Depression is characterized
by a persistent depressed mood and or interest in things that previously gave
pleasure, which is a change for that individual.1 It is estimated
that 6.6% of the population in the USA will experience depression.
The mauve factor is
hydroxylactam of hemopyrrole, hydroxyhemopyrrolin-3-one (HPL). Elevated urinary HPL results in neurobehavioral
symptoms, which can be improved with nutrients vitamin B6 and zinc. Increased excretion of HPL is associated with
oxidative stress and emotional stress.
High-mauve factor is found
in patients with Down syndrome, schizophrenia, autism, ADHD, and alcoholism.2
Pfeiffer et al. reports symptoms of high-mauve include upper abdominal
pain, hyperactivity, explosive anger, low stress tolerance, and musculoskeletal
pain. These symptoms are expansive and
can be difficult to distinguish from many mental health conditions such as
major depression and schizophrenia.
The development of depression is complex and two
major models in the literature describe the pathogenesis. The
monoamine-deficiency hypothesis states that symptoms related to decreased
norepinephrine and serotonin in multiple regions of the brain may be responsible
for depression. Abnormalities in the
cortisol response, and chronically elevated cortisol may be contributory. Additionally,
abnormal circadian rhythms and impaired synthesis or metabolism of
neurotransmitters can result in inflammation causing depression. Twin studies
suggest a 37% concordance suggesting genetics contribute to the development of
depression.
HPL is correlated inversely
with plasma glutathione and red-cell catalase, and directly with plasma nitric
oxide. High-mauve denotes individuals that excrete excess HPL, and have
resulting erythroid heme depression, low zinc, and increased nitric oxide. Heme depression and increased nitric oxide
results in considerable oxidative stress and inflammation throughout the body
and brain. There are many heme-dependent
enzymes, which play vital roles in anti-oxidant defense, including catalase,
peroxidase, and CYP450 synthesis.
Heme synthesis begins with
condensation of glycine and succinyl-CoA to form d-aminolevulinic acid (ALA). Vitamin
B6, or pyridoxal phosphate (PLP) serves as a coenzyme for d-aminolevulinate
synthesis (which is the rate-limiting step in heme synthesis). Aminolevulinic
acid (ALA) condensation forms porphobilinogen by zinc-containing ALA
dehydratase. The porphyrias are classified as erythropoietic
or hepatic, depending on where the enzyme deficiency occurs in the
erythropoietic cells of the bone marrow, or the liver.
Depression and other mental
health conditions have been associated with mitochondria dysfunction. Bioenergetics
and neurodevelopment are highly influenced by mitochondrial function, and poor
function is often due to altered redox balance and chronic low-grade
inflammation. N-acetylcysteine has protective effects in multiple models of
mitochondrial dysfunctions.3
Research completed by Torres
et al. demonstrated protective effects in neurotoxicity associated with
pyrroles in urine. The sulfhydryl groups
provided by NAC appear to inhibit the pyrrole-pyrrole crosslinking and prevent
2,5-hexanedion toxicity in a rat model.4
Anti-depressants,
escitalopram, and placebo compared to S-adenosyle methionine (SAMe) showed
inferior responses in major depression. Results of the study suggest that SAMe
provide evidence for the use of SAMe in major depression.5
1. Domino, Frank J. The 5-minute Clinical Consult Standard. Philadelphia,
PA: Wolters Kluwer Health; 2015. 380-381 p.
2. Pfeiffer, C. C., Sohler, A., Jenney, E. H., & Iliev,
V."Treatment of pyroluric schizophrenia (malvaria) with large doses of
pyridoxine and a dietary supplement of zinc." J Orthomol Psychiat 3
(1974): 292-300.
3. Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M.
Mitochondrial dysfunction in schizophrenia: Pathways, mechanisms and
implications. Neurosci Biobehav Rev. 2015;48:10-21.
doi:10.1016/j.neubiorev.2014.11.005.
4. Torres ME, dos Santos a. PM, Gonçalves LL, Andrade V,
Batoréu MC, Mateus ML. Role of N-acetylcysteine in protecting against
2,5-hexanedione neurotoxicity in a rat model: Changes in urinary pyrroles
levels and motor activity performance. Environ Toxicol Pharmacol.
2014;38(3):807-813. doi:10.1016/j.etap.2014.09.008.
5. Sarris J, I. Papakostas G, Vitolo O, Fava M, Mischoulon
D. S-adenosyl methionine (SAMe) versus escitalopram and placebo in major depression
RCT: Efficacy and effects of histamine and carnitine as moderators of response.
J Affect Disord. 2014;164:76-81. doi:10.1016/j.jad.2014.03.041.
