Evidence that hippocampal–parahippocampal dysfunction is related to genetic risk for schizophrenia

Giorgio, Annabella Di; Franke, Barbara; Caforio, Grazia; Romano, Raffaella; Andriola, Ileana; D’Ambrosio, Enrico; Papazacharias, Apostolos; Elifani, Francesca; Bianco, Luciana Lo; Taurisano, Paolo; Fazio, Leonardo; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

doi:10.1017/s0033291712002413

Cited by 21 publications

(23 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge, so far, only 2 studies have explored hippocampal-parahippocampal abnormalities during declarative memory with fMRI in genetically high-risk populations. 24,25 Both found abnormal hippocampal-parahippocampal recruitment similar to our results, although the differences in clinical status, 24 sex, and performance 25 of the high-risk participants vs the comparison group of NCs left unresolved whether the observed deficit was due to familial/genetic background or was due to these other confounding factors. Our findings are also consistent with the results of 2 magnetic resonance spectroscopic imaging studies that found reduced Nacetylaspartate-an in vivo marker for neuronal synaptic abundance-in the hippocampus both in PTs and their SIBs 37,38 and with those from behavioral studies that reported deficient performance on declarative memory tests in unaffected relatives.…”

Section: Hippocampal-parahippocampal Function and Visual-memory Capacitysupporting

confidence: 84%

“…To our knowledge, so far, only 2 studies have reported impairment of HF recruitment in siblings of patients with schizophrenia during a declarative memory task. 24,25 However, it is uncertain whether the abnormality observed in these prior studies represents a pure trait phenomenon or is confounded by other state variables that could bias the results such as risk for conversion to psychosis 24 or poor memory performance 25 in these prior samples of siblings. It also is preferable to study siblings rather than parents because age is a state factor that affects memory and brain physiology.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Altered Hippocampal-Parahippocampal Function During Stimulus Encoding

et al. 2014

View full text Add to dashboard Cite

IMPORTANCE Declarative memory-the ability to learn, store, and retrieve information-has been consistently reported to be altered in schizophrenia, and hippocampalparahippocampal dysfunction has been implicated in this deficit. To elucidate the possible role of genetic risk factors in such findings, it is necessary to study healthy relatives of patients with schizophrenia who carry risk-associated genes but not the confounding factors related to the disorder. OBJECTIVE To investigate whether altered brain responses, particularly in the hippocampus and parahippocampus, during the encoding phase of a simple declarative memory task are also observed in unaffected siblings who are at increased genetic risk for schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Functional magnetic resonance imaging was used with a simple visual declarative memory paradigm to test for differences in neural activation across normal control participants, patients with schizophrenia, and their healthy siblings. This study was conducted at a research center and included a total of 308 participants (181 normal control participants, 65 healthy siblings, and 62 patients with schizophrenia); all participants were white of European ancestry. MAIN OUTCOMES AND MEASURES All participants completed a declarative memory task involving incidental encoding of neutral visual scenes interleaved with crosshair fixation while undergoing functional magnetic resonance imaging. Differences in hippocampus and parahippocampus activation and coupling across groups and correlations with accuracy were analyzed. Analyses were repeated in pairwise-matched samples. RESULTS Both patients with schizophrenia and their healthy siblings showed reduced parahippocampal activation (bilaterally) and hippocampal-parietal (BA 40) coupling during the encoding of novel stimuli when compared with normal control participants. There was a significant positive correlation between parahippocampal activation during encoding and the visual-memory score. CONCLUSIONS AND RELEVANCE These results suggest that altered hippocampalparahippocampal function during encoding is an intermediate biologic phenotype related to increased genetic risk for schizophrenia. Therefore, measuring hippocampalparahippocampal function with neuroimaging represents a potentially useful approach to understanding genetic mechanisms that confer risk for schizophrenia.

show abstract

Section: Hippocampal-parahippocampal Function and Visual-memory Capacitysupporting

confidence: 84%

mentioning

confidence: 99%

Altered Hippocampal-Parahippocampal Function During Stimulus Encoding

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Together with the amygdala, the parahippocampal gyrus assumes an important role in emotional processing and goal-directed processes ( 52 ). Furthermore, a recent functional study also provided evidence that hippocampal-parahippocampal dysfunction is related to genetic risk of developing schizophrenia ( 53 ). Our meta-analysis, however, did not find a grossly decreased volume of the hippocampus, which is has been reported as a pronounced change in non-psychotic first-degree relatives of schizophrenia patients in previous studies using ROI analysis ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Similar and Different Gray Matter Deficits in Schizophrenia Patients and Their Unaffected Biological Relatives

