Evaluating the effectiveness of a multi-component lifestyle therapy program versus psychological therapy for managing mood disorders (HARMON-E): protocol of a randomised non-inferiority trial.

BACKGROUND: Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despite some clinical guidelines endorsing the application of lifestyle therapies as a first-line treatment for individuals with mood disorders, there is limited evidence that this recommendation has been widely adopted into routine practice. A key obstacle is the insufficient evidence on whether lifestyle therapies match the clinical and cost effectiveness of psychological therapy, particularly for treating those with moderate to severe symptoms. The HARMON-E Trial seeks to address this gap by conducting a non-inferiority trial evaluating whether a multi-component lifestyle therapy program is non-inferior to psychological therapy on clinical and cost-effectiveness outcomes over 8-weeks for adults with major depressive disorder and bipolar affective disorder. METHODS: This trial uses an individually randomised group treatment design with computer generated block randomisation (1:1). Three hundred and seventy-eight adults with clinical depression or bipolar affective disorder, a recent major depressive episode, and moderate-to-severe depressive symptoms are randomised to receive either lifestyle therapy or psychological therapy (adjunctive to any existing treatments, including pharmacotherapies). Both therapy programs are delivered remotely, via a secure online video conferencing platform. The programs comprise an individual session and six subsequent group-based sessions over 8-weeks. All program aspects (e.g. session duration, time of day, and communications between participants and facilitators) are matched except for the content and program facilitators. Lifestyle therapy is provided by a dietitian and exercise physiologist focusing on four pillars of lifestyle (diet, physical activity, sleep, and substance use), and the psychological therapy program is provided by two psychologists using a cognitive behavioural therapy approach. Data collection occurs at baseline, 8-weeks, 16-weeks, and 6 months with research assistants blinded to allocation. The primary outcome is depressive symptoms at 8 weeks, measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) (minimal clinically important difference = 1.6). A pre-specified within-trial economic evaluation will also be conducted. DISCUSSION: Should lifestyle therapy be found to be as clinically and cost effective as psychological therapy for managing mood disorders, this approach has potential to be considered as an adjunctive treatment for those with moderate to severe depressive symptoms. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12622001026718, registered 22nd July 2022. PROTOCOL VERSION:  4.14, 26/06/2024.

Effects of cognitive training under hypoxia on cognitive proficiency and neuroplasticity in remitted patients with mood disorders and healthy individuals: ALTIBRAIN study protocol for a randomized controlled trial.

BACKGROUND: Cognitive impairment is prevalent across neuropsychiatric disorders but there is a lack of treatment strategies with robust, enduring effects. Emerging evidence indicates that altitude-like hypoxia cognition training may induce long-lasting neuroplasticity and improve cognition. We will investigate whether repeated cognition training under normobaric hypoxia can improve cognitive functions in healthy individuals and patients with affective disorders and the neurobiological underpinnings of such effects. METHODS: In sub-study 1, 120 healthy participants are randomized to one of four treatment arms in a double-blind manner, allowing for examination of separate and combined effects of three-week repeated moderate hypoxia and cognitive training, respectively. In sub-study 2, 60 remitted patients with major depressive disorder or bipolar disorder are randomized to hypoxia with cognition training or treatment as usual. Assessments of cognition, psychosocial functioning, and quality of life are performed at baseline, end-of-treatment, and at 1-month follow-up. Functional magnetic resonance imaging (fMRI) scans are conducted at baseline and 1-month follow-up, and [11C]UCB-J positron emission tomography (PET) scans are performed at end-of-treatment to quantify the synaptic vesicle glycoprotein 2A (SV2A). The primary outcome is a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference with minimum n = 26 per treatment arm. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data is analyzed with the FMRIB Software Library, while PET data is quantified using the simplified reference tissue model (SRTM) with centrum semiovale as reference region. DISCUSSION: The results will provide novel insights into whether repeated hypoxia cognition training increases cognition and brain plasticity, which can aid future treatment development strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06121206 . Registered on 31 October 2023.

Characteristic Changes of Prefrontal and Motor Areas in Patients with Type 2 Diabetes and Major Depressive Disorder During a Motor Task of Tai Chi Chuan: A Functional Near-Infrared Spectroscopy Study.

