Gabaergic dysfunction in mood disorders

ABSTRACT The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. γ-Aminobutyric acid (GABA) is an

inhibitory neurotransmitter present almost exclusively in the central nervous system (CNS), distributed across almost all brain regions, and expressed in interneurons modulating local

circuits. The role of GABAergic _dysfunction_ in mood disorders was first proposed 20 years ago. Preclinical studies have suggested that GABA levels may be decreased in animal models of

depression, and clinical studies reported low plasma and CSF GABA levels in mood disorder patients. Also, antidepressants, mood stabilizers, electroconvulsive therapy, and GABA agonists have

been shown to reverse the depression-like behavior in animal models and to be effective in unipolar and bipolar patients by increasing brain GABAergic activity. The hypothesis of reduced

GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these

disorders. However, low GABAergic cortical function may probably be a feature of a subset of mood disorder patients, representing a genetic susceptibility. In this paper, we discuss the

status of GABAergic hypothesis of mood disorders and suggest possible directions for future preclinical and clinical research in this area. Access through your institution Buy or subscribe

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calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Zachmann M, Tocci P, Nyhan WL

. The occurrence of gamma-aminobutyric acid in human tissues other than brain. _J Biol Chem_ 1966; 241: 1355–1358. Article  CAS  PubMed  Google Scholar  * Otsuka M, Iversen LL, Hall ZW,

Kravitz EA . Release of gamma-aminobutyric acid from inhibitory nerves of lobster. _Proc Natl Acad Sci USA_ 1966; 56: 1110–1115. Article  CAS  PubMed  PubMed Central  Google Scholar  *

Meldrum B . Pharmacology of GABA. _Clin Neuropharmacol_ 1982; 5: 293–316. Article  CAS  PubMed  Google Scholar  * Guidotti A, Corda MG, Wise BC, Vaccarino F, Costa E . GABAergic synapses.

Supramolecular organization and biochemical regulation. _Neuropharmacology_ 1983; 22: 1471–1479. Article  CAS  PubMed  Google Scholar  * Emrich HM, von Zerssen D, Kissling W, Moller HJ,

Windorfer A . Effect of sodium valproate on mania. The GABA-hypothesis of affective disorders. _Archiv Psychiatrie Nervenkrankheiten_ 1980; 229: 1–16. Article  CAS  Google Scholar  * Massat

I, Sourey D, Papadimitriou GN, Mendlewicz J . The GABAergic hypothesis of mood disorders. In: Soares JC, Gershon S (eds). _Bipolar Disorders, Basic Mechanisms and Therapeutic Implication_.

Marcel Dekker: New York, 2000, pp. 143–165. Google Scholar  * Peng L, Hertz L, Huang R, Sonnewald U, Petersen SB, Westergaard N _et al_. Utilization of glutamine and of TCA cycle

constituents as precursors for transmitter glutamate and GABA. _Dev Neurosci_ 1993; 15: 367–377. Article  CAS  PubMed  Google Scholar  * Schousboe A, Westergaard N, Sonnewald U, Petersen SB,

Huang R, Peng L _et al_. Glutamate and glutamine metabolism and compartmentation in astrocytes. _Dev Neurosci_ 1993; 15: 359–366. Article  CAS  PubMed  Google Scholar  * Durkin MM, Smith

KE, Borden LA, Weinshank RL, Branchek TA, Gustafson EL . Localization of messenger RNAs encoding three GABA transporters in rat brain: an _in situ_ hybridization study. _Brain Res Mol Brain

Res_ 1995; 33: 7–21. Article  CAS  PubMed  Google Scholar  * Borden LA . GABA transporter heterogeneity: pharmacology and cellular localization. _Neurochem Int_ 1996; 29: 335–356. Article 

CAS  PubMed  Google Scholar  * Cherubini E, Conti F . Generating diversity at GABAergic synapses. _Trends Neurosci_ 2001; 24: 155–162. Article  CAS  PubMed  Google Scholar  * Erlander MG,

Tillakaratne NJ, Feldblum S, Patel N, Tobin AJ . Two genes encode distinct glutamate decarboxylases. _Neuron_ 1991; 7: 91–100. Article  CAS  PubMed  Google Scholar  * Eder M, Rammes G,

Zieglgansberger W, Dodt H-U . GABAA and GABAB receptors on neocortical neurons are differentialy distributed. _Eur J Neurosci_ 2001; 13: 1065–1069. Article  CAS  PubMed  Google Scholar  *

Costa E, Auta J, Grayson DR, Matsumoto K, Pappas GD, Zhang X _et al_. GABAA receptors and benzodiapines: a role for dendritic resident subunit mRNAs. _Neuropharmacology_ 2002; 43: 925–937.

Article  CAS  PubMed  Google Scholar  * Bormann J . Electrophysiology of GABAA and GABAB receptor subtypes. _Trends Neurosci_ 1988; 11: 112–116. Article  CAS  PubMed  Google Scholar  *

Macdonald RL, Twyman RE, Ryan-Jastrow T, Angelotti TP . Regulation of GABAA receptor channels by anticonvulsant and convulsant drugs and by phosphorylation. _Epilepsy Res Suppl_ 1992; 9:

265–277. CAS  PubMed  Google Scholar  * Haefely W, Kulcsar A, Mohler H . Possible involvement of GABA in the central actions of benzodiazepines. _Psychopharmacol Bull_ 1975; 11: 58–59. CAS 

PubMed  Google Scholar  * Nicoll RA, Eccles JC, Oshima T, Rubia F . Prolongation of hippocampal inhibitory postsynaptic potentials by barbiturates. _Nature_ 1975; 258: 625–627. Article  CAS

  PubMed  Google Scholar  * Narahashi T, Arakawa O, Brunner EA, Nakahiro M, Nishio M, Ogata N _et al_. Modulation of GABA receptor-channel complex by alcohols and general anesthetics. _Adv

Biochem Psychopharmacol_ 1992; 47: 325–334. CAS  PubMed  Google Scholar  * Mhatre M, Ticku MK . Chronic ethanol treatment upregulates the GABA receptor beta subunit expression. _Brain Res

Mol Brain Res_ 1994; 23: 246–252. Article  CAS  PubMed  Google Scholar  * Curtis DR, Duggan AW, Felix D, Johnston GA . Bicuculline and central GABA receptors. _Nature_ 1970; 228: 676–677.

Article  CAS  PubMed  Google Scholar  * Bowery NG, Bettler B, Froestl W, Gallagher JP, Marshall F, Raiteri M _et al_. International Union of Pharmacology. XXXIII. Mammalian

gamma-aminobutyric acid(B) receptors: structure and function. _Pharmacol Rev_ 2002; 54: 247–264. Article  CAS  PubMed  Google Scholar  * Karbon EW, Duman RS, Enna SJ . GABAB receptors and

norepinephrine-stimulated cAMP production in rat brain cortex. _Brain Res_ 1984; 306: 327–332. Article  CAS  PubMed  Google Scholar  * Pycock CJ, Horton RW . Dopamine-dependent hyperactivity

in the rat following manipulation of GABA mechanisms in the region of the nucleus accumbens. _J Neural Transm_ 1979; 45: 17–33. Article  CAS  PubMed  Google Scholar  * Jones MW, Kilpatrick

IC, Phillipson OT . Dopamine function in the prefrontal cortex of the rat is sensitive to a reduction of tonic GABA-mediated inhibition in the thalamic mediodorsal nucleus. _Exp Brain Res_

1988; 69: 623–634. Article  CAS  PubMed  Google Scholar  * Reid M, Herrera-Marschitz M, Hokfelt T, Terenius L, Ungerstedt U . Differential modulation of striatal dopamine release by

intranigral injection of gamma-aminobutyric acid (GABA), dynorphin A and substance P. _Eur J Pharmacol_ 1988; 147: 411–420. Article  CAS  PubMed  Google Scholar  * Benes FM, Vincent SL,

Molloy R . Dopamine-immunoreactive axon varicosities form nonrandom contacts with GABA-immunoreactive neurons of rat medial prefrontal cortex. _Synapse_ 1993; 15: 285–295. Article  CAS 

PubMed  Google Scholar  * Dewey SL, Smith GS, Logan J, Brodie JD, Yu DW, Ferrieri RA _et al_. GABAergic inhibition of endogenous dopamine release measured _in vivo_ with 11C-raclopride and

positron emission tomography. _J Neurosci_ 1992; 12: 3773–3780. Article  CAS  PubMed  PubMed Central  Google Scholar  * Schiffer WK, Gerasimov MR, Bermel RA, Brodie JD, Dewey SL .

Stereoselective inhibition of dopaminergic activity by gamma vinyl-GABA following a nicotine or cocaine challenge: a PET/microdialysis study. _Life Sci_ 2000; 66: L169–L173. Article  Google

Scholar  * Ring HA, Trimble MR, Costa DC, George MS, Verhoeff P, Ell PJ . Effect of vigabatrin on striatal dopamine receptors: evidence in humans for interactions of GABA and dopamine

systems. _J Neurol Neurosurg Psychiatry_ 1992; 55: 758–761. Article  CAS  PubMed  PubMed Central  Google Scholar  * Garbutt JC, van Kammen DP . The interaction between GABA and dopamine:

implications for schizophrenia. _Schizophr Bull_ 1983; 9: 336–353. Article  CAS  PubMed  Google Scholar  * Evangelista S, Borsini F, Meli A . Evidence that muscimol acts in the forced

swimming test by activating the rat dopaminergic system. _Life Sci_ 1987; 41: 2679–2684. Article  CAS  PubMed  Google Scholar  * Bonanno G, Raiteri M . Coexistence of carriers for dopamine

and GABA uptake on a same nerve terminal in the rat brain. _Br J Pharmacol_ 1987; 91: 237–243. Article  CAS  PubMed  PubMed Central  Google Scholar  * Retaux S, Besson MJ, Penit-Soria J .

