Anhedonia

The purpose of this study is to use smartphone technology to capture individual location emotional and cognitive data, to examine how real-world behaviors thoughts, emotions, and brain activity are related to one another.

This study is for adults with major depressive disorder (depression) who are currently taking an SSRI or SNRI antidepressant but continue to experience anhedonia (reduced interest or pleasure) and emotional blunting. The study will test whether a single 25 mg dose of psilocybin, compared with placebo, can improve these symptoms and improve the function of brain circuits involved in reward and motivation. Researchers will measure changes using brain imaging (fMRI) and clinical questionnaires, including the Dimensional Anhedonia Rating Scale (DARS).

The goal of this clinical trial is to learn if the proposed intermittent theta burst stimulation (iTBS) protocol can effectively improve anhedonia symptoms in depressed patients. The stimulation targets in our protocol include (1) dual-target stimulation at the left dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC). (2) single-target stimulation at the left DLPFC. The main questions it aims to answer are: * Whether iTBS of dual-target stimulation (left DLPFC and OFC) can improve the symptoms of anhedonia and better than single-target stimulation at the left DLPFC? * Whether iTBS of the dual targets of left DLPFC and OFC can improve the symptoms of anhedonia by correcting the abnormal functional connectivity of DLPFC-NAc and OFC-sgACC, regulating the functional abnormalities of NAc and sgACC, and indirectly repairing the overall dysfunction of the reward circuit. * Researchers will compare dual-target stimulation to single-target stimulation and sham dual-target stimulation (a dedicated sham coil is utilized which produces an identical audible click and physical sensation) to see if the proposed iTBS protocol works to treat anhedonia. Participants will: * Take 6 sessions of dual-target iTBS or single-target iTBS every day, for 5 consecutive days. * Visit our hospital at 1 week, 4 weeks, and 8weeks after the iTBS treatment completion, for clinical evaluation and brain image examination.

This prospective observational study evaluates the longitudinal changes in anhedonia levels and emotional eating behaviors among adult individuals initiating glucagon-like peptide-1 (GLP-1) receptor agonist therapy for weight loss. Participants are assessed at baseline (treatment initiation) and after a 6-month follow-up period using standardized psychometric instruments.

Anhedonia, the inability to seek-out and experience pleasure, is a common symptom in depression that predicts treatment-resistance and is sometimes exacerbated by first-line antidepressants. In our previous research, we found that anhedonia decreases goal-directed behavior and its related neural activity. In this study, we will investigate target engagement from five-consecutive days of stimulation for participants that are within a unipolar major depressive episode and also have high symptoms of anhedonia.

The goal of this clinical trial is to develop and test an app designed to reduce suicide risk and improve emotional well-being in adolescents. The study will test if the app's daily check ins and recommended mood boosting skills will improve the adolescent's overall mood and suicidality. The main question it aims to answer is: • Is the app practical and acceptable to use daily? In the study, adolescents will: * Participate in a focus group with other adolescents and provide feedback on the app itself (design, ease of use, etc.). * Complete surveys and assessments on their mood, thoughts, and experiences. * Complete assessments about their app experience. In the study, the legal guardian of the adolescent will: * Participate in a focus group with other adolescents and provide feedback on the app itself (design, ease of use, etc.). * Complete assessments about their app experience.

Major depressive disorder (MDD) is a serious condition that causes long-term symptoms such as feeling sad, losing interest in activities, and having thoughts of self-harm. Difficulty in making an effort is a key factor in functional impairment. Current methods to evaluate this difficulty use clinical assessments and computer-based tasks, but there is a gap between the measurements and real-life behavior. To address this, the study team proposes creating an instrumented behavioral test, HORMES, to objectively assess reduced motivation during everyday activities and measure physiological responses. The study will examine differences in brain activity, autonomic system function, and metabolic energy expenditure in patients with major depression during a decision-making task that involves physical effort.

