexual health issues. This holds even more true when sexual dysfunctions are SSRI-induced. Herbal compounds may have the power to counterbalance such sexual dysfunctions, though research is still scarce. Therefore, we assessed females with diagnosed MDD treated with a standard SSRI (sertraline) and reporting SSRI-induced sexual dysfunctions, and we asked whether compared to placebo, Aphrodite (a blend of ginger, saffron, cinnamon, thistle, and Tribulus terrestris ) may favorably impact on sexual dysfunctions, and on symptoms of depression, anxiety, and sleep disturbances. Materials and Methods: A total of 41 females (mean age: 35.05 years) with diagnosed MDD, treated with sertraline (a standard SSRI) at therapeutic dosages, and reporting SSRI-induced sexual dysfunction, were randomly assigned either to Aphrodite or to the placebo condition. At baseline and four and eight weeks later (study end), participants completed a series of self-rating questionnaires covering symptoms of sexual dysfunction, depression, anxiety, and sleep complaints. Results: Symptoms of sexual dysfunction, depression, and anxiety decreased over time, but more so in the Aphrodite condition, compared to the placebo condition (significant p -values and large effect sizes). Over time, sleep disturbances decreased irrespective of the study condition. Conclusions: The pattern of results suggests that compared to placebo, Aphrodite appeared to improve symptoms of sexual dysfunction, depression, and anxiety among females with diagnosed MDD and SSRI-induced sexual dysfunction. Further and similar studies should investigate the underlying psychophysiological mechanisms.

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 3 rd September 2018., (© 2023. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© 2023 CMA Impact Inc. or its licensors.)

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., (© 2022. The Author(s).)