Opposing effects of dopamine D2 receptor stimulation on the spontaneous and the electrically evoked release of [3H]GABA on rat prefrontal cortex slices. _Neuroscience_ 1991; 42: 61–71.

Article  CAS  PubMed  Google Scholar  * Floran B, Floran L, Sierra A, Aceves J . D2 receptor-mediated inhibition of GABA release by endogenous dopamine in the rat globus pallidus. _Neurosci

Lett_ 1997; 237: 1–4. Article  CAS  PubMed  Google Scholar  * Grobin AC, Deutch AY . Dopaminergic regulation of extracellular gamma-aminobutyric acid levels in the prefrontal cortex of the

rat. _J Pharmacol Exp Ther_ 1998; 285: 350–357. CAS  PubMed  Google Scholar  * Harsing Jr LG, Zigmond MJ . Influence of dopamine on GABA release in striatum: evidence for D1−D2 interactions

and non-synaptic influences. _Neuroscience_ 1997; 77: 419–429. Article  CAS  PubMed  Google Scholar  * Seamans JK, Gorelova N, Durstewitz D, Yang CR . Bidirectional dopamine modulation of

GABAergic inhibition in prefrontal cortical pyramidal neurons. _J Neurosci_ 2001; 21: 3628–3638. Article  CAS  PubMed  PubMed Central  Google Scholar  * Wang X, Zhong P, Yan Z . Dopamine D4

receptors modulate GABAergic signaling in pyramidal neurons of prefrontal cortex. _J Neurosci_ 2002; 22: 9185–9193. Article  CAS  PubMed  PubMed Central  Google Scholar  * Cobb WS,

Abercrombie ED . Distinct roles for nigral GABA and glutamate receptors in the regulation of dendritic dopamine release under normal conditions and in response to systemic haloperidol. _J

Neurosci_ 2002; 22: 1407–1413. Article  CAS  PubMed  PubMed Central  Google Scholar  * Biswas B, Carlsson A . The effect of intracerebroventricularly administered GABA on brain monoamine

metabolism. _Naunyn Schmiedebergs Arch Pharmacol_ 1977; 299: 41–46. Article  CAS  PubMed  Google Scholar  * Biswas B, Carlsson A . The effect of intraperitoneally administered GABA on brain

monoamine metabolism. _Naunyn Schmiedebergs Arch Pharmacol_ 1977; 299: 47–51. Article  CAS  PubMed  Google Scholar  * Scatton B, Zivkovic B, Dedek J, Lloyd KG, Constantinidis J, Tissot R _et

al_. Gamma-Aminobutyric acid (GABA) receptor stimulation. III. Effect of progabide (SL 76002) on norepinephrine, dopamine and 5-hydroxytryptamine turnover in rat brain areas. _J Pharmacol

Exp Ther_ 1982; 220: 678–688. CAS  PubMed  Google Scholar  * Scatton B, Lloyd KG, Zivkovic B, Dennis T, Claustre Y, Dedek J _et al_. Fengabine, a novel antidepressant GABAergic agent. II.

Effect on cerebral noradrenergic, serotonergic and GABAergic transmission in the rat. _J Pharmacol Exp Ther_ 1987; 241: 251–257. CAS  PubMed  Google Scholar  * Suzdak PD, Gianutsos G .

Differential coupling of GABA-A and GABA-B receptors to the noradrenergic system. _J Neural Transm_ 1985; 62: 77–89. Article  CAS  PubMed  Google Scholar  * Bonanno G, Raiteri M . Carriers

for GABA and noradrenaline uptake coexist on the same nerve terminal in rat hippocampus. _Eur J Pharmacol_ 1987; 136: 303–310. Article  CAS  PubMed  Google Scholar  * Bonanno G, Raiteri M .

Release-regulating GABAA receptors are present on noradrenergic nerve terminals in selective areas of the rat brain. _Synapse_ 1987; 1: 254–257. Article  CAS  PubMed  Google Scholar  *

Suzdak PD, Gianutsos G . Parallel changes in the sensitivity of gamma-aminobutyric acid and noradrenergic receptors following chronic administration of antidepressant and GABAergic drugs. A

possible role in affective disorders. _Neuropharmacology_ 1985; 24: 217–222. Article  CAS  PubMed  Google Scholar  * Ferraro L, Tanganelli S, Calo G, Antonelli T, Fabrizi A, Acciarri N _et

al_. Noradrenergic modulation of gamma-aminobutyric acid outflow from the human cerebral cortex. _Brain Res_ 1993; 629: 103–108. Article  CAS  PubMed  Google Scholar  * Mitoma H, Konishi S .

Monoaminergic long-term facilitation of GABA-mediated inhibitory transmission at cerebellar synapses. _Neuroscience_ 1999; 88: 871–883. Article  CAS  PubMed  Google Scholar  * Nishikawa T,

Scatton B . Evidence for a GABAergic inhibitory influence on serotonergic neurons originating from the dorsal raphe. _Brain Res_ 1983; 279: 325–329. Article  CAS  PubMed  Google Scholar  *

Nishikawa T, Tanaka M, Tsuda A, Kohno Y, Nagasaki N . Serotonergic−catecholaminergic interactions and foot shock-induced jumping behavior in rats. _Eur J Pharmacol_ 1983; 94: 53–58. Article

  CAS  PubMed  Google Scholar  * Nishikawa T, Scatton B . Inhibitory influence of GABA on central serotonergic transmission. Raphe nuclei as the neuroanatomical site of the GABAergic

inhibition of cerebral serotonergic neurons. _Brain Res_ 1985; 331: 91–103. Article  CAS  PubMed  Google Scholar  * Francois-Bellan AM, Hery M, Faldon M, Hery F . Evidence for GABA on

serotonin metabolism in the rat suprachiasmatic area. _Neurochem Int_ 1988; 134: 455–462. Article  Google Scholar  * Bagdy E, Kiraly I, Harsing LG . Reciprocal innervation between

serotonergic and GABAergic neurons in raphe nuclei of the rat. _Neurochem Res_ 2000; 25: 1465–1473. Article  CAS  PubMed  Google Scholar  * Shen RY, Andrade R . 5-Hydroxytryptamine2 receptor

facilitates GABAergic neurotransmission in rat hippocampus. _J Pharmacol Exp Ther_ 1998; 285: 805–812. CAS  PubMed  Google Scholar  * Abi-Saab WM, Bubser M, Roth RH, Deutch AY . 5-HT2

receptor regulation of extracellular GABA levels in the prefrontal cortex. _Neuropsychopharmacology_ 1999; 20: 92–96. Article  CAS  PubMed  Google Scholar  * Liu R, Jolas T, Aghajanian G .

Serotonin 5-HT(2) receptors activate local GABA inhibitory inputs to serotonergic neurons of the dorsal raphe nucleus. _Brain Res_ 2000; 873: 34–45. Article  CAS  PubMed  Google Scholar  *

Green AR, Johnson P, Mountford JA, Nimgaonkar VL . Some anticonvulsant drugs alter monoamine-mediated behaviour in mice in ways similar to electroconvulsive shock; implications for

antidepressant therapy. _Br J Pharmacol_ 1985; 84: 337–346. Article  CAS  PubMed  PubMed Central  Google Scholar  * Metz A, Goodwin GM, Green AR . The administration of baclofen to mice

increases 5-HT2-mediated head-twitch behaviour and 5-HT2 receptor number in frontal cortex. _Neuropharmacology_ 1985; 24: 357–360. Article  CAS  PubMed  Google Scholar  * Gray JA, Metz A,

Goodwin GM, Green AR . The effects of the GABA-mimetic drugs, progabide and baclofen, on the biochemistry and function of 5-hydroxytryptamine and noradrenaline. _Neuropharmacology_ 1986; 25:

711–716. Article  CAS  PubMed  Google Scholar  * Sibille E, Pavlides C, Benke D, Toth M . Genetic inactivation of the Serotonin(1A) receptor in mice results in downregulation of major

GABA(A) receptor alpha subunits, reduction of GABA(A) receptor binding, and benzodiazepine-resistant anxiety. _J Neurosci_ 2000; 20: 2758–2765. Article  CAS  PubMed  PubMed Central  Google

Scholar  * Maggi A, Perez J . Role of female gonadal hormones in the CNS: clinical and experimental aspects. _Life Sci_ 1985; 37: 893–906. Article  CAS  PubMed  Google Scholar  * Perez J,

Zucchi A, Maggi A . Sexual dimorphism in the response of the GABAergic system to estrogen administration. _J Neurochem_ 1986; 47: 1798–1803. Article  CAS  PubMed  Google Scholar  * McEwen BS

. Non-genomic and genomic effects of steroids on neural activity. _Trends Pharmacol Sci_ 1991; 12: 141–147. Article  CAS  PubMed  Google Scholar  * van Broekhoven F, Verkes RJ .

