Investigation into the Possible Genetic Role of Serotonin and Dopamine Transporters in Psychological Resilience

OBJECTIVES: Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. METHODS: A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene (SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene (DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. RESULTS: No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. CONCLUSIONS: Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.

Association between the 5-HTTLPR Genotype and Childhood Characteristics in Mood Disorders

OBJECTIVE: The features of childhood attention deficit hyperactivity disorder (ADHD) are significantly associated with adult mood disorders. Some genetic factors may be common to both ADHD and mood disorders underlie the association between these two phenotypes. The present study aimed to determine whether a genetic role may be played by the serotonin transporter-linked polymorphic region (5-HTTLPR) in the childhood ADHD features of adult patients with mood disorders. METHODS: The present study included 232 patients with major depressive disorder (MDD), 154 patients with bipolar disorder (BPD), and 1,288 normal controls. Childhood ADHD features were assessed with the Korean version of the Wender Utah Rating Scale (WURS-K). The total score and the scores of three factors (impulsivity, inattention, and mood instability) from the WURS-K were analyzed to determine whether they were associated with the 5-HTTLPR genotype. RESULTS: In the BPD type II group, the 5-HTTLPR genotype was significantly associated with the total score (p=0.029) and the impulsivity factor (p=0.004) on the WURS-K. However, the inattention and mood instability factors were not associated with the 5-HTTLPR genotype. BPD type I, MDD and normal control groups did not exhibit any significant associations between the WURS-K scores and the 5-HTTLPR genotype. CONCLUSION: The findings suggest that the 5-HTTLPR genotype may play a role in the impulsivity component of childhood ADHD in patients with BPD type II. Because of a small sample size and a single candidate gene, further studies investigating other candidate genes using a larger sample are warranted to determine any common genetic links.

Genetic Role of BDNF Val66Met and 5-HTTLPR Polymorphisms on Depressive Disorder

OBJECTIVE: We investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression. METHODS: Final analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed. RESULTS: The 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing. CONCLUSION: This result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.

Pediatric Narcolepsy: Diagnosis and Treatment / 대한소아신경학회지

Narcolepsy is chronic devastating disease that characterized by excessive daytime sleepiness, cataplexy, which often precipitated by intense emotion or excitement, hypnagogic, or hypnapompic hallucinations, sleep paralysis and nocturnal disrupted sleep. In child onset narcolepsy, the presentations of narcolepsy can be very variable, making misdiagnosis as seizure disorders or delaying diagnosis as much as several years after disease onset. For the diagnosis of narcolepsy, overnight polysomnography(PSG) and multiple sleep latency test(MSLT) should be evaluated. Test for Cerebrospinal fluid hypocretin(orexin) concentration and human leukocyte antigens(HLA) would be great helpful to confirm the narcolepsy with cataplexy even in early stage of disease in children. The mainstays of treatment are that reducing the excessive daytime sleepiness, preventing the intrusion of the REM related phenomena including cataplexy and consolidating the nighttime sleep. Central nervous system stimulators such as methylphenidate or amphetamine decrease excessive daytime sleepiness and tricyclic antidepressant(TCA) or selective serotonin reuptake inhibitors(SSRI) can prevent cataplexy. Recently, new therapeutic agents such as modafinil and sodium oxybate are emerging in clinical practice with much effectiveness. Counseling for poor school performance, social isolation and depression should be provided. Early diagnosis and treatment can greatly improve the quality of life. Awareness of excessive daytime sleepiness in children or adolescent will allow pediatricians to effectively identify hypersomnia such as narcolepsy.