Hippocampus and amygdala in schizophrenia: assessment of the relationship of neuroanatomy to psychopathology

Rajarethinam, Rajaprabhakaran; DeQuardo, John R.; Miedler, John; Arndt, Stephan; Kirbat, Ravi; Brunberg, James A.; Tandon, Rajiv

doi:10.1016/s0925-4927(01)00120-2

Cited by 109 publications

(69 citation statements)

References 24 publications

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“…Neuroimaging studies report reductions in amygdalar volumes in schizophrenic patients (Rajarethinam et al, 2001, Anderson et al, 2002. In addition, fMRI studies revealed reduced amygdalar activation in schizophrenic subjects when evaluating facial expressions for emotional salience (Gur et al, 2002, Hempel et al, 2003 and this impairment appears to be specific to patients with primary negative symptoms (Anderson et al, 2002).…”

Section: Discussionmentioning

confidence: 97%

Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin

Lee¹,

Brady²,

Shapiro³

et al. 2007

Brain Research

237

188

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Neurodevelopmental changes induced by environmental stress exposure play a significant but poorly defined role in the etiology of schizophrenia. Exposure of pregnant female rats to a series of unpredictable stresses during the final week of pregnancy generates behavioral deficits and molecular changes in the offspring similar to those observed in schizophrenic individuals. We used this rat prenatal stress preparation to investigate social withdrawal behaviors that may have relevance to the negative symptoms of schizophrenia. The cumulative time adult male offspring of stress-exposed pregnant female rats actively interacted with a weight-matched, same-sex peer was decreased approximately 76% relative to non-stress exposed control rats. Prenatal stress exposure also diminished the quality of the social interaction behavior indicative of reduced social drive. Analysis of the oxytocinergic system in the prenatally stressed male rats revealed significantly less oxytocin mRNA in the paraventricular nucleus and increased oxytocin receptor binding in the central amygdala. Moreover, oxytocin, but not vasopressin, administration into the central amygdala reversed the social incompetence of the prenatally stressed rats without increasing behavior in nonstressed control animals. In addition, cross-fostering pups from prenatally stressed mothers to nonstressed mothers failed to improve the social deficit of the prenatally stressed male offspring. Two behavioral assays designed to measure anxiety did not differentiate the prenatally stressed rats from non-stressed controls. These data indicate that prenatal stress may be an etiologically appropriate animal model for some aspects of schizophrenic social withdrawal. Furthermore, unpredictable prenatal stress exposure selectively degrades social interaction behaviors without increasing anxiety measures.

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Section: Discussionmentioning

confidence: 97%

Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin

Lee¹,

Brady²,

Shapiro³

et al. 2007

Brain Research

237

188

View full text Add to dashboard Cite

show abstract

“…Moreover, cognitive function such as verbal declarative memory is correlated with the fractional anisotropy of the hippocampus in schizophrenia [48]. This disruption of connectivity in this region could result in cognitive as well as clinical negative symptoms [28,47,56]. This is due to the fact that neuronal Wbers traversing the limbic pathways from the posterior part of the hippocampus are connected to prefrontal regions and pathways involved in higher cognition [25].…”

Section: Discussionmentioning

confidence: 99%

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

et al. 2008

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Structural magnetic resonance imaging and postmortem studies showed volume loss in the hippocampus in schizophrenia. The noted tissue reduction in the posterior section suggests that some cellular subfractions within this structure might be reduced in schizophrenia. To address this, we investigated numbers and densities of neurons, oligodendrocytes and astrocytes in the posterior hippocampal subregions in postmortem brains from ten patients with schizophrenia and ten matched controls using design-based stereology performed on Nissl-stained sections. Compared to the controls, the patients with schizophrenia showed a signiWcant decrease in the mean number of oligodendrocytes in the left and right CA4. This is the Wrst Wnding of reduced numbers of oligodendrocytes in CA4 of the posterior part of the hippocampus in schizophrenia. Our results are in line with earlier Wndings in the literature concerning decreased numbers of oligodendrocytes in the prefrontal cortex in schizophrenia. Our results may indicate disturbed connectivity of the CA4 of the posterior part of the hippocampus in schizophrenia and, thus, contribute to the growing number of studies showing the involvement of posterior hippocampal pathology in the pathophysiology of schizophrenia.

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“…In schizophrenia, many, but not all researchers (Flaum et al, 1995), have reported clinical/ size correlations. For example, in schizophrenia, shorter hippocampi bilaterally correlated with bizarre behavior (Fukuzako et al, 1996) and smaller hippocampal volumes with negative symptoms (Rajarethiam et al, 2001). Abnormal hippocampal volumes may be involved in the manifestation of such behavior across the spectrum.…”

Section: Discussionmentioning

confidence: 99%

MRI abnormalities of the hippocampus and cavum septi pellucidi in females with schizotypal personality disorder

Dickey

McCarley

et al. 2007

Schizophrenia Research

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Objective-This study examined MRI hippocampal volume and cavum septi pellucidi (CSP) in female subjects with schizotypal personality disorder (SPD) and comparison subjects.Method-MRI was performed on 20 SPD and 29 comparison subjects with delineation of left and right hippocampi. Number of slices containing the CSP was counted. Subjects were given a working memory task, the Delayed Alternation task and other measures of working memory including the Wechsler Memory Test-Revised and the California Verbal Learning Test. Clinical measures were derived from the SCID-II.Results-SPD females evinced bilaterally smaller hippocampal volumes compared with nonpsychiatric female subjects (15.1% on left, 15.7% on right). Additionally, SPD subjects showed statistically significantly more slices containing CSP, and a trend level difference when large CSP was defined as four or more slices (20% vs. 6.9%). SPD subjects demonstrated more errors, more perseverations, and a trend toward more failure to maintain set on the Delayed Alternating task, which were associated with smaller left hippocampal volumes. There was no difference between groups in logical memory, verbal learning or semantic clustering nor a significant correlation between these measures and hippocampal volumes. Clinically, in SPD subjects, right hippocampal volumes correlated negatively with odd appearance/behavior and positively with suspiciousness/paranoia, and odd speech was positively correlated with the number of slices containing a CSP in exploratory analyses.Conclusions-Female SPD subjects showed bilaterally smaller hippocampal volumes and larger CSP than comparison subjects, similar to what has been shown in schizophrenia. Moreover, these abnormalities have clinically significant associations which may help to explain some of the manifestations of the disorder.

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Hippocampus and amygdala in schizophrenia: assessment of the relationship of neuroanatomy to psychopathology

Cited by 109 publications

References 24 publications

Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin

Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

MRI abnormalities of the hippocampus and cavum septi pellucidi in females with schizotypal personality disorder

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