Neurosteroids in depression: a review. _Psychopharmacology_ 2003; 165: 97–110. Article  CAS  PubMed  Google Scholar  * Do-Rego JL, Mensah-Nyagan GA, Beaujean D, Vaudry D, Sieghart W, Luu-The

V _et al_. Gamma-Aminobutyric acid, acting through gamma-aminobutyric acid type A receptors, inhibits the biosynthesis of neurosteroids in the frog hypothalamus. _Proc Natl Acad Sci USA_

2000; 97: 13925–13930. Article  CAS  PubMed  PubMed Central  Google Scholar  * Haage D, Druzin M, Johansson S . Allopregnanolone modulates spontaneous GABA release via presynaptic Cl−

permeability in rat preoptic nerve terminals. _Brain Res_ 2002; 958: 405–413. Article  CAS  PubMed  Google Scholar  * McIntyre KL, Porter DM, Henderson LP . Anabolic androgenic steroids

induce age-, sex-, and dose-dependent changes in GABAA receptor subunit mRNAs in the mouse forebrain. _Neuropharmacology_ 2002; 43: 634–645. Article  CAS  PubMed  Google Scholar  * Porsolt

RD, Anton G, Blavet N, Jalfre M . Behavioural despair in rats: a new model sensitive to antidepressant treatments. _Eur J Pharmacol_ 1978; 47: 379–391. Article  CAS  PubMed  Google Scholar 

* Mancinelli A, D'Aranno V, Borsini F, Meli A . Lack of relationship between effect of desipramine on forced swimming test and brain levels of desipramine or its demethylated metabolite

in rats. _Psychopharmacology_ 1987; 92: 441–443. Article  CAS  PubMed  Google Scholar  * Borsini F, Mancinelli A, D'Aranno V, Evangelista S, Meli A . On the role of endogenous GABA in

the forced swimming test in rats. _Pharmacol Biochem Behav_ 1987; 29: 275–279. Article  Google Scholar  * Poncelet M, Martin P, Danti S, Simon P, Soubrie P . Noradrenergic rather than

GABAergic processes as the common mediation of the antidepressant profile of GABA agonists and imipraminelike drugs in animals. _Pharmacol Biochem Behav_ 1987; 28: 321–326. Article  CAS 

PubMed  Google Scholar  * Seligman ME, Maier SF . Failure to escape traumatic shock. _J Exp Psychol_ 1967; 74: 1–9. Article  CAS  PubMed  Google Scholar  * Sherman AD, Petty F .

Neurochemical basis of the action of antidepressants on learned helplessness. _Behav Neural Biol_ 1980; 30: 119–134. Article  CAS  PubMed  Google Scholar  * Petty F, Sherman AD . GABAergic

modulation of learned helplessness. _Pharmacol Biochem Behav_ 1981; 15: 567–570. Article  CAS  PubMed  Google Scholar  * Sherman AD, Petty F . Additivity of neurochemical changes in learned

helplessness and imipramine. _Behav Neural Biol_ 1982; 35: 344–353. Article  CAS  PubMed  Google Scholar  * Lloyd KG, Morselli PL, Depoortere H, Fournier V, Zivkovic B, Scatton B _et al_.

The potential use of GABA agonists in psychiatric disorders: evidence from studies with progabide in animal models and clinical trials. _Pharmacol Biochem Behav_ 1983; 18: 957–966. Article 

CAS  PubMed  Google Scholar  * Drugan RC, Morrow AL, Weizman R, Weizman A, Deutsch SI, Crawley JN _et al_. Stress-induced behavioral depression in the rat is associated with a decrease in

GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy. _Brain Res_ 1989; 487: 45–51. Article  CAS  PubMed  Google Scholar  * Nakagawa Y, Ishima T, Ishibashi Y,

Tsuji M, Takashima T . Involvement of GABAB receptor systems in experimental depression: baclofen but not bicuculline exacerbates helplessness in rats. _Brain Res_ 1996; 741: 240–245.

Article  PubMed  Google Scholar  * Nakagawa Y, Ishima T, Ishibashi Y, Tsuji M, Takashima T . Involvement of GABAB receptor systems in action of antidepressants. II: Baclofen attenuates the

effect of desipramine whereas muscimol has no effect in learned helplessness paradigm in rats. _Brain Res_ 1996; 728: 225–230. Article  CAS  PubMed  Google Scholar  * Martin P, Pichat P,

Massol J, Soubrie P, Lloyd KG, Puech AJ . Decreased GABA B receptors in helpless rats: reversal by tricyclic antidepressants. _Neuropsychobiology_ 1989; 22: 220–224. Article  CAS  PubMed 

Google Scholar  * Plaznik A, Tamborska E, Hauptmann M, Bidzinski A, Kostowski W . Brain neurotransmitter systems mediating behavioral deficits produced by inescapable shock treatment in

rats. _Brain Res_ 1988; 447: 122–132. Article  CAS  PubMed  Google Scholar  * Corda MG, Blaker WD, Mendelson WB, Guidotti A, Costa E . beta-Carbolines enhance shock-induced suppression of

drinking in rats. _Proc Natl Acad Sci USA_ 1983; 80: 2072–2076. Article  CAS  PubMed  PubMed Central  Google Scholar  * Drugan RC, Maier SF, Skolnick P, Paul SM, Crawley JN . An anxiogenic

benzodiazepine receptor ligand induces learned helplessness. _Eur J Pharmacol_ 1985; 113: 453–457. Article  CAS  PubMed  Google Scholar  * Guidotti A, Ferrero P, Costa E . On the brain

endocoid for benzodiazepine recognition sites. _Prog Clin Biol Res_ 1985; 192: 477–484. CAS  PubMed  Google Scholar  * Kelly JP, Wrynn AS, Leonard BE . The olfactory bulbectomized rat as a

model of depression: an update. _Pharmacol Ther_ 1997; 74: 299–316. Article  CAS  PubMed  Google Scholar  * Jancsar SM, Leonard BE . Changes in neurotransmitter metabolism following

olfactory bulbectomy in the rat. _Prog Neuropsychopharmacol Biol Psychiatry_ 1984; 8: 263–269. Article  CAS  PubMed  Google Scholar  * Lloyd KG, Pichat P . Decrease in GABAB binding to the

frontal cortex of olfactory bulbectomized rats. _Br J Pharmacol_ 1986; 87: 36. Google Scholar  * Dennis T, Beauchemin V, Lavoie N . Differential effects of olfactory bulbectomy on GABAA and

GABAB receptors in the rat brain. _Pharmacol Biochem Behav_ 1993; 46: 77–82. Article  CAS  PubMed  Google Scholar  * Joly D, Lloyd KG, Pichat P, Sanger DJ . Correlation between the

behavioral effect of desipramine and GABAB receptor regulation in the olfactory bulbectomized rat. _Br J Pharmacol_ 1987; 90: 125. Google Scholar  * Leonard BE, Tuite M . Anatomical,

physiological, and behavioral aspects of olfactory bulbectomy in the rat. _Int Rev Neurobiol_ 1981; 22: 251–286. Article  CAS  PubMed  Google Scholar  * Lloyd KG, Zivkovic B, Sanger D,

Depoortere H, Bartholini G . Fengabine, a novel antidepressant GABAergic agent. I. Activity in models for antidepressant drugs and psychopharmacological profile. _J Pharmacol Exp Ther_ 1987;

241: 245–250. CAS  PubMed  Google Scholar  * Grove J, Schechter PJ, Hanke NF, de Smet Y, Agid Y, Tell G _et al_. Concentration gradients of free and total gamma-aminobutyric acid and

homocarnosine in human CSF: comparison of suboccipital and lumbar sampling. _J Neurochem_ 1982; 39: 1618–1622. Article  CAS  PubMed  Google Scholar  * Loscher W . Relationship between GABA

concentrations in cerebrospinal fluid and seizure excitability. _J Neurochem_ 1982; 38: 293–295. Article  CAS  PubMed  Google Scholar  * Gold BI, Bowers Jr MB, Roth RH, Sweeney DW . GABA

levels in CSF of patients with psychiatric disorders. _Am J Psychiatry_ 1980; 137: 362–364. Article  CAS  PubMed  Google Scholar  * Kasa K, Otsuki S, Yamamoto M, Sato M, Kuroda H, Ogawa N .

Cerebrospinal fluid gamma-aminobutyric acid and homovanillic acid in depressive disorders. _Biol Psychiatry_ 1982; 17: 877–883. CAS  PubMed  Google Scholar  * Berrettini WH, Nurnberger Jr

JI, Hare TA, Simmons-Alling S, Gershon ES, Post RM . reduced plasma and CSF gamma-aminobutyric acid in affective illness: effect of lithium carbonate. _Biol Psychiatry_ 1983; 18: 185–194.

CAS  PubMed  Google Scholar  * Gerner RH, Hare TA . CSF GABA in normal subjects and patients with depression, schizophrenia, mania, and anorexia nervosa. _Am J Psychiatry_ 1981; 138:

1098–1101. Article  CAS  PubMed  Google Scholar  * Gerner RH, Fairbanks L, Anderson GM, Young JG, Scheinin M, Linnoila M _et al_. CSF neurochemistry in depressed, manic, and schizophrenic

patients compared with that of normal controls. _Am J Psychiatry_ 1984; 141: 1533–1540. Article  CAS  PubMed  Google Scholar  * Post RM, Ballenger JC, Hare TA, Goodwin FK, Lake CR, Jimerson

DC _et al_. Cerebrospinal fluid GABA in normals and patients with affective disorders. _Brain Res Bull_ 1980; 5 (Suppl 2): 755–759. Article  Google Scholar  * Berrettini WH, Nurnberger Jr

JI, Hare TA, Simmons-Alling S, Gershon ES . CSF GABA in euthymic manic-depressive patients and controls. _Biol Psychiatry_ 1986; 21: 844–846. Article  CAS  PubMed  Google Scholar  * Joffe R,

Post R, Rubinow D, Berrettini W, Hare T, Ballenger J _et al_. Cerebrospinal fluid GABA in manic-depressive illness. In: Bartholini G, Lloyd K, Morselli P (eds). _GABA and Mood Disorders:

Experimental and Clinical Research_. Raven Press: New York, 1986. Google Scholar  * Petty F, Kramer G, Feldman M . Is plasma GABA of peripheral origin? _Biol Psychiatry_ 1987; 22: 725–732.

Article  CAS  PubMed  Google Scholar  * Petty F . Plasma concentrations of gamma-aminobutyric acid (GABA) and mood disorders: a blood test for manic depressive disease? _Clin Chem_ 1994; 40:

296–302. Article  CAS  PubMed  Google Scholar  * Ferkany JW, Smith LA, Seifert WE, Caprioli RM, Enna SJ . Measurement of gamma-aminobutyric acid (GABA) in blood. _Life Sci_ 1978; 22:

2121–2128. Article  CAS  PubMed  Google Scholar  * Bohlen P, Huot S, Palfreyman MG . The relationship between GABA concentrations in brain and cerebrospinal fluid. _Brain Res_ 1979; 167:

297–305. Article  CAS  PubMed  Google Scholar  * Ferkany JW, Butler IJ, Enna SJ . Effect of drugs on rat brain, cerebrospinal fluid and blood GABA content. _J Neurochem_ 1979; 33: 29–33.

