Severe deep white matter lesions and outcome in elderly patients with major depressive disorder: follow up study

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="however" there="there" were="were" two="two" additional="additional" findings.="findings." first="first" certain="certain" types="types" of="of" lesion="lesion" more="more" likely="likely" to="to" be="be" associated="associated" with="with" incomplete="incomplete" recovery="recovery" or="or" chronic="chronic" symptoms="symptoms" depression.="depression." in="in" particular="particular" lesions="lesions" the="the" pontine="pontine" reticular="reticular" formation="formation" and="and" than="than" _5="_5" virchow="virchow" robins="robins" spaces="spaces" basal="basal" ganglia="ganglia" showed="showed" strongest="strongest" association.="association." fact="fact" a="a" forward="forward" conditional="conditional" logistic="logistic" regression="regression" collapsing="collapsing" outcome="outcome" categories="categories" into="into" good="good" bad="bad" presence="presence" was="was" only="only" factor="factor" poor="poor" at="at" significance="significance" level="level" p0.05.="p0.05." p="p"/> 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.