University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh EH10 5HF
Cochrane Schizophrenia Group, Middle Way, Summertown, Oxford OX2 7LG
Readers may remember the correspondence about the identification of studies for a review of volumetric magnetic resonance imaging (MRI) findings in schizophrenia (Lawrie & Abukmeil, 1998). Adams et al (1998) suggested that a more comprehensive search strategy would have identified other relevant studies. Lawrie (1998) questioned whether this effort would alter the results of the review particularly for a pre-specified region (the left amygdalo-hippocampus). We now report the outcome.
Clive Adams searched Medline between 1986 and June 1996 (inclusive) the same period covered by the original investigation. A simple MRI search identified 142 studies in total. Employing Boolean logic and adding a refined schizophrenia search term (by using and) found 27 studies. Refining the MRI search term resulted in the location of 196 studies. Out of interest, EMBASE, a more comprehensive database covering 67% of 506 indexed psychiatry journals (v. 47% in Medline), was searched similarly and identified 289 potentially relevant studies. PsycLit, covering 73% of indexed psychiatry journals, was not searched. Stephen Lawrie examined every identified citation for volumetric MRI studies in patients with DSM-III-R (American Psychiatric Association, 1987) schizophrenia and healthy controls, giving raw data that could generate case-control differences (expressed as a percentage) for relevant brain regions.
Five studies that should have been included in the original review were identified (see Table). One of these, Lim et al (1995), should have been identified in the simple Medline search, and all should have been identified in the hand search of journals. Indeed, Lawrie & Abukmeil were aware of two of the studies but mistakenly excluded them for not giving relevant raw data (Woods & Yurgelun-Todd, 1991) or for being published outside the time frame (Cowell et al, 1996). It should be noted, however, that two of the studies (DeLisi et al, 1992; Cowell et al, 1996) simply gave information on more subjects than in earlier papers which were included in the review, and another two included the data in subsequent papers.
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Incorporating the figures from the Table into the calculations of median percentage differences between patients with schizophrenia and controls generally has little effect for most brain regions probably as a consequence of the small amount of additional data gleaned for any particular region in specific subject groups. The only region in a subject group to have more than one additional datum was the left and right temporal lobes in both genders combined. The result for this region was also changed by more than any other cortical region, from -6% and -9.5% (left and right) to -3.5% and -7%. Similarly sized but opposite effects were found for the prefrontal lobes, rendering the revised median differences more compatible with those of the temporal lobes (-5.5% and -4%, respectively). The largest overall change was for the right lateral ventricle volume in both genders, the median difference being reduced from 36% to 23% in patients with schizophrenia. The pre-specified region of maximal interest (left amygdalo-hippocampus) was not altered the only relevant data (Waldo et al, 1994) reporting these structures separately. One previous study had reported data this way, giving a new median estimate (between the two studies) of -11.5% and -9% (left and right) for the amygdala, and -6 and -4% for the hippocampus.
The grey/white segmentation data in Woods & Yurgelun-Todd (1991), that only had two relevant previous studies, were the only data that actually altered the findings. Whereas prefrontal and temporal white matter was bilaterally increased before (Lawrie & Abukemil, 1998), such volume increases are only evident in the left temporal lobe after incorporating the new data and the other three regions are actually reduced in line with overall and grey matter reductions. However, the inclusion of one further study in an updated review (Lawrie, 1999) re-instates the previous finding. Overall, therefore, the main conclusions of the review that patients with schizophrenia have small reductions in whole brain volumes as well as greater reductions in medial temporal lobe structures remain unaltered.
What has this exercise taught us? First, systematic reviewers can fail to include relevant articles through oversight, despite doing appropriate searches. Second, full reporting of comprehensive searches is desirable as a general rule and because unidentified articles where there are few published papers are disproportionately important. Finally, readers with good memories will remember that we staked a bottle of Glenndronnach malt whisky on the outcome of our efforts. As there were exactly five additional articles identified (rather than more or fewer) we have declared an honourable draw.
REFERENCES
Adams, C. E., Thornley, B. & Joy, C. (1998) Systematic does not necessarily mean comprehensive (letter). British Journal of Psychiatry, 172, 450-451.
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders (3rd edn, revised) (DSM-III-R). Washington, DC: APA.
Cowell, P. E., Kostianovsky, D. J., Gur, R. C., et al (1996) Sex differences in neuroanatomical and clinical correlations in schizophrenia. American Journal of Psychiatry, 153, 799-805.[Abstract]
DeLisi, L. E., Hoff, A. L., Kushner, M., et al (1992) Left ventricular enlargement associated with diagnostic outcome of schizophreniform disorder. Biological Psychiatry, 32, 199-201.[Medline]
Lawrie, S. M. (1998) Comprehensiveness of systematic review (letter). British Journal of Psychiatry, 173, 87-88.
Lawrie, S. M. (1999) Neuropathology and brain imaging in schizophrenia. In Schizophrenia: Concepts and Clinical Management (eds E. C. Johnstone, M. Humphries, F. Lang, et al), pp. 70-128. New York: Cambridge University
Lawrie, S. M. & Abukmeil, S. (1998) Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry, 172, 110-120.[Abstract]
Lim, K. O., Beal, M., Harvey, R. L., et al (1995) Brain dysmorphology in adults with congenital rubella plus schizophrenia-like symptoms. Biological Psychiatry, 37, 764-776.[CrossRef][Medline]
Waldo, M. C., Cawthra, E., Adler, L. E., et al (1994) Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings. Biological Psychiatry, 12, 93-106.
Woods, B. T. & Yurgelun-Todd, D. (1991) Brain volume loss in schizophrenia: when does it occur. Schizophrenia Research, 5, 202-204.[CrossRef][Medline]
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