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About This Study

Objectives: To identify in patients with major depression different peripheral markers of neuroinflammation in relation to affective symptoms (anxiety, depression, irritability), fatigue and cognitive symptoms; and its relationship with the response to antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs). Methodology: This is a prospective observational cohort study in patients with major depression naturally subjected to treatment with SSRIs. For this, 30 patients with major depression attended in the Outpatient Psychiatry Consultations will be selected. All of them will be evaluated at baseline and after 3 months of treatment, collecting demographic and clinical variables, Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) psychiatric diagnoses, psychopathological scales and immunological and biochemical variables. The correlation between immunological markers and affective and cognitive symptoms at baseline, as well as their variation with treatment, will be analyzed. A group of 20 healthy subjects will be used as a control group. Subsequently, a bivariate comparative analysis will be carried out, where the statistically significant or marginally significant variables associated with psychopathological variables will be used to build a multivariate binary logistic regression model.

Design

Interventions / Regimen

• Drug: SSRI — Outpatients with a diagnosis of major depression in the Psychiatry Outpatient Clinics will be evaluated for recruitment. * Recruitment visit: It will be carried out by one of the psychiatrists participating in the study. The patient will be informed about the study and written consent will be requested. Subsequently, the inclusion and exclusion criteria will be reviewed, and all demographic and clinical variables will be collected. * Baseline visit: One of the psychiatrists will interview the patient and apply the semi-structured clinical interview and the psychopathological evaluation questionnaires. In addition, a blood draw will be performed for serum collection, spectral cytometric analysis of lymphocyte subpopulations and obtaining peripheral blood mononuclear cells (PBMCs). * Follow-up visit after 3 months of treatment: Clinical variables will be collected and the same procedures will be performed as during the baseline visit. Not in the control group.

Primary Outcomes

• Treatment Response (3 months)

About This Study

This study tests a new way to help reduce anxiety in hospitalized patients waiting for therapeutic gastrointestinal (GI) endoscopy procedures, like EMR or ESD. Anxiety before these procedures is common and can make preparation harder, increase medication needs, and affect recovery. We compare standard ward checks (twice a day) to enhanced checks (four times a day) with structured talks and simple relaxation exercises. The goal is to see if the enhanced approach lowers anxiety levels, measured by a standard scale called the Hamilton Anxiety Rating Scale (HAM-A), from baseline to 24 hours before the procedure. Who can join? Adults (18+) scheduled for inpatient GI endoscopy with at least 2 days hospital stay and mild anxiety. Exclusions include emergencies or severe mental health issues. The study is done in hospital wards, with groups assigned by ward periods to keep it real-world. Benefits may include less anxiety and better experience; risks are low as it's just more supportive talks. Participation is voluntary with informed consent. Results could improve hospital care routines.

Design

Interventions / Regimen

• Behavioral: Enhanced Ward-Round Frequency With Standardized Communication — In intervention wards/periods, the care team conducts four brief, structured ward-round contacts per day (morning, noon, afternoon, and a bedtime contact not later than 21:30), each lasting approximately 3-5 minutes. Each contact uses a standardized communication script that addresses patient concerns, provides concise procedure-related education, and includes a 2-3 minute relaxation/breathing exercise; for lower GI procedures, a bowel preparation checklist is reviewed and an information card is issued/verified. Delivery starts at enrollment and continues through 24-48 hours post-procedure or until discharge, whichever comes first. Staff receive standardized training; fidelity is monitored via daily checklists with an adherence target of ≥85%. Usual clinical care remains available at all times.
• Behavioral: Usual Care Ward Rounds (2/day) — Routine ward rounds twice daily (morning and afternoon) according to standard hospital practice, without additional rounds, the standardized communication script, relaxation exercise, or the structured bowel preparation checklist beyond usual education. Applied from enrollment through 24-48 hours post-procedure or until discharge, whichever comes first. Any clinically necessary deviations are permitted and recorded as protocol deviations; all other aspects of care follow standard pathways.

