The biological circuits behind every patient — visualized. Each diagram shows the steps, the cofactors, the genes that fail, and the interventions that rescue.
Ion-Channel Gates — ‘Treat the gates first’
Reed/Dickerson’s framework. An action potential opens the sodium gate (ANK3); sodium influx triggers the calcium gate (CACNA1C); calcium is the master key that releases all neurotransmitters. Toggle Variant gates to see what mood instability looks like — then toggle Lithium to stabilize.
Watch the calcium master-key open the vesicles.
Dickerson & Reed 2023 (JAANP) — low-dose lithium in CACNA1C-A-allele carriers: ~66% reduction in PHQ-9, ~65% reduction in GAD-7, both p<.001. Reed: ‘Lithium is the cake. Everything else is the icing.’
Methylation Cycle
Folate + B12 + B6 (P5P) + B2 → methyl groups for DNA, neurotransmitters, homocysteine clearance. Toggle MTHFR C677T T/T to see the throughput collapse — then toggle L-methylfolate to bypass the bottleneck.
MTHFD1L drives the mitochondrial folate cycle and rumination — needs folinic acid, not methylfolate
MTRR ×2 = 1.88× ADHD in males
GCH1 ×2 = severe BH4 deficiency → ADHD/depression/PMDD/SI
Use a methylated B-complex (NLite, Neuronutrients Mood Support) with P5P, not pyridoxine
Neurotransmitter Synthesis & Catabolism
Three parallel synthesis chains. Toggle a deficit to see what fails — and where. BH4 deficit kills serotonin AND dopamine. P5P (B6) deficit kills the final step of every line. Vitamin C deficit blocks NE synthesis (Catherine’s DBH problem). Inflammation diverts tryptophan into kynurenine — the toxin that gives you ‘flu brain.’
COMT Met/Met = 4× longer to clear adrenaline; ‘engineer brain’
GABA cofactors: P5P, magnesium, zinc — most patients are deficient in at least one
CNR1 Tri-Loop — Catherine’s Pathology
When two aberrant CB1 receptors meet stress, three reinforcing loops crash the brain. Found in 3.2% of the population. The loops feed back on themselves — that’s why this profile is so devastating. Toggle Apply intervention to see PEA, olive oil, dark chocolate, and singing slow the cascade.
Watch the three loops accelerate, then break.
Cortisol load
↑↑↑
Inflammation
↑↑↑
Neurogenesis
↓↓↓
CB1 signal
broken
Inflammation → BBB → Brain
Why every flu, every COVID, every infection moves your TRD patient backward. Toggle Insult to fire the cascade — TNF-α loosens BBB tight junctions, IL-6 enters and triggers the kynurenine shunt. Toggle NF-κB inhibitors (curcumin · CoQ10 · sulforaphane · omega-3 · PQQ) to seal the wall back up.
Watch the BBB tight junctions open and the kynurenine counter climb.
BBB integrity
intact
Brain cytokines
trace
Kynurenine load
trace
Cortisol
baseline
BDNF
normal
HPA Axis & Stress Response
The cortisol cascade. Click Stress! to fire it. Toggle Ashwagandha or Diaphragmatic breathing to dampen the response and watch the negative-feedback brakes engage.
Cortisol counter shows accumulation.
CRH
baseline
ACTH
baseline
Cortisol
baseline
Brake function
intact
Blood-Brain Barrier — Why Blood Tests Fail in Psych
Endocannabinoid receptors are virtually absent in blood; concentrated in amygdala, hypothalamus, midbrain, cerebellum, and PFC.
Inflammatory cytokines may run 4–10× higher in brain than periphery.
Magnesium L-threonate is uniquely BBB-crossing; pick it for any brain symptom.
Lithium orotate may cross the BBB more readily than carbonate; carbonate gives higher serum levels for severe SI.
Methylfolate crosses the BBB — folic acid does not. Methylcobalamin crosses; cyanocobalamin requires conversion.
Reed’s ‘Genetic Jobs’ Framework
Patients are not broken — they were optimized for a different environment. Each genotype maps to a behavioral archetype that helped our ancestors survive.
Hausman-Cohen’s ‘Fundamentals’ Pillars
Always check these four pillars before chasing diagnostic-specific genes — they apply to every chronic disease state. ‘Put out the fire first before remodeling the house.’ — Dr. Heather Way
Reed’s Treatment Algorithm
Drug hierarchy
Kraker’s Brain ‘Office’
Memorize the personalities — they’re what fail in TRD.