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.