Depression in Multiple Sclerosis:
A Quantitative Review of the Evidence
E. Jane Dalton and R. Walter Heinrichs
York University
Toronto, Ontario, Canada
Supplementary Information File
Table 1: Effect sizes and depression scores for studies comparing MS patients to healthy
participants
Table 2: Effect sizes and depression scores for studies comparing MS and other chronic
disorders
Table 3: Effect sizes and moderator variables for studies comparing MS patients to
healthy participants
Table 4: Effect sizes and moderator variables for studies comparing MS and other
chronic disorders
Primary studies in meta-analytic literature base
Supplemental Table 1
Effect sizes and depression scores for studies comparing MS patients to healthy participants
________________________________________________________________________________________________________________
Study Effect Size (d) Depression MS Patients Healthy Controls
Scale Used
Mean SD n Mean SD n
________________________________________________________________________________________________________________
Aikens, Reinecke, Pliskin et al., 1999 .82 BDI-21 9.6 7.1 105 4.5 4.7 80
Clark, Fleming, Li et al., 1992 .76 BDI-21 9.0 5.2 143 5.15 4.8 70
DeLuca, Johnson, Beldowicz & Natelson, 1995 1.24 BDI-21 8.7 7.62 12 2.1 2.62 20
Fassbender, Schmidt, Mobner et al., 1998 1.08 HRSD-21 9.65 9.23 23 1.80 1.52 17
Huber, Paulsen, Shuttleworth et al., 1987 1.24 Zung SDS 40.56 10.25 32 29.08 4.32 12
Huber, Rammohan, Bornstein & Christy, 1993 .90* BDI-21 11.9 n/a 89 5.2 n/a 47
Johnson Deluca & Natelson, 1996b 2.50 NEO-depression 9.8 1.5 20 7.0 0.8 35
Johnson, Lange, Deluca, Korn & Natelson, 1997 1.25 BDI-21 6.27 5.24 15 1.2 1.49 15
Johnson, Deluca, Diamond & Natelson, 1998 1.18 BDI-21 6.3 5.23 15 1.4 2.24 17
Kahl, Kruse, Faller, Weib & Rieckmann, 2002 1.83 BDI-21 13.6 5.5 16 4.6 2.5 10
Krupp, Alvarez, LaRocca & Scheinberg, 1988 1.02 CES-D 18.2 12.2 32 7.6 8.0 33
Supplemental Table 1… continued
Krupp, Sliwinski, David, Friedberg & Coyle, 1994 .60 CES-D 10.0 5.1 20 6.4 6.6 20
Litvan, Grafman, Vendrell & Martinez, 1988 .57 HRSD 5.6 4.3 16 3 4.3 16
Mohr, Goodkin, Likosky et al., 1997 .54** BDI-21 10.6 n/a 184 6.8 n/a 555
Nyenhuis, Rao, Zajecka et al., 1995 .70 BDI-21 11.0 8.8 84 6.0 5.3 101
Rao, Leo, & Aubin-Fauber, 1989 .78 Zung SDS 39.7 9.5 37 33.2 6.0 26
Sadovnick, Remick, Allen et al., 1996 1.48*** SCID 76/221 n/a 221 20/1207 n/a 1207
Schiffer, Caine, Bamford, & Levy, 1983 .73*** SADS 11/30 n/a 30 0/15 n/a 15
Verdier-Taillefer, Gourlet, Fuhrer et al., 2001 1.06 CES-D 21.2 11.1 696 10.5 7.8 342 Wilson, Olson, Gasco & Brumback, 1982 1.15 MMPI-Scale 2 (D) 64.1 12.0 27 52.5 7.2 26
___________________________________________________________________________________________________________________
* Effect Size derived from t-test
** Effect size derived from ANOVA
***Effect size derived from proportion of sample that had diagnosis of depression according to DSM-III or DSM-IIIR
Supplemental Table 2
Effect sizes and depression scores for studies comparing MS and other chronic disorders
___________________________________________________________________________________________________________________
Study Effect size d ___________________________________________________________________________________________________________________
Aikens, Reinecke, Pliskin et al., 1999 -.51 BDI-21 9.6 7.1 105 13.85 9.65 151
DeLuca, Johnson, Beldowicz & Natelson, 1995 -.72 BDI-21 8.7 7.62 12 14.5 8.0 26
Devins, Edworthy, Leendert et al., 1993 -.18 CES-D 12.2 9.24 94 14.13 9.8 387
Fournier, Ridder & Bensing, 2002 .18 HADS-D 3.7 3.4 98 3.15 2.6 199
Johnson Deluca & Natelson, 1996a -.93 BDI-21 7.5 6.62 27 14.3 7.55 48
