Antipsychotics Linked to Cortical Loss in Patients With Schizophrenia
Abstract
Though antipsychotic use in patients with schizophrenia was found to be associated with reduction in cortical gray matter volume, first-generation antipsychotics may cause greater reduction than second-generation antipsychotics.
Although it is well established that patients with schizophrenia have deficits in cortical gray matter, a meta-analysis published in the September issue of Biological Psychiatry suggests that cumulative antipsychotic intake and the type of antipsychotic a patient with schizophrenia takes may influence the degree of gray matter loss over time.
Researchers from the Department of Mental Health at the University of Brescia School of Medicine in Italy led a retrospective study to determine whether changes in cortical gray matter differ between patients with schizophrenia who take first-generation antipsychotics and those who take second-generation antipsychotics.
“The role played by antipsychotic treatment on the pathophysiologic trajectory of brain abnormalities in schizophrenia is currently a matter of lively debate,” explained the study’s lead author, Antonio Vita, M.D., Ph.D., a professor of psychiatry at the University of Brescia, in an interview with Psychiatric News.
As Vita and his colleagues noted in the paper, qualitative reviews and independent studies addressing the topic of structural brain changes in schizophrenia in relation to antipsychotic treatment have yielded inconclusive results, with few looking at whether a patient was prescribed first-generation or second-generation antipsychotics.
To evaluate the influence of antipsychotic treatment on cortical gray matter volume in patients with schizophrenia, the researchers compiled data from 18 longitudinal magnetic resonance imaging studies, published from January 1, 1983, to March 31, 2014, totaling 1,155 patients with schizophrenia and 911 healthy controls.
The results showed that patients with schizophrenia showed significantly greater loss of total cortical gray matter volume than healthy controls, which was related to cumulative antipsychotic intake during the interval between imaging scans among the longitudinal studies. When comparing changes in cortical gray matter volumes in patients who were treated with first-generation antipsychotics (FGAs) with those who were treated with second-generation antipsychotics (SGAs), the researchers found that greater gray matter loss was correlated with higher mean daily dose in studies including patients treated with FGAs, whereas less progressive loss was observed in studies including only patients treated with SGAs.
“On the whole, our results indicate that the putative contributory role of antipsychotic treatment in reducing the volume of cortical [gray matter] in schizophrenia cannot be generalized and appears to be less evident for SGAs, which seem to be associated with less loss of brain tissue,” the study authors wrote.
Vita told Psychiatric News that many issues remain to be clarified. “We still do not know whether the effects on the brain of antipsychotics vary as a function of age and stage of illness, or whether they may occur only when a certain threshold of exposure [daily dose or cumulative dose] is reached,” said Vita.
He concluded that “clarification of these issues will have crucial importance in the clinical management of schizophrenia and will allow a better understanding of the mechanisms underlying the progression of structural brain abnormalities in schizophrenia.”
The study was funded by a grant from the Lombardia Region. ■
“The Effect of Antipsychotic Treatment on Cortical Gray Matter Changes in Schizophrenia: Does the Class Matter? A Meta-analysis and Meta-regression of Longitudinal Magnetic Resonance Imaging Studies” can be accessed here.
