Page 249 - Read Online

mechanism through which GADA develop and to 4. Duman RS. Pathophysiology of depression and innovative
clarify whether a genetic liability may play a role. treatments: remodeling glutamatergic synaptic connections.
Regarding the latter, it is of interest that a recent 5. Dialogues Clin Neurosci 2014;16:11‑27.
Berns GS, Nemeroff CB. The neurobiology of bipolar disorder. Am
pharmacogenomic analysis [70] in Han Chinese BD J Med Genet C Semin Med Genet 2003;123C: 76‑84.
patients found a strong association between glutamate 6. Jun C, Choi Y, Lim SM, Bae S, Hong YS, Kim JE, Lyoo IK.
decarboxylase‑like protein 1 (GADL1) gene and Disturbance of the glutamatergic system in mood disorders. Exp
response to lithium. The physiological functions of 7. Neurobiol 2014;23:28‑35.
Andreazza AC, Young LT. The neurobiology of bipolar disorder:
GADL1 gene are not clear, which may be, however, identifying targets for specific agents and synergies for combination
similar to those of GAD. treatment. Int J Neuropsychopharmacol 2014;17:1039‑52.
8. Brambilla P, Perez J, Barale F, Schettini G, Soares JC. GABAergic
CONCLUSION 9. dysfunction in mood disorders. Mol Psychiatry 2003;8:721‑37, 715.
Emrich HM, von Zerssen D, Kissling W, Moller HJ, Windorfer A.
Effect of sodium valproate on mania. The GABA‑hypothesis of
Several studies found that a decrease of brain GABA affective disorders. Arch Psychiatr Nervenkr 1980;229:1‑16.
levels in mood disorder cases can be associated with 10. Chiu CT, Wang Z, Hunsberger JG, Chuang DM. Therapeutic
manic or depressive states. This apparent incongruity potential of mood stabilizers lithium and valproic acid: beyond
bipolar disorder. Pharmacol Rev 2013;65:105‑42.
may indicate more a mood‑stabilizing role of GABA 11. Lan MJ, McLoughlin GA, Griffin JL, Tsang TM, Huang JT, Yuan P,
rather than an action on different mood phases. It Manji H, Holmes E, Bahn S. Metabonomic analysis identifies
remains to be established why GABA levels, both in molecular changes associated with the pathophysiology and drug
CNS and peripherally, might also present elevation treatment of bipolar disorder. Mol Psychiatry 2009;14:269‑79.
in specific clinical cases. In an attempt to clarify 12. Petty F, Schlesser MA. Plasma GABA in affective illness. A preliminary
investigation. J Affect Disord 1981;3:339‑43.
the mechanisms behind these abnormal levels of 13. Sanacora G, Mason GF, Rothman DL, Krystal JH. Increased
GABA in the brain, it has been hypothesized an occipital cortex GABA concentrations in depressed patients after
abnormal function of the enzyme GAD that catalyzes therapy with selective serotonin reuptake inhibitors. Am J Psychiatry
2002;159:663‑5.
the conversion from GLU to GABA. A weak action 14. Manyam NV, Katz L, Hare TA, Gerber JC 3rd, Grossman MH.
of this enzyme would justify decreased levels of the Levels of gamma‑aminobutyric acid in cerebrospinal fluid in various
neurotransmitter. The aforementioned lines of evidence neurologic disorders. Arch Neurol 1980;37:352‑5.
suggest that the autoantibody to GAD may be a possible 15. Gold BI, Bowers MB Jr, Roth RH, Sweeney DW. GABA levels
causative factor. If this is confirmed, a relatively simple in CSF of patients with psychiatric disorders. Am J Psychiatry
1980;137:362‑4.
test to assess the level of GADA may provide a better 16. Gerner RH, Hare TA. CSF GABA in normal subjects and patients
diagnosis of a mood disorder and to improve treatment. with depression, schizophrenia, mania, and anorexia nervosa. Am
J Psychiatry 1981;138:1098‑101.
If an abnormal level of this antibody is present as a trait 17. Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M,
rather than being associated with illness episodes, it Linnoila M, Hare TA, Shaywitz BA, Cohen DJ. CSF neurochemistry
would allow an early diagnosis of such prevalent and in depressed, manic, and schizophrenic patients compared with that
disabling disorder. of normal controls. Am J Psychiatry 1984;141:1533‑40.
18. Enna SJ, Stern LZ, Wastek GJ, Yamamura HI. Cerebrospinal fluid
gamma‑aminobutyric acid variations in neurological disorders. Arch
Financial support and sponsorship Neurol 1977;34:683‑5.
Nil. 19. Rimon R, Lepola U, Jolkkonen J, Halonen T, Riekkinen P.
Cerebrospinal fluid gamma‑aminobutyric acid in patients with panic
Conflicts of interest disorder. Biol Psychiatry 1995;38:737‑41.
There are no conflicts of interest. 20. Mann JJ, Oquendo MA, Watson KT, Boldrini M, Malone KM,
Ellis SP, Sullivan G, Cooper TB, Xie S, Currier D. Anxiety in major
depression and cerebrospinal fluid free gamma‑aminobutyric acid.
REFERENCES Depress Anxiety 2014;31:814‑21.
21. Vieira DS, Naffah‑Mazacoratti MG, Zukerman E, Senne Soares CA,
1. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Alonso EO, Faulhaber MH, Cavalheiro EA, Peres MF. Cerebrospinal
Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni L, Gannon B, fluid GABA levels in chronic migraine with and without depression.
Jones DH, Jennum P, Jordanova A, Jonsson L, Karampampa K, Brain Res 2006;1090:197‑201.
Knapp M, Kobelt G, Kurth T, Lieb R, Linde M, Ljungcrantz C, 22. Baldessarini RJ. Chemotherapy in Psychiatry. 1st ed. New York:
Maercker A, Melin B, Moscarelli M, Musayev A, Norwood F, Springer; 2013.
Preisig M, Pugliatti M, Rehm J, Salvador‑Carulla L, Schlehofer B, 23. Sartorius A, Mahlstedt MM, Vollmayr B, Henn FA, Ende G. Elevated
Simon R, Steinhausen HC, Stovner LJ, Vallat JM, Van den Bergh P, spectroscopic glutamate/gamma‑amino butyric acid in rats bred for
van Os J, Vos P, Xu W, Wittchen HU, Jonsson B, Olesen J, learned helplessness. Neuroreport 2007;18:1469‑73.
Group CD. Cost of disorders of the brain in Europe 2010. Eur 24. Luo J, Min S, Wei K, Li P, Dong J, Liu YF. Propofol protects against
Neuropsychopharmacol 2011;21:718‑79. impairment of learning‑memory and imbalance of hippocampal
2. Kessler RC. The global burden of anxiety and mood disorders: Glu/GABA induced by electroconvulsive shock in depressed rats.
putting the European Study of the Epidemiology of Mental J Anesth 2011;25:657‑65.
Disorders (ESEMeD) findings into perspective. J Clin Psychiatry 25. Fosse R, Read J. Electroconvulsive treatment: hypotheses about
2007;68 Suppl 2:10‑9. mechanisms of action. Front Psychiatry 2013;4:94.
3. World Health Organization. The Global Burden of Disease: 2004 26. Sanacora G, Mason GF, Rothman DL, Hyder F, Ciarcia JJ,
Update. Geneva: The World Health Organization; 2008. Ostroff RB, Berman RM, Krystal JH. Increased cortical GABA

240 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 241