3′(2′)-Phosphoadenosine 5′-phosphate phosphatase is reduced in postmortem frontal cortex of bipolar patients

Objective: 3′(2′)-Phosphoadenosine 5′-phosphate (PAP) phosphatase is a novel lithium (Li) inhibitable enzyme. Thus the enzyme seemed an important candidate for studies of the molecular etiology of bipolar disorder. Methods: RT-PCR, Western-blot analysis and Pi liberation were used to measure PAP phosphatase mRNA levels, protein levels and enzyme activity (respectively) in postmortem frontal cortex specimens of bipolar patients versus normal subjects. Results: The PAP phosphatase protein levels were 24% significantly lower in bipolar patients than in normal subjects. PAP phosphatase mRNA levels and enzymatic activity did not differ between normal controls and bipolar patients. Conclusions: Abnormality of PAP phosphatase in bipolar patients offers a new direction for study of bipolar disorder etiology.