AIM: This cross-sectional study aims to identify the characteristic changes of prefrontal and motor areas during a tai chi chuan task in patients with Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) using wearable functional near-infrared spectroscopy (fNIRS). METHODS: Three parallel groups (T2DM with DD group, T2DM group, and healthy group) were recruited from December 10, 2022, to May 31, 2023. Participants in three groups conducted a motor task of tai chi chuan designed by Eprime 3.0, and fNIRS was used to monitor the brain activation, functional connectivity (FC), and lateralization of prefrontal and motor areas. Correlation analyses were performed to examine the relationship between depressive symptoms and the function of prefrontal and motor areas. RESULTS: Ninety elder adults (aged ≥ 60), including 30 patients with T2DM and MDD, 30 patients with T2DM, and 30 healthy subjects, were enrolled. In contrast with the patients with T2DM and healthy subjects, the patients with T2DM and MDD had decreased activation and abnormal lateralization in prefrontal and motor areas and decreased FC among supplementary motor area, motor area, and dorsolateral prefrontal cortex (DLPFC). Furthermore, the oxyhemoglobin (HbO2) concentration value of DLPFC in patients with T2DM and MDD was negatively associated with scores of Hamilton Depression Scale-24 (HAMD-24). CONCLUSIONS: Patients with T2DM and MDD had characteristic functional changes in prefrontal and motor areas. DLPFC may be a potential target of diagnosis and intervention for patients with T2DM and MDD.

Gut Microbiota and Mood Disorders: How Bottom-Up Techniques Can Improve Mental Health.

The microbiome is dynamic and changes with early development, environmental factors such as diet and antibiotics, and in response to disease. Recently, its role in psychiatric disorders has gained interest. A new class of probiotics, psychobiotics, has emerged as a non-toxic intervention for psychiatric conditions. The relationship between gut microbial metabolism and mental health is gaining attention, with the gut microbiome playing a role in major depressive disorder. Understanding the microbiota offers new therapeutic opportunities for various medical conditions.

Treatment for Depression in Patients Who Have Suffered from Early Life Stress.

BACKGROUND: People with Major Depressive Disorder (MDD) are far more likely to suffer from Early Life Stress (ELS) than the average population. This typically increases severity of symptoms, and often leads to treatment resistance. This study set out to examine which treatments work best to treat depression in patients who have suffered from ELS, as well as possible interactions between ELS and antidepressant effects in therapies. METHOD: A literature review was conducted in July 2020 using the databases Embase, PsychInfo, and MEDLINE. The search looked for clinical trials treating MDD with psychotherapies and pharmacotherapies with patients who suffered from ELS. Data regarding demographics, comorbidities, measurement tools, and outcomes (generally response rates and remission) were extracted. The data was compared according to treatment types. RESULTS: Cognitive Behavioural Therapy (CBT) had the best evidence for treating MDD in people with ELS. There was some mixed evidence for Interpersonal Therapy, SSRIs, and SNRIs as suitable treatments for MDD. There was also very promising but limited evidence for Cognitive Behavioural Analysis of System Therapy and combination treatments (pharmacotherapy and psychotherapy together). Nefazodone (a SARI) had the weakest evidence. CONCLUSIONS: CBT was the most effective treatment for MDD with ELS. However, more research needs to be conducted to ascertain a proper hierarchy of treatments, particularly with combination treatments.

Dose-dependent effects of transcranial photobiomodulation on brain temperature in patients with major depressive disorder: a spectroscopy study.

This study aimed to evaluate the dose-dependent brain temperature effects of transcranial photobiomodulation (t-PBM). Thirty adult subjects with major depressive disorder were randomized to three t-PBM sessions with different doses (low: 50 mW/cm2, medium: 300 mW/cm2, high: 850 mW/cm2) and a sham treatment. The low and medium doses were administered in continuous wave mode, while the high dose was administered in pulsed wave mode. A 3T MRI scanner was used to perform proton magnetic resonance spectroscopy (1H-MRS). A voxel with a volume of 30 × 30 × 15 mm3 was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing 1H-MRS spectrum chemical shift differences between the water (~ 4.7 ppm) and N-acetyl aspartate (NAA) (~ 2.01 ppm) peaks. After quality control of the data, the following group numbers were available for both pre- and post-temperature estimations: sham (n = 10), low (n = 11), medium (n = 10), and high (n = 8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (p-value range = 0.105 and 0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for t-PBM active groups, the lowest fluctuation (variance) was observed for the medium dose (σ2 = 0.29), followed by the low dose (σ2 = 0.47), and the highest fluctuation was for the high dose (σ2 = 0.67). t-PBM sham condition showed the overall lowest fluctuation (σ2 = 0.11). Our 1H-MRS thermometry results showed no significant brain temperature elevations during t-PBM administration.

Recognizing and Treating Major Depression in Fibromyalgia: A Narrative Primer for the Non-Psychiatrist.

