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PAPERS: John O'Brien, David Ames, Edmond Chiu, Isaac Schweitzer, Patricia Desmond, and Brian Tress Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study BMJ 1998; 317: 982-984 [Abstract] [Full text]

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Vasculitis, the cause of deep white matter lesions in elderly depressive patients ?

Michael Schirmer   (16 November 1998)

Deep white matter lesions and prognosis of depression

Robert Baldwin   (17 November 1998)

Vasculitis, the cause of deep white matter lesions in elderly depressive patients ? 16 November 1998
Michael Schirmer, rheumatologist Dept. of Internal Medicine, University Hospital, A-6020 Innsbruck, Austria Send response to journal: Re: Vasculitis, the cause of deep white matter lesions in elderly depressive patients ?	Editor - The study of O'Brien et al. clearly shows that deep white matter lesions on magnetic resonance images are relevant for the outcome of elderly depressed patients.(1) This result is not only important for psychiatrists. Although O'Brien et al. excluded all patients, if they had a known history of other diseases, depression with such an organic correlate might be secondary to a distinct CNS-disease. Unfortunately, neuropathological studies are difficult to perform. Until now biopsies of deep white matter lesions are not available from the group of depressive patients.(1) Interestingly, deep white matter lesions have also been described in vascular diseases like systemic lupus erythematosus(2) or Behcet's disease.(3) Patients with these diseases may present with depressive symptoms, possibly as a correlate of CNS- vasculitis. To our opinion, there is a good chance that the deep white matter lesions described by O'Brien et al. represent a type of localized CNS- vasculitis. As these patients have a poor outcome with a median survival time of only 4 months, we think that clinical trials testing immunosuppressive therapy would be justified despite lack of a proven pathogenetical mechanism. In severe forms of CNS-vasculitis, drug regimens using corticosteroids, chlorambucil and cyclophosphamide are well- established.(4) Lower doses of immunosuppressants might help to prevent serious side effects in this group of geriatric patients. Michael Schirmer, Rheumatologist. Sandra Fels, Medical Student. Department of Internal Medicine, University Hospital, A-6020 Innsbruck, Austria References: 1. O'Brien J, Ames D, Chiu E, Schweitzer I, Desmond P, Tress B. Severe deep white matter lesions and outcome in elderly patients with major depressive disorders: follow up study. BMJ 1998;317:982-4. 2. Sailer M, Burchert W, Ehrenheim C, Smid HG, Haas J, Wildhagen K, Wurster U, Deicher H. Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus. J Neurol 1997;244:186-93. 3. Serdaroglu P. Behçet's disease and the nervous system. J Neurol 1998;245:197-205. 4. Calabrese LH, Duna GF, Lie JT. Vasculitis in the central nervous system. Arthr Rheum 1997;40:1189-201.
Deep white matter lesions and prognosis of depression 17 November 1998
Robert Baldwin Send response to journal: Re: Deep white matter lesions and prognosis of depression	Dear Sir, O'Brien and colleagues (1) have shown that severe deep white matter lesions in elderly patients with depressive disorder are associated with a poorer outcome, as measured by the quality of recovery from depression and time to relapse and/or recurrence. Our group has established that brain changes similar to those described by O'Brien et al predict a poorer response to antidepressants in the acute phase of treatment (2). We have now completed a 3 year follow-up of this cohort to assess the prognosis of depression. Of the original 44 subjects who had undergone Magnetic Resonance Imaging (MRI), 37 case notes were examined using a structured proforma and, for 22 survivors (of 29 contactable), an interview administered, both by SW. The ‘interrogation' of case notes and the interview were based on an earlier study (3). Course of illness vignettes were constructed from all the information available, again in a structured way, and two experienced clinicians assigned a final outcome category identical to those of O'Brien et al: continuously well; relapse with recovery; ‘depressive invalidism'; continuously ill; dead; demented. Cause