Deficits in Small Interneurons in Prefrontal and Cingulate Cortices of Schizophrenic and Schizoaffective Patients

Beneš, Francine M.; McSparren, Jennifer; Bird, Edward D.; SanGiovanni, John Paul; Vincent, Stephen L.

doi:10.1001/archpsyc.1991.01810350036005

Cited by 841 publications

(445 citation statements)

References 31 publications

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“…Abnormalities in cellular orientation, connectivity, receptor distribution and sensitivity, and neurotransmitter distribution, among other factors, are not detectable by MRI and have been previously reported (Benes et al, 1986(Benes et al, , 1991. However, a histological study reporting abnormalities in prefrontal areas did not find a significant difference between schizophrenic and control subjects in the cortical thickness of area 9 of the prefrontal cortex because the differences were not large enough to reach significance (Selemon et al, 1995).…”

Section: Discussionmentioning

confidence: 93%

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Wible

Anderson

Shenton

et al. 2001

Psychiatry Research: Neuroimaging

185

100

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The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions -two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

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Section: Discussionmentioning

confidence: 93%

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Wible

Anderson

Shenton

et al. 2001

Psychiatry Research: Neuroimaging

185

100

View full text Add to dashboard Cite

show abstract

“…Our sub-chronic PCP dosing regime causes reduced density of parvalbumin-immunoreactive neurons in hippocampal regions (Abdul-Monim et al, 2007) and levels of brain-derived neurotrophic factor mRNA (BDNF) in cortical regions (Snigdha et al, 2007) in rats. Reductions in GABAergic interneurones in these areas have been found in post-mortem analysis from patients with schizophrenia (Benes et al, 1991;Benes and Berretta, 2001;Beasley et al, 2002;Zhang and Reynolds, 2002). We have shown that atypical but not classical antipsychotics can reverse these cognitive deficits; however, in the clinic there is differing evidence for the efficacy of atypical antipsychotics in improving cognition with the CATIE study (Lieberman, 2006;Keefe et al, 2007) and the UK Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS; Jones et al, 2006; suggesting that antipsychotics actually have a limited effect.…”

Section: Introductionmentioning

confidence: 80%

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

et al. 2009

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“…Alternatively, repeated subchronic exposure to psychomotor stimulant drugs such as PCP, and d-amphetamine, produce enduring behavioural, molecular, structural and cellular changes, which are believed to mimic schizophrenia more accurately than acute dosing [18,32,56]. Postmortem analysis of brain tissue from schizophrenic patients has shown a reduction in GABAergic interneurons in the frontal cortex [5] and hippocampus [6]. We have recently demonstrated reduced density of parvalbumin immuno reactive neurons in the hippocampus and M1 (motor area 1) region of the frontal cortex following sub-chronic PCP treatment in the rat [3].…”

Section: Introductionmentioning

confidence: 99%

A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats

McLean

Beck

Woolley

et al. 2008

Behavioural Brain Research

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Rationale: The NMDA receptor antagonist, phencyclidine (PCP), has been shown to induce symptoms characteristic of schizophrenia. A loss in executive function and the ability to shift attention between stimulus dimensions is impaired in schizophrenia; this can be assessed in rodents by the perceptual attentional set-shifting task. Objective: The aim of this study was to investigate whether the deficits induced by sub-chronic PCP in attentional set-shifting could be reversed by sub-chronic administration of clozapine, risperidone or haloperidol. Methods: Adult female hooded-Lister rats received subchronic PCP (2 mg/kg) or vehicle (1 ml/kg) i.p. twice daily for seven days, followed by a seven-day washout period. PCP-treated rats then received clozapine, risperidone, haloperidol or vehicle once daily for seven days and were then tested in the perceptual set-shifting task. Results: PCP significantly (p<0.01) increased the number of trials to reach criterion in the EDS phase when compared to vehicle and this deficit was significantly (p<0.01) attenuated by sub-chronic clozapine (2.5 mg/kg) and risperidone (0.2 mg/kg), but not by sub-chronic haloperidol treatment (0.05 mg/kg). Conclusions:These data show that sub-chronic PCP produced a robust deficit within the EDS phase in the attentional set-shifting task, in female rats. Atypical antipsychotics, clozapine and risperidone, but not the classical agent, haloperidol, significantly improved the PCPinduced cognitive deficit.

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Deficits in Small Interneurons in Prefrontal and Cingulate Cortices of Schizophrenic and Schizoaffective Patients

Cited by 841 publications

References 31 publications

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats

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