Four weeks of treatment with lithium, a drug commonly used for the treatment of bipolar disorder (manic-depressive illness), increases gray matter volume in the human brain, according to a study by Wayne State University School of Medicine researchers published in the October 7 issue of The Lancet.
The findings suggest mood stabilizers, such as lithium and valproate, also may have future implications for the treatment of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases, said Gregory Moore, PhD, director of the Brain Imaging Research Division of WSU’s School of Medicine.
“If one can prevent neurons from dying or even increase the number or size of neurons in the brain after there has been some neuronal degeneration, one could potentially slow down, halt or even reverse some of the effects of these devastating diseases,” Dr. Moore said. “Our study’s findings indicate that lithium may have these beneficial effects in the human brain and suggest that trials in patients with neurodegenerative disorders may be warranted.”
This is the first time a drug has been proven to increase gray matter in the human brain. Several previous basic science studies have shown that neurons in cell cultures and in mouse and rat brains can increase in size and number when exposed to certain medications. It now appears that these studies are of relevance for humans.
“The findings are striking and will likely have a significant impact on the field of psychiatry, as well as neurology and neurosurgery,” said Thomas Uhde, MD, associate dean for research and graduate programs. “This study is an outstanding demonstration of the value of WSU School of Medicine’s translational research approach bringing key findings in molecular neuroscience from the bench-top to the patient bedside.”
Ten subjects diagnosed with bipolar disorder were studied using three-dimensional magnetic resonance imaging (3D MRI) before they were medicated and then again after four weeks of treatment with lithium. The later brain scans revealed that gray matter volume was significantly increased compared to the earlier scans.
Dr. Moore along with Husseini Manji, MD, associate professor of psychiatry and behavioral neurosciences, and their colleagues are now investigating specific sub-regions of the brain to determine where the most significant changes are occurring.
The study was funded by the National Institute of Mental Health, the State of Michigan (Joe Young Sr. Research Fund), the Stanley Foundation and the National Alliance for Research on Schizophrenia and Affective Disorders.
Distinct regions of the cerebellum show gray matter decreases in autism, ADHD, and developmental dyslexia.
- 1Department of Psychology, American University Washington, DC, USA.
Differences in cerebellar structure have been identified in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental dyslexia. However, it is not clear if different cerebellar regions are involved in each disorder, and thus whether cerebellar anatomical differences reflect a generic developmental vulnerability or disorder-specific characteristics. To clarify this, we conducted an anatomic likelihood estimate (ALE) meta-analysis on voxel-based morphometry (VBM) studies which compared ASD (17 studies), ADHD (10 studies), and dyslexic (10 studies) participants with age-matched typically-developing (TD) controls. A second ALE analysis included studies in which the cerebellum was a region of interest (ROI). There were no regions of significantly increased gray matter (GM) in the cerebellum in ASD, ADHD, or dyslexia. Data from ASD studies revealed reduced GM in the inferior cerebellar vermis (lobule IX), left lobule VIIIB, and right Crus I. In ADHD, significantly decreased GM was found bilaterally in lobule IX, whereas participants with developmental dyslexia showed GM decreases in left lobule VI. There was no overlap between the cerebellar clusters identified in each disorder. We evaluated the functional significance of the regions revealed in both whole-brain and cerebellar ROI ALE analyses using Buckner and colleagues’ 7-network functional connectivity map available in the SUIT cerebellar atlas. The cerebellar regions identified in ASD showed functional connectivity with frontoparietal, default mode, somatomotor, and limbic networks; in ADHD, the clusters were part of dorsal and ventral attention networks; and in dyslexia, the clusters involved ventral attention, frontoparietal, and default mode networks. The results suggest that different cerebellar regions are affected in ASD, ADHD, and dyslexia, and these cerebellar regions participate in functional networks that are consistent with the characteristic symptoms of each disorder. Child Psychol Psychiatry. 2008 Dec;49(12):1287-95. doi: 10.1111/j.1469-7610.2008.01933.x. Epub 2008 Jul 29.
Distinct patterns of grey matter abnormality in high-functioning autism and Asperger’s syndrome.
- 1Department of Psychiatry, University of Hong Kong, Pokfulam, Hong Kong SAR China. firstname.lastname@example.org
Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger’s syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high-functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance imaging (MRI) studies of autism are in disagreement. One possible reason is that the diagnosis of autism takes precedence over Asperger’s syndrome and a distinction in language acquisition is rarely made. (WOW!) We therefore planned to examine a whole brain hypothesis that the patterns of grey matter differences in Asperger’s syndrome and HFA can be distinguished.
We used voxel-based computational morphometry to map grey matter volume differences in 33 children with either Asperger’s syndrome or high-functioning autism compared to 55 typical developing control children balanced for age, IQ, gender, maternal language and ethnicity.
Children with HFA had significantly smaller grey matter volumes in subcortical, posterior cingulate and precuneus regions than the Asperger’s group. Compared to controls, children with HFA had smaller grey matter volumes in predominantly fronto-pallidal regions, while children with Asperger’s had less grey matter in mainly bilateral caudate and left thalamus. In addition we found a significant negative correlation between the size of a grey matter cluster around BA44 language area and the age of acquisition of phrase speech in the children with HFA. When the groups were combined we confirmed a mixed picture of smaller grey matter volumes in frontal, basal ganglia, temporal and parietal regions.
Our study suggests that the underlying neurobiology in HFA and Asperger’s syndrome is at least partly discrete. Future studies should therefore consider the history of language acquisition as a valuable tool to refine investigation of aetiological factors and management options in pervasive developmental disorders.