Research · PMID 23428746 · Landmark study
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Knockout of c-Jun N-terminal kinases 1, 2 or 3 isoforms induces behavioural changes.
Behavioural brain research · May 2013 · Kirstin Reinecke, Thomas Herdegen, Sevgi Eminel, Josef B Aldenhoff, Thomas Schiffelholz
What this study found
c-Jun N-terminal kinases (JNKs) are central and ubiquitous mediators of cellular signaling for both physiogical-regenerative and pathological-apoptotic processes. Their impact on degeneration or inflammation is well documented, but so far little is known about their roles in higher brain functions.
Why this trial matters
Combination therapy meta-analysis
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Core study
Does combination T3/T4 therapy improve symptoms versus levothyroxine alone?
Randomized trials and meta-analyses show inconsistent symptom benefit from adding liothyronine to levothyroxine compared with levothyroxine monotherapy. Guidelines generally recommend levothyroxine as first-line therapy.
Open evidence analysisCore study
Should subclinical hypothyroidism be treated with levothyroxine?
The TRUST trial found no meaningful symptom or quality-of-life benefit from levothyroxine in older adults with subclinical hypothyroidism. Treatment may still be considered with very high TSH, pregnancy plans, or specific clinical contexts.
Open evidence analysisCore study
Is desiccated thyroid extract superior to levothyroxine for hypothyroidism?
Levothyroxine is standard first-line therapy with the strongest outcome evidence. Desiccated thyroid extract lacks modern RCT data demonstrating superiority and has variable hormone content between batches.
Open evidence analysisCore study
What TSH target is appropriate for treated hypothyroidism?
Most guidelines suggest maintaining TSH within the reference range on levothyroxine, often near the lower half for many patients. Pregnancy and specific comorbidities require tighter targets.
Open evidence analysisCore study
Does treated hypothyroidism fully explain difficulty losing weight?
Hypothyroidism can contribute to weight gain, but levothyroxine normalization typically yields modest weight loss rather than resolving obesity. Persistent weight difficulty usually involves additional metabolic and behavioral factors.
Open evidence analysisCore study
What factors interfere with levothyroxine absorption?
Levothyroxine absorption is reduced by concurrent iron, calcium, PPIs, and some foods including coffee and fiber. Consistent fasting dosing separated from interfering substances improves TSH stability.
Open evidence analysis