Fibromyalgia (FM) affects 2% to 8% of the general population. FM patients often experience self-stigma and feel rejected by healthcare providers and families, resulting in isolation and distressing symptoms of pain, fatigue, and poor cognitive functioning, increasing the risk of depressive symptoms. Major Depressive Disorder (MDD) is the most common comorbidity in FM patients (Any depression: 43%; MDD: 32%). Genome-wide association studies (GWAS) have identified a common genetic risk loci for major depression and fibromyalgia. Given that even minor symptoms of depression worsen the outcomes of FM patients, clinicians are challenged to identify and manage depression in these patients. However, due to overlapping symptoms, limited screening, and contamination bias, MDD often goes undiagnosed and presents a critical challenge. Unrecognized and untreated MDD in FM patients can exacerbate fatigue, sleep disturbances, and pain, reduce physical functioning, and increase the risk of developing comorbid conditions, such as substance abuse and cardiovascular disease. These comorbidities are associated with a lower treatment response rate, a higher dropout rate, and a greater risk of relapse. Clinicians may effectively identify and treat MDD in FM patients with appropriate pharmacologic agents combined with aerobic exercise and cognitive-behavioral therapies for core FM symptoms, thus significantly reducing symptom severity for both MDD and FM. Such a comprehensive approach will result in a much-improved quality of life. MedLine content was searched via PubMed to identify eligible articles between 1995 and 2023 using search terms fibromyalgia, major depressive disorder, and treatment of depression in fibromyalgia, and the most current information is presented. In this primer for clinicians caring for FM patients, we describe clinically relevant pharmacologic and non-pharmacologic management approaches for treating MDD in FM patients.

Originalbeiträge (Originals). Patientencharakteristika an einer psychodynamischen Ausund Weiterbildungsambulanz.

Patient characteristics at a psychodynamic training institute Outpatient clinics affiliated with psychotherapeutic training institutions play a crucial role in ensuring the quality of future psychotherapists' training. OBJECTIVE: In the present study we examined the characteristics of patients in terms of symptomatology and psychodynamic dimensions. METHODS: The study utilized online questionnaires completed by n = 421 patients between September 2020 and March 2021. These questionnaires gathered information on sociodemographics, symptomatology (PHQ-D), relationship dynamics (IIP), personality functioning (OPD-SQS, IPO-16), and intrapsychic conflicts (OPD-KF). RESULTS: The sample consisted of 71.0 % females, with 65 % having prior experience with psychotherapeutic treatments. Notably, 74.9 % of the patients fulfilled the criteria of a depressive disorder in PHQ-D (with 34.8 % identified as Major Depressive Disorder, MDD). Additionally, 53.1 % of all patients surpassed the threshold for the diagnosis of a personality disorder based on the IPO-16. DISCUSSION: Findings suggest that patients seeking treatment at these clinics exhibit significant psychological distress and often have a history of prior psychotherapeutic interventions.

Strategies to overcome mental health stigma: Insights and recommendations from young people with major depressive disorder (MDD).

BACKGROUND: Young people with depression are met with stigma related to their mental health, which exacerbates loneliness, social isolation, and depression symptoms. While disclosing depression could improve one's mental health, stigma can also make social interactions more challenging and reduce the likelihood of receiving treatment. This research explored young people's experiences with stigma and recommendations for addressing it. METHODS: Semi-structured interviews conducted with N = 35 young people aged 18-25 years (Mage = 20.09) were analyzed with thematic analysis. Participants met the criteria for clinical depression using the Mood and Feelings Questionnaire (score >27) or had recently obtained a medical diagnosis (N = 18) of depression by a medical professional. RESULTS: Participants faced stigma when deciding to disclose their depression, which fed into a vicious cycle influencing feelings of loneliness, social isolation, and withdrawal. Their recommendations for others to avoid this cycle can be summarized under three main themes: (1) Social affirmation: identify allies and build meaningful connections; (2) Self-affirmation: build a constructive relationship with the self; and (3) Societal affirmation: structural changes are needed. CONCLUSIONS: The current research indicates that social, self-, and societal affirmation are considered important for reducing the detrimental impacts of stigma. Policies and programs are needed that provide mental health support to young people, and public awareness campaigns that guide young people to appropriate resources (i.e., support and intervention) via governmental public health bodies.

Acupuncture and Escitalopram for Treating Major Depression Clinical Study (AE-TMDCS): protocol for a factorial randomised controlled trial.