Article  CAS  PubMed  Google Scholar  * Loscher W . GABA in plasma and cerebrospinal fluid of different species. Effects of gamma-acetylenic GABA, gamma-vinyl GABA and sodium valproate. _J

Neurochem_ 1979; 32: 1587–1591. Article  CAS  PubMed  Google Scholar  * Apud JA, Racagni G, Iuliano E, Cocchi D, Casanueva F, Muller EE . Role of central nervous system-derived or

circulating gamma-aminobutyric acid on prolactin secretion in the rat. _Endocrinology_ 1981; 108: 1505–1510. Article  CAS  PubMed  Google Scholar  * Loscher W, Frey HH . Transport of GABA at

the blood−CSF interface. _J Neurochem_ 1982; 38: 1072–1079. Article  CAS  PubMed  Google Scholar  * Uhlhaas S, Lange H, Wappenschmidt J, Olek K . Free and conjugated CSF and plasma GABA in

Huntington's chorea. _Acta Neurol Scand_ 1986; 74: 261–265. Article  CAS  PubMed  Google Scholar  * Loscher W, Rating D, Siemes H . GABA in cerebrospinal fluid of children with febrile

convulsions. _Epilepsia_ 1981; 22: 697–702. Article  CAS  PubMed  Google Scholar  * Schmidt D, Loscher W . Plasma and cerebrospinal fluid gamma-aminobutyric acid in neurological disorders.

_J Neurol Neurosurg Psychiatry_ 1982; 45: 931–935. Article  CAS  PubMed  PubMed Central  Google Scholar  * Berrettini WH, Nurnberger Jr JI, Hare T, Gershon ES, Post RM . Plasma and CSF GABA

in affective illness. _Br J Psychiatry_ 1982; 141: 483–487. Article  CAS  PubMed  Google Scholar  * Petty F, Schlesser MA . Plasma GABA in affective illness. A preliminary investigation. _J

Affect Disord_ 1981; 3: 339–343. Article  CAS  PubMed  Google Scholar  * Petty F, Sherman AD . Plasma GABA levels in psychiatric illness. _J Affect Disord_ 1984; 6: 131–138. Article  CAS 

PubMed  Google Scholar  * Petty F, Kramer GL, Dunnam D, Rush AJ . Plasma GABA in mood disorders. _Psychopharmacol Bull_ 1990; 26: 157–161. CAS  PubMed  Google Scholar  * Petty F, Kramer GL,

Gullion CM, Rush AJ . Low plasma gamma-aminobutyric acid levels in male patients with depression. _Biol Psychiatry_ 1992; 32: 354–363. Article  CAS  PubMed  Google Scholar  * Petty F, Kramer

GL, Fulton M, Moeller FG, Rush AJ . Low plasma GABA is a trait-like marker for bipolar illness. _Neuropsychopharmacol_ 1993; 9: 125–132. Article  CAS  Google Scholar  * Petty F, Steinberg

J, Kramer GL, Fulton M, Moeller FG . Desipramine does not alter plasma GABA in patients with major depression. _J Affect Disord_ 1993; 29: 53–56. Article  CAS  PubMed  Google Scholar  *

Petty F, Kramer GL, Fulton M, Davis L, Rush AJ . Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression. _Biol Psychiatry_ 1995; 37: 806–810. Article 

CAS  PubMed  Google Scholar  * Prosser J, Hughes CW, Sheikha S, Kowatch RA, Kramer GL, Rosenbarger N _et al_. Plasma GABA in children and adolescents with mood, behavior, and comorbid mood

and behavior disorders: a preliminary study. _J Child Adolesc Psychopharmacol_ 1997; 7: 181–199. Article  CAS  PubMed  Google Scholar  * Petty F, Kramer G . Stability of plasma

gamma-aminobutyric acid with time in healthy controls. _Biol Psychiatry_ 1992; 31: 743–745. Article  CAS  PubMed  Google Scholar  * Schulz P, Lustenberger S, Degli Agosti R, Rivest RW .

Plasma concentration of nine hormones and neurotransmitters during usual activities or constant bed rest for 34 H. _Chronobiol Int_ 1994; 11: 367–380. Article  CAS  PubMed  Google Scholar  *

Schulz P, Lloyd KG, Voltz C, Lustenberger S, Agosti RD . The plasma concentration of GABA shows no evidence of a circadian rhythm and is stable over weeks in normal males. _Biol Rhythm Res_

1994; 25: 291–300. Article  CAS  Google Scholar  * Berrettini WH, Umberkoman-Wiita B, Nurnberger Jr. JI, Vogel WH, Gershon ES, Post RM . Platelet GABA-transaminase in affective illness.

_Psychiatry Res_ 1982; 7: 255–260. Article  CAS  PubMed  Google Scholar  * Kaiya H, Namba M, Yoshida H, Nakamura S . Plasma glutamate decarboxylase activity in neuropsychiatry. _Psychiatry

Res_ 1982; 6: 335–343. Article  CAS  PubMed  Google Scholar  * Nurnberger Jr. JI, Berrettini WH, Simmons-Alling S, Guroff JJ, Gershon ES . Intravenous GABA administration is anxiogenic in

man. _Psychiatry Res_ 1986; 19: 113–117. Article  PubMed  Google Scholar  * Devanand DP, Shapira B, Petty F, Kramer G, Fitzsimons L, Lerer B _et al_. Effects of electroconvulsive therapy on

plasma GABA. _Convuls Ther_ 1995; 11: 3–13. CAS  PubMed  Google Scholar  * Petty F, Rush AJ, Davis JM, Calabrese JR, Kimmel SE, Kramer GL _et al_. Plasma GABA predicts acute response to

divalproex in mania. _Biol Psychiatry_ 1996; 39: 278–284. Article  CAS  PubMed  Google Scholar  * Rode A, Bidzinski A, Puzynski S . GABA levels in the plasma of patients with endogenous

depression and during the treatment with thymoleptics. _Psychiatr Pol_ 1991; 25: 4–7. CAS  PubMed  Google Scholar  * Petty F, Fulton M, Moeller FG, Kramer G, Wilson L, Fraser K _et al_.

Plasma gamma-aminobutyric acid (GABA) is low in alcoholics. _Psychopharmacol Bull_ 1993; 29: 277–281. CAS  PubMed  Google Scholar  * Halbreich U, Petty F, Yonkers K, Kramer GL, Rush AJ, Bibi

KW . Low plasma gamma-aminobutyric acid levels during the late luteal phase of women with premenstrual dysphoric disorder. _Am J Psychiatry_ 1996; 153: 718–720. Article  CAS  PubMed  Google

Scholar  * Yonkers KA . The association between premenstrual dysphoric disorder and other mood disorders. _J Clin Psychiatry_ 1997; 58 (Suppl 15): 19–25. PubMed  Google Scholar  * Roy A,

DeJong J, Lamparski D, George T, Linnoila M . Depression among alcoholics. Relationship to clinical and cerebrospinal fluid variables. _Arch Gen Psychiatry_ 1991; 48: 428–432. Article  CAS 

PubMed  Google Scholar  * Goddard AW, Narayan M, Woods SW, Germine M, Kramer GL, Davis LL _et al_. Plasma levels of gamma-aminobutyric acid and panic disorder. _Psychiatry Res_ 1996; 63:

223–225. Article  CAS  PubMed  Google Scholar  * Gerner RH, Cohen DJ, Fairbanks L, Anderson GM, Young JG, Scheinin M _et al_. CSF neurochemistry of women with anorexia nervosa and normal

women. _Am J Psychiatry_ 1984; 141: 1441–1444. Article  CAS  PubMed  Google Scholar  * Bjork JM, Moeller FG, Kramer GL, Kram M, Suris A, Rush AJ _et al_. Plasma GABA levels correlate with

aggressiveness in relatives of patients with unipolar depressive disorder. _Psychiatry Res_ 2001; 101: 131–136. Article  CAS  PubMed  Google Scholar  * Perry EK, Gibson PH, Blessed G, Perry

RH, Tomlinson BE . Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. _J Neurol Sci_

1977; 34: 247–265. Article  CAS  PubMed  Google Scholar  * Cheetham SC, Crompton MR, Katona CLE, Horton RW . Brain 5-HT2 receptor binding sites in depressed suicide victims. _Brain Res_

1988; 443: 272–280. Article  CAS  PubMed  Google Scholar  * Cross JA, Cheetham SC, Crompton MR, Katona CL, Horton RW . Brain GABAB binding sites in depressed suicide victims. _Psychiatry

Res_ 1988; 26: 119–129. Article  CAS  PubMed  Google Scholar  * Arranz B, Cowburn R, Eriksson A, Vestling M, Marcusson J . Gamma-aminobutyric acid-B (GABAB) binding sites in postmortem

suicide brains. _Neuropsychobiology_ 1992; 26: 33–36. Article  CAS  PubMed  Google Scholar  * Stocks GM, Cheetham SC, Crompton MR, Katona CL, Horton RW . Benzodiazepine binding sites in

amygdala and hippocampus of depressed suicide victims. _J Affect Disord_ 1990; 18: 11–15. Article  CAS  PubMed  Google Scholar  * Sundman I, Allard P, Eriksson A, Marcusson J . GABA uptake

sites in frontal cortex from suicide victims and in aging. _Neuropsychobiology_ 1997; 35: 11–15. Article  CAS  PubMed  Google Scholar  * Korpi ER, Kleinman JE, Wyatt RJ . GABA concentrations

in forebrain areas of suicide victims. _Biol Psychiatry_ 1988; 23: 109–114. Article  CAS  PubMed  Google Scholar  * Benes FM, Todtenkopf MS, Logiotatos P, Williams M . Glutamate

decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. _J Chem Neuroanat_ 2000; 20: 259–269. Article  CAS  PubMed  Google Scholar

