Effects of haloperidol on CSF glutamate levels in drug-naive schizophrenic patients

Labarca, Rafael; Silva, Hernán Alejandro Fierro; Jerez, Sonia; Ruiz, Aida; Renterías, Patricia; Ogalde, Claudia; Bustos, Gonzalo

doi:10.1016/0920-9964(95)91301-u

Cited by 9 publications

(4 citation statements)

References 14 publications

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“…To our knowledge, there are no published reports that have investigated glutamatergic dysfunction in adult OCD. Although, studies have investigated glutamate levels in CSF in schizophrenia (Kim et al, 1980;Gattaz et al, 1982;Korpi et al, 1987;Labarca et al, 1995;Faustman et al, 1999), similar studies are lacking in OCD. In the background of the MRS data, we decided to investigate CSF glutamate levels in adult OCD probands and compare it to psychiatrically normal controls.…”

Section: Introductionmentioning

confidence: 99%

Glutamatergic Dysfunction in OCD

Chakrabarty

Bhattacharyya

Christopher

et al. 2005

Neuropsychopharmacol

310

191

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The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (mmol/l) level was found to be significantly higher [F(1,31) ¼ 6.846, p ¼ 0.014] in OCD patients (47.1274.25) compared to control subjects (41.3673.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.

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Section: Introductionmentioning

confidence: 99%

Glutamatergic Dysfunction in OCD

Chakrabarty

Bhattacharyya

Christopher

et al. 2005

Neuropsychopharmacol

310

191

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“…Finally, drugs that alter glutamate transmission can ameliorate schizophrenic symptoms (Heresco-Levy et al 1996;Javitt et al 1994;Tsai et al 1998 NO . 3 antipsychotic drug treatment alters EAA levels in the CSF and serum of schizophrenic patients (Evins et al 1997;Labarca et al 1995).Preclinical research also supports a role for EAAs in the pathogenesis of schizophrenia. When tested in rats, NMDA receptor antagonists produce behavioral responses that model schizophrenic symptoms and are blocked by antipsychotic drugs, including clozapine (e.g., Hauber 1993).…”

mentioning

confidence: 95%

Section: Many Lines Of Evidence Implicate Dysfunctional Excitatory Ammentioning

confidence: 99%

Expression of AMPA Receptor Flip and Flop mRNAs in the Nucleus Accumbens and Prefrontal Cortex after Neonatal Ventral Hippocampal Lesions

Stine

Wolf

2001

Neuropsychopharmacology

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Many lines of evidence implicate dysfunctional excitatory amino acid (EAA) transmission in schizophrenia. The present study examined ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) receptor expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) using a rat model of schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) on postnatal day (PD) 7 lead to the postpubertal emergence of behavioral abnormalities that resemble schizophrenic symptoms. In situ hybridization histochemistry with 35 S-labeled oligonucleotide probes was used to quantify mRNA levels for respectively Recent hypotheses about the pathophysiology of schizophrenia have posited defects in excitatory amino acid (EAA) transmission (e.g., Carlsson and Carlsson 1990; Coyle 1996;Krystal et al. 1999;Olney and Farber 1995). A number of different lines of evidence support the involvement of EAAs. First, N-methyl-D-aspartate (NMDA) receptor antagonists produce effects in normal human subjects that resemble those associated with schizophrenia (Krystal et al. 1999). Second, schizophrenic brains exhibit abnormalities in glutamate metabolism (Bartha et al. 1997; Do et al. 1995; Faustman et al. 1999;Tsai et al. 1995) and glutamate receptor expression (reviewed by Meador-Woodruff and Healy 2000). Finally, drugs that alter glutamate transmission can ameliorate schizophrenic symptoms (Heresco-Levy et al. 1996;Javitt et al. 1994;Tsai et al. 1998 NO . 3 antipsychotic drug treatment alters EAA levels in the CSF and serum of schizophrenic patients (Evins et al. 1997;Labarca et al. 1995).Preclinical research also supports a role for EAAs in the pathogenesis of schizophrenia. When tested in rats, NMDA receptor antagonists produce behavioral responses that model schizophrenic symptoms and are blocked by antipsychotic drugs, including clozapine (e.g., Hauber 1993). Chronic administration of antipsychotic drugs alters glutamate receptor expression in rat brain (Chen et al. 1998; Eastwood et al. 1994 Eastwood et al. , 1996 Fitzgerald et al. 1995;Healy and Meador-Woodruff 1997;Riva et al. 1997;Tascedda et al. 1999) and alters EAA levels as measured by microdialysis (Daly and Moghaddam 1993;See and Chapman 1994;See and Lynch 1996;Yamamoto and Cooperman 1994).The ␣ -amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) subtype of glutamate receptor mediates the majority of excitatory transmission in brain. Different combinations of four AMPA receptor subunits (GluR1-4) give rise to heteromeric receptors with distinct properties (Hollman and Heinemann, 1994). The purpose of the present study was to examine the possible role of alterations in AMPA receptor expression in schizophrenia, using a rat model for schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) are produced on postnatal day (PD) 7 . By interrupting connections between the limbic system and cortex during the vulnerable neonatal period, neonatal VH lesions may produce developmental changes related to those that are believed to underlie schizophre...

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“…They found a reduction in levels of GAD 65 and GAD 67 proteins in all psychiatric subjects. These findings could explain increased blood and CSF GLU and glutamine levels in schizophrenic, [43,44] and depressed subjects, [45] probably due to an accumulation of these two precursor compounds of GABA. Indeed, normal production of GAD 65 and GAD 67 , as well as of Reelin 410, 330 and 180 kDa, reflects normal GABAergic cell function in several parts of the brain including cerebellum.…”

Section: Gad In Mdsmentioning

confidence: 98%