Cell loss in the hippocampus of schizophrenics

Falkai, P.; Bogerts, P.

doi:10.1097/00002093-198802040-00023

Cited by 87 publications

(122 citation statements)

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“…Measurements of the hippocampal formation included all CA segments (CA1, CA2, CA3, and CA4), the dentate gyrus, the alveus, and the subicular region. Neuroanatomical boundaries were primarily based on criteria from postmortem histological work (Bogerts et al, 1985; Falkai and Bogerts, 1986) and prior published studies (Ashtari et al, 1991; 1999). However, owing to the clarity of the atlas, the most posterior section of the hippocampus was defined as the slice where the fornix was not interrupted by the pulvinar and clearly observed as one piece.…”

Section: Methodsmentioning

confidence: 99%

Medial temporal structures and memory functions in adolescents with heavy cannabis use

Ashtari

Avants

Cyckowski

et al. 2011

Journal of Psychiatric Research

214

200

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Converging lines of evidence suggest an adverse effect of heavy cannabis use on adolescent brain development, particularly on the hippocampus. In this preliminary study, we compared hippocampal morphology in 14 "treatment-seeking" adolescents (aged 18-20) with a history of prior heavy-cannabis use (5.8 joints/day) after an average of 6.7 months of drug abstinence, and 14 demographically matched normal controls. Participants underwent a high-resolution 3D MRI as well as cognitive testing including the California Verbal Learning Test (CVLT). Heavy-cannabis users showed significantly smaller volumes of the right (p< .04) and left (p< .02) hippocampus, but no significant differences in the amygdala region compared to controls. In controls, larger hippocampus volumes were observed to be significantly correlated with higher CVLT verbal learning and memory scores, but these relationships were not observed in cannabis users. In cannabis users, a smaller right hippocampus volume was correlated with a higher amount of cannabis use (r= -.57, p< .03). These data support a hypothesis that heavy-cannabis use may have an adverse effect on hippocampus development. These findings, after an average 6.7 month of supervised abstinence, lend support to a theory that cannabis use may impart long-term structural and functional damage. Alternatively, the observed hippocampal volumetric abnormalities may represent a risk factor for cannabis dependence. These data have potential significance for understanding the observed relationship between early cannabis exposure during adolescence and subsequent development of adult psychopathology reported in the literature for schizophrenia and related psychotic disorders.

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Section: Methodsmentioning

confidence: 99%

Medial temporal structures and memory functions in adolescents with heavy cannabis use

Ashtari

Avants

Cyckowski

et al. 2011

Journal of Psychiatric Research

214

200

View full text Add to dashboard Cite

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“…B) SCHIZOPHRENIA AND NEUROLEPTICS. Developmental dysfunction of the HF is thought to play a major role in the pathogenesis of schizophrenia (206,488), and defects such as a reduction in hippocampal volume (53,400,558), hippocampal shape deformations (101), abnormalities in the GCL (357), the MF pathway (170), the hippocampal cell density (41,150,233) and orientation (93,288), and in several cellular markers (203,313) have been reported. These changes are believed to underlie the progressive deficit in cognition that is a hallmark of schizophrenia.…”

Section: Iv) Summarymentioning

confidence: 99%

Adult Neurogenesis: From Precursors to Network and Physiology

Abrous¹,

Koehl²,

Moal³

2005

Physiological Reviews

876

701

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The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.

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“…Postmortem (Falkai and Bogerts, 1986; Sherman et al, 1991) and imaging studies (Liddle et al, 1992; Raine et al, 1992; Tamminga et al, 1992; Bogerts et al, 1993) provide evidence that both structures play a role in schizophrenia. Thus, functional disruptions in these systems induce deficits consistent with those observed in schizophrenia such as interference with prepulse inhibition (Braff et al, 1992), thought to involve gating within the vSub (Caine et al, 2001), and working memory deficits (Weinberger and Gallhofer, 1997) involving the mPFC (Roberts et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Critical Role of the Prefrontal Cortex in the Regulation of Hippocampus–Accumbens Information Flow

Belujon¹,

Grace²

2008

J. Neurosci.

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The nucleus accumbens (NAc) is an integral part of limbic circuits proposed to play a central role in the pathophysiology of schizophrenia, and is positioned to integrate information from limbic and cortical regions, including the medial prefrontal cortex (mPFC) and the hippocampus. The ventral subiculum (vSub) of the hippocampus, in particular, is proposed to gate information flow within the NAc, a factor that is disrupted in models of schizophrenia. Using in vivo extracellular recordings in anesthetized rats, we examined the response of NAc neurons to vSub stimulation and how this is modulated by the mPFC. We found that inactivation of mPFC by tetrodotoxin attenuates the ability of the vSub to drive spike firing in the NAc. Thus, a contribution of the mPFC is required for the activation of NAc by the vSub. However, when long-term potentiation is induced in the vSub-NAc pathway, the vSub is now capable of driving the NAc without the participation of the mPFC. Moreover, this interaction is dependent on activation of dopaminergic D 2 receptors in the NAc.This work demonstrates the critical role of the mPFC in the ability of vSub to drive NAc neurons in normal anesthetized animals. One model of schizophrenia posits that vSub hyperactivity may underlie both the hyperdopaminergic state and disruption of information flow in this circuit in schizophrenia. Therefore, inactivation of the mPFC, as would occur with mPFC leukotomy in schizophrenia, may prevent the abnormal vSub drive of the NAc.

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Cell loss in the hippocampus of schizophrenics

Cited by 87 publications

References 0 publications

Medial temporal structures and memory functions in adolescents with heavy cannabis use

Medial temporal structures and memory functions in adolescents with heavy cannabis use

Adult Neurogenesis: From Precursors to Network and Physiology

Critical Role of the Prefrontal Cortex in the Regulation of Hippocampus–Accumbens Information Flow

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