This project will examine how multiple biological measures from the brain and the body's stress response system contribute to anhedonia (the loss of pleasure) in adolescence. The goal of this project is to see if it is possible to combine these biological measures to describe different patterns of activity in the brain and body that adolescents may have in response to stress. The main question this study aims to answer is whether different patterns of activity in the brain and body are related to whether adolescents develop anhedonia and how high or low levels of anhedonia are over time. This study will enroll 192 adolescents who are between 13 and 15 years. Adolescents will complete tasks three times: at the beginning of the study, 10 months after that, and then 10 months after that. In total, they will be part of the study for 20 months. At each time, adolescents will complete surveys, provide samples of spit to measure hormones and provide pictures of their brain to measure brain activity, participate in mildly stressful tasks, and complete different activities that measure how they think. The investigators will also ask each adolescent's parent or legal guardian to answer some surveys about themselves and their child.

Despite efforts to prevent suicide, US rates are climbing, and suicide is the second leading cause of death amongst youth. Digital tools, especially personal smartphones, are promising avenues to address these issues and can be used to increase engagement with effective interventions such as suicide safety planning. The BRITE suicide safety planning app was developed on evidence-based principles and has undergone rigorous formative development and effectiveness evaluations. However, to optimize its functionality, commercial viability, and scale its implementation, issues related to user engagement needed to be addressed. This 3 month Pragmatic Randomized Trial will evaluate the impact of the ViraSafe app-an enhanced version of the BRITE suicide safety planning app-on improving engagement with coping skills and safety planning among suicidal adolescents by comparing its intervention components to those of the original BRITE app.

The goal of this proposal is to provide a first assessment of the efficacy of our innovative non-invasive brain stimulation system, kTMP, in the treatment of anhedonia in MDD.

This project focuses on clinical translational research into personalized transcranial alternating current stimulation (tACS) for treating anhedonia in late-life depression (LLD). Key components include: (1) Optimizing individualized tACS treatment parameters through randomized, double-blind, controlled trials and establishing precise treatment protocols using deep learning algorithms; (2) Assessing the short-term (2 weeks) and long-term (3 months) efficacy of tACS on depressive symptoms and anhedonia using scales such as the HAMD, SHAPS, and DARS, while monitoring safety; (3) Integrating multimodal detection technologies (64-channel EEG, inflammatory factors/neurotransmitters, etc.) to elucidate the mechanisms by which tACS alleviates anhedonia through modulating prefrontal neural oscillations (y-band), improving synaptic plasticity (increased BDNF), and regulating neurotransmitters (5-HT, DA). This study will establish, for the first time, an individualized parameter system for tACS treatment of LLD, providing a novel non-pharmacological intervention strategy for clinical practice.

The study will adapt and deploy a digital Behavioral Activation app with mobile sensing, supported by health coaches, that encourages youth to engage in positive activities. The study has the potential to offer a low-cost and scalable behavioral intervention that may decrease risk of suicide among at-risk youth. This research will examine specifically whether an intervention involving an app called Vira, combined with health coaching (GET ActivE) can improve enjoyment for teens coping with depression. Research participants will be randomly assigned to one of two study intervention. One study intervention involves a) downloading an app called Vira and engaging by responding to a daily question, and b) participating in a conversation via text, phone, or messages through an appt with a health coach. The health coach will use the Vira app and principles from evidence-based therapy and behavior change to provide users with insights to sustain well-being and better manage risk factors for suicidal thoughts and behaviors such as depressed mood and behavioral withdrawal. The second study intervention involves downloading an app called EARS and responding to a daily question.

The purpose of this 10-week, double-blind, placebo-controlled study is to determine whether inflammation impacts reward and motor neural circuitry to contribute to depressive symptoms like anhedonia and psychomotor slowing in people with Human Immunodeficiency Virus (HIV) and depression. Sixty male and female patients with HIV who have depression, anhedonia and high inflammation and are stable on effective treatment for their HIV will be randomized to receive either the anti-inflammatory drug baricitinib or a placebo for 10 weeks. Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing, functional MRI (fMRI) scans, and optional spinal taps as part of the study.

