Patients with schizophrenia show reductions in hippocampal volume. However, the time course of these changes is still unresolved. The aim of this study is to examine the extent to which hippocampal volume change in patients with schizophrenia is confounded by effects of age and/or antipsychotic medication.
Between 1995 and 2003, two structural magnetic resonance imaging brain scans were acquired from 96 patients with DSM-IV-diagnosed schizophrenia and 113 healthy subjects within an interval of approximately 5 years. Hippocampal volume change was measured and related to age and cumulative medication intake during the scan interval.
Patients with schizophrenia and healthy controls demonstrated significantly different age-related trajectories of hippocampal volume change. Before the age of 26 years, patients with schizophrenia showed increased volume loss relative to controls. In contrast, after the age of 40 years, controls showed larger volume loss than patients with schizophrenia. Higher exposure to atypical antipsychotic medication was related to a smaller decrease in hippocampal volume over time.
Our findings suggest progressive hippocampal volume loss in the early course of the illness in patients with schizophrenia but not in the more chronic stages of the illness. The relationship between larger exposure to atypical antipsychotic medication and smaller hippocampal volume loss during the interval may suggest neuroprotective effects of these agents on hippocampal volume.
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"This improvement was found in global cognition and specific cognitive domains such as learning and processing speed (Kucharska-Pietura et al., 2012). Recent evidence from structural magnetic resonance imaging scans showed increased hippocampal volume loss in schizophrenia patients, and AAPs yield neuroprotective effects on the hippocampal volume (Koolschijn et al., 2010). Such a finding suggests that the hippocampus may be a critical brain region in this process of cognitive improvement. "
[Show abstract][Hide abstract]ABSTRACT: Schizophrenia patients exhibit a wide range of impairments in cognitive functions. Clinically, atypical antipsychotic drugs (AAPs) such as olanzapine (OLZ) have a therapeutic effect on memory function among schizophrenia patients rather than typical antipsychotics, e.g., haloperidol. To date, however, little is known about the neuroplasticity mechanism underlying the effect of AAPs on the impairment of cognitive functions. Here, we treated schizophrenia rat models with a systematic injection of MK-801 (0.1mg/kg) and chose the drug OLZ as a tool to investigate the mechanisms of AAPs when used to alter cognitive function. The results showed that the systematic administration of MK-801 results in the impairment of spatial learning and memory as well as spatial working memory in a Morris water maze task. OLZ but not HAL improved these MK-801-induced cognitive dysfunctions. After MK-801 application, the hippocampal LTP was profoundly impaired. In conjunction with the results of the behavioral test, the administration of OLZ but not of HAL resulted in a significant reversal effect on the impaired LTP induced via MK-801 application. Furthermore, we found that OLZ but not HAL can upregulate the phosphorylation of GluR1 Ser845. These data suggest that the therapeutic effect of OLZ on cognitive dysfunctions may be due to its contribution to synaptic plasticity via the ability to upregulate the state of GluR1 Ser845 phosphorylation. We therefore suggest that the upregulated state of GluR1 Ser845 phosphorylation may be a promising target for developing novel therapeutics for treating schizophrenia.
Full-text · Article · Sep 2014 · Schizophrenia Research
"volumetric atrophy) changes in the hippocampus (Adriano et al., 2012). Despite some supporting evidence (Spoletini et al., 2011), it is still unclear whether hippocampal volumetric damage is associated with subtle microstructural tissue abnormalities (Koutsouleris et al., 2008; Meisenzahl et al., 2008; Ebdrup, 2010; Koolschijn et al., 2010). "
[Show abstract][Hide abstract]ABSTRACT: Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window.
Full-text · Article · Aug 2014 · Schizophrenia Research
"A possible mechanism of this action could be through the neuroprotective effects of BDNF , . A recent large longitudinal neuroimaging study showed that higher exposure to atypical antipsychotic medication was related to a smaller decrease in hippocampal volume over time and these findings have been suggested to reflect neuroprotective effects of SGAs on hippocampal volume . Conversely, a longitudinal neuroimaging study in first-episode patients with schizophrenia showed that 6 months after the initiation of a SGA, quetiapine, patients had significant hippocampal volume loss, which was more pronounced with higher doses of quetiapine . "
[Show abstract][Hide abstract]ABSTRACT: Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels.
In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs).
We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024).
The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.