INTRODUCTION: Major depressive disorder (MDD), the second leading cause of disability globally, is considered to be associated with a consequent deterioration in the quality of life and can lead to a major economic burden on medical service and suicide-related costs. Previous research has shown that acupuncture may be beneficial for treating MDD. However, there is a lack of rigorous evidence from previous studies comparing acupuncture with antidepressant medications. This study aims to assess the therapeutic potential of acupuncture in the management of depressive disorders. METHODS AND ANALYSIS: A multicentre, randomised, participant-blind, sham-controlled, 2×2 factorial clinical trial, Acupuncture and Escitalopram for Treating Major Depression Clinical Study, aims to compare the efficacy of acupuncture versus escitalopram in treating depression. This study will be conducted at three hospitals in China, enrolling 260 patients with moderate-to-severe major depression, as defined by DSM-5 criteria and Hamilton Depression Rating Scale (HDRS-17) Scores above 17. Participants will be randomly assigned in equal proportions to one of four groups (acupuncture/escitalopram, sham acupuncture/escitalopram, acupuncture/placebo and sham acupuncture/placebo) and undergo 30 sessions across 10 weeks. The primary outcome is change in HDRS-17 Score and secondary outcomes include BDI, Clinical Global Impression, Generalised Anxiety Disorder-7 and Mini-Mental State Examination Scores, alongside potential biological markers. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the Ethics Committees of the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine (2023-7th-HIRB-020), Shanghai Mental Health Centre (2022-86) and Shanghai Pudong New Area Hospital of Traditional Chinese Medicine (2023-003). Informed consent will be obtained from all participants. The study's findings are intended for publication in a scholarly journal. TRIAL REGISTRATION: NCT05901571.

Induce Pluripotent Stem Cells (iPSC) Technology in Depression.

Induced pluripotent stem cells (iPSCs) are a promising in vitro model for drug-screening and precision-based psychiatry for the treatment of major depressive disorders (MDD). In this chapter, we explore different uses for iPSC technology, three-dimensional (3D) organoids models, and mesenchymal stem cells therapy in MDD, as well their potential and limitations.

Probiotics and Fecal Microbiota Transplantation in Major Depression: Doxa or Episteme?

In the human body, eukaryotic somatic cells and prokaryotic microorganisms live together. In this state, the body can be viewed as a "superorganism." Symbiotic life with commensal microorganisms can be observed in almost every part of the body. Intestinal microbiota plays an important role in health and disease, and in shaping and regulating neuronal functions from the intrauterine period to the end of life. Microbiota-based treatment opportunities are becoming more evident in both understanding the etiopathogenesis and treatment of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first choice in the treatment of depression, also have antimicrobial and immunomodulatory mechanisms of action. From these perspectives, direct probiotics and fecal microbiota transplantation are treatment options to modulate microbiota composition. There are few preclinical and clinical studies on the effectiveness and safety of these applications in depression. The information obtained from these studies may still be at a doxa level. However, the probability that this information will become episteme in the future seems to be increasing.

Application of Transcranial Direct and Alternating Current Stimulation (tDCS and tACS) on Major Depressive Disorder.

The exploration of brain stimulation methods offers a promising avenue to overcome the shortcomings of traditional drug therapies and psychological treatments for major depressive disorder (MDD). Over the past years, there has been an increasing focus on transcranial electrical stimulation (tES), notably for its ease of use and potentially fewer side effects. This chapter delves into the use of transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), which are key components of tES, in managing depression. It begins by introducing tDCS and tACS, summarizing their action mechanisms. Following this introduction, the chapter provides an in-depth analysis of existing meta-analyses, systematic reviews, clinical studies, and case reports that have applied tES in MDD treatment. It also considers the role of tES in personalized medicine by looking at specific patient groups and evaluating research on possible biomarkers that could predict how patients with MDD respond to tES therapy.

Repetitive Transcranial Magnetic Stimulation (rTMS) in Major Depression.

Major depressive disorder (MDD) is a psychiatric disorder with several effective therapeutic approaches, being antidepressants and psychotherapies the first-line treatments. Nonetheless, due to side effects, limited efficacy, and contraindications for these treatments, alternative treatment options are required. Neurostimulation is a non-pharmacological and non-psychotherapeutic approach that has been under study for diverse neuropsychiatric conditions in the form of electrical or magnetic stimulation of the brain. Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulation method designed to generate magnetic fields and deliver magnetic pulses to stimulate the brain cortex. The magnetic pulses produce electrical currents in the brain which are not intense enough to provoke seizures, differentiating this method from other forms of neurostimulation that produce seizures. Although the exact rTMS mechanisms of action are not completely understood, rTMS seems to cause its beneficial effects through changes in neuroplasticity. Devices and protocols for rTMS are still evolving, becoming more efficient over time. There are still some challenges to be addressed, including further refinement of parameters (coil/device type, location, intensity, frequency, number of sessions, and duration of treatment); treatment cost and burden for patients; and treatment resistance. However, the efficacy, tolerability, and safety of some rTMS protocols have been demonstrated in different double-blind sham-controlled randomized controlled trials and meta-analyses for treatment-resistant depression.

