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SSRI Pharmacogenomic Testing: CYP2D6, CYP2C19, Remission

MHD featured image for SSRI Pharmacogenomic Testing: CYP2D6, CYP2C19, Remission.

A 2026 methylome-wide association study by Shen et al. found 48 CpG methylation sites tied to the quadratic CYP2C19 metabolizer-status term in 18,396 Generation Scotland participants, with 19 sites showing non-linear patterns and targeted replication in 1,238 older adults.1 That supports CYP2C19 as real biology beneath SSRI pharmacogenomics, but it does not prove universal antidepressant …

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Alpha-Synuclein SAA Predicts Parkinson’s Levodopa Response Durability

Photoreal illustration of CSF biomarker testing alongside dopaminergic neuron pathways, representing PD biomarker stratification.

A 2026 PPMI analysis found that Parkinson’s patients with positive CSF α-synuclein seed amplification assay results kept gaining levodopa benefit over follow-up, while SAA-negative patients showed faster ON-medication motor progression than SAA-positive patients: 0.87 vs. 3.47 MDS-UPDRS Part III points/year in 183 matched SAA-positive and 40 SAA-negative patients.1 Research Highlights ON-state progression split sharply: SAA-positive …

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Lecanemab Clears Amyloid via Microglia and Fc Receptors

Photoreal illustration of microglia clustering around an amyloid plaque, conveying immune-mediated clearance mechanism.

A 2026 Nature Neuroscience study found that lecanemab cleared amyloid in a humanized-microglia Alzheimer’s disease model only when microglia and the antibody’s intact Fc fragment were both present: X-34 plaque area differed across IgG1, lecanemab, and Fc-silenced LALA-PG groups (P = 0.0003), 82E1 plaque area differed across groups (P < 0.0001), and microglia-deficient mice showed …

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Esketamine Can Trigger Trauma Re-Experiencing in PTSD

Photoreal illustration of a patient receiving nasal spray with overlay of trauma memory imagery, conveying esketamine + PTSD interaction.

A 2026 retrospective case series of 22 adults with treatment-resistant depression and comorbid PTSD found that trauma re-experiencing during intranasal esketamine disappeared over later sessions in 72.7% of patients, while 27.3% stopped esketamine because the flashbacks persisted.1 Research Highlights Flashbacks usually faded, but not always: In 16 of 22 patients (72.7%), esketamine-related trauma re-experiencing disappeared …

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Prior Cocaine Use Disrupts Orbitofrontal Hidden-State Coding

MHD featured image for Prior Cocaine Use Disrupts Orbitofrontal Hidden-State Coding.

A 2026 eLife study recorded 3,881 lateral orbitofrontal cortex units in rats and found that prior cocaine use made the OFC over-distinguish task positions that controls treated as functionally equivalent. The headline result was not gross task failure: cocaine-experienced rats still performed the odor task, but their OFC ensembles showed higher S1-vs.-S2 decoding than sucrose …

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