Γ-Aminobutyric-Acid DEFICIENCY IN BRAIN OF SCHIZOPHRENIC PATIENTS

Perry, ThomasL.; Buchanan, Janet A.; Kish, StephenJ; Hansen, Shirley

doi:10.1016/s0140-6736(79)90767-0

Cited by 171 publications

(57 citation statements)

References 21 publications

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“…In accordance with the hypothesis of a GABA deficit in schizophrenia, GABAergic cells and markers of GABAergic cells have usually been reported to be decreased in postmortem studies in patients with schizophrenia (Bird et al 1977;Perry et al 1979;Simpson et al 1989;Reynolds et al 1990;Benes et al 1991;Sherman et al 1991;Akbarian et al 1995b;Beasley and Reynolds 1997). However, few of these observations have been replicated (Bennett et al 1979;Cross et al 1979;Akbarian et al 1995b;Woo et al 1997).…”

Section: I]iomazenil; Spectmentioning

confidence: 77%

No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia

Abi‐Dargham

Laruelle

Krystal

et al. 1999

Neuropsychopharmacology

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Section: I]iomazenil; Spectmentioning

confidence: 77%

No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia

Abi‐Dargham

Laruelle

Krystal

et al. 1999

Neuropsychopharmacology

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“…These studies showed reductions in the concentration of cortical GABA [6] and the activity of glutamate decarboxylase (GAD) [7], the enzyme that synthesizes GABA. These observations were confirmed and extended in subsequent studies showing alteration in several presynaptic components of the GABAergic system [8][9][10][11][12][13][14].…”

Section: Gaba Hypofunctionmentioning

confidence: 99%

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

Lisman

Coyle

Green

et al. 2008

Trends in Neurosciences

922

824

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Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We have developed a circuit-based framework for understanding gene and neurotransmitter interactions. NMDAR hypofunction has been implicated in schizophrenia because NMDAR antagonists reproduce symptoms of the disease. One action of antagonists is to reduce the excitation of fast-spiking interneurons, resulting in disinhibition of pyramidal cells. Overactive pyramidal cells, notably those in the hippocampus, can drive a hyperdopaminergic state that produces psychosis. Additional aspects of interneuron function can be understood in this framework, as follows. (i) In animal models, NMDAR antagonists reduce parvalbumin and GAD67, as found in schizophrenia. These changes produce further disinhibition and can be viewed as the aberrant response of a homeostatic system having a faulty activity sensor (the NMDAR). (ii) Disinhibition decreases the power of gamma oscillation and might thereby produce negative and cognitive symptoms. (iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.

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“…In the 1970s, perhaps prompted by the speculations of Eugene Roberts (Roberts 1972), a series of neurochemical investigations focusing on various markers for this system were reported. The first study to appear examined the concentrations of GABA in the nucleus accumbens and thalamus of patients with schizophrenia and compared them with a group of subjects with Huntington's chorea (Perry et al 1979). The results demonstrated a reduction of this transmitter that was equivalent in the two disorders.…”

Section: Postmortem Evidence For a Gaba Defect In Schizophreniamentioning

confidence: 99%

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

Beneš

Berretta

2001

Neuropsychopharmacology

996

643

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Neurons that express the compound, ␥ -aminobutyric acid (GABA), are broadly present throughout the central nervous system, although telencephalic structures, such as the cerebral cortex, show the most abundant quantities of this neurotransmitter (Jones 1987). In the discussion that follows, the anatomy and physiology of various types of GABAergic interneurons in the cortex and hippocampus will be discussed and related to recent postmortem studies implicating this transmitter system in the pathophysiology of schizophrenia and bi- 25 , NO . 1 polar disorder and their treatment with neuroleptic drugs (for more comprehensive reviews on cortical and hippocampal neurons see: Hof et al. 1993;Freund and Buzsaki 1996;Somogyi et al. 1998). NEUROBIOLOGY OF GABAERGIC INTERNEURONSBased on Golgi-impregnation studies, Ramon y Cajal provided the first descriptions of several different morphological subtypes of interneurons in the cerebral cortex and hippocampus (Ramon y Cajal 1893, 1911. In more recent years, it has been shown that, with some overlap, different morphological subtypes also have distinct distributions, connectivity, neurochemistry, and electrophysiological properties (for reviews see Hof et al. 1993;Freund and Buzsaki 1996). It is interesting to note that every segment of a pyramidal neuron, such as the soma, dendritic branches and spines, and the initial axonal segment, receives dense GABAergic synaptic innervation (O'Kusky and Colonnier 1982;Hendry et al. 1983;Houser et al. 1983; Beaulieu et al. 1992; for reviews see Jones 1993;Freund and Buzsaki 1996). Even more interestingly, each of these segments appears to be innervated by distinct GABAergic neuronal subtypes (see below).These differences strongly suggest that each of these subtypes plays a fundamentally different role in physiological and pathological mechanisms. In the discussion that follows, cortical interneurons will be described first, since our most basic understanding of GABAergic cells is derived from these populations. In more recent years, however, similar characterizations of interneurons in hippocampus have emerged. Although these cells show some striking similarities to their cortical counterparts, there are also some unique features that distinguish them. For this reason, interneurons in the hippocampus are discussed separately. Cortex Neuroanatomical Studies of Cortical Interneurons.Various types of GABAergic neurons can be categorized according to the type of synaptic profiles they are associated with, as this has direct implications for understanding the physiological role of these cells in cortical circuits. These categories are discussed below.A XO -S OMATIC I NHIBITORY S YNAPSES (B ASKET C ELLS ). The most commonly encountered interneurons ( Figure 1A) are multipolar in shape, i.e., they may have three or more primary dendritic branches emanating from their cell bodies, some having somata that are as large as those of pyramidal neurons (Jones and Hendry 1984). Using immunocytochemistry to localize the enzyme ). These cells also ...

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Γ-Aminobutyric-Acid DEFICIENCY IN BRAIN OF SCHIZOPHRENIC PATIENTS

Cited by 171 publications

References 21 publications

No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia

No Evidence of Altered In Vivo Benzodiazepine Receptor Binding in Schizophrenia

Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

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