  * Guidotti A, Auta J, Davis JM, DiGiorgi Gerevini V, Dwivedi Y, Grayson DR _et al_. Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar

disorder. _Arch Gen Psychiatry_ 2000; 57: 1061–1069. Article  CAS  PubMed  Google Scholar  * Cotter D, Landau S, Beasley C, Stevenson R, Chana G, MacMillan L _et al_. The density and spatial

distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive, disorder, bipolar disorder and schizophrenia. _Biol

Psychiatry_ 2002; 51: 377–386. Article  CAS  PubMed  Google Scholar  * Heckers S, Stone D, Walsh J, Shick J, Koul P, Benes F . Differential expression of glutamic acid decarboxylase 65 and

67 messenger RNA in bipolar disorder and schizophrenia. _Arch Gen Psychiatry_ 2002; 59: 521–529. Article  CAS  PubMed  Google Scholar  * Honig A, Bartlett JR, Bouras N, Bridges PK . Amino

acid levels in depression: a preliminary investigation. _J Psychiatric Res_ 1988; 22: 159–164. Article  CAS  Google Scholar  * Northoff G, Steinke R, Czcervenka C, Krause R, Ulrich S, Danos

P _et al_. Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of _in vivo_ benzodiazepine receptor binding. _J Neurol Neurosurg

Psychiatry_ 1999; 67: 445–450. Article  CAS  PubMed  PubMed Central  Google Scholar  * Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA _et al_. Reduced cortical

gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy. _Arch Gen Psychiatry_ 1999; 56: 1043–1047. Article  CAS  PubMed  Google Scholar  *

Sanacora G, Mason GF, Rothman DL, Krystal JH . Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. _Am J

Psychiatry_ 2002; 159: 663–665. Article  PubMed  Google Scholar  * Epperson CN, Haga K, Mason GF, Sellers E, Gueorguieva R, Zhang W _et al_. Cortical _γ_-aminobutyric acid levels across the

menstrual cycle in healthy women and those with premenstrual dysphoric disorder. _Arch Gen Psychiatry_ 2002; 59: 851–858. Article  CAS  PubMed  Google Scholar  * Soares JC, Mann JJ . The

anatomy of mood disorders−review of structural neuroimaging studies. _Biol Psychiatry_ 1997; 41: 86–106. Article  CAS  PubMed  Google Scholar  * Brambilla P, Barale F, Caverzasi E, Soares JC

. Anatomical MRI findings in mood and anxiety disorders. _Epidemiol Psychiatr Soc_ 2002; 11: 88–99. Article  Google Scholar  * Gamse R, Vaccaro DE, Gamse G, DiPace M, Fox TO, Leeman SE .

Release of immunoreactive somatostatin from hypothalamic cells in culture: inhibition by gamma-aminobutyric acid. _Proc Natl Acad Sci USA_ 1980; 77: 5552–5556. Article  CAS  PubMed  PubMed

Central  Google Scholar  * Racagni G, Apud JA, Civati C, Cocchi D, Casanueva F, Locatelli V _et al_. Neurochemical aspects of GABA and glutamate in the hypothalamo-pituitary system. _Adv

Biochem Psychopharmacol_ 1981; 26: 261–271. CAS  PubMed  Google Scholar  * Koulu M, Lammintausta R, Dahlstrom S . Stimulatory effect of acute baclofen administration on human growth hormone

secretion. _J Clin Endocrinol Metab_ 1979; 48: 1038–1040. Article  CAS  PubMed  Google Scholar  * Shiah I-S, Yatham LN, Lam R, Tam EM, Zis PA . Growth hormone response to baclofen in

patients with mania: a pilot study. _Psychopharmacology_ 1999; 147: 280–284. Article  CAS  PubMed  Google Scholar  * Shiah I-S, Robertson HA, Lam R, Yatham LN, Tam EM, Zis PA . Growth

hormone response to baclofen in patients with seasonal affective disorder: effects of light therapy. _Psychoneuroendocrinology_ 1999; 24: 143–153. Article  CAS  PubMed  Google Scholar  *

Marchesi C, Chiodera P, De Ferri A, De Risio C, Dasso L, Menozzi P _et al_. Reduction of GH response to the GABA-B agonist baclofen in patients with major depression.

_Psychoneuroendocrinology_ 1991; 16: 475–479. Article  CAS  PubMed  Google Scholar  * O'Flynn K, Dinan TG . Baclofen-induced growth hormone release in major depression: relationship to

dexamethasone suppression test result. _Am J Psychiatry_ 1993; 150: 1728–1730. Article  CAS  PubMed  Google Scholar  * Monteleone P, Maj M, Iovino M, Steardo L . GABA, depression and the

mechanism of action of antidepressant drugs: a neuroendocrine approach. _J Affect Disord_ 1990; 20: 1–5. Article  CAS  PubMed  Google Scholar  * Davis LL, Trivedi M, Choate A, Kramer GL,

Petty F . Growth hormone response to the GABAB agonist baclofen in major depressive disorder. _Psychoneuroendocrinology_ 1997; 22: 129–140. Article  CAS  PubMed  Google Scholar  * Heninger

C, Saito N, Tallman JF, Garrett KM, Vitek MP, Duman RS _et al_. Effects of continuous diazepam administration on GABAA subunit mRNA in rat brain. _J Mol Neurosci_ 1990; 2: 101–107. Article 

CAS  PubMed  Google Scholar  * Kang I, Miller LG . Decreased GABAA receptor subunit mRNA concentrations following chronic lorazepam administration. _Br J Pharmacol_ 1991; 103: 1285–1287.

Article  CAS  PubMed  PubMed Central  Google Scholar  * Primus RJ, Gallager DW . GABAA receptor subunit mRNA levels are differentially influenced by chronic FG 7142 and diazepam exposure.

_Eur J Pharmacol_ 1992; 226: 21–28. Article  CAS  PubMed  Google Scholar  * Holt RA, Bateson AN, Martin IL . Chronic treatment with diazepam or abecarnil differently affects the expression

of GABAA receptor subunit mRNAs in the rat cortex. _Neuropharmacology_ 1996; 35: 1457–1463. Article  CAS  PubMed  Google Scholar  * Tanay VA, Glencorse TA, Greenshaw AJ, Baker GB, Bateson AN

. Chronic administration of antipanic drugs alters rat brainstem GABAA receptor subunit mRNA levels. _Neuropharmacology_ 1996; 35: 1475–1482. Article  CAS  PubMed  Google Scholar  * Wang

J-F, Sun X, Chen B, Young LT . Lamotrigine increases gene expression of GABAA receptor _β_3 subunit in primary cultured rat hippocampus cells. _Neuropsychopharmacology_ 2002; 26: 415–421.

Article  CAS  PubMed  Google Scholar  * Lloyd KG, Thuret F, Pilc A . Upregulation of gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated

administration of different classes of antidepressants and electroshock. _J Pharmacol Exp Ther_ 1985; 235: 191–199. CAS  PubMed  Google Scholar  * Motohashi N, Ikawa K, Kariya T . GABAB

receptors are up-regulated by chronic treatment with lithium or carbamazepine. GABA hypothesis of affective disorders? _Eur J Pharmacol_ 1989; 166: 95–99. Article  CAS  PubMed  Google

Scholar  * Motohashi N . GABA receptor alterations after chronic lithium administration. Comparison with carbamazepine and sodium valproate. _Prog Neuropsychopharmacol Biol Psychiatry_ 1992;

16: 571–579. Article  CAS  PubMed  Google Scholar  * Mendlewicz J . Population and family studies in depression and mania. _Br J Psychiatry_ 1988; 1539Suppl 3): 16–25. Article  Google

Scholar  * Oruc L, Verheyen GR, Furac I, Ivezic S, Jakovljevic M, Raeymaekers P _et al_. Positive association between the GABRA5 gene and unipolar recurrent major depression.

_Neuropsychobiology_ 1997; 36: 62–64. Article  CAS  PubMed  Google Scholar  * Papadimitriou GN, Dikeos DG, Karadima G, Avramopoulos D, Daskalopoulou EG, Vassilopoulos D _et al_. Association

between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) and bipolar affective disorder. _Am J Med Genet_ 1998; 81: 73–80. Article  CAS  PubMed  Google Scholar  * Massat I, Souery D,

Del-Favero J, Van Gestel S, Van Broeckhoven C, Mendlewicz J . GABRA1 receptor polymorphism and unipolar affective disorder: evidence for a protective gene in a European multicenter

association study of affective disorders. _Eur Neuropsychopharmacol_ 2001; 11(Suppl 1): 19. Google Scholar  * Massat I, Souery D, Del-Favero J, Oruc L, Noethen MM, Blackwood D _et al_.