Primary Outcomes

• Change in Hamilton Anxiety Rating Scale (HAM-A) Score (Baseline and 3 hours (±1 hours) before scheduled endoscopy procedure (assessed up to 14 days after enrollment))

About This Study

To examine the effectiveness and clinical care outcomes of cognitive-behavioral therapy interventions at Massachusetts General Hospital (MGH).

Design

Interventions / Regimen

• Behavioral: Cognitive behavioral therapy (CBT) — The participant will then undergo a structured clinical interview with a supervised psychology intern/fellow, which will take approximately 1-3 hours over the course of 1-3 sessions. The initial assessment will be followed by up to 24 sessions of cognitive behavioral therapy tailored to their particular diagnosis (most diagnoses/problems require approximately 12 sessions, some require fewer, others require more). The length of treatment will depend on the primary diagnosis/ problem and the complexity and severity of the case. The clinician and patient will agree on a treatment plan after the initial evaluation, targeting a particular mental health or health related behavioral problem with Cognitive Behavioral Therapy. This treatment plan will include an agreed upon number of treatment sessions (up to 24).

Primary Outcomes

• The Schwartz Outcome Scale (SOS-10) (at baseline, and at visits 1 through 24, which will occur approximately 1 week apart.)

About This Study

This study will recruit 30 subjects diagnosed with Major Depressive Disorder (MDD). Subjects will be recieve one infusion treatment of citalopram or placebo and 10 treatments of a form of transcranial magnetic stimulation, theta burst stimulation (TBS). Subjects will also undergo brain scans, quantitative electroencephalography (qEEG) brain activity recordings, and mood surveys. Study activities will be performed over the course of 4 weeks.

Design

Interventions / Regimen

• Drug: Placebo — saline PBO will be administered intravenously using established clinical procedures. A single dose if saline PBO will be delivered intravenously under double-blind conditions via pump over a 40-minute period.
• Device: intermittent theta burst stimulation — 10 sessions of treatment with cTBS to right DLPFC TBS consists of three TMS pulses given at 50 Hz, with this triplet repeated at a frequency of 5 Hz (every 200 ms). iTBS paradigm of a 2 s train repeated every 10 seconds
• Drug: intravenous citalopram hydrochloride (CIT) — CIT will be administered intravenously using established clinical procedures. A single 40 mg dose of CIT diluted in 60 cc normal saline will be delivered intravenously under double-blind conditions via pump over a 40-minute period.
• Device: continuous theta burst stimulation — 10 sessions of treatment with iTBS to left or cTBS to right DLPFC TBS consists of three TMS pulses given at 50 Hz, with this triplet repeated at a frequency of 5 Hz (every 200 ms). 1800 pulses of cTBS will be delivered

Primary Outcomes

• Percent change in Hamilton Depression Scale (through study completion, an average of 10 days)

About This Study

The goal of this clinical trial is to assess the effect of commercial multi-strains psychobiotics supplementation as an ad-on therapy on depressive symptoms and metabolic syndrome components (HDL-C, FPG, TGs, WC, BP) in adult depressed patients with pre-metabolic syndrome and metabolic syndrome. The second goal is to explore the effect of commercial multi-strains psychobiotics supplementation on the anthropometric measurement (weight, body mass index (BMI)) in adult depressed patients with pre-metabolic syndrome and metabolic syndrome. The main questions they aim to answer are: * Will commercial multi-strains psychobiotics supplementation help to ease depressive symptoms as an ad-on therapy in patients with pre-metabolic syndrome and metabolic syndrome? * Will commercial multi-strains psychobiotics supplementation improve anthropometric measurements and metabolic syndrome components (WC, FPG, BP, TGs, HDL-C) in depressed patients? Researchers will compare psychobiotics to a placebo (a look-alike substance that contains no drug) to see if psychobiotics work to improve depression and metabolic syndrome components. Participants will: * Be examined for depression, anxiety, and metabolic syndrome components (waist circumference, diabetes, blood pressure, triglycerides, and high-density lipoprotein). * Be asked to conduct laboratory tests to determine the inclusion and exclusion criteria. * Be given probiotics/ placebo to consume every day for 3 months (12 weeks). * Repeat the examination and laboratory tests to determine the results. * Be followed up weekly for adverse events and to insure their compliance with the study instructions. * Be followed up after 4 weeks as an end-visit and will conduct the examination and the laboratory blood tests.

