Antipsychotic Drug Effects on Brain Morphology in First-Episode Psychosis (original) (raw)
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Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia
Journal of Psychiatry and Neuroscience, 2010
Background: Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive firstepisode schizophrenia. Methods: We obtained high-resolution 3-dimensional T 1 -weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse. Results: We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psychopathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia. Limitations: This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small. Conclusion: Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychoticnaive first-episode schizophrenia patients are warranted. fax 45 4323 4653; bebdrup@cnsr.dk Trial Registration Clinicaltrials.gov NCT00207064, http://clinicaltrials.gov/ct2/show/NCT00207064 J Psychiatry Neurosci 2010;35(2):95-104. 26(5):395-410 6. Ecological momentary assessment: what it is and why it is a method of the future in clinical psychopharmacology Moskowitz and Young J Psychiatry Neurosci 2006;31(1):13-20 7. Antidepressant effects of exercise: Evidence for an adult-neurogenesis hypothesis? Ernst et al. J Psychiatry Neurosci 2006;31(2):84-92 8. Conversion sensory symptoms associated with parietal lobe infarct: case report, diagnostic issues and brain mechanisms Ramasubbu J Psychiatry Neurosci 2002;27(2):118-22 9. How do the atypical antipsychotics work? Anath et al. J Psychiatry Neurosci 2001;26(5):385-94 10. A review of olanzapine-associated toxicity and fatality in overdose Chue and Singer J Psychiatry Neurosci 2003;28(4):253-61
Schizophrenia Research, 2007
Background: Previous studies have reported that hippocampal volumes correlate with symptom severity in schizophrenia. This longitudinal study measured changes in symptoms and hippocampal volume in patients switched from typical antipsychotics to olanzapine. Methods: MRI scans were acquired from patients with chronic schizophrenia (n = 10) and healthy volunteers (n = 20). At baseline, patients were treated with typical antipsychotics for at least one year, then switched to olanzapine, and rescanned approximately one year later. Results: Olanzapine treatment resulted in no significant change in right or left hippocampal volume. Individual changes in right hippocampal volume correlated significantly with changes in symptoms. Conclusions: Hippocampal volume change may serve as a marker of symptom change in patients on olanzapine.
MRI correlates of treatment response in first episode psychosis
Schizophrenia Research, 1998
It is not known whether the magnitude of the structural brain abnormalities that underlie schizophrenia is a determinant of the extent to which patients respond to antipsychotic medication. This study was undertaken in order to explore this relationship. Twenty-six patients receiving treatment for a first expisode of psychosis were involved in both a study measuring treatment response and a magnetic resonance imaging (MRI) study. In the treatment study, haloperidol dose was increased weekly beginning at 2 mg/day until patients showed evidence of a response or extrapyramidal symptoms. MRI scans were analyzed using a computerized volumetric approach to yield estimates of cerebrospinal fluid (CSF), gray-matter and white-matter volumes. Improvement in positive and negative symptoms after 1 week of treatment was significantly correlated with cortical gray-matter volumes. Those patients who were maintained on 2 mg/day of haloperidol had greater cortical gray-matter volume than those who were treated with higher doses. The severity of structural brain abnormalities at the onset of psychosis may contribute to individual variation in response to antipsychotic medication. It remains to be determined whether the degree to which particular domains of symptomatology can improve is related to the severity of structural brain pathology in specific brain regions.
Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. Here, we report MRI findings from a triple-blind randomised placebo-controlled study where 62 antipsychotic-naive patients with first episode psychosis (FEP) received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. Structural MRI scans were obtained at baseline, 3-months and 12-months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term eff...
PLoS ONE, 2014
Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.
Brain Structural Effects of Antipsychotic Treatment in Schizophrenia: A Systematic Review
Current Neuropharmacology, 2015
The findings about the progressive brain changes in schizophrenia are controversial, and the potential confounding effect of antipsychotics on brain structure is still under debate. The goal of the current article was to review the existing longitudinal neuroimaging studies addressing the impact of antipsychotic drug treatment on brain changes in schizophrenia. A comprehensive search of PubMed was performed using combinations of key terms distributed into four blocks: "MRI", "longitudinal", "schizophrenia" and "antipsychotic". Studies were considered to be eligible for the review if they were original articles. Studies that examined only changes in brain density were excluded. A total of 41 MRI studies were identified and reviewed. Longitudinal MRI studies did not provide a consistent notion of the effects of antipsychotic treatment on the pattern of brain changes over time in schizophrenia. Overall, most of the included articles did not find a linear relationship between the degree of exposure and progressive brain changes. Further short-and longterm studies are warranted to a better understanding of the influence of antipsychotics in brain structural changes in schizophrenia and also to verify whether first and second generation antipsychotics may differentially affect brain morphometry.
Archives of General Psychiatry, 2000
Background: The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia. Methods: Sixty-five patients in this multicenter double-blind study were randomly assigned to olanzapine (5-20 mg), risperidone (4-10 mg), or haloperidol (5-20 mg). Standard measures of clinical and motor syndromes were administered, as well as a comprehensive battery of tests to assess (1) motor skills, (2) attention span, (3) verbal fluency and reasoning, (4) nonverbal fluency and construction, (5) executive skills, and (6) immediate recall at baseline and after 6, 30, and 54 weeks of treatment. Results: The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone, but no significant difference was shown between risperidone and haloperidol. The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment. Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain, and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test. Conclusions: These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone. A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implications of this change to cerebral function and quality of life for people with schizophrenia.
The effects of antipsychotic treatment on cerebral structure and function in schizophrenia
International Review of Psychiatry, 2007
This paper analyses the effects of antipsychotic drug treatment on cerebral structure and function in schizophrenia reviewing qualitatively some of the relevant literature on the issue. Magnetic resonance imaging (MRI) studies of brain morphology in patients at different stages of illness and after varying times of neuroleptic exposure and longitudinal studies show possible different effects of first and second generation antipsychotics. This is true also for functional parameters, such as regional cerebral blood flow and metabolism, analysed, both in resting condition and after specific activation paradigms, with such diverse techniques as positron emission tomography (PET), single photon emission computed tomography (SPECT), functional MRI and MR spectroscopy. The possible molecular mechanisms underlying such differences and whether they represent direct drug effects or indirect consequences of their different and specific interactions with the 'natural' pathophysiological trajectory of brain abnormalities in schizophrenia are matter of present research and debate.
European Archives of Psychiatry and Clinical Neuroscience, 2010
To date, few studies have addressed the relationship between brain structure alterations and responses to atypical antipsychotics in schizophrenia. To this end, in this study, magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) were used to assess the relationship between the brain volumes of gray (GM) and white (WM) matters and the clinical response to risperidone or olanzapine in 30 schizophrenia patients. In comparison with healthy controls, the patients in this study showed a bilateral decrease in the anteromedial cerebellar hemispheres, the rectal gyrus and the insula, together with bilateral increases in GM in the basal ganglia. Both patient groups had a significantly smaller volume of WM in a region encompassing the internal and external capsules as compared to the controls. We found an inverse association between striatal size and the degree of clinical improvement, and a direct association between the degree of insular volume deficit and its improvement. The non-responder patient group showed a significant decrease in their left rectal gyrus as compared with the responder group. This study reveals a pattern of structural alterations in schizophrenia associated with the response to risperidone or olanzapine.