Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.
Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.
Ehrenreich
H
H
Division of Clinical Neuroscience, Max-Planck-Institute of Experimental Medicine, Göttingen, Germany. ehrenreich@em.mpg.de
Hinze-Selch
D
D
Stawicki
S
S
Aust
C
C
Knolle-Veentjer
S
S
Wilms
S
S
Heinz
G
G
Erdag
S
S
Jahn
H
H
Degner
D
D
Ritzen
M
M
Mohr
A
A
Wagner
M
M
Schneider
U
U
Bohn
M
M
Huber
M
M
Czernik
A
A
Pollmächer
T
T
Maier
W
W
Sirén
A-L
AL
Klosterkötter
J
J
Falkai
P
P
Rüther
E
E
Aldenhoff
J B
JB
Krampe
H
H
D000328:Adult; D002908:Chronic Disease; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy*; D004921:Erythropoietin / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D009473:Neuronal Plasticity / Q000187:drug effects; D015990:Placebo Effect; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D004921:Erythropoietin