Design

Interventions / Regimen

• Dietary Supplement: Winclove's Ecologic® Barrier Probiotics — The investigational product is a multispecies probiotic formulation consisting of 9 selected probiotic strains: the following bacterial strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and Lactococcus lactis W58.
• Dietary Supplement: Winclove's Ecologic® Barrier Probiotics Placebo — The placebo is composed of the carrier of the probiotic product that are identical in physical appearance, it includes maize starch and maltodextrins but contains no bacteria.

Primary Outcomes

• Psychological Assessment (depression1) (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)
• Psychological Assessment (depression2) (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)
• Psychological Assessment (Anxiety) (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)
• Anthropometric Measurements (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)
• Metabolic Syndrome Components (Waist circumference) (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)
• Metabolic Syndrome Components (Medical Assessments/ Laboratory Tests) (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)
• Metabolic Syndrome Components (Medical Assessments/ Blood Pressure) (at baseline, after the end of the 12th week of the intervention, and after 4 weeks post-intervention follow-up (end visit).)

About This Study

This implementation research project aims to test the effectiveness and implementation outcomes of suicide safety planning along and a transdiagnostic cognitive behavioral intervention for suicide prevention on decreasing suicidal behaviors in secondary school students in Mozambique. This study will also result in hypothesized mechanisms of intervention effects, costs and cost-effectiveness.

Design

Interventions / Regimen

• Behavioral: Safety Planning Intervention — All behavioral interventions will be provided by a trained nonspecialist healthcare worker, descriptions of each intervention can be found under treatment arm/group descriptions.
• Behavioral: Enhanced Usual Care — All behavioral interventions will be provided by a trained nonspecialist healthcare worker, descriptions of each intervention can be found under treatment arm/group descriptions.
• Behavioral: Transdiagnostic Cognitive Behavioral Therapy for Suicide Prevention — All behavioral interventions will be provided by a trained nonspecialist healthcare worker, descriptions of each intervention can be found under treatment arm/group descriptions.

Primary Outcomes

• Suicidal Behavior (6-months post intervention)

About This Study

This prospective, open-label clinical trial aims to compare a novel "Venous Tourniquet with Regional Low-Dose Sugammadex" method against the gold standard "Arterial Tourniquet" (Isolated Forearm Technique - IFT) for monitoring motor seizure activity during Electroconvulsive Therapy (ECT). Using a within-subject (intra-individual) design, each of the 40 enrolled patients will receive an arterial tourniquet on one arm and a venous tourniquet on the other arm simultaneously. The study will evaluate clinical efficacy in observing motor seizures, comparing the duration and visibility between the two limbs of the same patient, as well as assessing overall patient comfort and hemodynamics.

Design

Interventions / Regimen

• Device: Device: Arterial Tourniquet — Within the same patient, the arm without intravenous access is fitted with an arterial tourniquet (\>250 mmHg or 100 mmHg above systolic BP) before the systemic administration of 0.6 mg/kg rocuronium.
• Device: Device: Venous Tourniquet — Within the same patient, the arm with intravenous access receives a venous tourniquet (elastic or 70 mmHg) after systemic rocuronium administration, followed by a regional IV injection of 0.3 mg/kg sugammadex (diluted in 20 ml saline) into that specific limb.
• Drug: Sugammadex — Regional IV injection of 0.3 mg/kg sugammadex into the experimental limb.

Primary Outcomes

• Motor Seizure Duration (From the initiation of the ECT electrical stimulus until the complete cessation of visible motor seizure activity in the limbs, assessed up to a maximum of 5 minutes.)

