Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide

• Published in: Molecular psychiatry Vol. 13; no. 11; pp. 1001 - 1010
• Main Authors: Dracheva, S, Patel, N, Woo, D A, Marcus, S M, Siever, L J, Haroutunian, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2008; Nature Publishing Group
• Subjects: Adenosine; Adult; Adult and adolescent clinical studies; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Bipolar disorder; Bipolar Disorder - genetics; Bipolar Disorder - pathology; Bipolar Disorder - psychology; Bipolar disorders; Comorbidity; Diagnosis; Drug abuse; Editing; Enzymes; Female; Gene Expression; Genetic aspects; Health aspects; Humans; Isoforms; Male; Medical sciences; Medicine; Medicine & Public Health; Mental depression; Mental disorders; Middle Aged; Models, Molecular; Mood disorders; mRNA; Neurosciences; original-article; Pharmacotherapy; Prefrontal cortex; Prefrontal Cortex - metabolism; Psychiatry; Psychological aspects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Public health; Receptor, Serotonin, 5-HT2C - genetics; Receptor, Serotonin, 5-HT2C - metabolism; Receptors; Risk Factors; RNA editing; RNA Editing - genetics; RNA splicing; RNA, Messenger - metabolism; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Schizophrenic Psychology; Serine - genetics; Serotonin; Serotonin S2 receptors; Suicidal behavior; Suicide; Suicide - psychology; Suicides & suicide attempts; Valine - genetics; United States; United States > US; bipolar disorder; RNA editing; ADAR; schizophrenia; prefrontal cortex; suicide; Psychosis; Mood disorder; Central nervous system; Risk factor; Schizophrenia; Bipolar disorder; Prefrontal cortex; Serotonine receptor; Suicide; Encephalon
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4002081

Suicide is a major public health problem with ∼1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2C R mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants ( ACD and ABCD ) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156–Ser158–Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior.