Review of the Evidence E. Jane Dalton and R. Walter Heinrichs



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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

Aikens, J.E., Reinecke, M.S., Pliskin, N.H., Fischer, J.S., Wiebe, J.S.,

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).

Neuropsychological impairments in chronic fatigue syndrome, MS and

depression. Journal of Neurology, Neurosurgury and Psychiatry, 58, 38-

43.


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.

Huber, S.J., Paulson, G.W., Shuttle worth, E.C., Chakeres, D., Clapp, L.E.,

Pakalnis, A., Weiss, K. & Rammohan, K. (1987). Magnetic resonance imaging correlates of dementia in MS. Archives of neurology, 44, 732-736.

Huber, S., Rammohan, K., Bornstein, R. & Christy, J. (1993). Depressive

symptoms are not influenced by severity in MS. Neuropsychiatry, Neuropsychology and Behavioral Neurology, 6, 177-180.

Johnson, S.K., DeLuca, J., Diamond, B.J., & Natelson, B.H. (1998). Memory dysfunction in fatiguing illnesses: examining interference and distraction

in short-term memory. Cognitive Neuropsychiatry, 3, 269-285.

Johnson, S.K., DeLuca, J., Natelson, B.H. (1996a). Depression in fatiguing

illnesses: comparing patients with chronic fatigue syndrome, MS and depression. Journal of Affective Disorders, 39, 21-30.

Johnson, S.K., DeLuca, J. & Natelson, B.H. (1996b). Personality dimensions in

chronic fatigue syndrome: a comparison to MS and depression. Journal of



Psychiatry Research, 30, 9-20.

Johnson, S.K., Lange, G., DeLuca, J., Korn, L.R. & Natelson, B. (1997). The

effects of fatigue on neuropsychological performance in patients with chronic fatigue syndrome, MS and depression. Applied Neuropsychology, 4, 145-153.

Kahl, K., Kruse, N., Faller, H., Weib, H. & Rieckmann, P. (2002). Expression

of tumor necrosis factor-a and interferon-y mRNA in blood cells correlates with depression scores during an acute attack of patients with MS. Psychoneuroendocrinology, 27, 671-681.

Krupp, L.B., Alvarez, L.A., LaRocca, N.G. & Scheinberg, L.C. (1988). Fatigue

in MS. Archives of Neurology, 45, 435-440.

Krupp, L.B., Sliwinski, M., David, M.M., Friedberg, F. & Coyle, P.K. (1994).

Cognitive functioning and depression in patients with CFS and MS. Archives of Neurology, 51, 705-710.

Litvan, I., Grafman, J., Vendrell, P. & Martinez, JM. (1988). Slowed

information processing in MS. Archives of Neurology, 45, 281-285.

MacLeod, L. & Macleod, G. (1998). Control cognitions and psychological

disturbance in people with contrasting physically disabling conditions.

Disability and Rehabilitation, 20(, 448-456.

Minden, S., Orav, J. & Reich P. (1987). Depression in MS. General Hospital



Psychiatry, 9, 426-434.

Mohr, D.C., Goodkin, D.E., Likosky, W., Beutler, L., Gatto, N. & Langan, M.K.

(1997). Identification of Beck Depression Inventory items related to MS. Journal of Behavioral Medicine, 20, 407-413.

Nyenhuis, D.L., Rao, S.M., Zajecka, J.M., Luchetta, T., Bernardin, L. & Garron,

D.C. (1995). Mood disturbance versus other symptoms of depression in MS. Journal of International Neuropsychological Society, 1, 291-296.

Psychosomatics, 66, 286-292.

Pepper, C.M., Krupp, L.B., Friedberg, F., Doscher, C. & Coyle, P.K. (1993). A

comparison of neuropsychiatric characteristics in chronic fatigue syndrome, MS and major depression. Journal of Neuropsychiatry and Clinical Neurosciences, 5, 200-205.

Rabins, P.V., Brooks, B.R., O’Connell, P. Pearlson, G., Moberg, P. & Jubelt.K.

(1986). Structural brain correlates of emotional disorder in MS. Brain, 109, 585-597.

Rao, S.M., Leo, G.J. & Aubin-Fauber, A. (1989). On the nature of memory

disturbance in MS. Journal of Clinical and Experimental Neuropsychology, 11, 699-712.

Ron, M.A. & Logsdail, S.J. (1989). Psychiatric morbidity in MS: a clinical and

MRI study. Psychological Medicine, 19, 887-895.

Sadovnick, A., Remick, M., Allen, E., Swartz, I., Yee, K. & Eisen, K. (1996).

Depression and MS. The American Academy of Neurology, 46, 628-635.

Schiffer, R.B., Caine, E.D., Bamford, K.A. & Levy, S. (1983). Depressive

episodes in patients with MS. American Journal of Psychiatry, 140, 1498-1500.

Shnek, Z.M., Foley, F.W., LaRocca, N.G., Grodon, W., DeLuca, J.,

Schwartzman, H.G., Halper, J., Lennox, S. & Irvine, J. (1997). Helplessness, self-efficacy, cognitive distortions and depression in MS and spinal cord injury. Annals of behavioral medicine, 19, 287-294.

Sullivan, M.J., Edgley, K., Mikail, S., Dehoux, E. & Fisher, R. (1992).

Psychological correlates of health care utilization in chronic illness. Canadian Journal of Rehabilitation, 6, 13-21.

Surridge, D. (1969). An investigation into some psychiatric aspects of MS.



British Journal of Psychiatry, 115, 749-764.

Taillefer, S.S., Kirmayer, L.J., Robbins, S.M. & Lasry, J.C. (2002).

Psychological correlates of functional status in CFS. Journal of

Psychosomatic Research, 53, 1097-1106.

Verdier-Taillefer, M.H., Gourlet, V., Fuhrer, R. & Alperovitch, J. (2001).

Psychometric properties of the center for Epidemiologic studies-depression scale in MS. Neuroepidemiology, 20, 262-267.
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MS. Journal of Neurology, 43, 861-865.

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