Aim
The aim of this study is to examine whether there is an association between cumulative life adversities and treatment-resistant schizophrenia.
Methods
We recruited 186 participants diagnosed with schizophrenia spectrum disorders. Adverse life-events were assessed using the Stressful Life Events Screening Questionnaire (SLESQ) and the Childhood Trauma Questionnaire (CTQ). Treatment resistant status was identified using the criteria of the American Psychiatric Association for refractory schizophrenia. We performed a multiple logistic regression model, including life adversities, to predict the treatment resistant status controlling for confounding variables.
Results
Forty two percent of the patients were found to be treatment resistant (n = 78) and 58% were non-treatment resistant (n = 108). The treatment resistant group had higher score on both SLESQ and CTQ (4.5 ± 3.3 and 54.7 ± 19.7) than the non-treatment resistant group (2.5 ± 2.3 and 47.7 ± 17.5) and the difference between the two groups was significant for both SLESQ (p < 0.001) and CTQ (p = 0.011). After adjustment for demographic variables and previously reported risk factors of treatment resistance, the association remained significant for SLESQ (OR = 1.20, 95% CI 1.05–1.38; p = 0.009) but not for CTQ (p = 0.13).
Discussion
The results suggest that cumulative lifetime adversities could have an independent effect on the resistance to treatment in schizophrenia spectrum disorders. Routine assessment of trauma exposures and an individualized bio-psycho-social formulation is necessary for a personalized treatment.
Antipsychotic treatment has the ability to ameliorate schizophrenia symptoms. However, approximately 20 to 30% of schizophrenia patients fail to respond to pharmacotherapy despite their adherence (Kane et al., 1988).
The prevalence of treatment resistant schizophrenia has ranged in several studies from 5% up to 60% (Elkis, 2007 and Dammak, 2013). This wide range was due to the different criteria used to define treatment resistance. Treatment resistant patients have more severe symptoms, greater disabilities, higher suicidal risk and lower quality of life than non-treatment resistant patients (Kane et al., 1988 and Mamo, 2007). In addition, the burden of treatment resistant patients is between 60 to 80% of the total cost of schizophrenia (Kennedy et al., 2014).
Several demographic and clinical factors have been identified for their ability to predict poor response to treatment in schizophrenia such as early age of onset at psychosis which has been consistent across different studies (Hollis, 2000 and Reichert et al., 2008) and duration of untreated psychosis (Owens et al., 2010).
Other risk factors for treatment resistance includes family history of psychosis, family environment of highly expressed emotions (Butzlaff and Hooley, 1998, Murray and Van Os, 1998 and Malaspina et al., 2000), substance abuse history (Gupta et al., 1996), and male gender (Murray and Van Os, 1998). In addition, negative symptoms, such as flat affect were able to predict poor response to treatment (Cuesta et al., 1994).
Despite the previous search for prognostic factors, to date, the effect of the cumulative lifetime adversities on ongoing treatment has not been investigated.
Cumulative lifetime adversity is the exposure to potential traumatic events that threaten the life or the physical or the mental integrity of the subject or of those around him (Shrira et al., 2011).
Cumulative childhood adversities increased the risk of onset of several psychiatric disorders and their continuity increases the risk of relapse (Turner and Lloyd, 1995). Trauma and specifically childhood trauma has a close tight with psychosis onset. A meta-analysis of 41 studies revealed that all types of childhood adversities increased the risk of psychosis (Varese et al., 2012). Furthermore, childhood abuse predicted psychotic symptoms in a dose–response relationship which remained significant after controlling for family history of psychosis (Janssen et al., 2004).
Childhood trauma has been also found to be a risk factor for symptoms that are commonly found in treatment resistant schizophrenia such as persistent positive symptoms, suicidal behavior and substance abuse (Scheller-Gilkey et al., 2002, Roy, 2005 and Üçok and Bıkmaz, 2007).
Overall, the relationship between lifetime adversities and treatment resistant in schizophrenia is not clear. In this study we aimed to compare the prevalence of adverse lifetime events in treatment resistant and non-treatment resistant schizophrenia.
