
Y. KANEDA
comes than depressive symptoms. Therefore, in order to obtain
a better functional outcome, it may be important to place more
emphasis on pretreatment verbal WM than depressive symp-
toms.
The findings of this study also suggest again that MDD-as-
sociated deficits in verbal WM exist both in acute depression
and after the treatment of depression. These findings are con-
sistent with those of previous studies conducted by the author
(Kaneda, 2009b) and by Nebes et al. (2003), who found that
verbal WM dysfunction persisted in older depressed patients
even after their mood disorder had responded to antidepressant
medications. The observations made herein may be explained
by an impairment of WM/central executive functions in MDD,
as suggested by Rose & Ebmeier (2006), since executive func-
tion impairment is considered to be, at least to some degree,
trait-related (Porter et al., 2003).
Regarding the effects of antidepressant medications on cog-
nitive function, a significant increase in DST scores was ob-
served during 12-week treatment with paroxetine in the present
study. Although a potential effect which would be maximized
by testing twice within 5 days (Keefe et al., 2004), cannot be
completely ruled out, paroxetine is suggested to possibly im-
prove cognitive function in depressed subjects. Antidepressant
medications may also have some negative effects on cognitive
function (Gorenstein et al., 2006, Hindmarch, 2009). Cassano et
al. (2002), in their double-blind, randomized, parallel-group,
multicenter study comparing paroxetine and fluoxetine treat-
ment for 1 year, found that improvement, rather than deteriora-
tion, was observed in most of the tested cognitive functions. It
has been speculated that paroxetine may have indirect effects
which improve cognitive function via amelioration of depres-
sion, and that this could outweigh the mildly toxic effects of
paroxetine (Hindmarch, 2009).
A limitation of this study is that the possible influence of
benzodiazepines (Stewart, 2005) on verbal WM function could
not be completely ruled out. Another limitation of this study is
that patients with full and partial remission (mild depression)
were analyzed together, mainly because there were few patients
with full remission. Also, a longer observation may be needed
to allow sufficient recovery of verbal WM function. Therefore,
a further long-term study of patients showing remission of de-
pression, who are no longer taking medication, might be neces-
sary to confirm the present results.
Acknowledgements
This work was supported in part by grants from Daido Life
Welfare Foundation (2009), the Japanese Association of Neuro-
Psychiatric Clinics (Ken TANAKA Memorial Grant, 2008),
and the Charitable Trust Kimi IMAI Memorial Stress Associ-
ated Diseases Research Aid Fund (2009, 2010). This study was
presented in part at the 20th Annual Meeting of the Japanese
Society of Clinical Neuropsychopharmacology, held jointly with
the 40th Annual Meeting of the Japanese Society of Neuropsy-
chopharmacology, in Sendai, Japan, and 164th Annual Meeting
of the American Psychiatric Association in Honolulu, USA.
REFERENCES
American Ps ych iat ric Asso ciat ion (19 94). Diagnostic and statistical man-
ual of mental disorders, Fourth Edition (DSM-IV). Washington DC:
American Psychiatric Association.
Biringer, E., Mykletun, A. , Sundet, K., Kr oken, R., Stordal, K. I., & L und,
A. (2007). A longitudinal analysis of neurocognitive function in uni-
polar depression. Journal of Clinical and Experimental Neuropsy-
chology, 29, 879-891. doi:10.1080/13803390601147686
Cassano, G. B., Puca, F., Scapicchio, P. L., & Trabucchi, M. (2002).
Paroxetine and fluoxetine effects on mood and cognitive functions in
depressed nondemented elderly patients. The Journal of Clinical P sy -
chiatry, 63, 396-40 2. doi:10.4088/JCP.v63n0504
Gorenstein, C., de Carvalho, S. C., Artes, R., Moreno, R. A., & Marcour-
akis, T. (2006). Cognitive performance in depressed patients after
chronic use of antidepressants. Psychopharmacology, 185 , 84-92.