Background: While there is sufficient evidence that Crocus Sativus L. (saffron) improves symptoms of depression in young and middle-aged adults, research on older people are missing. The purpose of the double-blind, randomized intervention study was to compare the effect of saffron and sertraline on MDD among a sample of older people., Methods: A total of 50 older out-patients with MDD (mean age = =65 years; 70% males) were randomly assigned either to the saffron condition (60 mg/d) or to the sertraline condition (100 mg/day) for six consecutive weeks. Experts employed the Hamilton Depression Rating Scale (HDRS) to rate participants' degree of depression. Timepoints were baseline, week 2, week 4 and week 6, the end of the study., Results: Symptoms of depression decreased over time, with no advantages or disadvantages for the saffron or sertraline condition., Conclusion: The pattern of results suggests that both saffron and sertraline have the potential to significantly decrease symptoms of depression. The results are clinically relevant, because major depressive disorders in older people is a health concern. The results are further relevant, because saffron appears to be a powerful antidepressant for older people, who might be more reluctant to the use of synthetic drugs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: A key feature of major depressive disorders is the lack of emotional processing such as empathy. To counter this, we tested, if brain stimulation on areas rich of mirror neurons on the left inferior parietal lobe (lIPL) might improve emotional processing, including empathy, compared to a standard brain stimulation on the left dorsolateral prefrontal cortex (lDLPFC)., Methods: Twenty inpatients (mean age: 38.9 years; 55% females) with severe major depressive disorders and stable treatment of sertraline at therapeutic dosages were randomly assigned to either the rTMS condition on areas of mirror neuron stimulation, that is, the left inferior parietal lobe (rTMS-lIPL), or to the left dorsolateral prefrontal cortex (rTMS-lDLPFC; control condition). Interventions lasted for two consecutive weeks (2 × 5 interventions of 30'). At baseline and at the end of the study, patients completed questionnaires on current mood state and emotion regulation. In parallel, experts rated patients' depression severity., Results: Mood improved over time, but more so in the control condition, compared to the rTMS-lIPL condition (medium-large effect sizes). Emotion regulation improved over time; specifically, empathy improved, but only in the rTMS-lIPL condition, compared to the control condition. Symptoms of depression decreased over time, but more so in the rTMS- lIPL condition., Conclusions: The pattern of results suggests that among inpatients with severe major depressive disorders, and compared to a standard procedure of rTMS, rTMS targeting on areas rich of mirror neurons appeared to improve emotion regulation, and specifically empathy, while there was no advantage on acute mood., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Background: Extant literature shows that adjuvant omega-3-polyunsaturated fatty acids (O3PUFAs) to a standard antidepressant medication impacts favorably on symptoms of depression in participants with major depressive disorders (MDD). The aim of the present study was to investigate, if and to what extent compared to placebo adjuvant O3PUFAs had a favorable impact on symptoms of depression, anxiety, sleep and emotion regulation among outpatients with MDD., Method: A total of 50 outpatients (mean age: M = 42.46; 68% females) took part in this randomized, double-blind and placebo-controlled study. They were randomly assigned either to the O3PUFA- or to the placebo-condition. Standard medication was sertraline at therapeutic dosages. At baseline, six weeks and 12 weeks later at study completion participants completed questionnaires covering symptoms of depression, anxiety sensitivity, intolerance of uncertainty, sleep disturbances, and emotion regulation. In parallel, experts blind to participants' group assignment rated participants' depression with the Montgomery-Asberg Depression Scale., Results: Symptoms of depression (self- and experts' ratings) decreased over time, but more so in the O3PUFA condition, compared to the placebo condition. Likewise, anxiety sensitivity, intolerance of uncertainty and sleep disturbances improved, but again more so in the O3PUFA condition. Further, regulation and control of emotions and perception of other's emotions improved over time, but more so in the O3PUFA condition., Conclusions: Among outpatients with MDD, and compared to placebo, adjuvant O3PUFAs to a standard medication improved not only symptoms of depression, but also dimensions of anxiety and sleep, and above all patients' competencies to regulate their emotions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Physical activity (PA) may be therapeutic for people with severe mental illness (SMI) who generally have low PA and experience numerous life style-related medical complications. We conducted a meta-review of PA interventions and their impact on health outcomes for people with SMI, including schizophrenia-spectrum disorders, major depressive disorder (MDD) and bipolar disorder. We searched major electronic databases until January 2018 for systematic reviews with/without meta-analysis that investigated PA for any SMI. We rated the quality of studies with the AMSTAR tool, grading the quality of evidence, and identifying gaps, future research needs and clinical practice recommendations. For MDD, consistent evidence indicated that PA can improve depressive symptoms versus control conditions, with effects comparable to those of antidepressants and psychotherapy. PA can also improve cardiorespiratory fitness and quality of life in people with MDD, although the impact on physical health outcomes was limited. There were no differences in adverse events versus control conditions. For MDD, larger effect sizes were seen when PA was delivered at moderate-vigorous intensity and supervised by an exercise specialist. For schizophrenia-spectrum disorders, evidence indicates that aerobic PA can reduce psychiatric symptoms, improves cognition and various subdomains, cardiorespiratory fitness, whilst evidence for the impact on anthropometric measures was inconsistent. There was a paucity of studies investigating PA in bipolar disorder, precluding any definitive recommendations. No cost effectiveness analyses in any SMI condition were identified. We make multiple recommendations to fill existing research gaps and increase the use of PA in routine clinical care aimed at improving psychiatric and medical outcomes., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