Johnson Deluca & Natelson, 1996b -.31 NEO-Depression 9.8 1.5 20 10.2 1.1 35
Johnson, Deluca, Diamond & Natelson, 1998 -1.15 BDI-21 6.3 5.23 15 14.0 7.04 23
Johnson, Lange, Deluca, Korn & Natelson, 1997 -1.16 BDI-21 6.27 5.24 15 14.21 7.48 15
Krupp, Sliwinski, David, Friedberg et al., 1994 -1.08 CES-D 10.0 5.1 20 17.1 8.1 20
MacLeod & Macleod, 1998 -.36 BDI-21 8.28 6.57 25 11 7.89 45
Minden, Orav & Reich, 1987 .80 BDI-21 12.7 8.4 50 7.8 6.0 679
Pepper, Krupp, Friedberg, Doscher, & Coyle, 1993 .22* MCMI-MD Scale 1/42 n/a 42 0/45 n/a 45
Supplemental Table 2…continued
Rabins, Brooks, O’Connell et al., 1986 .30 GHQ-D subscale .9 1.4 87 .5 .8 16
Ron & Logsdail, 1989 .82 BDI-21 10.6 8.0 116 4.6 5.1 48
Shnek, Foley, LaRocca et al., 1997 .23 CES-D 15.6 12.8 80 12.8 11.6 80
Sullivan, Edgley, Mikail, Dehoux & Fisher, 1992 -.56 BDI-21 13.2 8.8 35 18.2 9.0 35
Surridge, 1969 .33** DSM-III 29/108 n/a 108 5/39 n/a 39
Taillefer, Kirmayer, Robbins & Lasry, 2002 -.16 SCL-90R-D 11.4 6.8 40 12.5 6.5 45
Verdier-Taillefer, Gourlet, Fuhrer et al., 2001 .25 CES-D 21.2 11.1 696 18.3 12.1 1308
Whitlock & Siskind, 1980 .82*** BDI-21 n/a n/a 30 n/a n/a 30
Wilson, Olson, Gasco & Brumback, 1982 .12 MMPI- Scale 2(D) 64.1 12.0 27 62.7 13 51
* Effect size based on proportion of participants with cut-off on MCMI of over 85
** Effect size based on proportion of participants with past or present DSM-III diagnosis of major depressive disorder
***Effect size based on Mann-Whitney test used by author that indicated MS patients more depressed than medical patients
Supplemental Table 2…continued Note: RA = rheumatoid arthritis, ESRD = end-stage renal disease, FP = family practice patients with miscellaneous complaints, hosp = hospitalized medical patients with mixed diagnoses.
Supplemental Table 3
Effect sizes and moderator variables for studies comparing MS patients to healthy participants
________________________________________________________________________________________________________________
Study Effect Size (d) EDDS Mean Age MS Mean Age NC % of females in MS
vs. NC*
________________________________________________________________________________________________________________
Aikens, Reinecke, Pliskin et al., 1999 .82 3.8 (high) 42 (old) 34 (young) higher
Clark, Fleming, Li et al., 1992 .76 n/a 36 (young) 35 (young) higher
DeLuca, Johnson, Beldowicz & Natelson, 1995 1.24 1.2 (low) 36 (young) 37 (young) n/a
Fassbender, Schmidt, Mobner et al., 1998 1.08 n/a 35 (young) 30 (young) higher
Huber, Paulsen, Shuttleworth et al., 1987 1.24 5.1 (high) 40 (old) 44 (old) n/a
Huber, Rammohan, Bornstein & Christy, 1993 .90 3.9 (high) 42 (old) 41 (old) n/a
Johnson Deluca & Natelson, 1996b 2.50 1.6 (low) 38 (young) 35 (young) lower
Johnson, Lange, Deluca, Korn & Natelson, 1997 1.25 1.8 (low) 38 (young) 34 (young) n/a
Johnson, Deluca, Diamond & Natelson, 1998 1.18 1.8 (low) 38 (young) 35 (young) lower
Kahl, Kruse, Faller, Weib & Rieckmann, 2002 1.83 2.5 (low) 30 (young) 31 (young) lower
Supplemental Table 3…continued
Krupp, Alvarez, LaRocca & Scheinberg, 1988 1.02 n/a 39 (young) 39 (old) higher
Krupp, Sliwinski, David, Friedberg & Coyle, 1994 .60 2.3 (low) 40 (old) 46 (old) n/a
Litvan, Grafman, Vendrell & Martinez, 1988 .57 3.84 (high) 36 (young) 36 (young) lower
Mohr, Goodkin, Likosky et al., 1997 .54 n/a 44 (old) 48 (old) higher
Nyenhuis, Rao, Zajecka et al., 1995 .70 4.74 (high) 49 (old) 49 (old) higher
Rao, Leo, & Aubin-Fauber, 1989 .78 4.3 (high) 44 (old) 45 (old) higher
Sadovnick, Remick, Allen et al., 1996 1.48 n/a n/a n/a n/a
Schiffer, Caine, Bamford, & Levy, 1983 .73 n/a 44 (old) 42 (old) higher
Verdier-Taillefer, Gourlet, Fuhrer et al., 2001 1.06 n/a 47 (old) 43 (old) higher
