State-related changes in cerebral white matter may underlie psychosis exacerbation

Christensen, James; Holcomb, Jennifer; Garver, David L.

doi:10.1016/j.pscychresns.2003.08.002

Cited by 64 publications

(38 citation statements)

References 28 publications

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“…We note also that even though we did not demonstrate correlations between diffusion measures and age of onset, duration of illness, or medication, we can not totally rule them out as possible confounds. Further, even though there is some evidence of white matter loss after treatment with antipsychotic medications (Christensen et al, 2004), this evidence is weak, and requires further investigation. We also realize that since we study chronic schizophrenics, duration of illness is closely associated with age.…”

Section: Discussionmentioning

confidence: 98%

Age-related deficits in fronto-temporal connections in schizophrenia: A diffusion tensor imaging study

Rosenberger

Kubicki

Nestor

et al. 2008

Schizophrenia Research

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Objective-Impairment of white matter connecting frontal and temporal cortices has been reported in schizophrenia. Yet, not much is known about the effects of age on fibers connecting these brain regions. Using diffusion tensor imaging tractography, we investigated the relationship between age and fiber integrity in patients with schizophrenia vs. healthy adults.Methods-DTI tractography was used to create 3D reconstructions of the cingulum, uncinate and inferior occipito-frontal fasciculi in 27 patients with schizophrenia and 34 healthy volunteers (23-56 years of age, group-matched on age). Fractional anisotropy (FA), describing fiber integrity, was then calculated along the entire length of these tracts, and correlated with subjects' age.Results-Patients revealed a significant decline in FA with age in both the cingulum and uncinate, but not in the inferior occipito-frontal fasciculi. No statistically significant correlations were found in these fiber bundles in controls. ContributorsRosenberger G. and Kubicki M. designed the study. Connor E., Bushell G., and Markant D. collected some of the data and did PUBMED searchers. Nestor P.G., Niznikiewicz M., and Saykin A., undertook the statistical analyses. Rosenberger G.wrote the first draft of the manuscript. Shenton M.,Kikinis R.,Westin C-F., and McCarley R.W. had substantial input on aspects of the design of the study and Shenton M. and Saykin A. had substantial input in editing multiple versions of the manuscript. Shenton M. and McCarley R.W. also had input on clinical aspects of the design including the selection of diagnostic and clinical measures. All other authors contributed to and have improved the final manuscript. Conflict of interestThere are no conflicts of interest. Conclusions-These results suggest an age-associated reduction of frontal-temporal connectivity in schizophrenia, but not in healthy controls. NIH Public Access

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Section: Discussionmentioning

confidence: 98%

Age-related deficits in fronto-temporal connections in schizophrenia: A diffusion tensor imaging study

Rosenberger

Kubicki

Nestor

et al. 2008

Schizophrenia Research

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“…It is possible that these drugs do not block receptors or molecules that are blocked by haloperidol and the other drugs tested in this study. These observations could be relevant to treatment of humans, since there is increasing evidence that schizophrenia is a progressive disease with ongoing neuropathology that might be slowed or preventable using antipsychotics and other types of drugs (Christensen et al, 2004). Perhaps treatment with typical and atypical antipsychotics, antioxidants, and perhaps Src inhibitors that are best at blocking neuronal injury in the MK-801/PCP rodent model might be most useful for slowing neuropathological injury in schizophrenia and other human diseases associated with psychosis.…”

Section: Discussionmentioning

confidence: 99%

Atypical Antipsychotics and a Src Kinase Inhibitor (PP1) Prevent Cortical Injury Produced by the Psychomimetic, Noncompetitive NMDA Receptor Antagonist MK-801

Dickerson

Sharp

2005

Neuropsychopharmacol

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Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine, ketamine, and MK-801 produce schizophrenia-like psychosis in humans. The same NMDA antagonists injure retrosplenial cortical neurons in adult rats. We examined the effects of atypical antipsychotics and an inhibitor of nonreceptor tyrosine kinase pp60 (Src) on the cortical injury produced by MK-801. An atypical antipsychotic (either clozapine, ziprasidone, olanzapine, quetiapine, or risperidone) or vehicle was administered to adult female Sprague-Dawley rats. PP1 (Src inhibitor), PP3 (nonfunctional analog of PP1) or vehicle (DMSO) was administered to another group of animals. After pretreatment, animals were injected with MK-801, killed 24 h after the MK-801, and injury to retrosplenial cortex assessed by neuronal Hsp70 protein expression. All atypical antipsychotics examined significantly attenuated MK-801-induced cortical damage. PP1 protected compared to vehicle, whereas PP3 did not protect. The ED50s (decrease injury by 50%) were as follows: PP1 o0.1 mg/kg; olanzapine 0.8 mg/kg; risperdal 1 mg/kg; clozapine 3 mg/kg; ziprasidone 32 mg/kg; and quetiapine 45 mg/kg. The data show that the atypical antipsychotics tested as well as a Src kinase inhibitor prevent the injury produced by the psychomimetic MK-801, and the potency of the atypical antipsychotics for preventing cortical injury was roughly similar to the potency of these drugs for treating psychosis in patients.

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“…Therefore, the allocation of subjects to each of these three groups was nonrandomized, but based on the medication prescribed by the in-charge clinician at the time of MRI scan. According to the existing literature on brain changes following administration of antipsychotics (Chakos et al, 1994;Cohen et al, 2003;Christensen et al, 2004;Grunder et al, 2003;Honey et al, 1999;Huang et al, 1999;Miller et al, 1997aMiller et al, , b, 2001Wotanis et al, 2003), the mean length of treatment of 8 weeks of our sample would be sufficient to observe brain changes in association with antipsychotic use.…”

Section: Pharmacological Treatmentmentioning

confidence: 96%

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

Dazzan

Morgan

Orr

et al. 2005

Neuropsychopharmacol

248

160

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Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

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State-related changes in cerebral white matter may underlie psychosis exacerbation

Cited by 64 publications

References 28 publications

Age-related deficits in fronto-temporal connections in schizophrenia: A diffusion tensor imaging study

Age-related deficits in fronto-temporal connections in schizophrenia: A diffusion tensor imaging study

Atypical Antipsychotics and a Src Kinase Inhibitor (PP1) Prevent Cortical Injury Produced by the Psychomimetic, Noncompetitive NMDA Receptor Antagonist MK-801

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

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