اختلالات همزمان مصرف مواد در اسکیزوفرنی: یک رویکرد کلاس پنهان

Schizophrenia is a complex psychiatric disorder with a characteristic disease course and heterogeneous etiology. While substance use disorders and a family history of psychosis have individually been identified as risk factors for schizophrenia, it is less well understood if and how these factors are related. To address this deficiency, we examined the relationship between substance use disorders and family history of psychosis in a sample of 1219 unrelated patients with schizophrenia. The lifetime rate of substance use disorders in this sample was 50%, and 30% had a family history of psychosis. Latent class mixture modeling identified three distinct patient subgroups: (1) individuals with low probability of substance use disorders; (2) patients with drug and alcohol abuse, but no symptoms of dependence; and (3) patients with substance dependence. Substance use was related to being male, to a more severe disease course, and more acute symptoms at assessment, but not to an earlier age of onset of schizophrenia or a specific pattern of positive and negative symptoms. Furthermore, substance use in schizophrenia was not related to a family history of psychosis. The results suggest that substance use in schizophrenia is an independent risk factor for disease severity and onset.

Schizophrenia is a severe, complex psychiatric disorder characterized by lack of feeling or emotion, lack of initiative, and alterations in thoughts, perceptions, and behavior. Delusions and hallucinations, as well as misinterpretation of reality, are present in many patients as well (American Psychiatric Association, 2013). The prevalence of schizophrenia is about 0.5% worldwide (Saha et al., 2005) and the age of onset ranges from adolescence to adulthood, but the cause of the disorder remains unknown (National Institute of Mental Health, 2014). About a third of patients have a family history of psychosis, and twin studies have supported the hypothesis that inherited genetic risk factors could lead to the manifestation of the disorder (Owen et al., 2010 and Sullivan et al., 2003). However, the search for causal genetic mutations has been challenging (Claes et al., 2012). In addition, de novo genetic mutations (Xu et al., 2011), prenatal adverse events (Brown, 2011, Brown and Patterson, 2011 and Rothman and Greenland, 1998), and severe use of alcohol and illegal substances have been discussed as other risk factors (Barondes, 1999, Connell, 1958, Griffiths et al., 1972, Horowitz, 1969, Malone et al., 2010, McLaren et al., 2010, Minozzi et al., 2010, Moore et al., 2007, Roncero et al., 2014 and Vollenweider et al., 1998). Substance use disorders are defined as conditions in which either abuse of or dependence on substances, such as alcohol, cocaine, opioids, phencyclidine, amphetamine, cannabis or nicotine, among others, has had negative effects on the patient׳s family and social life, work, or school, or has resulted in financial problems. According to DSM-IV criteria, substance use disorders have been differentiated into disorders of abuse or dependence (American Psychiatric Association, 2000). In substance abuse, the consumption of substances has led to impairment or distress, but criteria of dependence have not been met. Substance dependence is characterized by tolerance and symptoms of withdrawal. It is often implied that abuse is a less severe form of substance use disorder compared to dependence, and this is reflected in the new DSM-V classifications (American Psychiatric Publishing, 2014). Genetic risk factors appear to contribute to the manifestation of substance use disorders. In several studies, a family history of substance use was an important predictor of disease onset and disease severity in substance abusers without comorbid psychiatric diagnoses (Bierut et al., 1998, Boyd et al., 1999, Coviello et al., 2004, Kendler et al., 2008 and Merikangas et al., 1998). The relationship between substance use disorders and schizophrenia has been extensively explored in multiple population-based studies (Kendler et al., 1996, Kessler et al., 1994 and Regier et al., 1990). So far, convincing evidence has been found for a causal, dose-dependent relationship between substance use disorders and the onset of schizophrenia, if the onset of substance use disorders preceded the onset of schizophrenia (Andreasson et al., 1987, Miller et al., 2001, Tien and Anthony, 1990, van Os et al., 2002 and Zammit et al., 2002). On the other hand, significant predictors of comorbid substance use disorders in patients with schizophrenia were male gender, low educational attainment, previous violent offending, and a family history of substance use disorders (Cantor-Graae et al., 2001, Dixon et al., 1991 and Westermeyer, 2006). Patients with schizophrenia and comorbid substance use disorders were less likely to adhere to treatment and more likely to have adverse disease outcomes (McLean et al., 2012 and Murthy and Chand, 2012). But even during the first episode of schizophrenia, substance users had more severe psychotic symptoms and an earlier age of onset compared to non-users (Mauri et al., 2006, Picci et al., 2013 and Schimmelmann et al., 2012). In patients with a dual diagnosis, high rates of substance use disorders were found in first and second-degree relatives of the patients, suggesting that genetic risk factors for substance use disorders and an adverse family environment could have contributed to the onset and severity of substance use disorders in patients with a dual diagnosis (Comtois et al., 2005 and Wilson et al., 2013). Even though the risk for comorbid substance use disorders in patients with schizophrenia is well recognized, not enough effort has been made to study the relationship between family history of psychosis and substance use disorders in patients with schizophrenia. Hence, we have focused on the relationship between familiarity of schizophrenia and substance use disorders in a large sample of patients ascertained for genetic studies.

The ethnicity of the sample was Caucasian, and the majority of individuals (70%) were male (Table 1). The mean age of the sample was 42.68 years (S.D.=9.46), and the average age of onset of schizophrenia was 21.21 years (S.D=7.58), indicating that most individuals in this data set had been ill for at least 20 years. Only one third of all cases with schizophrenia (31%) reported a family history of psychosis. Substance use disorders were prevalent in the sample (54%). The most commonly used substances were alcohol (43%), followed by cannabis (35%), and other illegal substances (27%). Substance use disorders preceded the onset of schizophrenia in about two-third of cases with substance use, and in about one-third of cases substance use disorders had been diagnosed after the onset of schizophrenia. Cannabis use was strongly correlated with other substance use disorders (r(1217)=0.64, p<0.01), particularly with alcohol dependence (r(1217)=0.53, p<0.01), substance dependence (r(1217)=0.41, p<0.01), and alcohol abuse (r(1217)=0.39, p<0.01) ( Table 2). Dependence on illegal substances other than cannabis was also strongly correlated with alcohol dependence (r(1217)=0.58, p<0.01). In addition, some individuals (21%) had been diagnosed with major depressive disorder (according to DSM-IV) (DEP), but DEP was negatively correlated with cannabis use (r(1217)=−0.09, p<0.01), substance dependence (r(1217)=−0.15, p<0.01), and substance abuse (r(1217)=−0.21, p<0.01).