Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

Abstract

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

“…Subjects were recruited in Southeast London as part of the AESOP study, which investigates, in three cities, the higher rates of schizophrenia in the African-Caribbean population in the UK (Dazzan et al, 2004;Dazzan et al, 2005). Ethical approval for the study was granted by the Ethical Committee of the Institute of Psychiatry, and the participants gave written informed consent, in accordance with the Declaration of Helsinki.…”

“…Furthermore, the small sample size did not allow us to evaluate any possible differences associated with specific diagnoses within psychoses. To clarify these issues, we have investigated the pituitary volume, using high-resolution MRI, in a different sample of 78 subjects at their first psychotic episode, recruited in London as part of the UK AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study (Dazzan et al, 2004;Dazzan et al, 2005). This is an epidemiologically based sample of patients at the first psychotic episode, which includes both antipsychotictreated and antipsychotic-free subjects, and both affective and nonaffective psychoses.…”

Motion‐related artifacts in structural brain images revealed with independent estimates of in‐scanner head motion

“…Structural magnetic resonance imaging (MRI) can provide high‐resolution measurements of gray and white matter anatomy that are often the focus of within‐ and between‐participant comparisons of aging [see Dickerson et al, 2009; Fjell et al, 2009; Fotenos et al, 2005], development [e.g., Tamnes et al, 2010], clinical disorders [e.g., Cannon et al, 2015; Dickerson et al, 2009; Kempton et al, 2011], and therapeutic intervention [e.g., Bearden et al, 2008; Dazzan et al, 2005]. In practice, structural MRI scans are readily analyzed with convenient, automated image segmentation tools that derive measurements from an individual's regional neuroanatomy (e.g., thickness, surface area, volume), often implemented with freely available software packages [e.g., FreeSurfer [FS], VBM8, FSL‐VBM; Ashburner and Friston, 2000; Dale et al, 1999; Fischl et al, 1999a; Smith et al, 2004] that have been externally validated with manual tracing and post‐mortem analyses [Cardinale et al, 2014; Kennedy et al, 2009; Kuperberg et al, 2003; Rosas et al, 2002; Salat et al, 2004; Sanchez‐Benavides et al, 2010].…”

Frontale Hirnvolumenminderung durch Antipsychotika?

“…Die frontale graue Substanz wurde bildgebend nicht erfasst. Bei Dazzan et al [73] zeigte sich unter FGA im Vergleich mit unbehandelten Patienten in Korrelation mit der aktuellen Dosis eine Reduktion der grauen Substanz frontal, temporal und im Zingulum, in der Insula rechts und Präku-neus links. Unter Olanzapin fanden sich dagegen eine Volumenzunahme im Thalamus verglichen mit dem unbehandelten Zustand, jedoch im Gruppenvergleich der SGA mit FGA nur geringe Unterschiede, was nach Ansicht der Autoren für eine quantitative, aber nicht qualitative Differenz spricht.…”

“…Insgesamt werden die Unterschiede in den hirnstrukturellen Veränderungen unter Behandlung mit FGA und SGA als weitgehend quantitativ und nicht qualitativ interpretiert [73]. Möglicherweise besteht diese Differenz aufgrund der unterschiedlichen Trajektorien des Abbauprozesses nur vorübergehend [29].…”