We investigated the influence of detached mindfulness (DM) in treating symptoms of depression and anxiety among elderly women. Thirty-four elderly females (mean age: 69.23 years) suffering from moderate major depressive disorders (MDD) and treated with a standard medication (citalopram) at therapeutic doses were randomly assigned either to an intervention condition (DM; group treatment, twice weekly) or to a control condition (with leisure activities, twice weekly). At baseline (BL), four weeks later at study completion (SC), and four weeks after that at follow-up (FU), participants completed ratings for symptoms of depression and anxiety; experts blind to patients' group assignments rated patients' symptoms of depression. Symptoms of depression (self and experts' ratings) and anxiety declined significantly over time in the DM, but not in the control condition. Effects remained stable at FU. The pattern of results suggests that, compared to a control condition, a specific psychotherapeutic intervention such as DM can have a beneficial effect in elderly female patients with MDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Patients with psychiatric disorders have an exceptionally high risk of completed or attempted suicide. This holds particularly true for patients with major depressive disorders. The aim of the present study was to explore whether patients with major depressive disorders (MDD) and a history of suicide attempts differed in their early maladaptive schemas from patients with MDD but without such a history or from healthy controls., Method: Ninety participants took part in the study. Of these, 30 were patients with MDD who had made a recent suicide attempt; 30 were patients with MDD but no suicide attempts, and 30 were gender- and age-matched healthy controls. Participants completed questionnaires covering socio-demographic characteristics and the Young Schema Questionnaire (YSQ- RE2R) to assess early maladaptive schemas. Experts rated patients' MDD with the Montgomery-Asberg Depression Rating Scale., Results: Patients did not differ in experts' ratings of symptoms of depression. Compared to healthy controls, patients with MDD recorded higher scores on maladaptive schemas such as recognition seeking, negativity/pessimism, and insufficient self-control. Compared to patients without suicide attempts and healthy controls, those who had made a suicide attempt had higher scores on dimensions such as failure, mistrust, emotional inhibition, social isolation, and abandonment/instability., Conclusion: Compared to healthy controls, patients with MDD had more pronounced maladaptive schemas, but this was more marked in patients with a history of suicide attempts. The results suggest that suicide attempts and poorer psychological functioning are related., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients suffering from major depressive disorders (MDD) report anhedonia, low concentration and lack of goal-oriented behavior. Data from imaging and quantitative EEG (QEEG) studies show an asymmetry in the prefrontal cortex (PFC), with lower left as compared to right PFC-activity, associated with specific depression-related behavior. Cordance is a QEEG measurement, which combines absolute and relative power of EEG-spectra with strong correlations with regional perfusion. The aim of the present study was to investigate to what extent a four weeks lasting treatment with a standard SSRI had an influence on neuronal activation and MDD-related symptoms., Method: Twenty patients suffering from severe MDD were treated with citalopram (40mg) for four consecutive weeks. At baseline and at the end of the treatment, patients underwent QEEG. Experts rated the degree of depression with the Hamilton Depression Rating Scale (HDRS)., Results: Over time, theta cordance increased over right ventromedial and left dorsolateral PFC, whereas alpha cordance decreased over dorsolateral PFC. Improvement in MDD-related symptoms was higher in patients showing decreased EEG theta cordance over right dorsal PFC and increased EEG alpha cordance over left dorsolateral PFC., Conclusions: In patients suffering from MDD, treatment response was associated with favorable changes in neuronal activity., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Given that antidepressants (ADs) work slowly, there is interest in means to accelerate their therapeutic effect and to reduce side effects. In this regard, thiamine (vitamin B 1 ) is attracting growing interest. Thiamine is an essential nutrient, while thiamine deficiency leads to a broad variety of disorders including irritability and symptoms of depression. Here, we tested the hypothesis that adjuvant thiamine would reduce depression, compared to placebo. A total of 51 inpatients (mean age: 35.2 years; 53 % females) with MDD (Hamilton Depression Rating Scale score (HDRS) at baseline: >24) took part in the study. A standardized treatment with SSRI was introduced and kept at therapeutic levels throughout the study. Patients were randomly assigned either to the thiamine or the placebo condition. Experts rated (HDRS) symptoms of depression at baseline, and after 3, 6, and 12 weeks (end of the study). Between baseline and the end of the study, depression had reduced in both groups. Compared to placebo, adjuvant thiamine improved symptoms of depression after 6 week of treatment, and improvements remained fairly stable until the end of the study, though mean differences at week 12 were not statistically significant anymore. No adverse side effects were reported in either group. Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo. Importantly, improvements were observed within 6 weeks of initiation of treatment. Thus, thiamine might have the potential to counteract the time lag in the antidepressant effects of ADs.

