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J Psychiatry Neurosci. 2010 May; 35(3): 215.
PMCID: PMC2861139

Hippocampal alterations in ultra-high risk patients are independent from medication and cannabis use

Henning Witthaus, MD, Martin Brüne, MD, PhD, and Georg Juckel, MD, PhD

In their comment on our article entitled “Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia,”1 Borgwardt and colleagues raise some critical questions regarding our finding that hippocampal volume loss is related to an at-risk mental state. Instead, they argue that smaller right hippocampus corpus and tail volumes in ultra-high risk patients (UHR) who later developed schizophrenia compared with those who did not develop schizophrenia may be attributable to cannabis abuse and/or medication effects.

In fact, in our sample, one patient who transitioned into psychosis was taking antipsychotic medication and 7 who transitioned had never taken an antipsychotic. In comparison, in the UHR group that did not transition, 10 were taking antipsychotic medication and 11 were not. Notably, there was no significant difference in right hippocampal corpus and tail volume between these 4 groups (F3,27 = 0.668, p = 0.58).

Among the UHR patients who transitioned into psychosis, only 1 had previous cannabis abuse (see the 3-month criterion we used1), whereas 7 did not use cannabis. Among the UHR patients who did transition, 8 had comorbid cannabis abuse and 13 were free of cannabis abuse. Again, when we compared the volumes of the right hippocampal corpus and tail, we found no significant difference between the groups (F3,27 = 1.146, p = 0.35).

These findings suggest that the differences in the volume of the hippocampus corpus and tail between UHR patients who transitioned into psychosis and those who did not could not be accounted for by the effect of antipsychotic medication or cannabis abuse. Although 2 previous studies did not reveal hippocampal volume differences between converters and nonconverters,2,3 we believe that it would be premature to rule out anatomic abnormalities in UHR states in these brain regions. Our study indicates that hippocampal volume reduction may precede the onset of schizophrenia and may be present in prodromal stages, independent of medication effects or the presence or absence of cannabis abuse.

Footnotes

Competing interests: None declared for Drs. Witthaus or Brüne. Dr. Juckel has received consultancy fees from Janssen-Cilag, AstraZeneca and Eli Lilly. He has received speakers fees and/or educational grants from Janssen-Cilag, AstraZeneca and Eli Lilly, Wyeth and Pfizer.

Contributors: All authors contributed to and have approved this letter.

References

1. Witthaus H, Mendes U, Brune M, et al. Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia. J Psychiatry Neurosci. 2010;35:33–40. [PMC free article] [PubMed]
2. Buehlmann E, Berger GE, Aston J, et al. Hippocampus abnormalities in at risk mental states for psychosis? A cross-sectional high resolution region of interest magnetic resonance imaging study. J Psychiatr Res. 2009 Epub 2009 Nov. 24 ahead of print. [PubMed]
3. Velakoulis D, Wood SJ, Wong MT, et al. Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra high-risk individuals. Arch Gen Psychiatry. 2006;63:139–49. [PubMed]

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