About This Study

This is a single-site open-label clinical trial of fMRI-guided accelerated intermittent theta burst stimulation. The goal of this clinical trial is to learn if a new form of transcranial magnetic stimulation (TMS)-known generally as accelerated intermittent theta burst stimulation (aiTBS)-is effective as a first-line therapy in treating adolescents aged 13-20 years-old in their first episode of depression who have not undergone a full course of depression treatment prior to starting the trial and who remain antidepressant-free throughout the trial. The main questions this trial aims to answer are: * Does aiTBS relieve symptoms of depression as a first-line therapy in adolescents? * Is aiTBS a feasible option as a first-line treatment for adolescent depression? Researchers will measure the depression symptoms in adolescent participants before and after aiTBS. Parents of the adolescent participant will also participate in the study providing information about their experience and preference for TMS as a first-line treatment. Adolescent participants will: * Remain antidepressant-free throughout the study period of 6-7 weeks. * Receive an fMRI of their head for precision targeting * Receive 5 days of aiTBS

Design

Interventions / Regimen

• Device: MagPro X100 edition (MagVenture, Skovlunde, Denmark) — 10 daily sessions (50 total over 5-days) of aiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).
• Device: MagPro X100 edition (MagVenture, Skovlunde, Denmark) — 5 daily sessions (25 total over 5-days) of aiTBS (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds) guided by MNS, delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).

Primary Outcomes

• Childhood Depression Rating Scale-Revised (CDRS-R) Remission Rates (Baseline, One Month Follow Up Visit)
• Childhood Depression Rating Scale-Revised (CDRS-R) Remission Rates (Baseline, One Month Follow Up Visit)

About This Study

This study aims to evaluate the effectiveness of a 12-session cognitive-behavioral transdiagnostic protocol for Spanish children aged 8 to 12 within an educational context, Super Skills for Life. The program, designed to enhance emotional management and social interaction skills, will be delivered in a group format and supplemented with multimedia materials. The study will compare outcomes between an intervention group and a wait-list control group.

Design

Interventions / Regimen

• Behavioral: Super Skills Schools — Super Skills Structured and manualized intervention with a manual for the therapist and a workbook for the children. The intervention will be administered by Super Skills-trained clinical psychologists. Sessions will take place once a week for twelve weeks, with each session lasting approximately fifty minutes. The program includes emotional education and social skills training. These contents are learned through playful exercises, activities, readings and role-playing. The intervention modality will be face-to-face.

Primary Outcomes

• Social Skills Questionnaire (SSQ) (Pupil Version) (Baseline)
• Social Skills Questionnaire (SSQ) (Pupil Version) (Immediately after the intervention)
• Social Skills Questionnaire (SSQ) (Pupil Version) (6 months after the intervention)
• Social Skills Questionnaire (SSQ) (Pupil Version) (12 months after the intervention)
• The Positive and Negative Affect Schedule for Children-Short Form (PANAS-C-SF) (Baseline)
• The Positive and Negative Affect Schedule for Children-Short Form (PANAS-C-SF) (Immediately after the intervention)
• The Positive and Negative Affect Schedule for Children-Short Form (PANAS-C-SF) (6 months after the intervention)
• The Positive and Negative Affect Schedule for Children-Short Form (PANAS-C-SF) (12 months after the intervention)

About This Study

The objective of this study is to evaluate the safety, tolerability, and preliminary efficacy of the Motif XCS System when used as indicated for treatment-resistant depression (TRD).

Design

Interventions / Regimen

• Device: Motif XCS System — The Motif XCS System is a programmable device that delivers stimulation through surface electrodes implanted in a burr hole in the skull, positioned over the left DLPFC, without penetrating the dura.

