I made some posts on the association between the low levels of dopamine found in patients with MS and brain gray matter loss under the thread "Some Interesting Connections". Patients with MS lack the essential amino acid that dopamine is derived from-phenylalanine. Research in other autoimmune diseases associated with an inability to properly digest proteins (which contain amino acids) has found that dysregulation of amino acids "precedes" the immune response. For instance, in the following study on type 1 diabetes the amino acid dysregulation was found to precede the islet autoimmunity.
J Exp Med. 2008 Dec 22;205(13):2975-84. doi: 10.1084/jem.20081800. Epub 2008 Dec 15.Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes.Autoimmunity may thus be a relatively late response to the early metabolic disturbances.
Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.
The inability to properly metabolize amino acids, such as phenylalanine, would lead to the same lack of dopamine found in patients with MS, which would result in brain gray matter loss. The following study found that patients with type 1 diabetes had lower density of gray matter in several brain regions.
Diabetes. 2006 Feb;55(2):326-33.
Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry.
Musen G, Lyoo IK, Sparks CR, Weinger K, Hwang J, Ryan CM, Jimerson DC, Hennen J, Renshaw PF, Jacobson AM.
"...In comparison with control subjects, diabetic patients showed lower density of gray matter in several brain regions..."
Here are the posts I made on the other thread on the association between low dopamine and brain gray matter loss in MS. general-discussion-f1/topic22806-90.html
LOW DOPAMINE AND BRAIN GRAY MATTER LOSS
Low dopamine can also cause brain gray matter loss.
The gray matter involves regions of the brain concerned with muscle control, emotions, learning and memory, speech, and sensory perception such as seeing and hearing. In the following study published in Neurology the researchers stated that gray matter atrophy is detected even in the earliest stages of MS.
Neurology. 2007 Feb 27;68(9):634-42.
Gray matter involvement in multiple sclerosis.
Pirko I, Lucchinetti CF, Sriram S, Bakshi R.
“Gray matter (GM) involvement is detected even in the earliest stages of multiple sclerosis (MS), and GM atrophy occurs at a faster rate than white matter (WM) atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independently of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression…”
In the next study the researchers discussed the entensive involvement of the thalmus, which consists of gray matter, in MS. The study authors stated that extensive involvement of gray matter, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in MS patients.
Neurology. 2013 Jan 8;80(2):210-9. doi: 10.1212/WNL.0b013e31827b910b.
The thalamus and multiple sclerosis: modern views on pathologic, imaging, and clinical aspects.
Minagar A, Barnett MH, Benedict RH, Pelletier D, Pirko I, Sahraian MA, Frohman E, Zivadinov R.
“The paired thalamic nuclei are gray matter (GM) structures on both sides of the third ventricle that play major roles in cortical activation, relaying sensory information to the higher cortical centers that influence cognition. Multiple sclerosis (MS) is an immune-mediated disease of the human CNS that affects both the white matter (WM) and GM. A number of clinical observations as well as recent neuropathologic and neuroimaging studies have clearly demonstrated extensive involvement of the thalamus, basal ganglia, and neocortex in patients with MS. Modern MRI techniques permit visualization of GM lesions and measurement of atrophy. These contemporary methods have fundamentally altered our understanding of the pathophysiologic nature of MS. Evidence confirms the contention that GM injury can be detected in the earliest phases of MS…extensive involvement of GM, and particularly of the thalamus, is associated with a wide range of clinical manifestations including cognitive decline, motor deficits, fatigue, painful syndromes, and ocular motility disturbances in patients with MS…”
In the following study, published in The Journal of Pain, researchers found a strong correlation between dopamine metabolism and gray matter density.
Changes in gray matter density in fibromyalgia: correlation with dopamine metabolism.
Wood, P.B., M.F. Glabus, R. Simpson, J.C. Patterson 2nd. 2009. J Pain 10(6):609-18. Epub 2009 Apr 23.
“Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder, the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes.”
Dopamine regulates prolactin, so we should find elevated levels of prolactin in patients with fibromyalgia. Researchers in the following study found that prolactin was “significantly increased” in patients with fibromyalgia.
Biochemical changes in fibromyalgia.
Samborski, W., T. Stratz, T. Schochat, P. Mennet, W. Müller. 1996. Z Rheumatol. 55(3):168-73.
“In comparison to healthy controls, patients with fibromyalgia revealed…significantly increased level of prolactin.”