Background: To treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF)., Methods: 60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication., Results: pBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression., Conclusions: The pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Treating major depressive disorders (MDD) with selective serotonin-reuptake inhibitors (SSRIs) may impact negatively on sexual function. On the other hand, a satisfying sexual life is associated with overall life satisfaction. Therefore, managing this negative side effect of SSRIs may have an important role in the treatment of MDD. In a former study, adjuvant Rosa damascena oil improved sexual dysfunction in male patients suffering from both MDD and SSRI-induced sexual dysfunction (SSRI-I SD). The aim of the present study was to test whether the same pattern of results would be observed among female patients suffering from both SSRI-I SD and MDD., Method: In a double-blind, randomized and placebo-controlled clinical trial, a total of 50 female patients (mean age: 34 years) treated with an SSRI and suffering from MDD and SSRI-I SD were randomly assigned either to the verum (Rosa damascena oil) or to the placebo condition. Patients completed self-ratings of depression and sexual function at baseline, 4 weeks later, and at the end of the study 8 weeks after its start., Results: Sexual desire, sexual orgasms, and sexual satisfaction increased over time. Patients in the verum group reported decreased pain. Overall sexual score increased in the verum as compared to the placebo condition., Conclusions: Whereas in male patients suffering from both MDD and SSRI-I SD adjuvant Rosa damascena oil improved sexual function, data on female patients are less robust and suggest only modest effects on female sexual function., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background/aims: In major depression cognitive impairment is common and may persist despite improvement in psychopathology. So far it is unclear how closely related improvement in cognitive functioning is to the clinical course of depression. Further, it is unclear whether recovery from cognitive impairment is linked to changes in serum brain-derived neurotrophic factor (sBDNF). The objectives of this study were (1) to explore the predictive value of cognitive impairment for therapeutic outcome, and (2) to assess the association between cognitive performance and sBDNF levels over a 6-week course of antidepressant treatment., Methods: Twenty-five adult patients suffering from major depression underwent standardized treatment with duloxetine. Both severity of depression as assessed by the Hamilton Depression Rating Scale and sBDNF levels were measured at baseline, and after 1, 2 and 6 weeks of treatment. Cognitive performance, i.e. alertness, working memory, and divided attention, was assessed at baseline, after 1 week, and at the end of treatment after 6 weeks., Results: Higher performance in alertness and divided attention at baseline correlated with less severe depression at week 6. During the first week of treatment, a greater increase in sBDNF was associated with a greater improvement in alertness at week 6., Conclusion: Greater alertness at baseline was a predictor of favorable antidepressive treatment outcome. Moreover, the early increase in sBDNF correlated with improvement in attention functioning. Thus, recovery from cognitive impairment and an early increase in sBDNF seem to be associated.

