Abstract Some physical illnesses are potentially associated with the development of schizophrenia. However, few studies have investigated these associations. Here, we examined physical illnesses and medical utilization patterns existing before patients received a diagnosis of schizophrenia. We enrolled a large representative cohort of the general population in Taiwan (N = 1 000 000) and identified 1969 young patients with a new diagnosis of schizophrenia from January 1, 2000 to December 31, 2013. We conducted a nested case-control study based on risk-set sampling. Each case was age-matched and sex-matched with 4 controls selected from the general population. The case and control groups were compared on the basis of various clinical characteristics. Conditional logistic regression was used to estimate the magnitude of risk associated with newly diagnosed schizophrenia. Within the 1 year before the schizophrenia diagnosis, the cases were most likely to visit the psychiatry department, followed by internal medicine and family medicine departments. According to multivariate analysis, compared with the controls, the cases had substantially higher risk of physical conditions in the prodromal phase, including hypertension (adjusted risk ratio [aRR] = 1.93, P = .001), other forms of heart disease (aRR = 2.07, P < .001), cerebrovascular diseases (aRR = 2.96, P = .001), chronic obstructive pulmonary disease (aRR = 1.50, P = .005), asthma (aRR = 1.76, P = .003), and irritable bowel syndrome (aRR = 2.00, P < .001). A wide range of psychiatric diseases and concomitant use of medications were significantly associated with schizophrenia development. In conclusion, several physical illnesses were identified to be associated with schizophrenia development, indicating that people with these illnesses could be vulnerable to schizophrenia.

Octaprenyl diphosphate synthase (OPPS) catalyzes consecutive condensation reactions of farnesyl diphosphate (FPP) with five molecules of isopentenyl diphosphates (IPP) to generate C(40) octaprenyl diphosphate, which constitutes the side chain of ubiquinone or menaquinone. To understand the roles of active site amino acids in substrate binding and catalysis, we conducted site-directed mutagenesis studies with Escherichia coli OPPS. In conclusion, D85 is the most important residue in the first DDXXD motif for both FPP and IPP binding through an H-bond network involving R93 and R94, respectively, whereas R94, K45, R48, and H77 are responsible for IPP binding by providing H-bonds and ionic interactions. K170 and T171 may stabilize the farnesyl carbocation intermediate to facilitate the reaction, whereas R93 and K225 may stabilize the catalytic base (MgPP(i)) for H(R) proton abstraction after IPP condensation. K225 and K235 in a flexible loop may interact with FPP when the enzyme becomes a closed conformation, which is therefore crucial for catalysis. Q208 is near the hydrophobic part of IPP and is important for IPP binding and catalysis.

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