Investigation of the functional vesicular monoamine transporter 1 (VMAT1/SLC18A1) Thr136Ile gene variant in bipolar disorder

Background and objectives: Bipolar disorder (BD) is an episodic and recurrent mood disturbance ranging from mania to severe depression. Because of the heterogeneity of psychiatric disorders, enlightening the possible molecular risk drivers is crucial. Vesicular monoamine transporter 1 (VMAT1) is an important candidate gene to study the underlying molecular mechanisms in BD pathogenesis since it has a significant role in the packaging of monoaminergic neurotransmitters into presynaptic storage vesicles. The aim of this study was to ascertain whether functional and evolutionarily important variant of VMAT1 gene (Thr136Ile (rs1390938)) would affect the susceptibility of the individuals to BD in a Turkish population.MethodOne hundred twenty BD patients and one hundred one healthy control individuals were recruited for the study. Samples were genotyped using PCR-RFLP method to detect VMAT1 gene variant (Thr136Ile (rs1390938)).ResultsContrary to our expectations, VMAT1 Thr136Ile (rs1390938) gene variant was not associated with BD in our population. There was also no relationship between VMAT1 genotypes and some clinically significant parameters in BD patients.ConclusionOur data showed no association between VMAT1 Thr136Ile (rs1390938) and BD in Turkish population. We strongly recommend the analysis of this variant in other populations to draw a precise conclusion about the role of this variant in bipolar disorder. Further large-scale research for the other variants of VMAT1 is also required to clarify the strong hypothesis focused on VMAT1 variants in the development of neuropsychiatric disorders. (AU)

Antecedentes y Objetivos: El trastorno bipolar (TB) es una alteración del ánimo episódica y recurrente, que fluctúa entre la manía y la depresión severa. Debido a la heterogeneidad de los trastornos psiquiátricos, es esencial esclarecer los posibles impulsores del riesgo molecular. El transportador 1 vesicular de monoaminas (VMAT1) es un importante gen candidato para estudiar los mecanismos moleculares subyacentes en la patogenia del TB, dado que tiene un rol significativo de embalaje de los neurotransmisores monoaminérgicos en las vesículas de almacenaje presinápticas. El objetivo de este estudio fue comprobar si la variante funcional y evolutivamente importante del gen VMAT1 (Thr136Ile (rs1390938)) afectaría a la susceptibilidad de los individuos relativa a TB en una población turca.MétodoSe seleccionaron para el estudio ciento veinte pacientes con TB y ciento un individuos sanos. Se genotipificaron las muestras mediante el método PCR-RFLP, para detectar la variante del gen VMAT1 (Thr136Ile (rs1390938)).ResultadosContrariamente a nuestras expectativas, la variante del gen VMAT1 (Thr136Ile (rs1390938)) no estuvo asociada al TB en nuestra población. Tampoco se encontró relación entre los genotipos de VMAT1 y algunos parámetros clínicamente significativos de los pacientes de TB.ConclusiónNuestros datos no reflejaron asociación ninguna entre la variante Thr136Ile (rs1390938) de VMAT1 y el TB en la población turca. Recomendamos encarecidamente el análisis de esta variante en otras poblaciones, para obtener una conclusión precisa sobre el rol de la misma en el trastorno bipolar. También son necesarios más estudios a gran escala sobre las demás variantes de VMAT1 para esclarecer la sólida hipótesis centrada en las variantes de VAT1, en cuanto al desarrollo de trastornos neuropsiquiátricos. (AU)

Factors associated with response to simple behavioral intervention in primary enuresis nocturna.