Primary Outcomes

• Incidence of device and/or procedure-related adverse events (AEs) (During procedure to 12 months follow-up)

About This Study

Background: We aim to examine the effectiveness of Learning Through Play and Cognitive Behaviour Therapy (LTP+CaCBT), a culturally appropriate psychosocial intervention to address postnatal depression among Nigerian women and improve the well-being of their children. Women of reproductive age (ages 16 to 49) comprise about 60 million of Nigeria's 230 million people. About 30% of these mothers experience postnatal depression. The global health challenge our research addresses is that one in three women worldwide experience postnatal depression and suicidal thoughts after childbirth, with long-term negative consequences on their children and families. Since 30% of Nigerian mothers suffer from postnatal depression, they have significant risks of transferring intergenerational mental health problems to their children. Over 250 million children are at risk of lacking developmental support in low- or middle-income countries, including Nigeria, due to postnatal depression, and this limits the children from reaching their full potential in life. The treatment gap for postnatal depression in Nigeria is huge due to a shortage of mental health specialists. Culturally appropriate, nonspecialist-delivered interventions are very limited in Nigeria. Our proposal aims to address this gap in treating postnatal depression using non-specialists called Indigenous Community Health Workers (CHWs), who are more culturally knowledgeable, as the World Health Organisation recommended in their task-shifting strategy. Methods: We will evaluate the treatment, costs and implementation outcomes of LTP+CaCBT with 432 depressed mothers. Eligible participants (mother-child pairs) will be randomly selected to receive LTP+CaCBT and Treatment As Usual (TAU) or TAU alone. Our LTP+CaCBT intervention is a manualised 12-session (90-minute each) of mother-child play activities delivered in-person by CHWs under the supervision of clinical psychologists/psychiatrists. The eligible mothers (aged 16-49 years who have children between ages 0-36 months) will be assessed for depression before the intervention and then again at 4 months and 6 months afterwards. We will conduct interviews and focus group discussions to understand participants' and CHWs' experiences of the intervention

Design

Interventions / Regimen

• Behavioral: Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) — LTP+CaCBT has two components. LTP is underpinned by Piaget's theory of cognitive development and Bowlby's theory of attachment. The CBT component uses active listening techniques, changing negative thinking, and guided discovery (i.e., Socratic questioning style to gently probe for cultural beliefs on mental health and stimulate alternative positive thinking). This includes a culturally adapted pictorial calendar devised for women, depicting successive stages of child well-being from 0-3 years, with illustrations of mother-child play and other culturally relevant activities that promote healthy parenting and mother-child attachment.
• Drug: Treatment as Usual (TAU) — TAU is the routine care currently available for the treatment of postnatal depression at the health care sites of intervention (e.g. diagnosis, management, antidepressant prescription and/or other forms of mental health care).

Primary Outcomes

• Change in postnatal depression is being assessed (Change is being assessed from baseline, end of intervention at 4 and at 6 months post-intervention)

About This Study

The goal of this clinical trial is to investigate the effects of ketamine, in combination with standard inpatient addiction therapy, for adults with depression and alcohol use disorder. After screening and enrollment, participants will undergo baseline assessments of depression, measures of alcohol use and craving, as well as neurocognitive function. Participants will then be randomized to either ketamine (intervention) or midazolam (control). All participants will be admitted for standard inpatient addiction therapy while receiving ketamine or midazolam. Measures on safety, depression and alcohol use disorder will be repeatedly assessed during and after treatment. Final follow-up assessment is scheduled 6 months after baseline assessment.

Design

Interventions / Regimen

• Drug: Ketamine Hydrochloride — Four single-doses, given two times per week for two weeks Dose: 0,8 mg/kg body weight Route of administration: intravenous infusions over 40 minutes
• Drug: Midazolam Hydrochloride — Four single-doses, given two times per week for two weeks Dose: 0,02 mg/kg body weight Route of administration: intravenous infusions over 40 minutes

Primary Outcomes

• Depression (Within 3 days after final treatment session)

