Sex-Dependent Hippocampal Volume Reductions in Schizophrenia Relate to Episodic Memory Deficits

Exner, Cornelia; Nehrkorn, Barbara; Martin, Vera; Huber, Martin; Shiratori, Kiyoshi; Rief, Winfried

doi:10.1176/jnp.2008.20.2.227

Cited by 30 publications

(13 citation statements)

References 14 publications

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“…Together with other mechanisms such as endogenous steroid levels, these differences may also underlie sexual dimorphism and left-right asymmetry in the hippocampus. Nevertheless, the hippocampus implicated in the etiology of several mental health disorders, many of which exhibit some degree of sex difference, and there are also subtle sex differences in hippocampal-associated behaviors such as spatial learning strategies and stress responsivity (Castle and Murray 1991;von Wilmsdorff et al 2010;DeCarolis and Eisch 2010;Exner et al 2008;Frazier et al 2008). Future studies will be needed to determine the possible involvement of IGF-1R and InsR in these gender differences of hippocampal function and dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Sex differences and left–right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus

et al. 2011

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Sex differences and laterality of rat hippocampus with respect to insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression as two important contributors to/regulators of developmental and cognitive functions were examined using real-time PCR and western blot analysis at P0, P7 and P14. Expression of the IGF-1R gene was lowest at P0 in all studied hippocampi. In males, we found the highest expression at P7 in the right hippocampus, and at P14 in the left one. In contrast, the peaked IGF-1R expression occurred at P7 in female hippocampi independent of laterality. Hippocampal InsR expression in males decreased significantly between P0 and P7, followed by a marked upregulation at P14. Conversely, the expression of InsR in females peaked at P7 and then decreased again significantly at P14. We found significant interhemispheric differences in IGF-1R mRNA levels in both male and female hippocampi at different time points. In contrast, we only found significant interhemispheric differences in InsR mRNA expression in P14 male rats, with higher values in the left hippocampus. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that IGF-1R and InsR transcription is not subject to modulatory effects during the first two weeks of development. These findings indicate that there are prominent interhemispheric and sex differences in IGF-1R and InsR expression in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development and function of the hippocampus.

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Section: Discussionmentioning

confidence: 99%

Sex differences and left–right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus

et al. 2011

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“…Studies that focus on sexual dimorphism may also be an important piece of the puzzle, given the marked paucity of female schizophrenia subjects in the majority of studies in the literature and also in light of equivocal findings of sexual dimorphism in hippocampal pathology for this patient population (as reviewed in Exner et al 2008). Findings of abnormal orbitofrontal cortex to amygdala ratios in men and women with schizophrenia relative to healthy controls have led Gur et al (2004) to suggest that schizophrenia may involve a reversal of normal sexual dimorphism, i.e., a 'feminization' of men and a 'masculinization' of women (as reviewed by Guillem et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Findings of abnormal orbitofrontal cortex to amygdala ratios in men and women with schizophrenia relative to healthy controls have led Gur et al (2004) to suggest that schizophrenia may involve a reversal of normal sexual dimorphism, i.e., a 'feminization' of men and a 'masculinization' of women (as reviewed by Guillem et al 2009). A recent study that investigated hippocampal volumes of male and female individuals with schizophrenia found bilateral hippocampal volume reductions in male, but not female, patients (Exner et al 2008). The authors proposed that reduced right hippocampal volumes in male patients may be responsible for deficits in visual episodic memory, but point out that the presence of similar deficits in female patients may be attributable to separable pathophysiological mechanisms between the sexes.…”

Section: Discussionmentioning

confidence: 99%

Episodic Memory in Schizophrenia

Leavitt

Goldberg

2009

Neuropsychol Rev

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Episodic memory impairments in individuals with schizophrenia have been well documented in the literature. However, despite the abundance of findings, constituent cognitive, neural, behavioral, and genetic components of the deficits continue to elude full characterization. This review provides a characterization of these deficits by organizing findings within three frameworks of interest: 1) neuroanatomical; 2) genetic; and 3) behavioral. Within each approach, evidence from imaging studies as well as behavioral studies is examined. The hope is that by synthesizing the cognitive science paradigms, molecular genetic neurophysiological findings, and computational algorithms applied to medial temporal lobe subregions, we will be able to expand our understanding of the types of compromises in episodic memory systems of individuals with schizophrenia.

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“…The role of the hippocampus/perirhinal cortex in NORT performance parallels studies in humans suggesting the key role of medial temporal lobe in declarative memory (Squire and Zola-Morgan, 1991). Specifically, right hippocampal volume is related to visual learning (Exner et al, 2008). In a study directly comparing schizophrenia patients and patients with temporal lobe epilepsy (either right or left), schizophrenia patients showed similar deficits in a visual memory task as those observed in right temporal lobe epilepsy patients (Yoo et al, 2006).…”

Section: Visual Learning and Memorymentioning

confidence: 99%

Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia

Young

Powell

Risbrough

et al. 2009

Pharmacology & Therapeutics

289

323

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Cognitive deficits in schizophrenia are among the core symptoms of the disease, correlate with functional outcome, and are not well treated with current antipsychotic therapies. In order to bring together academic, industrial, and governmental bodies to address this great ‘unmet therapeutic need’, the NIMH sponsored the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. Through careful factor analysis and consensus of expert opinion, MATRICS identified seven domains of cognition that are deficient in schizophrenia (attention/vigilance, working memory, reasoning and problem solving, processing speed, visual learning and memory, verbal learning and memory, and social cognition) and recommended a specific neuropsychological test battery to probe these domains. In order to move the field forward and outline an approach for translational research, there is a need for a “preclinical MATRICS” to develop a rodent test battery that is appropriate for drug development. In this review, we outline such an approach and review current rodent tasks that target these seven domains of cognition. The rodent tasks are discussed in terms of their validity for probing each cognitive domain as well as a brief overview of the pharmacology and manipulations relevant to schizophrenia for each task.

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Sex-Dependent Hippocampal Volume Reductions in Schizophrenia Relate to Episodic Memory Deficits

Cited by 30 publications

References 14 publications

Sex differences and left–right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus

Sex differences and left–right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus

Episodic Memory in Schizophrenia

Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia

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