Presentation on theme: "Brain-morphological changes associated with acute antipsychotic treatment in first-episode schizophrenia Laila Asmal1, Bonginkosi Chiliza1, Stéfan du Plessis1,"— Presentation transcript:
1Brain-morphological changes associated with acute antipsychotic treatment in first-episode schizophreniaLaila Asmal1, Bonginkosi Chiliza1, Stéfan du Plessis1, Jonathan Carr2, Anneke Goosen1, Martin Kidd3, Matthijs Vink4, Rene Kahn4, Robin Emsley1From the Department of Psychiatry,1 Department of Neurology,2 Centre for Statistical Consultation, Stellenbosch University, South Africa,3 Department of Psychiatry, University Medical Centre Utrecht, The Netherlands.4
2Morphological brain changes in schizophrenia Global and regional structural brain abnormalities.1Present at the first episode and even in the prodromeconsistent with a neuro-developmental originBUT …Longitudinal studies indicate that progressive changes also occur.2Mostly in the early years of illness, and only in a subset.3Haijma SV, et al. Schizophr Bull. (in press); 2. Olabi B, et al. (2011). Biol.Psychiatry 70, 88-96; 3. Andreasen NC, et al. (2013) Am.J Psychiatry (in press);) .
3There is debate as to the causes of the progressive changes Illness progression4Related to antipsychotic medication5,6,7Non-specific, due tosubstance abusepoor adherenceeffects of co-morbid conditions84. Lieberman J, et al. (2001). Biol.Psychiatry 49, ; 5. Smieskova R, et al. (2009). Curr.Pharm.Des 15, ; 6. Ho BC, et al. (2011). Arch.Gen.Psychiatry 68, ; 7. Dorph-Petersen R,et al. Neuropsychopharmacology (2005) 30, 1649–1661; 8. Zipursky RB, et al. Schizophr Bull (in press
4Brain changes and treatment response Baseline symptoms predict brain changes during the course of treatment.9Baseline brain abnormalities in turn predict treatment response.10But the chronological relationships require elucidation.May provide clues as to the neurobiological underpinnings of treatment response and adverse antipsychotic effects.9. Collin G, et al. (2012). Schizophr Res 138[2-3], ;10. Szeszko PR, et al. (2012). Schizophr Bull 38,
5Our studyAim:To further investigate the effects of acute antipsychotic treatment on global and regional brain structure using cortical/subcortical reconstruction
6Methodological considerations Treatment naïve patients with a first-episode of schizophrenia:to avoid the influences of disease chronicity and previous treatment.Long-acting injectable antipsychotics:to avoid the confounding effect of covert non-adherence.We also took care to exclude patients with substance abuse and comorbid pathology.
7Methods and MaterialsSingle-site, double-blinded RCT over 13 weeks comparing long-acting risperidone injection and flupenthixol decanoate in antipsychotic-naive patients with a first-episode of schizophrenia.Treatment:Flexible doses starting at 25mg risperidone long-acting injection or 10mg flupenthixol decanoate 2-weeklyNo treatment group effects were demonstrated in any of the MRI ROIs so treatment groups were pooled for all of the subsequent analyses.
8Participants Inclusion: Male or female; in- or outpatients; aged 16 to 45 yrs;DSM-IV schizophreniform, schizophrenia or schizoaffective disorderNo previous exposure to antipsychotic medicationRight handednessExclusion:Substance abuse in the previous 6 months, significant general medical condition, mental retardation (IQ<70).Healthy controls:Matched by age, sex, ethnicity and educational status
9Structural brain imaging High-resolution T1-weighted data on a 3T Siemens Allegra MRI scannerScans were processed and analyzed using Freesurfer stable release version 5.1.Analyses: modified ITT, MMRM
13Baseline MRI differences patients vs. controls dfpMeanSDL inferior lateral ventricle in mm34202702761462.22342.032L thalamus in mm3792897373787352.126.039L caudate in mm3416563435725863.227.002R caudate in mm3415560336385682.925.006R parahippocampal cortical thickness in mm2.4700.2452.3100.2422.167.036
17Brain changes associated with treatment response: Improvements were associated with greater reductions in GM.CGI-S and QoL significantly correlated with reductions in total GM volumeGeneral psychopathology and PANSS total score improvements were associated with reductions in left entorhinal cortical thickness.However, improvements in negative (and depressive) symptoms associated with lesser GM reductionsNotably, there were no significant correlations between changes in insight, positive symptoms or SOFAS and brain changes.
18Brain changes associated with antipsychotic adverse effects ESRS total and parkinsonism scores associated with greater total GM volumes.Weight was associated with ventral diencephalon bilaterally and HDL with left ventral diencephalon.triglycerides associated with subcortical and total GM volumeNo significant correlations between changes in prolactin, glucose, LDL and cholesterol levels and brain changes.
19Conclusions i.e. shrinkage! Further evidence of acute brain plasticity in response to antipsychotic treatmentSome brain changes occurred in association with treatment response and others with emergent adverse-effects.No differential effects between RLAI and FDGenerally, changes occurred bilaterally, with volume reductions for cortical and subcortical structures, and volume increases for ventricular measuresi.e. shrinkage!