The aim of this study is to explore relation between the comorbidity of different bipolar disorders with alcoholism and neuropsychiatric function and candidate genes. The investigators plan to establish genetic validity for this subtype of alcoholism. In addition, by comparing this subtyped alcoholism to normal control, the investigators plan to examine the genetic validity of such comorbidity. The investigators plan to find specific clinical characteristic from neuropsychiatric aspects of such subtype for future early diagnosis, prediction and prevention.

From family, twin and adoption studies supported a strong hereditary component in unsubtyped alcohol dependency (Cloninger et al., 1981; Reich et al., 1999; Huang et al., 2004). Dopamine, serotonin related genes and ADH, ALDH genes have been considered as candidate genes for alcohol dependency (Goldman, 1995; Reich et al., 1999; Noble et al., 2000). However, both in simple or family-base association studies have generated controversy about the relationship between candidate genes and alcoholism (Edenberg et al., 1998; Reich et al., 1999; Noble et al., 2000). One of the possible explanations may be due to that those studies did not subtype alcohol dependency, even though alcoholism is a complex phenotype with a heterogeneous etiology (Huang et al., 2004; Lu et al., 2005a).

Our previous research results had already categorized AD among Han Chinese in Taiwan into four subtypes, pure alcoholism (Pure ALC), anxiety-depression alcoholism (ANX/DEP ALC), antisocial alcoholism (Antisocial ALC) and mixed type alcoholism (Mixed ALC) （Huang et al., 2004; Lu et al., 2005; Wang et al., 2007）. Except for Mixed ALC, we have established fundamental genetic validity, and confirmed several candidate genes including MAOA、ADH、ALDH、DRD2.

Mixed ALC is categorized by alcoholism comorbid with other psychiatric disorders including schizophrenia and bipolar disorder. Among them all, bipolar disorders most frequently comorbid with alcohol and substance dependence. The high comorbidity between alcohol dependence among patients with bipolar disorder worsens the treatment effect and prognosis. Bipolar disorders are divided into several categories, including bipolar I disorder (BP-I), bipolar II disorder (BP-II), and cyclothymic disorder. Previous literatures have documented that BP-I and BP-II might have different etiology, phenomenology, characteristics and neuropsychiatric functional impairments in the course of the illness (APA, 1994).

The aim of this study is to explore relation between the comorbidity of different bipolar disorders with alcoholism and neuropsychiatric function and candidate genes. We plan to establish genetic validity for this subtype of alcoholism. In addition, by comparing this subtyped alcoholism to normal control, we plan to examine the genetic validity of such comorbidity. We plan to find specific clinical characteristic from neuropsychiatric aspects of such subtype for future early diagnosis, prediction and prevention.

Inclusion Criteria:

1. Signed informed consent by patient or legal representative.
2. Male or female patient aged ≧18 and ≦65 years.
3. A diagnosis of Bipolar I or Bipolar II Disorder according to DSM-IV criteria made by a specialist in psychiatry.
4. Patients who were diagnosed with alcohol dependence or abuse according to DSM-IV criteria made by a specialist in psychiatry.

Exclusion Criteria:

1. Patients, except those are Bipolar disorder with alcoholsim who were diagnosed substance abuse/depence
2. Patients with brain injury or regrated neurological diseases
3. Patients who are with I axis major mental illess according to DSM-IV criteria

Bipolar disorders