Longitudinal Gene Expression Changes in PTSD Following Sub-Anaesthetic Oral Ketamine Administration

This study investigates the differential gene expression in response to sub-anaesthetic oral ketamine treatment of PTSD to identify key molecular markers in building a predictive profile in determining longer term treatment outcomes. This study highlights the utility of integrating gene expression data with clinical outcomes to elucidate a molecular profile receptive to ketamine's sustained therapeutic effects. Overall design: Building on clinical data gathered from the sub- anaesthetic Oral Ketamine Trial of PTSD (OKTOP) (Prince Charles Hospital (PCH) Human Research Committee ethics number: HREC/18/QPCH/288. USC ethics number: A181190), a six week open-label, dose-ranging clinical trial conducted between 2021 and 2024 by the Thompson Institute (QLD, Australia) we collected and processed blood samples from the same participants at Baseline (BAS), 1 Week post ketamine treatment (Week 7) and 4 weeks post ketamine treatment (Week 10) Twenty three Adult male and female participants, aged 18 and above, diagnosed with PTSD were recruited. Eligibility was confirmed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). Baseline assessments, including a physical examination, urinalysis, standard clinical blood tests, and medical history, were completed within 14 days prior to the ketamine treatment. Participants received a sub-anaesthetic dose of oral ketamine weekly, monitored by a psychiatrist and health clinician. The initial dose was set at 0.5 mg/kg and gradually increased by 0.1-0.5 mg/kg each week based on individual tolerance, with a maximum dose of 3.0 mg/kg. Samples were collected within 24 hours of post administration, processed into whole blood, serum, plasma, and peripheral blood mononuclear cells (PBMCs). RNA was extracted and 20 million RNA-Seq read was conducted through NovaSeq. Reads were QC'd, trimmed and mapped to GRCh38.p14 for differential expression analysis using CLC Genomics Workbench 25.0 (Qiagen).