Do antipsychotics differ in their effect on cortical thickness? Psych.Med .Jan.2015


Chronic administration of antipsychotics are shown to reduce grey matter volumes in animal studies.  Differentials effects between  First Generation Antipsychotics (FGA) and  Second Generation Antipsychotics (SGA) are noted in human studies. FGAs were shown to reduce frontotemporal volumes and SGAs to increase frontal cortical thickness.  Large RCT data show that (Lieberman et al. 2005; Thompson et al. 2009) haloperidol can reduce frontal volumes where as olanzapine showed no reductions over a 6 month period. It is also contended that such structural effects will be seen only after many years of use.SGA is shown to increase anterior cingulate cortex volume at 3 years. Another study suggested that such differences are seen at an average follow up of 7.2 years. The role of illness and the interaction with medication need to be considered carefully before making conclusions on such effects.

 B. R. E. Ansell and colleagues from Melbourne neuropsychiatric centre addressed such issues ( role of illness, role on medications etc)  in this study. A sample of first-episode schizophrenia and affective psychosis patients  who were treated with either FGA or SGA participated in this.Cortical thickness differences within the diagnostic and medication subgroups when compared to each other and to a matched healthy control group (162 patients and  87 controls).Patients were not on any antipsychotics before entry to the study. They also had no neurological disorders.


First episode  schizophrenia group showed decreased thickness compared to controls in frontal, parietal, temporal and occipitotemporal regions. First-episode affective psychosis  revealed reductions in two  smaller areas only ( right inferior parietal lobe & the right cingulate sulcus).Large area of the frontoparietal region showed decreased thickness in the FGA compared to the SGA group,Those medicated with SGAs also displayed increased cortical thickness compared with controls of the left precentral and right postcentral gyri, but no increases were detected in the FGA group.

In the FGA-treated patients, cortical thinning was associated with higher negative symptom scores. Increased cortical thickness in the SGA- treated group was associated with lower positive symptom scores.Medication and diagnosis did not interact, suggesting independent effects

Conclusion: FGA-treated patients tended to show decreased cortical thickness whereas the SGA group showed increases.


SGAs show increase as well as decrease in cortical thickness ( i.e. in different areas). It would be interesting to see whether there are individual differences between medications with in classes as well. However a larger sample would be required to answer that question. Whether such differential effects are similar in their pattern over longer term is another key question.

Summary of the article

Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis. Ansell BR, Dwyer DB, Wood SJ, Bora E, Brewer WJ, Proffitt TM, Velakoulis D, McGorry PD, Pantelis C.Psychol Med. Psychological Medicine (2015), 45, 515–527.

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