Excess of allel1 for 3 subunit GABA receptor gene (GABRA3) in bipolar patients: a multicentric association study. _Mol Psychiatry_ 2002; 7: 201–207. Article  CAS  PubMed  Google Scholar  *

De Bruyn A, Sourey D, Mendelbaum K, Mendlewicz J, Van Broeckhoven C . A linkage study between bipolar disorder and genes involved in dopaminergic and GABAergic neurotransmission. _Psychiatr

Genet_ 1996; 6: 67–73. Article  CAS  PubMed  Google Scholar  * Ewald H, Mors O, Flint T, Kruse TA . Linkage analysis between manic-depressive illness and the region on chromosome 15q

involved in Prader-Willi syndrome, including two GABA A receptor subtype genes. _Human Hered_ 1994; 44: 287–294. Article  CAS  Google Scholar  * Walsh C, Hicks A, Sham P . GABAA receptor

subunit genes as candidate genes for bipolar affective disorder: an association analysis. _Psychiatr Genet_ 1992; 2: 239–247. Article  Google Scholar  * Puertollano R, Visedo G, Saiz-Ruiz J,

Llinares C, Fernandez-Piqueras J . Lack of association between manic-depressive illness and a highly polymorphic marker from GABRA3 gene. _Am J Med Genet_ 1995; 60: 434–435. Article  CAS 

PubMed  Google Scholar  * Duffy A, Turecki G, Grof P, Cavazzoni P, Grof E, Joober R _et al_. Association and linkage studies of candidate genes involved in GABAergic neurotransmission in

lithium-responsive bipolar disorder. _J Psychiatry Neurosci_ 2000; 25: 353–358. CAS  PubMed  PubMed Central  Google Scholar  * Coon H, Hicks AA, Bailey ME, Hoff M, Holik J, Harvey RJ _et

al_. Analysis of GABAA receptor subunit genes in multiplex pedigrees with manic depression. _Psychiatr Genet_ 1994; 4: 185–191. Article  CAS  PubMed  Google Scholar  * Papadimitriou GN,

Dikeos DG, Karadima G, Avramopoulos D, Daskalopoulou EG, Stefanis CN . GABA-A receptor β3 and α5 subunit gene cluster on chromosome 15q11−q13 and bipolar disorder: a genetic association

study. _Am J Med Genetics_ 2001; 105: 317–320. Article  CAS  Google Scholar  * Oruc L, Furac I, Croux C, Jakovljevic M, Kracun I, Folnegovic V _et al_. Association study between bipolar

disorder and candidate genes involved in dopamine−serotonin metabolism and GABAergic neurotransmission: a preliminary report. _Psychiatr Genet_ 1996; 6: 213–217. Article  CAS  PubMed  Google

Scholar  * Puertollano R, Visedo G, Zapata C, Fernandez-Piqueras J . A study of genetic association between manic-depressive illness and a highly polymorphic marker from the GABR_β_-1 gene.

_Am J Med Gen_ 1997; 74: 342–344. Article  CAS  Google Scholar  * Bernasconi R . The GABA hypothesis of affective illness: influence of clinically effective antimanic drugs on GABA

turnover. In: Emrich HD, Aldenhoff HD, Lux HD (eds). _Excerpta Medica_. Amsterdam, 1982, pp. 183–191. Google Scholar  * Loscher W . Valproate enhances GABA turnover in the substantia nigra.

_Brain Res_ 1989; 501: 198–203. Article  CAS  PubMed  Google Scholar  * Cunningham MO, Jones RS . The anticonvulsant lamotrigine decreases spontaneous gluatamate release but increases

spontaneous GABA release in the rat enthorinal cortex _in vitro_. _Neuropharmacology_ 2000; 39: 2139–2146. Article  CAS  PubMed  Google Scholar  * Hassel B, Tauboll E, Gjerstad L . Chronic

lamotrigine treatment increases rat hippocampal GABA shunt activity and elevates cerebral taurine levels. _Epilepsy Res_ 2001; 43: 153–163. Article  CAS  PubMed  Google Scholar  * Otero

Losada ME, Rubio MC . Acute and chronic effects of lithium chloride on GABA-ergic function in the rat corpus striatum and frontal cerebral cortex. _Naunyn Schmiedebergs Arch Pharmacol_ 1986;

332: 169–172. Article  CAS  PubMed  Google Scholar  * Ahluwalia P, Grewaal DS, Singhal RL . Brain GABAergic and dopaminergic systems following lithium treatment and withdrawal. _Prog

Neuropsychopharmacol_ 1981; 5: 527–530. Article  CAS  PubMed  Google Scholar  * Gottesfeld Z . Effect of lithium and other alkali metals on brain chemistry and behavior. I. Glutamic acid and

GABA in brain regions. _Psychopharmacologia_ 1976; 45: 239–242. Article  CAS  PubMed  Google Scholar  * Weiss S, Kemp DE, Bauce L, Tse FW . Kainate receptors coupled to the evoked release

of [3H]-gamma-aminobutyric acid from striatal neurons in primary culture: potentiation by lithium ions. _Mol Pharmacol_ 1990; 38: 229–236. CAS  PubMed  Google Scholar  * Maggi A, Enna SJ .

Regional alterations in rat brain neurotransmitter systems following chronic lithium treatment. _J Neurochem_ 1980; 34: 888–892. Article  CAS  PubMed  Google Scholar  * Vargas C, Tannhauser

M, Barros HM . Dissimilar effects of lithium and valproic acid on GABA and glutamine concentrations in rat cerebrospinal fluid. _Gen Pharmacol_ 1998; 30: 601–604. Article  CAS  PubMed 

Google Scholar  * Iadarola MJ, Raines A, Gale K . Differential effects of _n_-dipropylacetate and amino-oxyacetic acid on gamma-aminobutyric acid levels in discrete areas of rat brain. _J

Neurochem_ 1979; 33: 1119–1123. Article  CAS  PubMed  Google Scholar  * Loscher W, Vetter M . _In vivo_ effects of aminooxyacetic acid and valproic acid on nerve terminal (synaptosomal) GABA

levels in discrete brain areas of the rat. Correlation to pharmacological activities. _Biochem Pharmacol_ 1985; 34: 1747–1756. Article  CAS  PubMed  Google Scholar  * Loscher W, Horstermann

D . Differential effects of vigabatrin, gamma-acetylenic GABA, aminooxyacetic acid, and valproate on levels of various amino acids in rat brain regions and plasma. _Naunyn Schmiedebergs

Arch Pharmacol_ 1994; 349: 270–278. Article  CAS  PubMed  Google Scholar  * Gram L, Larsson OM, Johnsen AH, Schousboe A . Effects of valproate, vigabatrin and aminooxyacetic acid on release

of endogenous and exogenous GABA from cultured neurons. _Epilepsy Res_ 1988; 2: 87–95. Article  CAS  PubMed  Google Scholar  * Phillips NI, Fowler LJ . The effects of sodium valproate on

gamma-aminobutyrate metabolism and behaviour in naive and ethanolamine-O-sulphate pretreated rats and mice. _Biochem Pharmacol_ 1982; 31: 2257–2261. Article  CAS  PubMed  Google Scholar  *

Macdonald RL, Bergey GK . Valproic acid augments GABA-mediated postsynaptic inhibition in cultured mammalian neurons. _Brain Res_ 1979; 170: 558–562. Article  CAS  PubMed  Google Scholar  *

Loscher W . Effect of inhibitors of GABA transaminase on the synthesis, binding, uptake, and metabolism of GABA. _J Neurochem_ 1980; 34: 1603–1608. Article  CAS  PubMed  Google Scholar  *

Larsson OM, Gram L, Schousboe I, Schousboe A . Differential effect of gamma-vinyl GABA and valproate on GABA-transaminase from cultured neurones and astrocytes. _Neuropharmacology_ 1986; 25:

617–625. Article  CAS  PubMed  Google Scholar  * Loscher W, Schmidt D . Increase of human plasma GABA by sodium valproate. _Epilepsia_ 1980; 21: 611–615. Article  CAS  PubMed  Google

Scholar  * Loscher W, Schmidt D . Plasma GABA levels in neurological patients under treatment with valproic acid. _Life Sci_ 1981; 28: 283–288. Article  CAS  PubMed  Google Scholar  * Shiah

IS, Yatham LN, Baker GB . Divalproex sodium increases plasma GABA levels in healthy volunteers. _Int Clin Psychopharmacol_ 2000; 15: 221–225. Article  CAS  PubMed  Google Scholar  * Post RM,

Ballenger JC, Hare TA, Bunney Jr WE . Lack of effect of carbamazepine on gamma-aminobutyric acid in cerebrospinal fluid. _Neurology_ 1980; 30: 1008–1011. Article  CAS  PubMed  Google

Scholar  * Prevett MC, Lammertsma AA, Brooks DJ, Bartenstein PA, Patsalos PN, Fish DR _et al_. Benzodiazepine-GABAA receptors in idiopathic generalized epilepsy measured with [11C]flumazenil

and positron emission tomography. _Epilepsia_ 1995; 36: 113–121. Article  CAS  PubMed  Google Scholar  * Petroff OA, Rothman DL, Behar KL, Lamoureux D, Mattson RH . The effect of gabapentin

on brain gamma-aminobutyric acid in patients with epilepsy. _Ann Neurol_ 1996; 39: 95–99. Article  CAS  PubMed  Google Scholar  * Kuzniecky R, Hetherington H, Ho S, Pan J, Martin R, Gilliam

F _et al_. Topiramate increases cerebral GABA in healthy humans. _Neurology_ 1998; 51: 627–629. Article  CAS  PubMed  Google Scholar  * Verhoeff NP, Petroff OA, Hyder F, Zoghbi SS, Fujita

M, Rajeevan N _et al_. Effects of vigabatrin on the GABAergic system as determined by [123I]iomazenil SPECT and GABA MRS. _Epilepsia_ 1999; 40: 1433–1438. Article  CAS  PubMed  Google

Scholar  * Brambilla P, Barale F, Soares JC . Perspectives on the use of anticonvulsants in the treatment of bipolar disorder. _Int J Neuropsychopharmacol_ 2001; 4: 421–446. Article  CAS 

PubMed  Google Scholar  * Shiah IS, Yatham LN, Lam RW, Zis AP . Divalproex sodium attenuates growth hormone response to baclofen in healthy human males. _Neuropsychopharmacology_ 1998; 18:

370–376. Article  CAS  PubMed  Google Scholar  * Serretti A, Lilli R, Lorenzi C, Franchini L, Di Bella D, Catalano M _et al_. Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes

and response to lithium prophylaxis in mood disorders. _Psychiatry Res_ 1999; 87: 7–19. Article  CAS  PubMed  Google Scholar  * Suranyi-Cadotte BE, Dam TV, Quirion R .

Antidepressant-−anxiolytic interaction: decreased density of benzodiazepine receptors in rat brain following chronic administration of antidepressants. _Eur J Pharmacol_ 1984; 106: 673–675.