We should also find brain gray matter loss in the other diseases we have been discussing that have high prolactin. As the previous studies posted confirm, high levels of prolactin are also found in rheumatoid arthritis, lupus, Sjogren's syndrome, Hashimoto's thyroiditis, diabetes, and celiac disease. In the following study the researchers concluded their results suggest that rheumatoid arthritis is associated with changes in the subcortical gray matter.
Structural changes of the brain in rheumatoid arthritis.
Wartolowska, K., M.G. Hough, M. Jenkinson, J. Andersson, B.P. Wordsworth, I. Tracey. 2012. Arthritis Rheum. 64(2):371-9. doi: 10.1002/art.33326.
“…Our results suggest that RA is associated with changes in the subcortical gray matter…”
Researchers in the following study discovered that the gray matter (GM) was “particularly affected” in patients with neuropsychiatric lupus (NPSLE).
Selective gray matter damage in neuropsychiatric lupus.
Steens, S.C., F. Admiraal-Behloul, G.P. Bosma, G.M. Steup-Beekman, H. Olofsen, S. Le Cessie, T.W. Huizinga, M.A. Van Buchem. 2004. Arthritis Rheum. 50(9):2877-81.
“…This is the first study to demonstrate… that in SLE patients with a history of NP symptoms …the GM is particularly affected. These findings support the hypothesis that neuronal injury may underlie central nervous system manifestations in NPSLE.”
In the following study the researchers concluded that patients with Sjögren's syndrome had decreased brain gray matter.
CNS involvement in primary Sjögren’s syndrome: assessment of gray and white
matter changes with MRI and voxel-based morphometry.
Tzarouchi, L.C., N. Tsifetaki, S. Konitsiotis, A. Zikou, L. Astrakas, A. Drosos, M.I. Argyropoulou. 2011. AJR Am J Roentgenol. 197(5):1207-12. doi: 10.2214/AJR.10.5984.
“…In comparison with the controls, patients with primary Sjögren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum…”
In our next study researchers found an association with reduced brain grey matter in children with Hashimoto’s thyroiditis and low performance in attention testing.
Low performance in attention testing is associated with reduced grey matter density of the left inferior frontal gyrus in euthyroid patients with Hashimoto’s thyroiditis.
Leyhe, T., T. Ethofer, J. Bretscher, A. Künle, A.L. Säuberlich, R. Klein, B. Gallwitz, H.U. Häring, A. Fallgatter, S. Klingberg, R. Saur, K. Müssig. 2013. Brain Behav Immun. 27(1):33-7. doi: 10.1016/j.bbi.2012.09.007. Epub 2012 Sep 23.
“…Recently we found an increased occurrence of weaknesses in sustained attention and response inhibition in a subgroup of euthyroid patients with HT as obtained by the d2 attention test…GM density was significantly reduced when comparing HT patients with control patients that scored in the lower third during d2 attention testing…Particularly low achievement was associated with reduced GM density of this brain region suggesting an influence of autoimmune processes on the frontal cortex in this disease…”
In the following study published in Diabetologia the researchers concluded that type 2 diabetes was associated with a smaller volume of brain grey matter.
Automated measurement of brain and white matter lesion volume in type 2 diabetes
Jongen, C., J. van der Grond, L.J. Kappelle, G.J. Biessels, M.A. Viergever, J.P. Pluim. Utrecht Diabetic Encephalopathy Study Group. 2007. Diabetologia. 50(7):1509-16. Epub 2007 May 11.
“Type 2 diabetes mellitus has been associated with brain atrophy and cognitive decline, but the association with ischaemic white matter lesions is unclear…Type 2 diabetes was associated with a smaller volume of grey matter… and with larger white matter lesion volume…The combination of atrophy with larger WML volume indicates that type 2 diabetes is associated with mixed pathology in the brain.”
Here is some information on celiac disease and brain gray matter damage. http://celiacdisease.about.com/b/2013/0
As we have discussed, low dopamine can also lead to restless legs syndrome (RLS). Due to reduced levels of dopamine, patients with RLS also have brain gray matter damage. In the following study the researchers concluded that patients with RLS had significant regional decreases of gray matter volume.
Cortical gray matter alterations in idiopathic restless legs syndrome: An optimized voxel-based morphometry study.
Unrath, A., F.D. Juengling, M. Schork, J. Kassubek. 2007. Mov Disord. Sep 15;22(12):1751-6.
“…The comparison of the RLS patients versus controls yielded significant regional decreases of gray matter volume...All clusters correlated both with the severity of RLS symptoms and with disease duration. These results, for the first time, give in vivo evidence to structural neocortical gray matter alterations in RLS patients…”