Wilson, Olson, Gasco & Brumback, 1982 1.15 3.5 (high) 40 (old) 38 (young) lower
___________________________________________________________________________________________________________________
* Variable coded “higher” when percentage of females in MS group was higher than NC group and “lower” when smaller percentage of females in MS than NC group
Supplemental Table 4
Effect sizes and moderator variables from studies comparing MS and other chronic disorders
___________________________________________________________________________________________________________________
Study Effect size d EDSS CFS Neurogolical ___________________________________________________________________________________________________________________
Aikens, Reinecke, Pliskin et al., 1999 -.51 3.8 (high) no no
DeLuca, Johnson, Beldowicz & Natelson, 1995 -.72 1.2 (low) yes no
Devins, Edworthy, Leendert et al., 1993 -.18 5.2 (high) no no
Fournier, Ridder & Bensing, 2002 .18 >7.0 (high) no no
Johnson Deluca & Natelson, 1996a -.93 1.5 (low) yes no
Johnson Deluca & Natelson, 1996b -.31 1.6 (low) yes no
Johnson, Deluca, Diamond & Natelson, 1998 -1.15 1.8 (low yes no
Johnson, Lange, Deluca, Korn & Natelson, 1997 -1.16 1.8 (low) yes no
Krupp, Sliwinski, David, Friedberg et al., 1994 -1.08 2.3 (high) yes no
MacLeod & Macleod, 1998 -.36 n/a no yes
Minden, Orav & Reich, 1987 .80 n/a no no
Pepper, Krupp, Friedberg, Doscher, & Coyle, 1993 .22* n/a yes no
Supplemental Table 4…continued
Rabins, Brooks, O’Connell et al., 1986 .30 n/a no yes
Ron & Logsdail, 1989 .82 n/a no yes
Shnek, Foley, LaRocca et al., 1997 .23 n/a no yes
Sullivan, Edgley, Mikail, Dehoux & Fisher, 1992 -.56 n/a no no
Surridge, 1969 .33 n/a no yes
Taillefer, Kirmayer, Robbins & Lasry, 2002 -.16 n/a yes no
Verdier-Taillefer, Gourlet, Fuhrer et al., 2001 .25 n/a no no
Whitlock & Siskind, 1980 .82 n/a no yes
Wilson, Olson, Gasco & Brumback, 1982 .12 3.5 (high) no yes
Primary Study References
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McCracken, L.M. & Taylor, J.L. (1999). Assessing depressive symptoms in MS: Is it necessary to omit items from the original Beck Depressive Inventory? Journal of Behavioral Medicine, 22, 127-135.
Clark, C.M., Fleming J.A., Li, D., Oger, J., Klonoff, H. & Paty, D. (1992).
Sleep disturbance, depression, and lesion site in patients with MS. Archives of Neurology, 49, 641-643.
DeLuca, J., Johnson, S.K., Beldowicz, D. & Natelson, B. (1995).
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depression. Journal of Neurology, Neurosurgury and Psychiatry, 58, 38-
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Devins, G.M., Edworthy, S.M., Leendert, C.P, Mandin, H., Seland, P. & Klein,
G.M. (1993). Illness intrusiveness and depressive symptoms over the adult years: Is there a differential impact across the chronic conditions? Canadian Journal of Behavioral Science, 25, 400-413.
Devins, G.M, Edworthy, S., Leendert, C.P, Mandin, H., Seland, T.P., Klein, G.,
Costello C.G. & Shapiro, C.M. (1993). Restless sleep, illness intrusiveness, and depressive symptoms in three chronic illness conditions: RA, End-stage renal disease and MS. Journal of Psychosomatic Research, 37, 163-170.
Fassbender, K., Schmidt, R., Mobner, R., Kischka, U., Kuhnen, J., Schwartz, A.
& Hennerici, M. (1998). Mood disorders and dysfunction of the Hypothalamic-Pituitary-Adrenal Axis in MS. Archives of Neurology, 55, 66-78.
Fournier, M., Ridder, D. & Bensing, J. (2002). Optimism and adaptation to
chronic disease: the role of optimism in relation to self-care options in type 1 diabetes mellitus, rheumatoid arthritis and MS. British Journal of Health Psychology, 7, 409-432.
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