[123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia

Verhoeff, Nicolaas Paul L.G.; Soares, Jair C.; D’Souza, Cyril; Gil, Roberto; Degen, Kathleen; Abi‐Dargham, Anissa; Zoghbi, Sami S.; Fujita, Masahiro; Rajeevan, Nallakkandi; Seibyl, John; Krystal, John H.; Dyck, Christopher H. van; Charney, Dennis S.; Innis, Robert B.

doi:10.1016/s0925-4927(99)00027-x

Cited by 45 publications

(27 citation statements)

References 52 publications

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“…While two such studies have found no differences in schizophrenics (Busatto et al 1997;AbiDargham et al 1999), two others have found a reduction in this binding activity (Verhoeff et al 1999;Ball et al 1998). In two of these studies, changes in the benzodiazepine receptor correlated with cognitive impairment (Ball et al 1998) or severity of illness (Busatto et al 1997).…”

Section: Postmortem Evidence For a Gaba Defect In Schizophreniamentioning

confidence: 96%

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

Beneš

Berretta

2001

Neuropsychopharmacology

997

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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Section: Postmortem Evidence For a Gaba Defect In Schizophreniamentioning

confidence: 96%

GABAergic Interneurons Implications for Understanding Schizophrenia and Bipolar Disorder

Beneš

Berretta

2001

Neuropsychopharmacology

997

643

View full text Add to dashboard Cite

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“…Electrophysiological methods provide indirect and inferential evidence of the involvement of inhibitory neuronal systems in schizophrenia (5). The only direct in vivo assessments of GABA-ergic systems are the distribution of benzodiazepine receptors (where no differences between patients and controls were found [6]), the use of radioactively labeled ligands of these receptors that are sensitive to GABA level changes induced by GABA-acting drugs (7)(8)(9), and overall GABA levels measured with magnetic resonance spectroscopy (MRS). Several MRS studies have been published, with variable results as to the presence, regional distribution, and directionality of change of GABA levels in schizophrenia.…”

Section: Objectivementioning

confidence: 99%

Prefrontal GABA Levels Measured With Magnetic Resonance Spectroscopy in Patients With Psychosis and Unaffected Siblings

Marenco¹,

Meyer²,

Kuo³

et al. 2016

AJP

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Objective:The authors sought to compare GABA levels in treated and untreated patients with psychosis with levels in their unaffected siblings and healthy control subjects, and to assess the effects of antipsychotic medications on GABA levels.Method: GABA+ levels (i.e., including signal from unrelated proteins or macromolecules) referenced to creatine or water were studied with J-edited proton spectroscopy in the dorsal anterior cingulate cortex of 289 individuals: 184 healthy control subjects, 83 treated patients with psychosis, 25 untreated patients, 31 unaffected siblings, and 17 patients studied both while off all medications and while on a single antipsychotic.Results: GABA+ levels in the dorsal anterior cingulate did not differ between untreated patients and healthy controls. For treated patients, levels were modestly lower for GABA+/ creatine but did not differ for GABA+/water compared with healthy controls. For both GABA+ measures, unaffected siblings had significantly lower levels compared with controls. GABA+/creatine showed a modest degree of familiality (intraclass correlation=0.36). Antipsychotic dosage was negatively correlated with GABA+ levels, but the on-off medication studies indicated no difference in GABA+ levels on antipsychotics compared with off antipsychotics.Conclusions: GABA+/creatine in the dorsal anterior cingulate may constitute an intermediate phenotype with low effect size for psychosis, but GABA+/water measures do not fully support this conclusion. Low GABA+ levels in unaffected siblings could suggest a genetic association, but the failure to find consistent evidence of this phenotype in the patients themselves weakens genetic inference on risk for psychosis. Replication in independent samples of siblings is warranted to confirm the potential genetic risk association.

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“…Converging lines of evidence, including postmortem (Benes, 2000;Benes and Berretta, 2001;Benes et al, 1996;Hashimoto et al, 2003;Lewis et al, 2005;Ohnuma et al, 1999;Volk et al, 2000;Woo et al, 1998), genetic (reviewed by Charych et al (2009), and brain imaging studies (Ball et al, 1998;Busatto et al, 1997;Schroder et al, 1997;Verhoeff et al, 1999;Yoon et al, 2010), suggest that dysfunction of the gamma-amino butyric acid (GABA) system contributes to the pathophysiology of schizophrenia. In postmortem studies of schizophrenic patients, alterations in GABAergic transmission have been shown in many ways, including (1) reduced mRNA levels for the GABA-synthesizing enzyme glutamic acid decarboxylase-67 (Impagnatiello et al, 1998;Volk et al, 2000), (2) decreased density of axon cartridges of chandelier neurons (Woo et al, 1998), (3) decreased gene expression of the GABA membrane transporter-1 (Ohnuma et al, 1999;, (4) increased density of GABA-A receptors (Benes et al, 1996), (5) elevated density of a 1 - (Impagnatiello et al, 1998;Ohnuma et al, 1999) and a 2 -subunit-containing GABA-A receptors at pyramidal neuron axon segments , (6) decreased Reelin mRNA, which is preferentially expressed in GABAergic interneurons (Impagnatiello et al, 1998), and (7) decreased levels of ankyrin-G, a membrane protein that anchors the GABA receptor complex onto initial axonal segments of pyramidal cells in the area of chandelier cell synapses in superficial cortical area (Cruz et al, 2009).…”

Section: Introductionmentioning

confidence: 99%