doi:10.1007/s00213-005-0274-2
Gualtieri, C. T., Johnson, L. G., & Benedict, K. B. (2006). Neurocogni-
tion in depression: Patients on and off medication versus healthy
comparison subjects. The Journal of neuropsychiatry and clinical neu-
rosciences, 18, 217-225. doi:10.1176/appi.neuropsych.18.2.217
Gualtieri, C. T., & Morgan, D. W. (2008). The frequency of cognitive
impairment in patients with anxiety, depression, and bipolar disorder:
An unaccounted source of variance in clinical trials. The Journal of
Clinical Psychiatry, 69, 1122-1130. doi:10.4088/JCP.v69n0712
Hindmarch, I. (2009). Cognitive toxicity of pharmacotherapeutic agents
used in social anxiety disorder. International Journal of Clinical Prac-
tice, 63, 1085-1094. doi:10.1111/j.1742-1241.2009.02085.x
Kaneda, Y. (2009a). Verbal working memory and functional outcome
in patients with unipolar major depressive disorder. World Journal of
Biological Psychiatry, 10, 591-594.
doi:10.1080/15622970903183705
Kaneda, Y. (2009b). Verbal working memory impairment in patients
with current episode of unipolar major depressive disorder and in
remission. Clinical Neurop harmacology, 32, 346-347.
doi:10.1080/15622970903183705
Kaneda, Y., Jayathilak, K., & Meltzer, H. (2010). Determinants of work
outcome in neuroleptic-resistant schizophrenia and schizoaffective
disorder: Cognitive impairment and clozapine treatment. Psychiatry
Research, 178, 57-62. doi:10.1016/j.psychres.2009.04.001
Kaneda, Y., Jayathilak, K., & Meltzer, H. Y. (2009). Determinants of
work outcome in schizophrenia and schizoaffective disorder: Role of
cognitive function. Psychiatry Research, 169, 178- 179.
doi:10.1016/j.psychres.2008.08.003
Keefe, R. S., Goldberg , T. E., Harv ey, P. D., Gold, J. M., Poe, M. P ., &
Coughenour, L. (2004). The brief assessment of cognition in schizo-
phrenia: Reliability, sensitivity, and comparison with a standard neu-
rocognitive battery. Schizophrenia Research, 68, 283-297.
doi:10.1016/j.schres.2003.09.011
Kennedy, N., Foy, K., Sherazi, R., McDonough, M., & McKeon, P. (2007).
Long-term social functioning after depression treated by psychiatrists:
A review. Bipolar Disorders, 9, 25-37.
doi:10.1111/j.1399-5618.2007.00326.x
Kitagawa, N., & Koyama, T. (2009). Assessment of neurocognitiv e func-
tion in mood disorders and its utilization to clinical practice. Rinsho
Seishin Igaku (Japanese Journal of Clinical Psychiatry), 38, 437-445.
Malone, D. C. (2007). A budget-impact and cost-effectiveness model
for second-line treatment of major depression. Journal of Managed
Care Pharmacy, 13, S8-18.
Marcos, T., Portella, M. J., Navarro, V., Gasto, C., Rami, L., Lazaro, L.,
& Salamero, M. (2005). Neuropsychological prediction of recovery
in late-onset major depression. Intern ational Journal of Geriatric Psy-
chiatry, 20, 790-79 5. doi:10.1002/gps.1363
McIntyre, R. S., Konarski, J. Z., Mancini, D. A., Fulton, K. A., Parikh,
S. V., Grigoriadis, S., Grupp, L. A., Bakish, D., Filteau, M. J., Gor-
man, C., Nemeroff, C. B., & Kennedy, S. H. (2005). Measuring the
severity of depression and remission in primary care: Validation of
the HAMD-7 scale. Canadian Medical Association Journal, 173,
1327-1334. doi:10.1503/cmaj.050786
Nebes, R. D., Pollock, B. G., Ho uck, P. R., Butters, M. A., Mu lsant, B.
H., Zmuda, M. D., & Reynolds III, C. F., (2003). Persistence of cog-
nitive impairment in geriatric patients following antidepressant treat-
ment: A randomized, double-blind clin ica l trial with nortriptyline and
paroxetine. Journal of Psychiatric Research, 37, 99-108.
doi:10.1016/S0022-3956(02)00085-7
Copyright © 2012 SciRes.
760