of death was ascertained from case notes and/or by direct enquiry from general practitioners; the dementia syndrome was diagnosed on the basis of DSMIV criteria (American Psychiatric Association, 1994). Our findings broadly correspond to those of O'Brien et al. The presence of deep white matter hyperintensities was associated with poor overall clinical outcome, the poorest mean survival time (31.58 months to death for large confluent deep white matter lesions; 33.11 months for those without, using Kaplan-Meier survival analysis), higher residual depression rating scores and higher re-admission rate (for these statistical results, all p values <0.05). However, there were two additional findings. First, certain types of lesion were more likely to be associated with incomplete recovery or chronic symptoms of depression. In particular, lesions in the pontine reticular formation and more than 5 Virchow Robins spaces in the basal ganglia showed the strongest association. In fact, in a forward conditional logistic regression, collapsing the outcome categories into ‘good' and ‘bad', the presence of Virchow Robins spaces was the only factor associated with a poor outcome at significance level of P<0.05. The second striking finding was that grade 3 periventricular lesions (PVL) (deep irregular lesions) were associated with a significantly increased risk of developing a dementia syndrome The Table shows that 12 patients had deep irregular hyperintensities and 5 developed a dementia syndrome. Of the other two types of less severe change, or absence of PVL change, only one developed dementia. O'Brien et al found no association of PVL with any of their outcome groups. Possibly by combining the outcome categories of death and dementia into one they may have overlooked an association. O'Brien and colleagues have elsewhere (4) reported that PVL is more often associated with Alzheimer dementia and deep white matter change with depression. There is uncertainty as to whether depression in old age is associated with a higher rate than expected of the development of dementia. Certain sub-groups, notably those with cognitive impairment at the outset of their depression, have been shown to have a much increased risk (5). PVL and deep white matter change may have different clinical implications. PVL may be more relevant in the prediction of dementia whereas deep white matter lesions influence the outcome both of acute treatment response (2) and the risk of longitudinal relapse. Further investigation of deep white matter lesions should be undertaken to establish more precisely their relevance to prognosis and treatment strategies, but PVL should not be overlooked as a potential marker of later dementia. Table. The association of periventricular change to dementia during the course of follow-up N Df Chi-squared P value Dementia Developed Yes No Periventricular Hyperin Absent 0 10 37 9 18.09 0.034 Capsulated 0 11 Smooth Halo 1 3 Deep Irreg' 5 7 References 1. O'Brien, J, Ames, D, Chiu, D, Schweitzer, I, Desmond, P, Tress, B. Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: a follow-up study BMJ (1998) 317:982-4. 2. Simpson, SW, Jackson, A, Baldwin RC, Burns, A. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment International Psychogeriatrics (1997) 9:257 -275. 3. Baldwin R.C. & Jolley, D.J. The prognosis of depression in old age. British Journal of Psychiatry (1986) 149 : 574583. 4. O'Brien, JT, Ames, D, Schwietzer, I. White matter chnages in depression and Alzheimer;s disease: a review of magnetic resonance imaging studies. (1996) International Journal of Geriatric Psychiatry 11:681-694. Authors Robert C Baldwin,.DM,, FRCP. FRCPsych.; Consultant Old Age Psychiatrist, York House, Manchester Royal Infirmary, Oxford Road, Manchester M13 9BX, England; Scott Walker, Medical Student, University of Manchester Medical School; Stephen W Simpson. MB ChB. MRCpsych. Consultant Psychiatrist, Forston Clinic, Herison, Dorchester, Dorset DT2 9TB Alan Jackson Bsc, MB ChB(hons), MRCP, FRCR, PHD, Professor of Neuroradiology, Manchester Medical School, Academic Department of Diagnostic Radiology, Oxford Road, Manchester; Alistair Burns Mphil, FRCpsych, FRCP, MD(Hons). Professor of Old Age Psychiatry. Academic Department of Old Age Psychiatry, Withington Hospital, Nell Lane, West Didsbury, Manchester.