Objective: Preclinical and clinical studies support a role for brain-derived neurotrophic factor (BDNF) in the pathophysiology of stress-related mood disorders. Furthermore, BDNF seems to be linked to antidepressant action. Available pharmacological treatments for depression are characterized by significant limitations with low efficacy and a major delay until treatment response. This demonstrates the urgent need for more efficient and fast-acting antidepressants. Besides ketamine, sleep deprivation (SD) as well as partial sleep deprivation (PSD) are effective and fast-acting antidepressant methods. However, the underlying molecular mechanisms of SD are not well understood; especially possible mechanisms explaining the rapid, but transient antidepressant effect of SD are unknown., Methods: We evaluated serum BDNF from 28 patients suffering from major depressive disorder (MDD), who were naïve to SD therapy at seven different time points within a 32 h time window before (day 0) and after PSD (day 1). PSD-response was assessed by 6-Items of the Hamilton Depression Rating Scale (HDRS) before (day 0) and at follow-up after 2 weeks (FU2)., Results: PSD induced a very fast increase in BDNF serum levels at day 1 which parallels clinical findings, since levels increased with decreasing depression scores in all participants. Notably, responders showed a significant diurnal BDNF serum variation not only after PSD but already before PSD treatment, while diurnal profile of serum BDNF from non-responders did not vary., Conclusions: The elasticity in diurnal serum BDNF variation is associated with favourable treatment response to PSD in patients suffering from MDD. Therefore, a normalized BDNF serum profile which oscillates in a circadian fashion seems to precede, rather than follow a favourable treatment outcome in depressed patients. Furthermore the fast increase of BDNF is comparable to effects seen with ketamine infusion., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The administration of statins seems to be a promising new avenue in the treatment of patients suffering from major depressive disorder (MDD), though patients suffering from severe MDD remain unstudied in this respect. The aim of the present study was therefore to investigate, in a randomized double-blind clinical trial, the influence of adjuvant atorvastatin on symptoms of depression in patients with MDD., Methods: A total of 60 patients suffering from MDD (mean age: 32.25 years; 53% males) received a standard medication of 40 mg/d citalopram. Next, patients were randomly assigned either to the atorvastatin group (20 mg/d) or to the placebo group. Blood lipid values were assessed at baseline and on completion of the study 12 weeks later. Experts rated depressive symptoms via Hamilton Depression Rating Scales (HDRS) at baseline and 3, 6 and 12 weeks later., Results: HDRS scores decreased over time; the significant Time by Group interaction showed that symptoms of depression decreased more in the atorvastatin than in the placebo group. Compared to the placebo group, in the atorvastatin group cholesterol, triglyceride, and Low Density Lipids (LDL) significantly decreased, and High Density Lipids (HDL) significantly increased over time. HDRS scores and blood lipid values were generally not associated., Conclusions: The pattern of results suggests that adjuvant atorvastatin favorably influences symptoms of depression among patients with severe MDD. Given that after 12 weeks of monotherapy and adjuvant atorvastatin patients were still moderately to severely depressed, more powerful treatment algorithms such as augmentation and change of medication are highly recommended., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: To treat patients suffering from treatment-resistant major depressive disorder (TR-MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three-arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2., Bdnf Methods: 60 patients with TR-MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 30 min, three times a week. Both depression severity and BDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication., Results: BDNF levels increased over time in all three study conditions. After completion of the intervention program, the ECT group showed significantly higher BDNF levels compared to the ECT + AET and the AET conditions. Depressive symptoms decreased in all three conditions over time. The combination of ECT + AET led to a significantly greater decrease than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression., Conclusions: The pattern of results suggests that ECT, AET and particularly their combination are promising directions for treatment patients suffering from TR-MDD, and that it remains unclear to what extent BDNF is key and a reliable biomarker for TR-MDD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Rationale: Major depressive disorder has been associated with low serum levels of brain-derived neurotrophic factor (sBDNF), which is functionally involved in neuroplasticity. Although sBDNF levels tend to normalize following psychopathological improvement with antidepressant treatment, it is unclear how closely sBDNF changes are associated with treatment outcome., Objectives: To examine whether baseline sBDNF or early changes in sBDNF are predictive of response to therapy., Methods: Twenty-five patients with major depressive disorder underwent standardized treatment with duloxetine. Severity of depression, measured by the Hamilton Depression Rating Scale, and sBDNF were assessed at baseline, and after 1, 2, and 6 weeks of treatment. Therapy outcome after 6 weeks was defined as response (≥50 % reduction in baseline Hamilton Depression Rating score) and remission (Hamilton Depression Rating score <8). The predictive values for treatment outcome of baseline sBDNF, and early (i.e., ≤2 weeks) changes in sBDNF and Hamilton Depression Rating score were also assessed., Results: At baseline, sBDNF correlated with Hamilton Depression Rating scores. Treatment response was associated with a higher baseline sBDNF concentration, and a greater Hamilton Depression Rating score reduction after 1 and 2 weeks. A greater early rise in sBDNF correlated with a decreased early Hamilton Depression Rating score reduction., Conclusions: Even though higher baseline sBDNF levels are associated with more severe depression, they may reflect an increased capacity to respond to treatment. In contrast, changes in sBDNF over the full course of treatment are not associated with psychopathological improvement.

Background: In patients suffering from major depressive disorders (MDD), improvements in MDD are related to increased activation of brain-derived neurotrophic factor (BDNF), an endogenous protein that facilitates neural functioning. To treat patients suffering from severe MDD, electroconvulsive therapy (ECT) is considered an efficacious and safe intervention, though the impact of ECT on plasma BDNF levels has thus far barely been investigated. The aim of the present study was therefore to assess plasma BDNF levels and depression of patients suffering from severe MDD treated with additional ECT compared to patients treated with citalopram only., Methods: A total of 40 patients (mean age: M = 31.45 years; females 30%) suffering from MDD and all receiving 40 mg/d citalopram were assigned either to a control group (N = 20), or to a target group (N = 20) undergoing additional 12 sessions of ECT. Plasma BDNF and symptom severity were assessed at baseline and four weeks later., Results: Plasma BDNF increased in both groups over time, though the significant Time by Group-interaction revealed an increase of 101% in the target group as compared to the control group. Symptom severity significantly decreased in both groups over time, though without being related to plasma BDNF levels., Conclusions: Data from the present study suggest that, in patients suffering from severe MDD, treatment with citalopram was associated both with an increase of plasma BDNF and amelioration of depression, while additional ECT was associated with even higher plasma BDNF levels. Further studies should focus on possible cognitive and behavioral consequences., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Data from the Iranian population for hypomania core symptom clusters are lacking. The aim of the present study was therefore to apply the Farsi version of the Hypomania-Check-List 32 (HCL-32), and to explore its factorial structure., Methods: A total of 163 Iranian out-patients took part in the study; 61 suffered from Major Depressive Disorder (MDD), and 102 suffered from Bipolar Disorders (BP). Participants completed the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist (HCL-32). Exploratory factor analyses were used to examine the properties of the HCL-32. A ROC-curve analysis was performed to calculate sensitivity and specificity., Results: The HCL-32 differentiated between patients with MDD and with BP. Psychometric properties were satisfactory: sensitivity: 73%; specificity: 91%. MDQ and HCL-32 did correlate highly. No differences were found between patients suffering from BP I and BP II., Discussion: Instead of the two-factorial structure of the HCL-32 reported previously, the present pattern of factorial results suggest a distinction between four factors: two broadly positive dimensions of hypomania ("physically and mentally active"; "positive social interactions") and two rather negative dimensions ("risky behavior and substance use"; "difficulties in social interaction and impatience")., Conclusion: The Farsi version of the HCL-32 proved to be applicable, and therefore easy to introduce within a clinical context. The pattern of results suggests a four factorial solution.

