Neurological Correlates

White Matter Days (à la January “white sales”)

Is aggressive behavior related to wobbly white matter caused by a genetic allele related to neuron dendrite growth? Mehbee.

Both bipolar as well as schizophrenia sufferers have similar white matter defects in particular regions of the brain.  This may be due to a particular gene, “ErbB4″ (normally associated with a neuroregulin), associated with reduced white matter myelination.  A particular ErbB4 variant predicts reduced connectivity with the left frontotemporal brain.  This brain region, when dialed down, is associated with hostility and aggression.   So perhaps this particular ErbB4/neuroregulin genotype is another genetic marker for plain vanilla aggressive hostility, even apart from suffering from bipolar or schizophrenia. (Note to self when retail gene scans come down in price: take surrepetitious cheek swabs from several people in my orbit.)

Interestingly, thyroid hormone (T3) induces brain neuron growth after de-myelination (in a rodent model), and so one can wonder if T3 is a “treatment” for aggression in general.   This would be a great drug mod, to figure out how to get a selective T3 to just remyelinate neurons, and not have any of the other thyroid-type effects (e.g., metabolism speeding up, etc.).

Harson et al. point out that T3 also increases brain neuron stem cells in situ .  Profound implications for disease, but, on a shallower level,  this strikes me as a poor-man’s rehab.  For some people, burning out neurons isn’t a disease, it’s a lifestyle. You could burn out neurons, take T3 and reload  neuron stem cells, and go right back to the alcohol/meth/whatever. Of course, you might actually remember all those things you did while you were busy burning out your neurons. Something to consider before regrowing neurons.

A bunch of recent citations and links after the jump.

Sussmann JE, Lymer GK, McKirdy J, Moorhead TW, Maniega SM, Job D, Hall J, Bastin ME, Johnstone EC, Lawrie SM, McIntosh AM, “White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging.,” Bipolar Disord. 2009 Feb;11(1):11-8:

Konrad A, Vucurevic G, Musso F, Stoeter P, Dahmen N, Winterer G, “ErbB4 genotype predicts left frontotemporal structural connectivity in human brain,” Neuropsychopharmacology. 2009 Feb;34(3):641-50. Epub 2008 Jul 30. PMID: 18668031

Winterer G, Konrad A, Vucurevic G, Musso F, Stoeter P, Dahmen N. Association of 5′ end neuregulin-1 (NRG1) gene variation with subcortical medial frontal microstructure in humans. Neuroimage. 2008 Apr 1;40(2):712-8. Epub 2008 Jan 5. PMID: 18255317

Goes FS, Willour VL, Zandi PP, Belmonte PL, Mackinnon DF, Mondimore FM, Schweizer B, Gershon ES, McMahon FJ, Potash JB; Bipolar Disorder Phenome Group, NIMH Genetics Initiative Bipolar Disorder Consortium. Family-based association study of Neuregulin 1 with psychotic bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 6. [Epub ahead of print]PMID: 19127563

Hirono N, Mega MS, Dinov ID, Mishkin F, Cummings JL.Left frontotemporal hypoperfusion is associated with aggression in patients with dementia Arch Neurol. 2000 Jun;57(6):861-6 PMID: 10867784

Harsan LA, Steibel J, Zaremba A, Agin A, Sapin R, Poulet P, Guignard B, Parizel N, Grucker D, Boehm N, Miller RH, Ghandour MS.Recovery from chronic demyelination by thyroid hormone therapy: myelinogenesis induction and assessment by diffusion tensor magnetic resonance imaging.J Neurosci. 2008 Dec 24;28(52):14189-201PMID: 19109501