Treatment of cognitive impairment in schizophrenia: potential value of phosphodiesterase inhibitors in prefrontal dysfunction

M. van Duinen, O.A.H. Reneerkens, L. Lambrecht, A. Sambeth, B.P.F. Rutten, J. van Os, A. Blokland, J. Prickaerts

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

No pharmacological treatment is available to date that shows satisfactory effects on cognitive symptoms in patients diagnosed with schizophrenia. Phosphodiesterase inhibitors (PDE-Is) improve neurotransmitter signaling by interfering in intracellular second messenger cascades. By preventing the breakdown of cAMP and/or cGMP, central neurotransmitter activity is maintained. Different PDE families exist with distinct characteristics among which substrate specificity and regional distribution. Preclinical data is promising especially with regard to inhibition of PDE2, PDE4, PDE5 and PDE10. In addition, cognitive improvement has been reported in both elderly and/ or non-impaired young human subjects after PDE1 or PDE4 inhibition. Moreover, some of these studies show effects on cognitive domains relevant to schizophrenia, in particular memory. The current review incorporates an overview of the distinct molecular characteristics of the different PDE families and their relationship to the neurobiological mechanisms related to cognitive dysfunction in schizophrenia. So far, procognitive effects of only three types of PDE-Is have been assessed in patients diagnosed with schizophrenia inhibiting PDE3, PDE5 and PDE10. However, the limited data available do not allow to draw firm conclusions on the value of PDE-Is as cognitive enhancers in schizophrenia yet. The field is still in its infancy, but nevertheless different PDE-Is seem promising as candidate to optimise neural communication in the prefrontal cortex favouring cognitive functioning in patients diagnosed with schizophrenia, in particular dual inhibitors including PDE1-Is, PDE3-Is and PDE10A-Is.
Original languageEnglish
Pages (from-to)3813-3828
Number of pages16
JournalCurrent Pharmaceutical Design
Volume21
Issue number26
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Schizophrenia
  • phosphodiesterase inhibitor
  • cognition
  • memory
  • pharmacological treatment
  • 1ST EPISODE SCHIZOPHRENIA
  • CEREBRAL-BLOOD-FLOW
  • OF-CONCEPT TRIAL
  • LATE-PHASE LTP
  • DOUBLE-BLIND
  • ALZHEIMERS-DISEASE
  • MESSENGER-RNA
  • NITRIC-OXIDE
  • IN-VIVO
  • NEUROCOGNITIVE DEFICITS

Cite this

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title = "Treatment of cognitive impairment in schizophrenia: potential value of phosphodiesterase inhibitors in prefrontal dysfunction",
abstract = "No pharmacological treatment is available to date that shows satisfactory effects on cognitive symptoms in patients diagnosed with schizophrenia. Phosphodiesterase inhibitors (PDE-Is) improve neurotransmitter signaling by interfering in intracellular second messenger cascades. By preventing the breakdown of cAMP and/or cGMP, central neurotransmitter activity is maintained. Different PDE families exist with distinct characteristics among which substrate specificity and regional distribution. Preclinical data is promising especially with regard to inhibition of PDE2, PDE4, PDE5 and PDE10. In addition, cognitive improvement has been reported in both elderly and/ or non-impaired young human subjects after PDE1 or PDE4 inhibition. Moreover, some of these studies show effects on cognitive domains relevant to schizophrenia, in particular memory. The current review incorporates an overview of the distinct molecular characteristics of the different PDE families and their relationship to the neurobiological mechanisms related to cognitive dysfunction in schizophrenia. So far, procognitive effects of only three types of PDE-Is have been assessed in patients diagnosed with schizophrenia inhibiting PDE3, PDE5 and PDE10. However, the limited data available do not allow to draw firm conclusions on the value of PDE-Is as cognitive enhancers in schizophrenia yet. The field is still in its infancy, but nevertheless different PDE-Is seem promising as candidate to optimise neural communication in the prefrontal cortex favouring cognitive functioning in patients diagnosed with schizophrenia, in particular dual inhibitors including PDE1-Is, PDE3-Is and PDE10A-Is.",
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author = "{van Duinen}, M. and O.A.H. Reneerkens and L. Lambrecht and A. Sambeth and B.P.F. Rutten and {van Os}, J. and A. Blokland and J. Prickaerts",
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Treatment of cognitive impairment in schizophrenia: potential value of phosphodiesterase inhibitors in prefrontal dysfunction. / van Duinen, M.; Reneerkens, O.A.H.; Lambrecht, L.; Sambeth, A.; Rutten, B.P.F.; van Os, J.; Blokland, A.; Prickaerts, J.

In: Current Pharmaceutical Design, Vol. 21, No. 26, 01.01.2015, p. 3813-3828.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - van Duinen, M.

AU - Reneerkens, O.A.H.

AU - Lambrecht, L.

AU - Sambeth, A.

AU - Rutten, B.P.F.

AU - van Os, J.

AU - Blokland, A.

AU - Prickaerts, J.

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AB - No pharmacological treatment is available to date that shows satisfactory effects on cognitive symptoms in patients diagnosed with schizophrenia. Phosphodiesterase inhibitors (PDE-Is) improve neurotransmitter signaling by interfering in intracellular second messenger cascades. By preventing the breakdown of cAMP and/or cGMP, central neurotransmitter activity is maintained. Different PDE families exist with distinct characteristics among which substrate specificity and regional distribution. Preclinical data is promising especially with regard to inhibition of PDE2, PDE4, PDE5 and PDE10. In addition, cognitive improvement has been reported in both elderly and/ or non-impaired young human subjects after PDE1 or PDE4 inhibition. Moreover, some of these studies show effects on cognitive domains relevant to schizophrenia, in particular memory. The current review incorporates an overview of the distinct molecular characteristics of the different PDE families and their relationship to the neurobiological mechanisms related to cognitive dysfunction in schizophrenia. So far, procognitive effects of only three types of PDE-Is have been assessed in patients diagnosed with schizophrenia inhibiting PDE3, PDE5 and PDE10. However, the limited data available do not allow to draw firm conclusions on the value of PDE-Is as cognitive enhancers in schizophrenia yet. The field is still in its infancy, but nevertheless different PDE-Is seem promising as candidate to optimise neural communication in the prefrontal cortex favouring cognitive functioning in patients diagnosed with schizophrenia, in particular dual inhibitors including PDE1-Is, PDE3-Is and PDE10A-Is.

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KW - CEREBRAL-BLOOD-FLOW

KW - OF-CONCEPT TRIAL

KW - LATE-PHASE LTP

KW - DOUBLE-BLIND

KW - ALZHEIMERS-DISEASE

KW - MESSENGER-RNA

KW - NITRIC-OXIDE

KW - IN-VIVO

KW - NEUROCOGNITIVE DEFICITS

U2 - 10.2174/1381612821666150605110941

DO - 10.2174/1381612821666150605110941

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JO - Current Pharmaceutical Design

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SN - 1381-6128

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