et al. 2013

View full text Add to dashboard Cite

Neuroimaging studies have revealed significant reductions in the gray matter (GM) of several brain regions in patients with schizophrenia, a neuropsychiatric disorder with high hereditability. However, it is unclear whether unaffected relatives have GM abnormalities in common with their affected relatives, which may relate to susceptibility to developing schizophrenia. To address this issue, we conducted two separate meta-analyses of voxel-based morphometry to investigate GM abnormalities in schizophrenia patients and their unaffected relatives. One meta-analysis compared a patient group with healthy controls, whereas the other meta-analysis compared the unaffected relatives with healthy controls. Eight studies comprising 495 patients with schizophrenia, 584 unaffected relatives of patients, and 596 healthy controls were systematically included in the present study. Compared to healthy controls, the patient group showed decreased GM in the right cuneus, the right superior frontal gyrus, the right insula and the left claustrum, and increased GM in the bilateral putamen, the right parahippocampal gyrus, the left precentral gyrus, the left inferior temporal gyri, and the right cerebellar tonsil. The comparison between unaffected relatives and healthy controls showed a GM reduction in the left claustrum, the bilateral parahippocampal gyri, the left fusiform gyrus, the right inferior temporal gyrus, and the bilateral medial prefrontal cortices, whereas increased GM was observed in the right hippocampus, the right fusiform gyrus, the right precentral gyrus, and the right precuneus. Thus, our meta-analyses show that the GM changes in schizophrenia patients and their unaffected relatives are largely different, although there is subtle overlap in some regions.

show abstract

“…In line with the consistently observed impaired memory performance in schizophrenia patients (Mesholam-Gately et al, 2009), previous neuroimaging studies in schizophrenia patients and at-risk populations repeatedly revealed decreased encoding-related activity in the hippocampal formation. In particular decreased parahippocampal activity during encoding of neutral visual and verbal stimuli has been associated with the strengths of memory impairments in schizophrenia patients as well as their first degree relatives and, thus, has been suggested to represent a potential intermediate biological phenotype related to an increased risk for schizophrenia (Rasetti et al, 2014, Thermenos et al, 2007Di Giorgio et al, 2013).…”

Section: Valence-unspecific Effects Of Ketaminementioning

confidence: 99%

General and emotion-specific neural effects of ketamine during emotional memory formation

et al. 2017

View full text Add to dashboard Cite

General and emotion-specific neural effects of ketamine during emotional memory formation, NeuroImage, http://dx.doi.org/10. 1016/j.neuroimage.2017.02.049 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractAnimal studies suggest that N-methyl-D-aspartate receptor (NMDAR) dependent signalling in limbic and prefrontal regions is critically involved in both cognitive and emotional functions. In humans, ketamine-induced transient, and disorder associated chronic NMDAR hypofunction (i.e. in schizophrenia) has been associated with deficient performance in the domains of memory and higher-order emotional functioning, as well as altered neural activity in the underlying limbicprefrontal circuits. To model the effects of NMDAR hypofunction on the integration of emotion and cognition the present pharmacological fMRI study applied the NMDAR antagonist ketamine (target plasma level = 100ng/ml) to 21 healthy volunteers in a within-subject placebo-controlled crossover 2 design during encoding of neutral, positive and negative pictures. Our results show that irrespective of emotion, ketamine suppressed parahippocampal and medial prefrontal activity. In contrast, ketamine selectively increased amygdala and orbitofrontal activity during successful encoding of negative stimuli. On the network level ketamine generally increased medial prefrontalparahippocampal coupling while specifically decreasing amygdala-orbitofrontal interplay during encoding of negative stimuli. On the behavioural level, ketamine produced generally decreased memory performance and abolished the emotional enhancement of memory after a wash-out period of 5 days. The present findings suggest that ketamine produces general as well as valencespecific effects during emotional memory formation. The pattern partly overlaps with alterations previously observed in patients with schizophrenia.

show abstract

Evidence that hippocampal–parahippocampal dysfunction is related to genetic risk for schizophrenia

Cited by 21 publications

References 67 publications

Altered Hippocampal-Parahippocampal Function During Stimulus Encoding

Altered Hippocampal-Parahippocampal Function During Stimulus Encoding

Similar and Different Gray Matter Deficits in Schizophrenia Patients and Their Unaffected Biological Relatives

General and emotion-specific neural effects of ketamine during emotional memory formation

Contact Info

Product

Resources

About