## 4 Discussion  
Our observations from the present study indicate that patients with D-SCZ, as opposed to those with ND-SCZ, show elevated levels of CRP, even after adjustment for lifestyle characteristics. Importantly, no significant differences between subgroups of patients and healthy controls were found with respect to lipid profile (the levels of HDL and triglycerides) or glucose metabolism alterations (HOMA-IR) after controlling for BMI, lifestyle characteristics and dosage of antipsychotics. These observations suggest that metabolic disturbances in patients with D-SCZ can be attributed to environmental exposures and lifestyle. Moreover, higher CRP levels were correlated with worse attention and higher levels of negative symptoms in patients with schizophrenia. In healthy controls, higher concentrations of CRP were correlated with lower scores of immediate memory and global cognition. There were no significant differences between subgroups of participants in terms of lipid profile or HOMA-IR after adjustment for lifestyle characteristics. Figure 1: Partial regression plots showing correlation of CRP levels in the whole sample of patients with schizophrenia (**A**,**B**) and healthy controls (**C**,**D**). It was observed that subclinical inflammation is associated with greater cardiovascular risk in people with schizophrenia [40]. Importantly, studies investigating immuninflammatory markers have consistently shown subclinical inflammation in subjects with D-SCZ. For instance, [PERSON] et al. [16] found elevated levels of interleukin (IL)-6 and tumor necrosis factor-\(\alpha\) (TNF-\(\alpha\)) in patients with D-SCZ compared with those with ND-SCZ and healthy controls. Another study demonstrated the association between elevated CRP levels in patients with D-SCZ and lower levels of global cognition [17]. Similarly, [PERSON] et al. [41] found increased concentrations of IL-4, IL-6 and TNF-\(\alpha\) in patients with D-SCZ compared with those with ND-SCZ and healthy controls. Recent systematic reviews and meta-analyses also show that subclinical inflammation might be associated with cognitive impairment in schizophrenia [42; 43]. [PERSON] et al. [42] found that increased CRP levels correlated with impairments, albeit with small effect size estimates, across all cognitive domains except for fluency. Importantly, the RBANS attention score is calculated from the subscores of two tasks: digit span and digit coding. Each task might not only measure attention, but also working memory and processing speed. Similarly, a more recent study by [PERSON] et al. [44], which also used the RBANS to measure cognition, revealed that higher concentrations of CRP were associated with lower attention scores and greater volume reductions in brain regions related to attention. Our findings are similar to those obtained by [PERSON] et al., who found a significantly higher prevalence of obesity and a greater 10-year risk of coronary heart disease in patients with schizophrenia (n = 1452) [14]. Notably, the authors did not observe significant differences in the distribution of dyslipidemia, hyperglycemia or hypertension between patients with D-SCZ and those with ND-SCZ. Although the authors recorded several characteristics of dietary habits, they did not control for their effects in the data analyses. Another study performed on a smaller sample of individuals with schizophrenia (n = 99) did not reveal any significant differences in cardiometabolic risk indicators between patients with D-SCZ and ND-SCZ [15]. However, neither study used the SDS, which is the gold standard instrument to diagnose D-SCZ. Moreover, the authors did not include healthy controls or adjust the findings for the effects of lifestyle characteristics. In both studies, the proxy measure of D-SCZ, based on the PANSS, was used. Although proxy measures of D-SCZ have good sensitivity and specificity, there are some concerns regarding face validity [30]. Moreover, the poor temporal stability of proxy measures was reported at a 1-year follow-up [45].