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Alcohol use disorders (AUDs) that consist of the abuse or dependence on alcohol are common among patients with schizophrenia [1]. One possible reason is using alcohol for relaxation and pleasure [2]. Schizophrenic patients with AUDs experience a wide range of negative impacts on the course of their illness and outcomes [3]. There are several reasons to identify the factors for AUDs. First, factors may be used by clinicians to improve detection of at-risk patients. Second, patients' characteristics related to AUDs may be related to the underlying mechanisms of AUDs in schizophrenia. Third, identifying these factors may lead to interventions better designed to prevent the development of AUDs in vulnerable subjects.

In Western countries, approximately 40% of patients with schizophrenia also have AUDs. In contrast, the rate of AUDs among Han Chinese populations has been much lower [4]. One explanation may be an inactive aldehyde dehydrogenase gene mutation occurs in about 40% of Han Chinese people, resulting in much higher levels of acetaldehyde after drinking. Such high levels of acetaldehyde are regarded as a biological protective factor. Research has suggested that AUDs are more likely to be detected among men than among woman [5] because of their lifestyles and their increased likelihood of engaging in antisocial behavior that would attract attention. From a biological aspect, higher dopamine receptor density in women may play a role in their decreased vulnerability to AUDs. Discharge against medical advice represents both a premature termination of treatment and a poor relationship between the patients and clinicians. One of the possible reasons patients with co-occurring AUDs have higher rates of discharge against medical advice is that a percentage of patients may still crave alcohol use after admission. Additionally, patients with co-occurring AUDs may resume alcohol use soon after discharge. Alcohol also increases the sedative effect of antipsychotics, and some patients deal with this by ceasing medication and avoiding their first appointments.

We monitored variables with possible association with AUDs and the time to rehospitalization for persons with a schizophrenia diagnosis with co-occurring AUDs compared with those without AUDs. Data are collected under naturalistic conditions at Kai-Syuan Psychiatric Hospital in Taiwan. Patients, with a diagnosis of DSM-IV schizophrenia, discharged from a psychiatric hospital between January 1, 2006, and December 31, 2006, were monitored. Variables related to schizophrenic patients with co-occurring AUDs were registered: gender, marital status, educational level, involuntary hospitalization, discharge against medical advice, missed first appointment after discharge, illicit substance abuse/dependence, age, age at onset of schizophrenia, the mean volume of the red blood cell (mean corpuscular volume; MCV) at admission, diazepam equivalents prescribed at discharge (mg/d), the number of previous hospitalizations within the past 5 years, lengths of hospital stays and low education (≤9 years school). Time to rehospitalization was regarded as a follow-up outcome measure of patients with co-occurring AUDs after discharge.

Of the 802 in-patients with schizophrenia discharged during the study period, seven hundred and fifty-six (94%) were included. Four hundred and thirty-six (58%) were men. The mean age was 37 ± 10 years old. One hundred and fifty-three of the subjects (20%) with co-occurring AUDs and 603 without were enrolled. In a forward stepwise logistic regression model, male gender (odds ratio = 3.75, 95% CI: 2.24–6.27, P < 0.001), lower educational levels (OR = 2.05, 95% CI: 1.35–3.01, P = 0.001), co-occurring illicit substance use disorders (OR = 8.27, 95% CI = 5.06–13.52, P < 0.001), and MCV at admission (OR = 1.04, 95% CI = 1.004–1.07, P = 0.026) were the most influential factors associated with schizophrenic patients with co-occurring AUDs. Using Kaplan–Meier survival analysis to determine time to rehospitalization between the two patient groups within 365 days after discharge, 95 (62%) of the patients with co-occurring AUDs and 311 (52%) of the patients without AUDs were rehospitalized (P = 0.02). Patients with co-occurring AUDs (mean time ± SD = 184 ± 12 days) had significantly shorter times to rehospitalization than those without AUDs (mean time ± SD = 223 ± 6 days) (P = 0.004) (Fig. 1).

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Figure 1. Compared time to rehospitalization within 365 days after discharge for schizophrenic patients with co-occurring alcohol use disorders (AUDs) and those without (log rank = 8.22, df = 1, P = 0.004).

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Alcohol use was strongly associated with polysubstance use. Sixty-five (43%) of the patients who used alcohol also used various illicit substances. Both alcohol and illicit substances stimulate dysfunctional reward circuitry and transiently improving reward circuitry dysfunctioning. Patients with polysubstance use may have a more severe dysfunction of reward circuitry. Therefore, they may have a more desire to use alcohol and other substances to achieve some feelings of normalcy [6]. The normal range of MCV is between 80 fL and 95 fL, and even a modest increase in the size of red blood cells, with a subsequent mean MCV higher than 90 fL, has long been recognized as a biomarker for AUDs [7]. Elevated MCV may also reflect physical illnesses after long-term alcohol use, such as liver problems, vitamin B12 deficiency, folate deficiency or hemopoietic problems. Patients with co-occurring AUDs often have symptoms of anxiety and sleep disturbance, resulting in larger benzodiazepine prescriptions [8]. Prescribing should be closely monitored and supervised to avoid risk of benzodiazepine abuse or dependence. If a patient with AUDs resumes alcohol use soon after discharge, alcohol intoxication may impair patient's judgment, decrease motivation to search for life goals, and cause the patient to disregard adherence to medications and ignore appointment attendance. The consequences are worsening symptom severity and a revolving door situation with a short of time to rehospitalization. Co-occurring AUDs in schizophrenia is an indicator of poor prognosis, and limitations should be taken to identify and to treat the co-occurring AUDs to break a vicious cycle whenever possible.

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