The goal of this clinical trial is to investigate how transcranial direct current stimulation (tDCS) affects emotion functions in young adults aged 18-35 from the local community, including both male and female participants. The main question\[s\] it aims to answer are: * Does tDCS improve emotional functions, such as mood regulation and motivation, in individuals with subthreshold depression (StD)? * Can tDCS enhance emotional regulation compared to a sham stimulation (placebo)? Researchers will compare participants receiving tDCS on either the left dorsolateral prefrontal cortex (lDLPFC) or right ventrolateral prefrontal cortex (rVLPFC) with those receiving sham stimulation to see if tDCS has a stronger effect on emotional functions. Participants will: * Complete online and in-person screening to assess depressive symptoms using the Chinese version of the Beck Depression Inventory II (C-BDI-II) and be selected based on their depressive symptoms (C-BDI-II score ≥ 13). * Be randomly assigned to one of three groups: lDLPFC tDCS, rVLPFC tDCS, or Sham control group (1:1:1 ratio). * Receive 10 sessions of tDCS or Sham tDCS over 2 weeks, with each session lasting 20 minutes. * Complete assessments at baseline, post-intervention, 1-month follow-up, and 3-month follow-up, with each assessment lasting 2-2.5 hours. This includes questionnaires and perform emotional and cognitive tasks.

This proposal will examine the effects of estradiol administration on perimenopausal-onset (PO) anhedonia and psychosis symptoms as well as on brain function using simultaneous positron emission tomography and functional magnetic resonance imaging (PET-MR).

The purpose of this study is to identify how trauma-focused psychotherapy changes the function of brain circuitry in posttraumatic stress disorder (PTSD) and how this mediates improvements in the diminished ability to experience positive emotions following a traumatic or extremely stressful life event. In this instance, the investigators will be using cognitive processing therapy (CPT), a widely-utilized and evidence-based treatment for PTSD.

The project investigates long-term prognosis and predictors of treatment outcomes for difficult-to-treat depression in patients in secondary psychiatric care. The current patient cohort was collected in 2012-2021 in the study "Pharmacogenetics in patients with depression with specific focus on difficult-to-treat depression, suicide attempt and CYP2D6". The cohort consists of 415 patients, examined carefully regarding diagnostic assessment and earlier treatment. All participants were also genotyped for the drug metabolizing enzymes CYP2D6 and CYP2C19. Blood samples were stored in biobank for other analyses linked to prognostic markers. The patient cohort will now be followed up with a review of medical records and extraction of register data for a period of 5 years after their participation in the original study. The purpose of the study is to improve treatment and increase knowledge about long-term prognosis in difficult-to-treat depression. This is done by examining symptom profiles, monitoring clinical course and suicidality, and examining prognostic markers.

The investigators are conducting a clinical trial of therapy for public speaking anxiety. There are many eligibility criteria, but the main ones are that participants need to be socially anxious and have public speaking anxiety. In this clinical trial, all participants will do exposure therapy. Before doing exposure therapy in the study, though, participants will be randomized to do one of two treatments: i) a positive mood treatment, which is designed to increase how positive people feel, and ii) a relaxation treatment, which is designed to help people feel more relaxed. The investigators are doing this study to see whether doing the positive mood treatment or relaxation treatment first will affect how well exposure therapy works.

This observational study investigates the use of Esketamine Intranasal Spray in patients with Treatment-Resistant Depression in Real-World Settings. The study aims to evaluate the clinical outcomes, including efficacy and safety, of esketamine treatment. It also explores predictors of treatment response, focusing on biological pathways such as genetics, neuroimaging, and psychophysical measures. Additionally, the study examines how esketamine impacts patients' life functioning, including social and occupational aspects. The goal is to better understand who benefits most from esketamine and how it affects daily life, to improve personalized care for patients with difficult-to-treat depression.

