Hippocampal abnormalities and memory deficits: New evidence of a strong pathophysiological link in schizophrenia

doi:10.1016/j.brainresrev.2006.12.008

Brain Research Reviews

Volume 54, Issue 1, April 2007, Pages 92-112

https://doi.org/10.1016/j.brainresrev.2006.12.008 Get rights and content

Abstract

The central goals of this manuscript are (1) to better characterize what appears to be the most parsimonious account of schizophrenic long-term memory impairment in the neuropsychological literature: a contextual binding deficit rooted in the medial temporal lobes; (2) to link this deficit to concrete abnormalities at the level of the hippocampus; and (3) to suggest that this deficit could lead to the functional impairment experienced by schizophrenia patients in their daily lives. As far as long-term memory is concerned in schizophrenia, there seems to be a general agreement to conclude that explicit mechanisms are disturbed compared to relatively spared implicit mechanisms. More precisely, both subsystems of explicit memory (i.e., episodic and semantic) appear to be dysfunctional in this patient population. Errors during the encoding processes could be responsible for this dysfunction even if retrieval per se is not totally spared. Recently, a number of studies have suggested that impairments in conscious recollection and contextual binding are closely linked to episodic memory deficit. Since the hippocampal formation is considered to be the central element in the neural support for contextual binding and episodic memory, we have conducted an extensive review of the literature concerning the hippocampal formation in schizophrenia. Emerging evidence from varying disciplines confirm the coherence of the different anomalies reported concurrently at the neuroanatomical, neurodevelopmental, biochemical, and genetic levels. It seems highly probable that the synaptic disorganization in the hippocampus concerns the regions crucial for encoding and contextual binding memory processes. The consequences of these deficits could result in schizophrenia patients experiencing major difficulties when facing usual events which have not been encoded with their proper context.

Section snippets

Reconsidering the position of centrality of prefrontal lobe deficits in schizophrenia

One of the goals of neuropsychological and cognitive research in schizophrenia has been to identify abnormalities, in particular cognitive processes, that are linked to specific brain regions or systems (Goldberg et al., 2003). During the past few decades, the cognitive literature has focused mainly on executive functions, a cluster of cognitive brain functions involved in attention, planning, sequencing, decision making, initiating, and inhibiting behaviors which are associated with the

Neurocognitive evidence of contextual binding deficit in schizophrenia

It has often been noted that the pattern of memory impairment observed in schizophrenia is similar to that found in patients with medial–temporal lobe lesions (Duffy and O’Carroll, 1994, Goldberg et al., 1990, McKenna et al., 1990, Rushe et al., 1999, Saykin et al., 1991, Tamlyn et al., 1992). McKenna and colleagues (1990) have even suggested the existence of a “schizophrenic amnesia”. There appear to be two separate lines of neurocognitive evidence which point to the medial–temporal lobes as

Hippocampal abnormalities which underlie the contextual binding deficit

The hippocampus has long been implicated in the pathophysiology of schizophrenia. In fact, the long-term memory impairments extensively documented in this condition may be a direct consequence of hippocampal circuit dysfunction. The hypothesis of hippocampal involvement is supported by evidence of neuroanatomical and neurodevelopmental abnormalities, biochemical correlates, and genetic vulnerability factors which implicate the hippocampal formation in these memory deficits.

Neuroimaging exploration of the hippocampal region in schizophrenia

The vast majority of morphometric studies conducted during the last decade have concluded to a grey and white matter reduction in some precise areas of the brain for schizophrenia patients when compared to control participants. Among these regions, the right and left hippocampal volumes have been repetitively reported as reduced, together with the orbitofrontal gyrus, the inferior and medial frontal lobes, and the anterior and posterior cingulate cortices (Davatzikos et al., 2005).