Combining Complementary and Alternative Medicine (CAM) with Conventional Treatments for Major Depressive Disorder.

For many of the complementary and alternative (CAM) medicine methods, it is biologically plausible to expect that they could provide additional benefits in the treatment of major depressive disorder (e.g., enhanced initial response, augmentation, and tolerability) when combined with conventional treatments. Although most likely not comprehensively, herein we critically review current explicit clinical data pertaining to the most extensively evaluated CAMs in this setting: physical activity/exercise, mind and body methods, acupuncture, light therapy, diet, probiotics, various nutrients, and herbal preparations. While the absolute amount of data is enormous, the number of reliable primary studies (randomized controlled trials) and, particularly, meaningful meta-analyses of such studies are very limited. Consequently, the certainty of evidence about benefit or no benefit is very low for each of the addressed CAMs.

Electroconvulsive Therapy (ECT) in Major Depression: Oldies but Goodies.

Electroconvulsive therapy is one of the useful treatment methods for symptom improvement and remission in patients with treatment-resistant depression. Considering the various clinical characteristics of patients experiencing depression, key indicators are extracted from structural brain magnetic resonance imaging, functional brain magnetic resonance imaging, and electroencephalography (EEG) data taken before treatment, and applied as explanatory variables in machine learning and network analysis. Studies that attempt to make reliable predictions about the degree of response to electroconvulsive treatment and the possibility of remission in patients with treatment-resistant depression are continuously being published. In addition, studies are being conducted to identify the correlation with clinical improvement by taking structural-functional brain magnetic resonance imaging after electroconvulsive therapy in depressed patients. By reviewing and integrating the results of the latest studies on the above matters, we aim to present the usefulness of electroconvulsive therapy for improving the personalized prognosis of patients with treatment-resistant depression.

Acceptance and Commitment Therapy for Major Depressive Disorder: Navigating Depression Treatment in Traditional and Digital Settings with Insights from Current Research.

Given the shortcomings of a mechanistic assumption of traditional cognitive behavioral therapy (CBT), a newer generation of CBT-grounded interventions focusing on process-orientated emotional and motivational aspects has emerged. These so-called third-wave CBTs emphasize function and context of inner experience over form and content, and have become evidence-based practice in the past four decades. Among these approaches, acceptance and commitment therapy (ACT) has both a large body of research for various (mental) health conditions, including major depressive disorder (MDD) in particular. ACT is a transdiagnostic approach that intends to increase psychological flexibility (PF) of clients as a universal mechanism of behavior change and a value-driven orientation in life. By focusing on present-moment awareness, acceptance, defusion, establishing a stable sense of self, clarifying personal valued life directions, and committing to behaviors consistent to these values, ACT targets the core processes of PF. Meta-analyses have indicated the efficacy and effectiveness of ACT in reducing depressive symptoms and increasing well-being, with mainly moderate effect sizes in clinical trials. ACT for MDD has been shown to be effective across different delivery modes (e.g., individual, group, digital). ACT can also be applied using self-help formats (e.g., mobile apps) and combined with features from compatible approaches like behavioral activation. There is also evidence for a high acceptability of ACT and adherence rates comparable to classic CBT. Moreover, process research has shown that ACT works specifically through the mediator of PF and by addressing its suggested core therapeutic processes. Given the essential role of offering a personalized therapeutic strategy in treatment outcomes and adherence, it is central to provide more effective options that match clients' needs and preferences. This chapter illustrates different applications of ACT for adults with MDD and the current evidence base to promote informed decisions on using ACT as additional or stand-alone therapeutic approach.

Biomarker-Guided Tailored Therapy in Major Depression.

This chapter provides a comprehensive examination of a broad range of biomarkers used for the diagnosis and prediction of treatment outcomes in major depressive disorder (MDD). Genetic, epigenetic, serum, cerebrospinal fluid (CSF), and neuroimaging biomarkers are analyzed in depth, as well as the integration of new technologies such as digital phenotyping and machine learning. The intricate interplay between biological and psychological elements is emphasized as essential for tailoring MDD management strategies. In addition, the evolving link between psychotherapy and biomarkers is explored to uncover potential associations that shed light on treatment response. This analysis underscores the importance of individualized approaches in the treatment of MDD that integrate advanced biological insights into clinical practice to improve patient outcomes.