The goal of this clinical trial is to systematically categorize potential prohedonic effects of psilocybin in patients with anhedonia in depression. The main questions it aims to answer are: Primary Objectives 1. Systematically categorize prohedonic effects (antianhedonic effects in patients with anhedonia in depression, increase in well-being in all participants). 2. Test effects of psilocybin on brain network complexity measures during the hedonic experience using fMRI as a correlate for prohedonic (anti-anhedonic and well-being increasing) effects. 3. Elucidate relevance of the psychedelic experience to these effects (clinical, behavioral, and imaging) in a pharmacological challenge using the 5-HT2A/D2 antagonist risperidone and extensive characterization of the psychedelic experience. Secondary Objectives 4. Test the differential effects of the psychedelic experience on fMRI paradigms measuring symptoms shown to be altered in anhedonia, more specifically reward processing and sexual arousal. 5. Test the relevance of neuroplasticity (BDNF) and inflammatory parameters to anti-anhedonic, well-being promoting, and brain network dynamic complexity effects. 6. Test the effects of the psychedelic experience on BDNF and inflammatory parameters. Researchers will compare the effects of psilocybin in two separate sessions (one with psilocybin alone, one with co-administration of risperidone) in both patients with depression and anhedonia and healthy control participants. Participants will: * Take 25 mg of psilocybin p.o. in two sessions, in one of the two sessions they will take 1 mg risperidone p.o. before ingestion of psilocybin, to block psilocybin's acute psychedelic effects. * Undergo 3 MRI sessions, one before the first psilocybin session ('baseline') and one session each on the day after each respective psilocybin session. * Perform a variety of tasks during each fMRI session to asses the treatment's effects on anhedonia.

Despite efforts to prevent suicide, US rates are climbing, and suicide is the second leading cause of death among youth. Digital tools, especially personal smartphones, are promising avenues to address these issues and can be used to provide a unique understanding of risk factors, including psychological distress, anhedonia and behavioral withdrawal, and sleep disturbance among high-risk individuals. This project aims to enhance the effectiveness of the delivery of preventative health care to youth at risk for suicide by developing a comprehensive digital platform that allows practitioners to integrate mobile sensing data and HIPAA-compliant client communication tools into their management of these young people.

The purpose of this study is to investigate whether transcranial direct-current stimulation (tDCS) will engage reward-related brain circuitry, more specifically the uncinate fasciculus (UF) tract, which connects the orbitofrontal cortex (OFC) and nucleus accumbens (NAcc) regions. Also to evaluate whether the changes in the fractional anisotropy (FA) of the UF tract are associated with changes of clinical symptoms of anhedonia and finally to investigate the moderation role of simulated electric fields (EFs) in an association between FA of the UF and symptoms of anhedonia.

The purpose of this 8-week, double-blind, placebo-controlled, study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Seventy male and female participants with depression, between 25-55 years of age, with higher levels of inflammation and anhedonia will be randomized to receive L-DOPA or matched placebo over 8 weeks. Participants will complete lab tests, medical and psychiatric assessments, motivation and motor tasks, and MRI scans as part of the study. The total length of participation is approximately 10 to 12 weeks.

The present study evaluates a two week ecological momentary intervention (EMI) in reducing anhedonia and psychological distress (i.e. elevated depression, stress and anxiety). Participants in the experimental group complete three daily exercises targeting reward-related processes, including positive mental imagery, savoring, gratitude, taking ownership for positive experience, and silver lining. These components were selected to improve reward anticipation as well as reward consumption and reward learning as the underlying mechanisms of anhedonia. An active control group receives progressive muscle relaxation training, matched in format and frequency. Exercise units are presented using audio recordings via smartphone app.

Research shows that high positive emotionality is an essential ingredient in building resilience in youngsters, especially those with a vulnerability to develop depressive symptomatology. It may empower them against actual depression and its various long-term adverse outcomes. One way to achieve positive emotions is via the recollection and anticipation of specific positive events. Therefore, to cultivate positive emotions in young people, a user-friendly group training program was developed, translated from basic research findings: Positive Event Training (PET). Through PET, adolescents learn to solidify positive memories and positive plans for the future. In this project, a comprehensive evaluation of PET's efficacy is conducted using a robust methodology with vulnerable youth.