Clinical evaluation of functional capacity in treatment resistant schizophrenia patients: Comparison and differences with non-resistant schizophrenia patients Felice Iasevoli a , Luigi D'Ambrosio a , Danilo Notar Francesco a , Eugenio Razzino a , Elisabetta Filomena Buonaguro a , Sara Giordano a , Thomas L. Patterson b , Andrea de Bartolomeis a, ⁎ a Section of Psychiatry - Unit on Treatment Resistant Psychosis, Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, University School of Medicine Federico II, Naples, Italy b Department of Psychiatry, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA abstract article info Article history: Received 24 October 2017 Received in revised form 5 April 2018 Accepted 11 June 2018 Available online xxxx Treatment resistant schizophrenia (TRS) is defined by poor or non-response to conventional antipsychotic agents. Functional capacity is defined as the baseline potential of a patient to function in the community, irrespec- tive of actual achievements gained, and has never been studied in TRS. Here, we screened 182 patients with psy- chotic symptoms and separated them in TRS (n = 28) and non-TRS (n = 32) ones, to evaluate whether they exhibited differential extents and predictive clinical variables of functional capacity. Functional capacity was measured by the UCSD Performance-Based Skills Assessment (UPSA). Psychotic symptoms by PANSS, social func- tioning by PSP and SLOF, clinical severity of the illness, cognitive functioning, and neurological soft signs (NSS) were assessed. TRS patients had non-significant lower UPSA scores compared to non-TRS (t-test: p N 0.05). In TRS, UPSA score correlated with multiple clinical variables. The highest effect sizes were observed for PANSS neg- ative score (r = -0.67, p b 0.005); SLOF Area1 score (r = 0.66, p b 0.005); NSS severity (r = -0.61, p b 0.005). Multivariate analysis showed that main predictors of UPSA score in TRS patients were PANSS negative score, ed- ucation years, NSS, Problem Solving performances, and PSP score (F = 11.12, R 2 = 0.75, p b 0.0005). These var- iables were not predictive of UPSA score in non-TRS patients. Hierarchical analysis found that variance in UPSA score mainly depended on negative symptoms, NSS, and problem solving (F = 15.21, R 2 = 0.65, p b 0.0005). Path analysis individuated two separate paths to UPSA score. These results delineate a limited and independent group of candidate predictors to be putatively accounted for therapeutic interventions to improve functional ca- pacity, and possibly social functioning, in TRS patients. © 2018 Elsevier B.V. All rights reserved. Keywords: Non-responder Psychosis Refractory Negative symptoms Antipsychotics 1. Background and aims According to recently proposed operational criteria (Howes et al., 2017), treatment resistant schizophrenia (TRS) is diagnosed in schizophrenia patients that failed to show adequate response to at least two prior different antipsychotic trials (each for a minimum dura- tion and dosage), that are currently symptomatic and suffer from moderate-to-severe functional impairment. Also, in our recent reports, we introduced operational criteria to rule out pseudo-resistance, i.e. the lack of antipsychotic response due to modifiable/not modifiable factors beyond the inherent pharmacological action (Iasevoli et al., 2017; Iasevoli et al., 2016). Schizophrenia patients show neurocognitive impairments and disability in community functioning, with poor insight of impaired neurocognitive functioning and increasing severity with aging (Burton et al., 2016; Muralidharan et al., 2017). Indeed, TRS patients appear to have more disturbed cognitive performances (de Bartolomeis et al., 2013; Frydecka et al., 2016; Iasevoli et al., 2013), more severe neurolog- ical soft signs (de Bartolomeis et al., 2018), and more relevant gluta- matergic dysfunctions compared to non-TRS ones (Demjaha et al., 2014; Mouchlianitis et al., 2016). In a previous work, we found that the impairment in functional milestones of everyday living was signifi- cantly more severe in TRS patients compared to schizophrenia re- sponders (Iasevoli et al., 2016). Functional milestones of everyday living are direct measures of patient's lifetime achievements in the com- munity, but they may be strongly biased by a number of concurrent en- vironmental or social conditions that may be only limitedly related to the patient's psychotic disorder (Moore et al., 2007). In recent years, it has become even more relevant to assess the baseline potential of a Schizophrenia Research xxx (2018) xxx–xxx ⁎ Corresponding author at: Department of Neuroscience, University School of Medicine of Napoli Federico II, Via Pansini 5 Edificio n.18 3rd floor, 80131 Napoli, Italia. E-mail address: adebarto@unina.it (A. de Bartolomeis). SCHRES-07909; No of Pages 9 https://doi.org/10.1016/j.schres.2018.06.030 0920-9964/© 2018 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Schizophrenia Research journal homepage: www.elsevier.com/locate/schres Please cite this article as: Iasevoli, F., et al., Clinical evaluation of functional capacity in treatment resistant schizophrenia patients: Comparison and differences with non-resi..., Schizophr. Res. (2018), https://doi.org/10.1016/j.schres.2018.06.030