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.
authors.forename: Marlies Van
authors.initials: MV
authors.lastname: Duinen
authors.forename: Olga A H
authors.initials: OA
authors.lastname: Reneerkens
authors.forename: Lena
authors.initials: L
authors.lastname: Lambrecht
authors.forename: Anke
authors.initials: A
authors.lastname: Sambeth
authors.forename: Bart P F
authors.initials: BP
authors.lastname: Rutten
authors.forename: Jim Van
authors.initials: JV
authors.lastname: Os
authors.forename: Arjan
authors.initials: A
authors.lastname: Blokland
authors.affiliation: Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6200 MD Maastricht, The Netherlands. jos.prickaerts@maastrichtuniversity.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy*; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents; D010726:Phosphodiesterase Inhibitors