About This Study

Anxiety and depression are highly prevalent mental health disorders that impose a significant burden on individuals and public health systems worldwide (GBD 2019 Mental Disorders Collaborators, 2022). Although many existing treatments focus on symptom reduction through targeting negative emotions, fewer interventions specifically enhance positive emotional experiences, despite growing evidence that low positive affect is a key feature of both anxiety and depression. Face-to-face psychologist-led positive affect therapy (PAT) is a promising intervention that aims to cultivate positive emotions, engagement, and meaning, potentially leading to greater improvements in emotional well-being than traditional approaches (Craske et al., 2019). However, empirical evaluations of digitally-delivered, asynchronously-coached, scalable versions of the PAT remain limited (Craske et al., 2024; Firth et al., 2017). The present study thus aims to investigate the comparative efficacy of a digital positive affect intervention (PAI) in reducing symptoms of anxiety and depression and enhancing overall mental health outcomes. We utilize a two-arm randomized controlled trial (RCT) design to investigate the effectiveness of a six-week digitally delivered positive affect intervention (vs. self-monitoring active control; Zainal \& Newman, 2023) in reducing self-reported symptoms of anxiety and depression, as well as other secondary psychosocial outcomes, including sleep quality, quality of life, and emotion regulation. The treatment program comprises weekly evidence-based therapeutic material delivered online, and daily mental health (MH) mobile application prompts delivered thrice a day for the 6-week treatment period, based on evidence-based positive affect therapy principles. The active comparator comprises self-monitoring MH mobile application prompts for the 6-week treatment period. All participants will be assessed on several psychosocial outcomes at mid-treatment, post-treatment, and at 3-, 6-, and 12-month follow-up. The study hypothesizes that participants randomized to the digital PAI will experience greater improvement in anxious and depressive symptoms both immediately after treatment and up to a year later, compared to the self-monitoring MH app. Findings will contribute to growing evidence that digital PAI is an efficacious and feasible treatment to target and enhance positive emotions and related mental health outcomes in adults experiencing anxiety and depression.

Design

Interventions / Regimen

• Behavioral: Digital positive affect intervention (PAI) — The Positive Affect Intervention (PAI) is a fully digital, self-guided program uniquely designed to deliver weekly 30-minute online sessions focused on cultivating positive emotions, meaning, and engagement, alongside daily ecological momentary prompts delivered thrice daily over six weeks. Distinctively, the intervention seamlessly integrates multimedia content (e.g., brief weekly videos introducing each session's core principles), practical exercises, and in-the-moment reflection, aiming to reinforce positive affect skills in real time. Its structure not only emphasizes proactive skill application through digital reminders but also systematically assesses user engagement and perceived helpfulness via ecological momentary assessments and post-session feedback questionnaires. Unlike conventional digital interventions that primarily focus on symptom reduction through passive content consumption, this PAI leverages continuous ecological momentary engagement via a dedicated mobile app, e
• Behavioral: Self-monitoring intervention — The self-monitoring intervention serves as an active comparator designed to isolate the effects of mood self-awareness without introducing therapeutic content. Participants in this arm receive daily prompts via the Qualtrics mEMA mobile app, three times per day over a six-week period, instructing them to track their mood and emotional states through brief ecological momentary assessments (EMAs). Unlike the digital positive affect intervention, this arm does not include psychoeducational material, skills training, or active enhancement strategies; instead, it focuses solely on routine self-monitoring to control for digital engagement and expectancy effects. This minimalist structure allows for a clean contrast between passive self-observation and active therapeutic engagement, enabling robust evaluation of the added value of the Positive Affect Intervention beyond self-monitoring alone

Primary Outcomes

• Change from baseline Generalized Anxiety Disorder Symptoms at 6 weeks post-randomization (Baseline to 6 weeks post-randomization)
• Change from baseline Generalized Anxiety Disorder symptoms at 3, 6, and 12 months post-randomization (Baseline to 3 months, 6 months, and 12 months post-randomization)
• Change from baseline depressive symptoms at 6 weeks post-randomization (Baseline to 6 weeks post-randomization)
• Change from baseline depressive symptoms at 3, 6, and 12 months post-randomization (Baseline to 3 months, 6 months, and 12 months post-randomization)

About This Study

This project will assess how depression, preclinical AD, and antidepressants affect driving behavior in cognitively normal older adults (65 years).