Objective: Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24h. Following the recovery night, however, a relapse into depression occurs in most patients. Recovery sleep, naps and even very short episodes of sleep (microsleep; MS) during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and stabilizes the treatment response to PSD compared to placebo., Methods: A total of 28 patients (13 men, 15 women; age 45.1+/-12.1 years) with a major depressive episode and a cumulative daytime microsleep of five or more minutes were investigated using a double-blind placebo-controlled study design. All patients were treated with a stable mirtazapine monotherapy. A partial SD (PSD) was performed after one week. Additional morning treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep-EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale before, during and after PSD and at follow-ups after one and two weeks., Results: Patients treated with modafinil showed significantly reduced microsleep during PSD (11.63+/-15.99 min) compared to the placebo group (47.77+/-65.31 min). This suppression of MS was not associated with the antidepressive effect of PSD., Conclusions: Compared to placebo, modafinil was efficient in reducing daytime microsleep following partial sleep deprivation but did not enhance the antidepressive effects of PSD and did not stabilize antidepressive effects over two weeks.

Background: Depressive disorders and restless legs syndrome (RLS) demand particular attention because sleepiness, daytime fatigue and loss of interest are symptoms attributable to both depressive disorders and RLS. Moreover, a high comorbidity rate is observed. The aim of the present study was to compare polysomnographic data of patients suffering from RLS, RLS and depressive symptoms, and major depressive disorders (MDD)., Methods: Sleep EEG recordings of patients suffering from RLS (n = 25), RLS and depressive symptoms (n = 38), as well as MDD (n = 15) were compared., Results: Compared to patients with MDD, both groups with RLS had statistically decreased values of sleep continuity, including sleep efficiency, sleep onset latency and wakening after sleep onset. Patients with RLS or RLS and depressive symptoms had also decreased slow-wave sleep compared to patients with MDD., Conclusions: Objective sleep assessment supports previous findings: RLS is a disorder seriously affecting sleep, even compared to MDD. Concomitant symptoms of depression do not seem to additionally deteriorate sleep, though they trigger differences in treatment., ((c) 2009 S. Karger AG, Basel.)

The antidepressive effect of sleep deprivation (SD) in depressed patients disappears after sleep of the recovery night and after early morning naps. Both can provoke a rapid relapse into depression in SD-responders. In addition, the occurrence of short episodes of sleep (termed microsleep, MS) during partial SD (PSD) is associated with SD-nonresponse, suggesting that MS during the time awake may be related to relapse or PSD-nonresponse. The GABA-benzodiazepine receptor antagonist flumazenil augments vigilance and reduces NonREM-sleep pressure in early morning recovery sleep in volunteers after SD. Therefore, in this study 27 patients with major depression were subjected to a PSD. In a double blind randomized design either flumazenil or placebo was orally applied during PSD in order to examine whether the application of flumazenil reduces sleep propensity and thus, increases antidepressant efficacy of PSD. EEG was registered continuously for 60h by a portable device for the assessment of microsleep episodes at baseline and during PSD. Flumazenil application significantly suppressed frequency and total amount of MS. While the antidepressant efficacy of PSD was not different between flumazenil and placebo during PSD, the subjective mood improved after the recovery night in patients treated with flumazenil. It is concluded that GABAergic mechanisms are involved in the regulation of MS during PSD, which may be related to a mood stabilizing effect after the recovery night. However, the mechanisms underlying the association between the occurrence of MS during PSD and mood variation have to be further clarified.

