Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics

Bogerts, Bernhard; Falkai, Peter; Haupts, M.; Greve, B.; Ernst, Stephan; Tapernon-Franz, U.; Heinzmann, U.

doi:10.1016/0920-9964(90)90013-w

Cited by 220 publications

(77 citation statements)

References 21 publications

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“…29 Neurodevelopmental models of schizophrenia suggest that cell migration, particularly in the medial temporal lobes and limbic system, is impaired during fetal brain growth in individuals who later develop schizophrenia. 30,31 Although a loss of cortical and subcortical neuronal mass, especially in the limbic system, has been well established in patients with chronic schizophrenia, 1,32 morphological changes in the hippocampus and amygdala -key areas involved in the schizophrenic disease process -have not unequivocally been demonstrated in early stages of schizophrenia. 33,34 In the last couple of years, several studies have been published both in support of or refuting the assumption of volume reductions in these areas in the prodromal stages as compared with firstepisode patients with schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Witthaus

Mendes

Brüne

et al. 2010

jpn

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33Background: Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR. Methods: We recruited 29 UHR patients, 23 first-episode patients and 29 age-and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail. Results: Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR. Limitations: Our study had a small sample size, and we were unable to control for the effects of medication. Conclusion: Our findings suggest that parts of the hippocampal-amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizo phrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Witthaus

Mendes

Brüne

et al. 2010

jpn

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“…Structural magnetic resonance imaging and postmortem studies in schizophrenia have shown volume loss in the medial temporal region, especially in the hippocampus, as one of the most consistent structural abnormalities [32]. Additionally, postmortem studies showed volume loss in the hippocampal subregions in schizophrenia, which may be related to positive symptoms [12][13][14]. The small tissue reduction of approximately 5% suggests that some cellular subfractions within this structure might be reduced in number.…”

Section: Introductionmentioning

confidence: 99%

“…Postmortem brains were obtained from the Düsseldorf brain collection [13]. Patients fulWlled ICD-9 criteria for schizophrenia.…”

Section: Human Postmortem Brainsmentioning

confidence: 99%

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

et al. 2008

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Structural magnetic resonance imaging and postmortem studies showed volume loss in the hippocampus in schizophrenia. The noted tissue reduction in the posterior section suggests that some cellular subfractions within this structure might be reduced in schizophrenia. To address this, we investigated numbers and densities of neurons, oligodendrocytes and astrocytes in the posterior hippocampal subregions in postmortem brains from ten patients with schizophrenia and ten matched controls using design-based stereology performed on Nissl-stained sections. Compared to the controls, the patients with schizophrenia showed a signiWcant decrease in the mean number of oligodendrocytes in the left and right CA4. This is the Wrst Wnding of reduced numbers of oligodendrocytes in CA4 of the posterior part of the hippocampus in schizophrenia. Our results are in line with earlier Wndings in the literature concerning decreased numbers of oligodendrocytes in the prefrontal cortex in schizophrenia. Our results may indicate disturbed connectivity of the CA4 of the posterior part of the hippocampus in schizophrenia and, thus, contribute to the growing number of studies showing the involvement of posterior hippocampal pathology in the pathophysiology of schizophrenia.

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“…For example, lower NAA levels in temporolimbic brain regions in schizophrenia (Bertolino et al 1996;Fukuzako et al 1995;Renshaw et al 1995;Yurgelun-Todd et al 1996;Yurgelun-Todd et al 1993) are consistent with reports of volume reduction in neuroanatomic MRI examinations (Barta et al 1990;Breier et al 1992;Lieberman et al 1992;Shenton et al 1992;Suddath et al 1989) and with postmortem abnormalities. Bogerts et al 1990;Brown et al 1986;Jeste and Lohr 1985). Detection of amino acids, which would include glutamate, remains essential for assessing the presence of excitatory dysfunction.…”

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confidence: 99%

Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

Cecil

Lenkinski

Gur

et al. 1999

Neuropsychopharmacology

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Studies with proton magnetic resonance spectroscopy (MRS) have reported abnormalities in N-acetyl-aspartate (NAA), amino acids (AA) and choline (Cho) to creatine (Cr) ratios associated with schizophrenia. We report data on the three ratios in a sample of 18 neuroleptic naive patients with first-episode schizophrenia (eight studied in the dorsolateral prefrontal and 10 in the midtemporal lobe) and 24 healthy controls (14 studied in prefrontal and 10 in midtemporal lobes). Frontal lobe proton spectra were acquired with the stimulated-echo acquisition mode (STEAM) pulse sequence (echo time 21 ms, repetition time 2 s). Temporal lobe proton spectra were acquired with the point-resolved spectroscopy (PRESS) pulse sequence (echo time 16-21 ms, repetition time 2 s). Upon comparison with KEY WORDS : Schizophrenia; Proton magnetic resonance spectroscopyMagnetic resonance imaging (MRI) and spectroscopy (MRS) provide noninvasive, risk-free methods with which to study the origins and the time course of progression of neuropsychiatric disorders. The development of spatial localization methods, which sample the relative levels of mobile metabolites from a volume of tissue defined from an MR image, has provided a basis for integrating the biochemical information obtained by MRS with the anatomical and pathological information obtained from MRI. In vivo MRS studies of schizophrenia have examined two primary nuclei, phosphorus (Calabrese et al. 1992;Deicken et al. 1995;Keshavan et al. 1993;Pettegrew et al. 1993Pettegrew et al. , 1995Pettegrew et al. , 1991Shioiri et al. 1994;Stanley et al. 1995b;Stanley et al. 1994) and proton (Bertolino et al. 1996, Buckley et al. 1994Choe et al. 1994;Fukuzako et al. 1995;Nasrallah et al. 1994;Radda and Taylor 1985;Stanley et al. 1996;Yurgelun-Todd et al. 1996;Yurgelun-Todd et al. 1993). Phosphorus MRS can detect alterations in the levels of compounds involved in the bioenergetics of cellular metabolism, such as inorganic phosphate, adenosine triphosphate (ATP), and phosphocreatine. Additional composite resonances from phosphorus monoesters (PME) and phosphorus diesters (PDE) can also be detected. Phosphorus MRS in schizophrenia research has revealed abnormalities with high-energy phosphates as well as alterations in membrane phospholipid metabolism (Pettegrew et al. 1995 (Birken and Oldendorf 1989), NAA/Cr levels may reflect neuronal viability and integrity. Creatine is a compound involved in the regulation of cellular energy metabolism. The creatine resonance observed by proton MRS, is a combination of creatine and phosphocreatine. Trimethyl ammonium residues primarily representing choline are detected with MRS. The choline resonance is a composite of a number of choline-containing compounds. These include phosphocholine, glycerophosphocholine, acetylcholine, and cytidine diphosphate choline, as well as choline itself. However, the most prominent form of choline in the brain, phosphatidylcholine, is, for the most part, not detected by MRS because of its restricted immobile form . Choline level...

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Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics

Cited by 220 publications

References 21 publications

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

Proton Magnetic Resonance Spectroscopy in the Frontal and Temporal Lobes of Neuroleptic Naive Patients with Schizophrenia

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