tDCS for Catatonic Depression in Down Syndrome: A Pilot Study

Justification: Depression is common in individuals with Down syndrome (DS), often accompanied by catatonia, and is under-treated. Conventional treatments are limited by tolerability and linguistic difficulties. Transcranial direct current stimulation (tDCS), safe and effective, has never been tested in DS.

Hypothesis: tDCS is effective and safe for depression with catatonia in DS, improving mood, cognition, and motor symptoms.

Objectives:

Primary: To evaluate the clinical efficacy of 15 sessions of bifrontal tDCS on depression with catatonia in DS (Bush-Francis Catatonia Rating Scale (BFCRS)).

Secondary: To evaluate safety, long-term clinical and cognitive effects (1 and 3 months), EEG correlates, and biological effects (cortisol, BDNF, cytokines).

Methodology: Multicenter (2 sites), randomized, double-blind, placebo-controlled study. 30 DS patients will receive 15 sessions of active tDCS (2 mA, 20 min, anode over left DLPFC, cathode over right DLPFC) or sham tDCS.

Outcomes:

Primary: Changes in depressive/catatonic symptoms (BFCRS) between Day 0 and Day 5.

Secondary: Safety, clinical (MADRS, UPDRS), cognitive (SIB), EEG, and biological (blood, saliva) assessments.

Target Population: Men and women with DS with a depressive episode and catatonia (30 patients).

Inclusion criteria

DS, age > 18 years, major depression with catatonia (DSM-5), informed consent.

Exclusion criteria

Pregnancy, contraindication to tDCS, refusal. Statistical Analyses: ANOVA or mixed models for BFCRS scores. Justification for Inclusion: To provide a safe, non-pharmacological therapeutic alternative.

Withdrawal Criteria: Withdrawal of consent, severe pathology. Procedures: Clinical, cognitive, EEG, and biological (blood, saliva) assessments at Day 0, Day 1, Day 5, 1 and 3 months.

Recruitment: 6 sites (CH Vinatier Lyon, CHU Nantes, CHU Dijon, CHU Clermont Ferrand, CH Rouen, GHU Neurosciences Paris). EEG and biological analyses at Lyon and Paris only.

Number of Subjects: 62 patients (31 per group). Duration: Inclusion (24 months), individual participation (3 months), total study (27 months).

Locations: CH Le Vinatier (Lyon), CHU Nantes, CHU Dijon, CHU Clermont Ferrand, CH Rouen, GHU Neurosciences Paris.

Benefit-Risk Ratio: Pioneering study on tDCS in DS, aiming for a safe alternative to current treatments and a better understanding of neurobiological mechanisms.

Inclusion criteria

• Patient with Down syndrome
• Age > 18
• Diagnosis of Major Depressive Disorder MDD with catatonic symptoms according to the DSM-5 criteria
• Informed consent signed by the patient, by the patient under curatorship, or by the legal representative in the case of a patient under guardianship.
• Person affiliated to the French social security system or equivalent

Exclusion criteria

• Pregnancy (checked with a pregnancy test)
• Contraindication for tDCS(i.e., cochlear implant)
• Refusal of the patients or their legal representatives
• Other persons protected under the CSP (judicial safeguard, family habilitation)