This 8-week longitudinal study examined predictors of response to simple behavioral intervention in primary enuresis nocturna (PEN). A total of 154 children, aged 8-18 years, diagnosed with PEN were evaluated. The results indicated that lack of constipation, milder enuresis severity, and higher bladder capacity are the primary predictors of good treatment response, and lower family dysfunction is the most robust familial predictor. Lack of constipation is the main predictor with unique variance in multiple regression. Specialists should be aware of conditions that hinder the success of simple behavioral intervention before implementing costly treatments. In treatment-refractory cases, it is important to examine each child for constipation. Family-centered approaches can be helpful if used in parallel with behavioral treatments.

Adaptation and the Psychometric Properties of Turkish version of the Structured Clinical Interview for the DSM-5-Personality Disorders - Clinician Version (SCID-5-PD/CV). / DSM-5 Kisilik Bozukluklari için Yapilandirilmis Klinik Görüsme (SCID-5-PD)'nin Türkçeye Uyarlanmasi ve Psikometrik Özellikleri.

OBJECTIVE: The aim of this study is to demonstrate the validity and reliability of the Categorical and Dimensional Psychometric Properties of the Structured Clinical Interview for DSM-5 Personality Disorders (SCID-5-PD) after its translation to the Turkish. METHOD: The study was carried out with 102 volunteers from two university hospitals. The SCID interview was conducted by two experienced psychiatrists who interchanged positions as interviewer and observer; and completed the research forms without discussing the patient. The diagnostic agreement between the interviewers and the Kappa coefficient were calculated. Divergent and convergent validity analyses were carried out for diagnostic validity and the scores obtained from the self-report form as well as the dimensional evaluation scores were used in the statistical analyses. RESULTS: The group mean age for volunteers was 39.6±11.6 years and 66.7% consisted of females. The Kappa values for personality categories were 0.79 for avoidant personality structure, 0.64 for dependent personality structure, 0.81 for obsessive-compulsive personality structure, 0.76 for paranoid personality structure, 0.49 for schizotypal personality structure, 0.90 for histrionic personality structure, 0.66 for narcissistic personality structure, 0.89 for borderline personality structure and 0.71 for antisocial personality structure. Dimensional evaluation showed significant correlation with the diagnostic agreement between the interviewers and also with the scores of the self-report forms completed by the participants. CONCLUSION: The results demosntrated that the Turkish version of the Structured Clinical Interview for DSM-5 Personality Disorders (SCID- 5-PD-CV-TR) is valid and reliable.

For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder.

Clock genes play significant roles in the regulation of circadian rhythms, which are thought to be involved in the pathophysiology of neurodegenerative and psychiatric diseases. We aimed to investigate the association of five gene polymorphisms (PER3 VNTR (rs57875989), PER2 rs2304672, CLOCK rs1801260, CLOCK rs10462028, CLOCK rs11932595) with PCR-based methods as potential risk factors in bipolar disorder (BD). We used a multiple testing methodology in BD patients (n = 121) and healthy control individuals (n = 121) of Turkish descent to analyze the effects of these gene variants both as risk factors for the disorder and for the evaluation of these variants in the patient group with multiple subscales. We evaluated the circadian rhythm disturbances and seasonal variations in mood and behavior in BD patients using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Seasonal Pattern Assessment Questionnaire (SPAQ) to enlighten the possible links between these scores and the studied circadian gene variants. The results of our study revealed significant associations: PER3 VNTR (rs57875989) 5/5 repeat genotype displayed a protective effect against BD when compared with 4/4 repeat genotype. Moreover, patients with PER3 VNTR 5/5 repeat genotype displayed a higher ratio of hypomania. PER2 rs2304672 G allele frequency increased the risk for BD. There was no association in terms of genotype/allele frequency comparisons between patients and controls for CLOCK gene variants. However, significant associations were found in patients in terms of clinical and behavioral patterns such as mean age at disease onset and BRIAN total scores enabling some risk stratifications for patients. Our results indicate the significance of circadian gene variants in BD, which need to be confirmed in different studies with larger samples. Thus, the possible endophenotypes of BD can be enlightened and advanced chronotherapeutics approaches can be manipulated in the future for clinical benefit.