Process and outcome quality of inpatient treatment of depression in Germany was described in a multicenter study of 10 hospitals in North-Rhine Westphalia, Baden-Württemberg and Bavaria. The treatment of more than 2000 depressive patients was assessed by quality indicators and outcome was compared between the hospitals (benchmarking). Results show great variance in length of stay between the hospitals. While in one hospital patients with depressive episodes were discharged after 36.8 days (average), the average length of stay in another hospital was 64.3 days. Furthermore the study revealed that hospitals differ strongly regarding their case-mix. Using stepwise multiple regression analyses potential confounding variables (sociodemographics, history of previous treatment, severity of depression) were identified and their influence on length of stay was calculated. After cross validation the regression analyses model explained 7% of the variance and included 5 predictors. Length of stay is prolonged by patients with a recurrent depressive disorder, by patients with impairment of social functioning and by severity of the depression. Length of stay is reduced if the indication of inpatient treatment was crisis intervention and if there was a previous suicide attempt. It was shown that differences in patient case-mix only account for a small percentage of hospital differences in length of stay. Method, effort and benefit of the regression analyses approach are discussed.

Altered electroencephalographic (EEG) sleep patterns are among the most prominent neurobiological findings in depression. Several of these alterations have been suggested to be associated with an unfavorable long-term outcome. However, the impact of pathological sleep parameters on a more recurrent course of illness or vice versa still warrants clarification. Underlying mechanisms may involve systems known to be related to both sleep regulation and long-term course of depression such as the hypothalamic-pituitary-adrenocortical (HPA) axis. Thus, EEG sleep profiles of patients with depression were examined to determine whether (1) the retrospective clinical course of depression, and (2) the prospective long-term outcome in follow-up are associated with EEG sleep parameters. To elucidate related mechanisms HPA system functioning was evaluated by using the combined DEX/CRH test. Fifteen patients with affective disorders who participated in an earlier controlled antidepressant treatment study over 6 weeks were consecutively enrolled in an exploratory follow-up study. The retrospective analysis revealed that during the acute state of depression predominantly sleep continuity measures were associated with the number of previously experienced episodes. While this relation disappeared during treatment and did not correlate with the prospective course, decreased slow wave sleep variables especially in the first sleep period and increased rapid eye movement density were predictive for the occurrence of recurrences in follow-up and, hence, probably reflect more trait-like markers. Additionally, EEG sleep variables unfavorable for long-term outcome were related to excessive stress hormone response in the DEX/CRH-test. These disturbances may reflect important mechanisms responsible of causing and maintaining the disease process of depression.

Neuroendocrine studies strongly suggest that the hypothalamic-pituitary-adrenocortical (HPA) system plays a crucial role in the development and course of depression. The interaction between the disease process and HPA system function in long-term course, however, is unclear. Since improvement of HPA system deterioration has been demonstrated to be associated with treatment response, the question has arisen whether the course of therapy response as reflected by, for example, early improvement or response (after 1 or 2 weeks of therapy) is also based on HPA system dysfunction and whether the course of HPA regulation during treatment is only a state marker or has additional predictive implications for long-term outcome. In order to elucidate these questions a long-term study was carried out to investigate whether HPA system disturbance is associated (1) with the course of treatment response, predominantly early treatment response, during acute depression and (2) with the long-term course of depression, i.e. number of episodes. Twenty patients with affective disorders who participated in earlier controlled antidepressant treatment studies over 6 weeks were enrolled in an exploratory follow-up study. Using the combined DEX/CRH test it was demonstrated that (1) early improvement, early treatment response and beneficial treatment outcome after 6 weeks were associated with a lower HPA system activity and that (2) in long-term course of depression the HPA system deterioration increases in parallel with the number of previous episodes. These findings suggest that HPA system alterations are closely related to treatment response and long-term outcome of depression.