Academic journal article Alcoholism and Psychiatry Research

Cytochrome p4502D6 and Serotonin Transporter Polymorphism in Patient with Bipolar Disorder Type II

Academic journal article Alcoholism and Psychiatry Research

Cytochrome p4502D6 and Serotonin Transporter Polymorphism in Patient with Bipolar Disorder Type II

Article excerpt

Introduction

Bipolar disorder (BD) is a complex psychiatric entity, which represents a diagnostic as well as a therapeutic challenge in clinical practice. The very definition and classification of BD is determined by a range of possible clinical presentations, which are sometimes difficult to distinguish from other psychiatric entities by means of a differential diagnosis, for example acute schizophrenic episode, schizoaffective disorder or psychotic depression. Furthermore, BD is frequently comorbid with other psychiatric disorders, especially substance abuse disorders, but also personality disorders or eating disorders, [1-4] which complicate the diagnosis and treatment further.

BD can manifest itself for years with recurring depressive episodes before the first manic, hypomanic or mixed episode occurs. The depressive episode of the BD thus frequently remains unrecognised and misdiagnosed as a major depressive disorder (MDD), and therefore inadequately treated with antidepressant monotherapy. According to the current psychiatric classification DSM-V, BD is not diagnosed before an occurrence of a manic or hypomanic episode, while ICD-10 describes, besides a manic and hypomanic episode, a mixed episode in BD as well. [5,6] However, a clinician can consider bipolar depression based on clinical characteristic of depressive episodes. Disease onset before the age of 20, recurrent depressive episodes, which cause the person to be ill most of the time, failure to respond to antidepressants, severe psychomotor retardation, hypersomnia, increased appetite, presence of psychotic symptoms or suicidal ideations are frequently present in patients with bipolar depression. [7,8]

Data on prevalence of mood disorders is significantly changing in the last decade. According to past epidemiological data, BD I is responsible for about 2% of prevalence among mood disorders, in the same percentage as BD II. MDD has been diagnosed in 86% of all patients with mood disorders, and non-specific mood disorder in 10% of the patients. Today, we believe that MDD represents 50 % of all mood disorders, BD I about 2%, BD II 15%, while 33% of mood disorders belong to a heterogeneous group of disorders from the bipolar spectrum. [9] Accordingly, it is necessary to adjust the pharmaco-therapeutic approach and introduce mood stabilizers to the treatment if BD or a disorder from the bipolar spectrum is suspected. Special attention should be paid to symptoms of the depressive episode, and all medical history data on patients with depression should be carefully analyzed for evidence of possible episodes of elevated mood in the past.

Clinical research has shown that the individual therapeutic response to psychotropic drugs considerably varies, from tendency to develop side effects to therapeutic resistance. In the treatment of a depressive episode, about one third of the patients show no therapeutic response after an adequate therapeutic trial. [8] It is a well known fact the therapeutic response can be affected by different factors, such as the age of the patient, liver or kidney dysfunction, diet, smoking or excessive alcohol use. Recent research shows the lack of response to antidepressant treatment is associated with bipolar disorder, [10] and the association of other psychopathological phenomena with the lack of therapeutic response is also being investigated. However, it is believed that the genetic basis is of key importance for the variability of response to antidepressants. [11,12] Pharmacogenetics studies the influence of specific gene polymorphisms, which are responsible for the function of enzymes important in pharmacokinetics and pharmacodynamics.

Biotransformation of most psychotropic drugs in the liver occurs via cytochrome P450 (CYP P450) superfamily, which consists of more than 50 different enzymes. CYP2D6 has an important role in biotransformation of a large number of antidepressants. [13,14] The gene that encodes the CYP2D6 is located at the locus 22q13. …

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