The GABAergic effect is also believed to contribute towards the anti-manic properties of valproate. In animals, sodium valproate raises cerebral and cerebellar levels of the inhibitory synaptic neurotransmitter, GABA, possibly by inhibiting GABA degradative enzymes, such as GABA transaminase, succinate-semialdehyde dehydrogenase and by inhibiting the re-uptake of GABA by neuronal cells.Prevention of neurotransmitter-induced hyperexcitability of nerve cells, via Kv7.2 channel and AKAP5, may also contribute to its mechanism. Also, it has been shown to protect against a seizure-induced reduction in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) as a potential therapeutic mechanism.It also has histone-deacetylase-inhibiting effects. The inhibition of histone deacetylase, by promoting more transcriptionally active chromatin structures, likely presents the epigenetic mechanism for regulation of many of the neuroprotective effects attributed to valproic acid. Intermediate molecules mediating these effects include VEGF, BDNF, and GDNF. Endocrine actions
Valproic acid has been found to be an antagonist of the androgen and progesterone receptors, and hence as a nonsteroidal antiandrogen and antiprogestogen, at concentrations much lower than therapeutic serum levels. In addition, the drug has been identified as a potent aromatase inhibitor, and suppresses estrogen concentrations. These actions are likely to be involved in the reproductive endocrine disturbances seen with valproic acid treatment.Valproic acid has been found to directly stimulate androgen biosynthesis in the gonads via inhibition of histone deacetylases and has been associated with hyperandrogenism in women and increased 4-androstenedione levels in men. High rates of polycystic ovary syndrome and menstrual disorders have also been observed in women treated with valproic acid.
Often children (and adults) with dysgraphia will become extremely frustrated with the task of writing specially on plain paper (and spelling); younger children may cry, pout, or refuse to complete written assignments. This frustration can cause the student a great deal of stress and can lead to stress-related illnesses. This can be a result of any symptom of dysgraphia. Causes
The underlying causes of the disorder are not fully understood  But dysgraphia is as well known to be a biologically based disorder with genetic and brain bases. More specifically, it is a working memory problem caused by specific neurodevelopmental dysfunction. In dysgraphia, individuals fail to develop normal connections among different brain regions needed for writing. People with dysgraphia have difficulty in automatically remembering and mastering the sequence of motor movements required to write letters or numbers. Dysgraphia is also in part due to underlying problems in orthographic coding, the orthographic loop, and graphmotor output (the movements that result in writing) by ones hands, fingers and executive functions involved in letter writing. The orthographic loop is when written words are stored in the minds eye, connected through sequential finger movement for motor output through the hand with feedback from the eye.Family history of specific learning disabilities may play a role. Children with developmental dysphasia, developmental dysgraphia and developmental dyslexia may be more likely to have family members with one of these conditions. Genetic studies suggest that verbal executive function tasks, orthographic skills, and spelling ability may have a genetic basis.