GABAergic dysfunction in mood disorders

被引:450
作者
Brambilla, P
Perez, J
Barale, F
Schettini, G
Soares, JC
机构
[1] IRCCS S Giovanni Dio, Biol Psychiat Unit, I-25125 Brescia, Italy
[2] Univ Pavia, IRCCS S Matteo, Dept Psychiat, I-27100 Pavia, Italy
[3] Univ Genoa, Adv Biotechnol Ctr, Genoa, Italy
[4] Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA
[5] S Texas VA Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA
关键词
GABA; bipolar disorder; unipolar disorder; mood disorders; antidepressants; mood stabilizers;
D O I
10.1038/sj.mp.4001362
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. gamma-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.
引用
收藏
页码:721 / 737
页数:17
相关论文
共 287 条
  • [1] 5-HT2 receptor regulation of extracellular GABA levels in the prefrontal cortex
    Abi-Saab, WM
    Bubser, M
    Roth, RH
    Deutch, AY
    [J]. NEUROPSYCHOPHARMACOLOGY, 1999, 20 (01) : 92 - 96
  • [2] BRAIN GABAERGIC AND DOPAMINERGIC SYSTEMS FOLLOWING LITHIUM TREATMENT AND WITHDRAWAL
    AHLUWALIA, P
    GREWAAL, DS
    SINGHAL, RL
    [J]. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY, 1981, 5 (5-6): : 527 - 530
  • [3] ROLE OF CENTRAL NERVOUS SYSTEM-DERIVED OR CIRCULATING GAMMA-AMINOBUTYRIC ACID ON PROLACTIN SECRETION IN THE RAT
    APUD, JA
    RACAGNI, G
    IULIANO, E
    COCCHI, D
    CASANUEVA, F
    MULLER, EE
    [J]. ENDOCRINOLOGY, 1981, 108 (04) : 1505 - 1510
  • [4] GAMMA-AMINOBUTYRIC ACID-B (GABA-B) BINDING-SITES IN POSTMORTEM SUICIDE BRAINS
    ARRANZ, B
    COWBURN, R
    ERIKSSON, A
    VESTLING, M
    MARCUSSON, J
    [J]. NEUROPSYCHOBIOLOGY, 1992, 26 (1-2) : 33 - 36
  • [5] Reciprocal innervation between serotonergic and GABAergic neurons in raphe nuclei of the rat
    Bagdy, E
    Kiraly, I
    Harsing, LG
    [J]. NEUROCHEMICAL RESEARCH, 2000, 25 (11) : 1465 - 1473
  • [6] EFFECTS OF THE ANTIDEPRESSANT PHENELZINE ON BRAIN LEVELS OF GAMMA-AMINOBUTYRIC-ACID (GABA)
    BAKER, GB
    WONG, JTF
    YEUNG, JM
    COUTTS, RT
    [J]. JOURNAL OF AFFECTIVE DISORDERS, 1991, 21 (03) : 207 - 211
  • [7] BARBACCIA ML, 1986, J PHARMACOL EXP THER, V236, P307
  • [8] DOPAMINE-IMMUNOREACTIVE AXON VARICOSITIES FORM NONRANDOM CONTACTS WITH GABA-IMMUNOREACTIVE NEURONS OF RAT MEDIAL PREFRONTAL CORTEX
    BENES, FM
    VINCENT, SL
    MOLLOY, R
    [J]. SYNAPSE, 1993, 15 (04) : 285 - 295
  • [9] Glutamate decarboxylase65-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain
    Benes, FM
    Todtenkopf, MS
    Logiotatos, P
    Williams, M
    [J]. JOURNAL OF CHEMICAL NEUROANATOMY, 2000, 20 (3-4) : 259 - 269
  • [10] BERNASCONI R, 1982, EXCERPTA MED, P183