Article  CAS  PubMed  Google Scholar  * Barbaccia ML, Ravizza L, Costa E . Maprotiline. An antidepressant with an unusual pharmacological profile. _J Pharmacol Exp Ther_ 1986; 236: 307–312.

CAS  PubMed  Google Scholar  * Bouthillier A, de Montigny C . Long-term antidepressant treatment reduces neuronal responsiveness to flurazepam: an electrophysiological study in the rat.

_Neurosci Lett_ 1987; 73: 271–275. Article  CAS  PubMed  Google Scholar  * Pilc A, Lloyd KG . Chronic antidepressants and GABA receptors: a GABA hypothesis of antidepressant drug action.

_Life Sci_ 1984; 35: 2149–2254. Article  CAS  PubMed  Google Scholar  * Kimber JR,, Cross JA, Horton RW . Benzodiazepine and GABAA receptors in rat brain following chronic antidepressant

drug administration. _Biochem Pharmacol_ 1987; 36: 4173–4175. Article  CAS  PubMed  Google Scholar  * McKenna KF, McManus DJ, Baker GB, Coutts RT . Chronic administration of the

antidepressant phenelzine and its _N_-acetyl analogue: effects on GABAergic function. _J Neural Transm Suppl_ 1994; 41: 115–122. CAS  PubMed  Google Scholar  * Todd KG, McManus DJ, Baker GB

. Chronic administration of the antidepressants phenelzine, desipramine, clomipramine, or maprotiline decreases binding to 5-hydroxytryptamine2A receptors without affecting benzodiazepine

binding sites in rat brain. _Cell Mol Neurobiol_ 1995; 15: 361–370. Article  CAS  PubMed  Google Scholar  * Suzdak PD, Gianutsos G . Effect of chronic imipramine or baclofen on GABA-B

binding and cyclic AMP production in cerebral cortex. _Eur J Pharmacol_ 1986; 131: 129–133. Article  CAS  PubMed  Google Scholar  * Pratt GD, Bowery NG . Repeated administration of

desipramine and a GABAB receptor antagonist, CGP 36742, discretely up-regulates GABAB receptor binding sites in rat frontal cortex. _Br J Pharmacol_ 1993; 110: 724–735. Article  CAS  PubMed

  PubMed Central  Google Scholar  * Szekely AM, Barbaccia ML, Costa E . Effect of a protracted antidepressant treatment on signal transduction and [3H](-)-baclofen binding at GABAB

receptors. _J Pharmacol Exp Ther_ 1987; 243: 155–159. CAS  PubMed  Google Scholar  * Cross JA, Horton RW . Are increases in GABAB receptors consistent findings following chronic

antidepressant administration? _Eur J Pharmacol_ 1987; 141: 159–162. Article  CAS  PubMed  Google Scholar  * McManus DJ, Greenshaw AJ . Differential effects of antidepressants on GABAB and

beta-adrenergic receptors in rat cerebral cortex. _Biochem Pharmacol_ 1991; 42: 1525–1528. Article  CAS  PubMed  Google Scholar  * Engelbrecht AH, Russell VA, Taljaard JJ . Lack of effect of

bilateral locus coeruleus lesion and antidepressant treatment on gamma-aminobutyric acidB receptors in the rat frontal cortex. _Neurochem Res_ 1994; 19: 1119–1123. Article  CAS  PubMed 

Google Scholar  * Gray JA, Green AR . Increased GABAB receptor function in mouse frontal cortex after repeated administration of antidepressant drugs or electroconvulsive shocks. _Br J

Pharmacol_ 1987; 92: 357–362. Article  CAS  PubMed  PubMed Central  Google Scholar  * Gray JA, Green AR . GABAB-receptor mediated inhibition of potassium-evoked release of endogenous

5-hydroxytryptamine from mouse frontal cortex. _Br J Pharmacol_ 1987; 91: 517–522. Article  CAS  PubMed  PubMed Central  Google Scholar  * Bowery NG, Hill DR, Hudson AL, Doble A, Middlemiss

DN, Shaw J _et al_. (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. _Nature_ 1980; 283: 92–94. Article  CAS  PubMed  Google Scholar

  * Borsini F, Giuliani S, Meli A . Functional evidence for altered activity of GABAergic receptors following chronic desipramine treatment in rats. _J Pharm Pharmacol_ 1986; 38: 934–935.

Article  CAS  PubMed  Google Scholar  * McManus DJ, Greenshaw AJ . Differential effects of chronic antidepressants in behavioural tests of beta-adrenergic and GABAB receptor function.

_Psychopharmacology_ 1991; 103: 204–208. Article  CAS  PubMed  Google Scholar  * Baker GB, Wong JT, Yeung JM, Coutts RT . Effects of the antidepressant phenelzine on brain levels of

gamma-aminobutyric acid (GABA). _J Affect Disord_ 1991; 21: 207–211. Article  CAS  PubMed  Google Scholar  * McManus DJ, Baker GB, Martin IL, Greenshaw AJ, McKenna KF . Effects of the

antidepressant/antipanic drug phenelzine on GABA concentrations and GABA-transaminase activity in rat brain. _Biochem Pharmacol_ 1992; 43: 2486–2489. Article  CAS  PubMed  Google Scholar  *

Paslawski TM, Sloley BD, Baker GB . Effects of the MAO inhibitor phenelzine on glutamine and GABA concentrations in rat brain. _Prog Brain Res_ 1995; 106: 181–186. Article  CAS  PubMed 

Google Scholar  * Parent M, Habib MK, Baker GB . Time-dependent changes in brain monoamine oxidase activity and in brain levels of monoamines and amino acids following acute administration

of the antidepressant/antipanic drug phenelzine. _Biochem Pharmacol_ 2000; 59: 1253–1263. Article  CAS  PubMed  Google Scholar  * Lai CT, Tanay VA, Charrois GJ, Baker GB, Bateson AN .

Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat

cortex. _Naunyn Schmiedebergs Arch Pharmacol_ 1998; 357: 32–38. Article  CAS  PubMed  Google Scholar  * Korf J, Venema K . Desmethylimipramine enhances the release of endogenous GABA and

other neurotransmitter amino acids from the rat thalamus. _J Neurochem_ 1983; 40: 946–950. Article  CAS  PubMed  Google Scholar  * Giardino L, Zanni M, Bettelli C, Savina MA, Calza L .

Regulation of glutamic acid decarboxylase mRNA expression in rat brain after sertraline treatment. _Eur J Pharmacol_ 1996; 312: 183–187. Article  CAS  PubMed  Google Scholar  * Herman JP,

Renda A, Bodie B . Norepinephrine–gamma-aminobutyric acid (GABA) interaction in limbic stress circuits: effects of reboxetine on GABAergic neurons. _Biol Psychiatry_ 2003; 53: 166–174.

Article  CAS  PubMed  Google Scholar  * Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D . St John's Wort for depression—an overview and meta-analysis of randomised

clinical trials. _BMJ_ 1996; 313: 253–258. Article  CAS  PubMed  PubMed Central  Google Scholar  * Wonnemann M, Singer A, Muller WE . Inhibition of synaptosomal uptake of 3H-L-glutamate and

3H-GABA by hyperforin, a major constituent of St. John's Wort: the role of amiloride sensitive sodium conductive pathways. _Neuropsychopharmacology_ 2000; 23: 188–197. Article  CAS 

PubMed  Google Scholar  * Griffin LD, Mellon SH . Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. _Proc Natl Acad Sci USA_. 1999; 96:

13512–13517. Article  CAS  PubMed  PubMed Central  Google Scholar  * Khisti RT, Chopde CT . Serotonergic agents modulate antidepressant-like effect on the neurosteroid 3 alpha-hydroxy-5

alpha-pregnan-20-one in mice. _Brain Res_ 2000; 865: 291–300. Article  CAS  PubMed  Google Scholar  * Khisti RT, Chopde CT, Jain SP . Antidepressant-like effect of the neurosteroid 3

alpha-hydroxy-5 alpha-pregnan-20-one in mice forced swim test. _Pharmacol Biochem Behav_ 2000; 67: 137–143. Article  CAS  PubMed  Google Scholar  * Romeo E, Strohle A, Spalletta G, di

Michele F, Hermann B, Holsboer F _et al_. Effects of antidepressant treatment on neuroactive steroids in major depression. _Am J Psychiatry_ 1998; 155: 910–913. Article  CAS  PubMed  Google

Scholar  * Strohle A, Romeo E, Hermann B, Pasini A, Spalletta G, di Michele F _et al_. Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with

major depression and after clinical recovery. _Biol Psychiatry_ 1999; 45: 274–277. Article  CAS  PubMed  Google Scholar  * Strohle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F

_et al_. Fluoxetine decreases concentrations of 3 alpha, 5 alpha-tetrahydrodeoxy-corticosterone (THDOC) in major depression. _J Psychiatr Res_ 2000; 34: 183–186. Article  CAS  PubMed  Google

Scholar  * Monteleone P, Steardo L, Tanzillo C, Maj M . Chronic antidepressant drug treatment does not affect GH response to baclofen in depressed subjects. _J Neural Transm Gen Sect_ 1990;

82: 147–152. Article  CAS  PubMed  Google Scholar  * Lavoie AM, Twyman RE . Direct evidence for diazepam modulation of GABAA receptor microscopic affinity. _Neuropharmacology_ 1996; 35:

1383–1392. Article  CAS  PubMed  Google Scholar  * Obata T, Morelli M, Concas A, Serra M, Yamamura HI . Modulation of GABA-stimulated chloride influx into membrane vesicles from rat cerebral

cortex by benzodiazepines and nonbenzodiazepines. _Adv Biochem Psychopharmacol_ 1988; 45: 175–187. CAS  PubMed  Google Scholar  * Loscher W, Schmidt D . Diazepam increases

gamma-aminobutyric acid in human cerebrospinal fluid. _J Neurochem_ 1987; 49: 152–157. Article  CAS  PubMed  Google Scholar  * Roy-Byrne PP, Cowley DS, Hommer D, Greenblatt DJ, Kramer GL,

