Estimation of Control Before and After Treatment of a Depressive Episode With Serotonin Reuptake Inhibitors (APTE-Sero)

The goal of this observational study is to better understand cognitive and affective processes involved in depression, in particular how individuals estimate their perception of control over events in their environment, as well as related processes such as memory and decision-making. The study also aims to investigate how these processes are affected by antidepressant treatment and how depressive symptoms evolve over time, as well as whether specific peripheral markers (including hormones) are associated with treatment effects.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression Disorder
• Intervention / Treatment: Drug: Selective Serotonin Reuptake Inhibitors (SSRIs) or serotonergic antidepressants; Other: Experimental tasks

Detailed Description

The main questions it aims to answer are:

How do individuals with a depressive episode differ from healthy controls in their estimation of control over environmental events? How does antidepressant treatment (selective serotonin reuptake inhibitors) influence perceived control, cognitive performance, and depressive symptoms over time? Are changes in perceived control and symptoms associated with biological markers measured during the study?

Researchers will compare participants with a current depressive episode to healthy control participants, and examine changes over time in the depressed group before and after treatment initiation, in order to assess the effects of antidepressant treatment on cognition, perceived control, and symptoms.

Participants will:

• Complete 4 study sessions over approximately 8 weeks, including 2 in-person visits at the Centre de Recherche en Neurosciences de Lyon (CRNL) and 2 online sessions.
• Complete questionnaires assessing depressive symptoms, personality traits, and life events.
• Perform computerized behavioral tasks involving prediction, learning, memory, and decision-making in virtual environments.
• Complete tasks designed to assess perceived control over outcomes in different contexts.
• Undergo non-invasive physiological recordings during in-person sessions, including eye-tracking, heart rate monitoring, and muscle activity measurement.
• Perform short online versions of the cognitive tasks between visits.
• Healthy control participants will complete the same procedures, except for antidepressant treatment exposure, while the depressed group will be followed over time before and after treatment.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Romain Ligneul, PhD; Phone Number: +33 04 72 13 89 00; Email: romain.ligneul@inserm.fr
• Study Contact Backup: Name: Méline Devaluez, PhD; Phone Number: +33 04 37 91 55 14

Study Locations

• France
  • Bron, France, 69500
    • Centre de Recherche en Neuroscience de Lyon
    • Contact: Romain Ligneul, PhD; Phone Number: +33 04 72 13 89 00; Email: romain.ligneul@inserm.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria - applicable to all participants:

• Affiliated with a social security or national health insurance system, or entitled to such coverage.
• Male or female, aged 18 to 55 years.
• Fluent in spoken and written French.
• Normal or corrected-to-normal vision.
• Access to a computer and an internet connection.
• Available for the 8-week study period following treatment initiation (patients) or the baseline visit (healthy controls).
• Willing to use an effective method of contraception (condom, oral contraceptive pill, abstinence, or intrauterine device).

Additional inclusion criteria for the depressed patient group:

• Eligible for antidepressant monotherapy with a selective serotonin reuptake inhibitor (SSRI: sertraline, fluoxetine, citalopram, or paroxetine) or a serotonin-norepinephrine reuptake inhibitor (SNRI: venlafaxine or duloxetine), with or without concomitant treatment with a short half-life benzodiazepine (<12 hours; e.g., oxazepam, lorazepam, or clotiazepam), for which the prescription has been issued but treatment has not yet been initiated.
• Montgomery-Åsberg Depression Rating Scale (MADRS) score >6 and <35 (corresponding to mild-to-moderate depression), assessed during the routine clinical visit with the treating physician.
• No evidence of suicidal ideation, high-risk behaviors, history of suicide attempt, or overt psychotic symptoms that could compromise participant safety.
• No severe medical condition or unstable physiological state considered incompatible with study participation by the referring physician, including but not limited to unstable chronic diseases (e.g., hypertension or diabetes), respiratory insufficiency, cardiovascular insufficiency, or renal insufficiency.

Exclusion criteria applicable to all participants:

• History of a major depressive episode within the past 3 years.
• Use of antidepressants, mood stabilizers, or antipsychotic medication within the past 3 years.
• Diagnosis of a neurological or psychiatric disorder affecting central nervous system function (including bipolar disorder, schizophrenia, or other psychotic disorders according to DSM-5 criteria).
• Pregnancy or breastfeeding (self-reported).
• Individuals under legal protection (guardianship, curatorship, or judicial protection measures).
• Current participation in another interventional clinical trial or ongoing exclusion period following a previous clinical trial.
• Planned initiation during the study of a medication or substance known to interfere with serotonergic activity (including MDMA, LSD, psilocybin, ketamine, cocaine, 5-HT2A receptor antagonist antipsychotics, triptans, or lithium).
• Use of serotonin-acting recreational drugs within the previous 6 months (including cocaine, MDMA, or psychedelic substances).
• Refusal to be informed of the potential discovery of a clinically significant incidental finding.

Additional exclusion criteria for the depressed patient group

• Antidepressant treatment already initiated before study enrollment.
• Use of benzodiazepines within the 12 hours preceding an experimental session.
• Treatment with benzodiazepines other than oxazepam, lorazepam, or clotiazepam.
• Current hospitalization.
• Risk of suicidal behavior, defined as a score of ≥2 on the "zest for life" ("élan de vie") item of the Montgomery-Åsberg Depression Rating Scale (MADRS).
• Current treatment considered clinically incompatible with study participation by the physician responsible for recruitment.

Additional exclusion criteria for the healthy volunteer group :

Current or previous diagnosis of a depressive or anxiety disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Depression group; Patients presenting a depressive episode and receiving serotonergic antidepressant treatment	Drug: Selective Serotonin Reuptake Inhibitors (SSRIs) or serotonergic antidepressants; Participants are prescribed serotonergic antidepressants such as fluoxetine, sertraline, escitalopram, paroxetine, or serotonin-norepinephrine reuptake inhibitor (SNRI). Dosage, formulation, frequency, and treatment duration are determined by the treating clinician. No experimental manipulation of medication is performed within the study. The intervention is characterized to assess its association with cognitive performance, reaction time (RT), accuracy, and controllability-related decision-making.; Other: Experimental tasks; Experimental tasks assessing cognition, decision-making, and perceived controllability.
Experimental: Control group; Healthy participants who are not receiving serotonergic antidepressant treatment.	Other: Experimental tasks; Experimental tasks assessing cognition, decision-making, and perceived controllability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controllability Estimation Bias in depressed patients	normalization of the controllability estimation bias in patients with depression after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). The assessment of controllability is not obtained directly from the participant, but through a computational model inferred from their behavioural data (reaction time (RT), prediction accuracy (percentage of correct responses) and error rate)	Change between baseline and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Controllability Estimation Bias in Depressed Patients vs Healthy Controls	This measure compares the controllability estimation bias between participants with a current depressive episode and healthy controls using a behavioral task assessing perceived control over environmental outcomes	Baseline

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier
• Collaborators: INSERM U1028
• Investigators: Principal Investigator: Romain Ligneul, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 16, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Depression; SSRI; serotonin; controllability; estimation of control
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Neurotransmitter Uptake Inhibitors; Serotonin Agents; Pharmacologic Actions; Chemical Actions and Uses; Selective Serotonin Reuptake Inhibitors
• Other Study ID Numbers: 2026-A00663-48

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No