Design

Interventions / Regimen

• Drug: F 18 AV-1451 (Flortaucipir) — A dosage range between 6.5 - 10.0 mCi (240-370MBq) is planned for \[18F\] AV-1451. A PET-certified medical professional will prepare and administer the \[18F\] AV-1451tracer. Prior to the administration, the dosage will be assayed in a dose calibrator. The volume of 18F-AV-1451 dose should not be adjusted by adding normal saline to the syringe. Participants will receive a maximum intravenous bolus injection of 10.0 mCi of \[18F\] AV-1451 followed by a 10 mL flush of 0.9% sodium chloride (normal saline).
• Drug: [11C]-Pittsburgh Compound B ([11C]PiB) — A dosage range between 6.0 - 20.0 mCi (222-740 MBq) is planned for \[11C\] PIB. A PET-certified medical professional will prepare and administer the \[11C\] PIB tracer. Prior to the administration, the dosage will be assayed in a dose calibrator and diluted with 0.9% sodium chloride (normal saline) up to a total 20 mL syringe volume. Participants will receive a maximum intravenous bolus injection of 20.0 mCi of \[11C\] PIB followed by a 10 mL 0.9% sodium chloride (normal saline) flush.

Primary Outcomes

• Latitude via DRIVES chip (Daily for up to five years)
• Longitude via DRIVES chip (Daily for up to five years)
• Vehicle Speed via DRIVES chip (Daily for up to five years)
• Speed Limit via DRIVES chip (Daily for up to five years)
• Difference via DRIVES chip (Daily for up to five years)
• Event Name via DRIVES Chip (Daily for up to five years)
• Address via DRIVES chip (Daily for up to five years)
• Event Type via DRIVES chip (Daily for up to five years)

About This Study

The proposed study consists of two phases. During Phase 1, the investigators will recruit a small sample of participants to complete a psychosocial intervention termed Amplification of Positivity (AMP) for individuals experiencing comorbid depression or anxiety disorders and alcohol use disorder (AMP-A). These participants will be asked to provide both qualitative and quantitative input about the AMP-A intervention. Based on their input and clinician input, the AMP-A manual will be modified for use in Phase 2. The goal is to recruit up to 20 participants in order to ensure there will be at least 8 participants who complete all sessions of AMP-A. Phase 2 is a randomized clinical trial (RCT) protocol in which individuals experiencing comorbid depression or anxiety disorders and alcohol use disorder will be randomized to complete AMP-A or an evidence-based cognitive-behavioral therapy (CBT) intervention. Up to 100 participants will be recruited in order to reach a target of N=60. Assessed outcomes will include participant acceptability and completion rates, participant compliance with the intervention, positive and negative affect, substance use- and depression and anxiety-related symptom severity, functional disability, and neural reactivity to reward and alcohol cues during functional magnetic resonance imaging (fMRI).

Design

Interventions / Regimen

• Behavioral: Cognitive Behavioral Therapy — Cognitive Behavioral Therapy
• Behavioral: Amplification of Positivity Therapy — Amplification of Positivity Therapy
• Behavioral: Surveys and Interviews — Participants will answer questions regarding their mental and physical health as well as their substance use on the computer and in an interview format.

Primary Outcomes

• Perceived acceptability and satisfaction of the intervention as measured with the Adherence and Acceptability Scale (AAS) (Average of total scores from the following time points: pre-treatment, 2 weeks after starting treatment, 6 weeks after starting treatment, and at post-treatment (average of 16 weeks after baseline assessment))
• Change in positive affect self-report measured with National Institute of Health (NIH) Patient Reported Outcome Measurement and Information System (PROMIS) Positive Affect score (Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment))
• Change in number of drinking days in the past month (Trajectory of change from pre-treatment to post-treatment (last time point assessed on average 16 weeks after baseline assessment))

About This Study

This observational study will employ a multi-modal observation methodology, integrating data from wearable devices and smartphones to establish comprehensive digital biomarkers for identifying symptoms of mental health conditions in university students. The study aims to identify the digital behavioural markers associated with mental health conditions, develop predictive algorithms for mental health states from digital markers, and identify university students at risk for mental health conditions.

