Neuroconnectivity and valproic acid: The myelin hypothesis

• Published in: Neuroscience and biobehavioral reviews Vol. 36; no. 8; pp. 1848 - 1856
• Main Authors: ROSENZWEIG, Ivana, VUKADINOVIC, Zoran, TURNER, Anthony J, CATANI, Marco
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 01.09.2012
• Subjects: Animals; Behavioral psychophysiology; Biological and medical sciences; Brain - drug effects; Brain - growth & development; Child clinical studies; Developmental disorders; Epilepsy - drug therapy; Epilepsy - metabolism; Fundamental and applied biological sciences. Psychology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Indexing in process; Infantile autism; Medical sciences; Models, Animal; Myelin Sheath - metabolism; Nervous system (semeiology, syndromes); Neuroimaging; Neurology; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Valproic Acid - therapeutic use; Neuroplasticity; Nervous system diseases; 4-Aminobutyrate transaminase; Enzyme; Myelin; Transferases; Epilepsy; Enzyme inhibitor; Diffusion imaging; Developmental disorder; Anticonvulsant; Cognition; HDAC inhibitors; Review; Valproic acid; Cerebral disorder; Autism; Histone deacetylase inhibitor; Myelination; Brain plasticity; Mood stabilizer; Transaminases; Imaging; Central nervous system disease
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2012.05.006

Neuropsychiatric medications that directly alter the epigenome, such as valproic acid, can under certain conditions reactivate critical developmental periods and thus impact adult neuroconnectivity. In animal models valproic acid was shown to inhibit the process of postnatal myelination and to replicate age-dependent decline in remyelination efficiency. The human central nervous system's myelination process, unlike that of non-human primates commonly used in the experimental models, is an intricate heterochronous process that continues well into adult life and which probably underlies later life neurocognitive changes and plasticity. Chronic exposure to valproic acid, especially in patients with epilepsy and neuropsychiatric disorders, may profoundly affect this process and its developmental trajectory. Further studies using novel MRI methods that allow in vivo mapping of myelination trajectories across the lifespan are urgently required to address the potential effects of valproic acid on brain development.