Consequences of hippocampal abnormalities for contextual binding

As previously detailed, in accord with these physiological abnormalities, there is now substantial evidence that schizophrenia patients experience long-term memory impairments. Specifically, while patients with schizophrenia are capable of storing information related to the content of an event, they do not properly link this information with its context, producing an episodic memory deficit (Danion et al., 1999, Rizzo et al., 1996a, Schwartz et al., 1991). This deficiency is probably a direct

Clinical consequences of contextual binding deficit

Impairment in long-term memory due to contextual binding deficit is likely to result in important clinical consequences. Two potential consequences (i.e., impaired autobiographical memory and delusions) are reviewed below.

Conclusion

We have highlighted the nature and importance of the hippocampal abnormalities reported in schizophrenia and theorized the clinical consequences of these abnormalities in terms of contextual binding deficit and episodic memory impairment. Numerous lines of evidence at the genetic, molecular, anatomical, and biochemical levels seem to converge towards the hypothesis of a hippocampal neurofunctional deficit in schizophrenia which concerns the different stages of long-term memory processing,

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ReviewHippocampal abnormalities and memory deficits: New evidence of a strong pathophysiological link in schizophrenia

Abstract

Section snippets

Reconsidering the position of centrality of prefrontal lobe deficits in schizophrenia

Neurocognitive evidence of contextual binding deficit in schizophrenia

Hippocampal abnormalities which underlie the contextual binding deficit

Neuroimaging exploration of the hippocampal region in schizophrenia

Consequences of hippocampal abnormalities for contextual binding

Clinical consequences of contextual binding deficit

Conclusion

Biol. Psychiatry

Biol. Psychiatry

Neuropsychopharmacology

Brain Cogn.

Brain Res.

Biol. Psychiatry

Neuron

Psychiatry Res.

Neuropsychologia

Biochem. Pharmacol.

Int. Rev. Neurobiol.

J. Verbal Learn. Verbal Behav.

Cognition

Conscious Cogn.

Neuropsychologia

Schizophr. Res.

Neuron

Neuroscience

Neuroscience

Brain Res. Mol. Brain Res.

Psychiatry Res.

Schizophr. Res.

Schizophr. Res.

Psychiatry Res.

Behav. Res. Ther.

Brain Res.

Schizophr. Res.

Schizophr. Res.

Biol. Psychiatry

Clin. Psychol. Rev.

Memory and attention dysfunctions in story recall in schizophrenia: evidence of a possible frontal malfunctioning

Biol. Psychiatry

Episodic memory-related activation in schizophrenia: meta-analysis

Br. J. Psychiatry

Effects of N-methyl-d-aspartate receptor antagonist ketamine on striatal dopamine release in schizophrenia

Schizophr. Res.

Why are you telling me that? A conceptual model of the social function of autobiographical memory

Memory

Memory impairment in schizophrenia: a meta-analysis

Am. J. Psychiatry

Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia

Arch. Gen. Psychiatry

Abnormal expression of two microtubule-associated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia

Proc. Natl. Acad. Sci. U. S. A.

Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions

Am. J. Psychiatry

Working Memory

Schizophrenic delusions and the construction of autobiographical memory

Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey

Hippocampus

Working and long-term memory deficits in schizophrenia: is there a common prefrontal mechanism?

J. Abnorm. Psychol.

Memory and frontal lobe dysfunction in schizophrenia and schizoaffective disorder

J. Nerv. Ment. Dis.

Cognitive approaches to schizophrenia: theory and therapy

Ann. Clin. Psychiatry

Reduced neuronal size in posterior hippocampus of schizophrenic patients

Schizophr. Bull.

Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates

Am. J. Psychiatry

Cognitive neuropsychiatric models of persecutory delusions

Am. J. Psychiatry

Persecutory delusions and the determination of self-relevance: an fMRI investigation

Psychol. Med.

Basal ganglia and limbic system pathology in schizophrenia

Arch. Gen. Psychiatry

Postmortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics: initial results from a new brain collection

Schizophrenia Res.

Review
Hippocampal abnormalities and memory deficits: New evidence of a strong pathophysiological link in schizophrenia