Petty F . Effect of acute and chronic benzodiazepines on plasma GABA in anxious patients and controls. _Psychopharmacology_ 1992; 109: 153–156. Article  CAS  PubMed  Google Scholar  * de Wit

H, Metz J, Wagner N, Cooper M . Effects of diazepam on cerebral metabolism and mood in normal volunteers. _Neuropsychopharmacology_. 1991; 5: 33–41. CAS  PubMed  Google Scholar  * Matthew

E, Andreason P, Pettigrew K, Carson RE, Herscovitch P, Cohen R _et al_. Benzodiazepine receptors mediate regional blood flow changes in the living human brain. _Proc Natl Acad Sci USA_ 1995;

92: 2775–2779. Article  CAS  PubMed  PubMed Central  Google Scholar  * Fujita M, Woods SW, Verhoeff NP, Abi-Dargham A, Baldwin RM, Zoghbi SS _et al_. Changes of benzodiazepine receptors

during chronic benzodiazepine administration in humans. _Eur J Pharmacol_ 1999; 368: 161–172. Article  CAS  PubMed  Google Scholar  * Wang GJ, Volkow ND, Overall J, Hitzemann RJ, Pappas N,

Pascani K _et al_. Reproducibility of regional brain metabolic responses to lorazepam. _J Nucl Med_ 1996; 37: 1609–1613. CAS  PubMed  Google Scholar  * Brambilla P, Soares JC . The

pharmacological treatment of acute mania. In: Dunner DL, Rosenbaum J (eds). _Psychiatric Clinics of North America: Annual of Drug Therapy_. W.B. Saunders Company: Philadelphia, PA, 2001,

Vol. 8, pp. 155–180. Google Scholar  * Kishimoto A, Kamata K, Sugihara T, Ishiguro S, Hazama H, Mizukawa R _et al_. Treatment of depression with clonazepam. _Acta Psychiatr Scand_ 1988; 77:

81–86. Article  CAS  PubMed  Google Scholar  * Rush AJ, Schlesser MA, Erman M, Fairchild C . Alprazolam in bipolar-I depressions. _Pharmacotherapy_ 1984; 4: 40–42. Article  CAS  PubMed 

Google Scholar  * Dunner D, Myers J, Khan A, Avery D, Ishiki D, Pyke R . Adinazolam-a new antidepressant: findings of a placebo-controlled, double-blind study in outpatients with major

depression. _J Clin Psychopharmacol_ 1987; 7: 170–172. Article  CAS  PubMed  Google Scholar  * Jonas JM, Cohon MS . A comparison of the safety and efficacy of alprazolam versus other agents

in the treatment of anxiety, panic, and depression: a review of the literature. _J Clin Psychiatry_ 1993; 54 (Supp 2): 25–45. PubMed  Google Scholar  * Farnbach-Pralong D, Bradbury R,

Copolov D, Dean B . Clozapine and olanzapine treatment decreases rat cortical and limbic GABA(A) receptors. _Eur J Pharmacol_ 1998; 349: R7–R8. Article  CAS  PubMed  Google Scholar  *

Bourdelais AJ, Deutch AY . The effects of haloperidol and clozapine on extracellular GABA levels in the prefrontal cortex of the rat: an _in vivo_ microdialysis study. _Cerebr Cort_ 1994; 4:

69–77. Article  CAS  Google Scholar  * See RF, Berglind WJ, Krentz L, Meshul CK . Convergent evidence from microdialysis and presynaptic immunolabeling for the regulation of

gamma-aminobutyric acid release in the globus pallidus following acute clozapine or haloperidol administration in rats. _J Neurochem_ 2002; 82: 172–180. Article  CAS  PubMed  Google Scholar

  * Brambilla, Barale F, Soares JC . Atypical antipsychotics and mood stabilization in bipolar disorder. _Psychopharmacology_ 2003; 166: 315–332. Article  CAS  PubMed  Google Scholar  * Fink

M . Convulsive therapy: a review of the first 55 years. _J Affect Disord_ 2001; 63: 1–15. Article  CAS  PubMed  Google Scholar  * Wielosz M, Stelmasiak M, Ossowska G, Kleinrok Z . Effects

of electroconvulsive shock on central GABA-ergic mechanisms. _Pol J Pharmacol Pharm_ 1985; 37: 113–122. CAS  PubMed  Google Scholar  * Green AR, Metz A, Minchin MC, Vincent ND . Inhibition

of the rate of GABA synthesis in regions of rat brain following a convulsion. _Br J Pharmacol_ 1987; 92: 5–11. Article  CAS  PubMed  PubMed Central  Google Scholar  * Bowdler JM, Green AR,

Minchin MC, Nutt DJ . Regional GABA concentration and [3H]-diazepam binding in rat brain following repeated electroconvulsive shock. _J Neural Transm_ 1983; 56: 3–12. Article  CAS  PubMed 

Google Scholar  * Green AR, Vincent ND . The effect of repeated electroconvulsive shock on GABA synthesis and release in regions of rat brain. _Br J Pharmacol_ 1987; 92: 19–24. Article  CAS

  PubMed  PubMed Central  Google Scholar  * Chabannes J, Baro P, Lambert P, Decade P, Musch B . Antidepressant activity of fengabide (SL 79229): results from an open pilot study. In:

Bartholini G, Lloyd K, Morselli P (eds). _GABA and Mood Disorders: Experimental and Clinical Research_. Raven Press: New York, 1986. Google Scholar  * Mendlewicz J, Linkowski P,

Coupez-Lopinot R . Treatment of depressed patients with fengabide (SL 79229): preliminary results. In: Bartholini G, Lloyd K, Morselli P (eds). _GABA and Mood Disorders: Experimental and

Clinical Research_. Raven Press: New York, 1986. Google Scholar  * Muscettola G, Casiello M, Giannini C, Bossi L . Pilot study of progabide in depression. In: Bartholini G, Lloyd K, Morselli

P (eds). _GABA and Mood Disorders: Experimental and Clinical Research_. Raven Press: New York, 1986. Google Scholar  * Perris C, Tjallden G, Bossi L, Perris H . Progabide versus

nortriptiline in depression: a controlled trial. In: Bartholini G, Lloyd K, Morselli P (eds). _GABA and Mood Disorders: Experimental and Clinical Research_. Raven Press: New York, 1986.

Google Scholar  * Weiss E, Brunner H, Clerc G, Guibert M, Orofiamma B, Pagot R _et al_. Multicenter double-blind study of progabide in depressed patients. In: Bartholini G, Lloyd K, Morselli

P (eds). _GABA and Mood Disorders: Experimental and Clinical Research_. Raven Press: New York, 1986. Google Scholar  * Nielsen NP, Cesana B, Zizolfi S, Ascalone V, Priore P, Morselli PL .

Therapeutic effects of fengabine, a new GABAergic agent, in depressed outpatients: a double-blind study versus clomipramine. _Acta Psychiatr Scand_ 1990; 82: 366–371. Article  CAS  PubMed 

Google Scholar  * Petty F, Trivedi MH, Fulton M, Rush AJ . Benzodiazepines as antidepressants: does GABA play a role in depression? _Biol Psychiatry_ 1995; 38: 578–591. Article  CAS  PubMed

  Google Scholar  * Blum BP, Mann JJ . The GABAergic system in schizophrenia. _Int J Neuropsychopharmacol_ 2002; 5: 159–179. Article  CAS  PubMed  Google Scholar  * Malizia AL, Cunningham

VJ, Bell CJ, Liddle PF, Jones T, Nutt DJ . Decreased brain GABA(A) −benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study. _Arch Gen

Psychiatry_ 1998; 55: 715–720. Article  CAS  PubMed  Google Scholar  * Bremner JD, Innis RB, White T, Fujita M, Silbersweig D, Goddard AW _et al_. SPECT [I-123]iomazenil measurement of the

benzodiazepine receptor in panic disorder. _Biol Psychiatry_ 2000; 47: 96–106. Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS This work was partly supported by

the National Institute of Mental Health (MH 01736), NARSAD, and the Veterans Administration. Dr Brambilla was supported by grants from the University of Pavia and from the

Fatebenefratelli-Brescia (Ministry of Health). We thank A Mangiò ([email protected]) for great help with the figure. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Biological Psychiatry

Unit, IRCCS S Giovanni di Dio, Fatebenefratelli, Brescia, Italy P Brambilla & J Perez * Department of Psychiatry, IRCCS S Matteo, University of Pavia, Italy F Barale * Advanced

Biotechnology Center, University of Genova, Italy G Schettini * Department of Psychiatry, The University of Texas Health Sciences Center, San Antonio, TX, USA J C Soares * Audie Murphy

Division, South Texas VA Health Care System, San Antonio, TX, USA J C Soares Authors * P Brambilla View author publications You can also search for this author inPubMed Google Scholar * J

Perez View author publications You can also search for this author inPubMed Google Scholar * F Barale View author publications You can also search for this author inPubMed Google Scholar * G

Schettini View author publications You can also search for this author inPubMed Google Scholar * J C Soares View author publications You can also search for this author inPubMed Google

Scholar CORRESPONDING AUTHOR Correspondence to P Brambilla. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Brambilla, P., Perez, J., Barale, F. _et al._

GABAergic dysfunction in mood disorders. _Mol Psychiatry_ 8, 721–737 (2003). https://doi.org/10.1038/sj.mp.4001362 Download citation * Received: 09 January 2003 * Revised: 11 April 2003 *

Accepted: 16 April 2003 * Published: 30 July 2003 * Issue Date: 01 August 2003 * DOI: https://doi.org/10.1038/sj.mp.4001362 SHARE THIS ARTICLE Anyone you share the following link with will

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content-sharing initiative KEYWORDS * GABA * bipolar disorder * unipolar disorder * mood disorders * antidepressants * mood stabilizers