Design

Interventions / Regimen

• Other: Observational — Participants will not receive any study intervention. During the six month study period, participants will complete four active assessments at Months 0, 1, 3 and 6, and data from the study-provided wearable (Fitbit Charge 6) and sensors from the participant's smartphone (through the Brightline app) will be collected passively throughout.

Primary Outcomes

• Patient Health Questionnaire-9 (PHQ-9) (Baseline (Month 0), Interim (Month 1), Mid-point (Month 3), End-point (Month 6))

About This Study

The purpose of this study is to identify pharmacogenetic profiles associated with selective serotonin reuptake inhibitors (SSRI)-induced behavioral disinhibition in children with Major depressive disorder (MDD), anxiety disorders and/or obsessive-compulsive disorder (OCD) that could be used clinically to reduce the incidence of this adverse event and improve health outcomes.

Design

Primary Outcomes

• Genetic variants in SSRI metabolism (4 years)
• Behavioural Disinhibition (4 years)

About This Study

This retrospective observational study examines the effects of psychedelic-assisted psychotherapy (PAP) with lysergic acid diethylamide (LSD) or psilocybin in patients with treatment-resistant depressive, anxiety, or addictive disorders. Data will be analyzed from patients treated at the University Hospitals of Geneva between June 2020 and April 2025 who obtained individual authorizations from the Swiss Federal Office of Public Health for use of LSD or psilocybin under compassionate use criteria. The main objective is to assess the effects of psychedelic-assisted psychotherapy with LSD or psilocybin on changes in depressive symptoms, anxiety symptoms. Secondary objectives include evaluating the association between psychedelic session intensity and the administered dose of LSD or psilocybin, changes in depressive symptoms, anxiety symptoms, and problematic substance use, as well as their association with intensity effects. Additionally physiological effects during session will be assessed. All data are retrospectively collected from clinical records with prior patient consent. This study aims to generate evidence on the feasibility, safety, and therapeutic potential of PAP in real-world clinical practice.

Design

Interventions / Regimen

• Drug: Lysergic Acid Diethylamide (LSD) or psilocybin — Psychedelic-assisted psychotherapy with LSD or psilocybin as a part of a clinical routine in our department

Primary Outcomes

• Self-reported depressive symptoms (BDI-II) (Baseline and 1 month after each psychedelic treatment session (sessions 1-3, up to 12 months))
• Self-reported symptoms of anxiety (STAI) (Baseline and 1 month after each psychedelic treatment session (sessions 1-3, up to 12 months))

About This Study

Evaluate the efficacy and safety of subcutaneous ketamine added to usual treatment in the management of depressive episodes with suicidal ideation or behavior in adolescent patients, compared to usual treatment added to placebo (midazolam).

Design

Interventions / Regimen

• Drug: ketamine — Ketamine will be administered as adjunctive therapy at an initial dose of 0.5 mg/kg via subcutaneous injection, twice weekly for four weeks, under double-blind conditions. Dose adjustments between 0.5 and 1.0 mg/kg will be based on depressive symptoms, efficacy, and tolerability. All procedures will occur at the Ketamine Clinic of Federal University of São Paulo.
• Drug: Midazolam — Midazolam will be administered subcutaneously twice weekly for four consecutive weeks, also under double-blind conditions. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.

Primary Outcomes

• Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score at 24 Hours Post First Dose (Baseline (predose) and 24 hours post first dose)

About This Study

An observational behavioural and neurophysiological study of the effects of controlled sensory stimulation (such as music, for example) on brain function

Design

Primary Outcomes

• Neuronal networks (All along the study (8 years))