Long-term Antipsychotic Treatment and Brain Volumes: A Longitudinal Study of First-Episode Schizophrenia
TLDR
It is suggested that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.Abstract:
Context Progressive brain volume changes in schizophrenia are thought to be due principally to the disease. However, recent animal studies indicate that antipsychotics, the mainstay of treatment for schizophrenia patients, may also contribute to brain tissue volume decrement. Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders, it is imperative to determine their long-term effects on the human brain. Objective To evaluate relative contributions of 4 potential predictors (illness duration, antipsychotic treatment, illness severity, and substance abuse) of brain volume change. Design Predictors of brain volume changes were assessed prospectively based on multiple informants. Setting Data from the Iowa Longitudinal Study. Patients Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset, yielding a total of 674 high-resolution magnetic resonance scans. On average, each patient had 3 scans (≥2 and as many as 5) over 7.2 years (up to 14 years). Main Outcome Measure Brain volumes. Results During longitudinal follow-up, antipsychotic treatment reflected national prescribing practices in 1991 through 2009. Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes. Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors. More antipsychotic treatment was associated with smaller gray matter volumes. Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted. Conclusions Viewed together with data from animal studies, our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time, suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use.read more
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NMDA receptor antagonist rodent models for cognition in schizophrenia and identification of novel drug treatments, an update.
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TL;DR: GMD biomarkers depicted unique brain structure characteristics within Biotypes, consistent with their cognitive and sensorimotor profiles, and provided stronger discrimination for biologically driven biotypes than symptom-based diagnoses.
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TL;DR: The available evidence supports the hypothesis that some of the neurobiological changes seen in treatment-resistant schizophrenia lie along a continuum with treatment-responsive schizophrenia, whereas other differences are categorical in nature and have potential to be used as biomarkers.
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White matter changes associated with antipsychotic treatment in first-episode psychosis.
Philip R. Szeszko,Philip R. Szeszko,Philip R. Szeszko,Delbert G. Robinson,Delbert G. Robinson,Delbert G. Robinson,Toshikazu Ikuta,Bart D. Peters,Bart D. Peters,Juan A. Gallego,Juan A. Gallego,Juan A. Gallego,John M. Kane,John M. Kane,John M. Kane,Anil K. Malhotra,Anil K. Malhotra,Anil K. Malhotra +17 more
TL;DR: The use of antipsychotics may be associated with a subtle loss of white matter integrity that is related to greater side effects, thus raising potentially important considerations regarding risk/benefit in their usage.
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The neuropathology of schizophrenia: A selective review of past studies and emerging themes in brain structure and cytoarchitecture.
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TL;DR: The evidence converges on a progressive neurodevelopmental model of schizophrenia related to altered neuroplasticity, which supports a particular vulnerability of inhibitory cortical circuits with markers of interneurons showing some of the more consistent reductions in schizophrenia.
References
More filters
Book
The global burden of disease: a comprehensive assessment of mortality and disability from diseases injuries and risk factors in 1990 and projected to 2020.
TL;DR: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors" and use historical trends in main determinants to project mortality and disease burden forward to 2020.
Journal ArticleDOI
The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance.
TL;DR: The relative simplicity, reliability, and validity of the GAS suggests that it would be useful in a wide variety of clinical and research settings.
Journal ArticleDOI
Mapping cortical change across the human life span
Elizabeth R. Sowell,Bradley S. Peterson,Paul M. Thompson,Suzanne E. Welcome,Amy L. Henkenius,Arthur W. Toga +5 more
TL;DR: A significant, nonlinear decline in GMD with age is found over dorsal frontal and parietal association cortices on both the lateral and interhemispheric surfaces, indicating that the posterior temporal cortices have a more protracted course of maturation than any other cortical region.
Journal ArticleDOI
The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology.
TL;DR: Research strategies suggest that investigators should maintain a flexible database to permit them to adapt to changes in diagnostic systems, to do comparative nosological studies, and, ultimately, to develop new diagnostic systems based on knowledge concerning the underlying neurobiological nature of disorders.
Journal ArticleDOI
Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17.
TL;DR: Abnormally high density in the cerebral cortices of schizophrenics suggests that neuronal atrophy is the anatomic substrate for deficient information processing in schizophrenia.