An exploratory genetic analysis: Associations between parent depression symptoms,child temperament,and the serotonin transporter gene polymorphism (5HTTLPR)

Child temperament has been shown to be biologically based and heritable; however, genetic association studies of temperament have been fairly inconclusive, and the role that parental depressive symptoms play is largely unexplored in this context. The relationship between parent depressive symptoms and the child temperament dimensions of fear and activity level (AL ) were examined in 100 sibling pairs 2.5–5.5 years of age and their mothers. Parent reports of child temperament and parent self‐reports of depressive symptoms were obtained from families, as well as DNA samples from each child during their lab visit. Associations between the serotonin transporter gene (SLC6A4 ) polymorphism 5‐HTTLPR /rs25531 and the phenotypic variables were also explored. Parent depressive symptoms were significantly related to higher child AL , but minimally associated with fear outcomes. More powerful regression analyses revealed that parent depressive symptoms, child gender, and child age predicted child AL , but only child gender and age predicted child fear. In our exploratory candidate gene analyses, the low‐expressing genotypes of the 5‐HTTLPR /rs25531 polymorphism predicted child fearfulness, but not child AL . Our phenotypic findings indicate that a child with at least one parent with depressive symptoms is more likely to have higher AL , and results of the initial genetic analyses show that the 5‐HTTLPR /rs25531 polymorphism is associated with child fearfulness. Future research employing larger samples, observational assessments, and related child behavioral maladjustment measures will further clarify these findings.     

Respiratory sinus arrhythmia and serotonin transporter promoter gene polymorphisms: Taking a triallelic approach makes a difference

It has been recently reported in Psychophysiology that carriers of the short allele of an insertion/deletion (ins/del) functional polymorphism in the promoter region (5‐HTTLPR) of the serotonin transporter gene may display decreased resting respiratory sinus arrhythmia (RSA). However, this region hosts another functionally connected single‐nucleotide polymorphism (rs25531), which should also be genotyped in order to correctly categorize the low‐ and high‐expressing alleles of 5‐HTTLPR. The present study investigated resting RSA in an ethnically homogenous sample (N = 143) of participants genotyped for both the ins/del and rs25531 polymorphisms in 5‐HTTLPR. In contrast with the biallelic genotypes, based only on the ins/del alleles, the triallelic 5‐HTTLPR genotypes (i.e., including rs25531) showed no association with resting RSA. Taking a triallelic approach to 5‐HTTLPR is thus necessary in order to avoid false positive results.     

三等位基因5-HTTLPR与青少年重性抑郁障碍的关联研究

目的:探讨三等位基因5-羟色胺转运体基因连锁多态区多态性(5-HTTLPR+rs25531)与青少年重性抑郁障碍之间有无关联。方法:404名研究对象(病例187人,正常对照217人)使用SNaPshot系统进行基因分型。结果:三等位基因5-HTTLPR与青少年抑郁症是否患病、抑郁严重程度、是否共病焦虑、是否出现自杀观念/行为/企图均无关。结论:尚不能认为三等位基因5-HTTLPR与青少年重性抑郁障碍有关。     

Impact of the Interaction Between the 5HTTLPR Polymorphism and Maltreatment on Adolescent Depression. A Population-Based Study

Serotonin plays a central role in mood regulation and the development of depressive disorders. The present study investigated whether a functional polymorphism (5HTTLPR) of the serotonin transporter gene interacts with maltreatment in the prediction of depression. A cohort of 17–18 years old students (n = 1,482) anonymously completed the Survey of Adolescent Life and Health in Vestmanland 2006 and gave a saliva sample for DNA extraction. An association between maltreatment and adolescent depression was found independent of sex. When the whole population was analyzed, no main effect of 5HTTLPR in association with depression was found. When separated by sex, a significant main effect and a G × E interaction effect of the SS allele was found among girls. No gene main effect or G × E interaction effect was found among boys. The present study confirms previous findings of sex differences in interaction effects between the 5HTTLPR polymorphism and maltreatment in the prediction of adolescent depression. Edited by Peter McGuffin.     

Subthreshold depression is linked to the functional polymorphism of the 5HT transporter gene

BACKGROUND: The functional polymorphism of the serotonin transporter gene (5HTTLPR) has been earlier associated with affective disorders. No research has however been carried out to identify the relationship between this polymorphism and depressive traits and subclinical depressive symptoms within a psychiatrically healthy population. METHODS: One hundred and twenty-eight female subjects with no lifetime or current history of DSM-IV Axis I disorders participated in the study. All subjects completed the Zung Self-Rating Depression Scale and were genotyped for the 5HTTLPR polymorphism. RESULTS: Significant differences were found on the Zung SDS and also on the physical-vegetative subscale of the Zung SDS according to both phenotype and genotype. Subjects carrying the s allele scored significantly higher on the Zung SDS and had also significantly higher scores on the physical-vegetative symptom subscale. Furthermore, subjects carrying the ss genotype scored highest and subjects carrying the ll genotype scored the lowest on both scales. CONCLUSION: Subclinical depressive symptoms (i.e. DSM-IV subthreshold depression) are associated with the functional polymorphism of the serotonin transporter gene. The main association between this polymorphism and subclinical depression is primarily carried by the physical symptoms of depression. The s allele of the 5HTTLPR gene is associated with a "low mood endophenotype".     

No association between polymorphism of serotonin transporter gene and depression in Parkinson's disease in Chinese

Depressive symptoms affect 40% to 50% of Parkinson's disease (PD) patients, and adversely impact their quality of life. The decrease of serotonin (5-HT) in the synaptic cleft is commonly considered as the cause of depression. The reuptake of 5-HT released into the synaptic cleft is mediated by the 5-HT transporter (5-HTT). Many studies have focused on the relationship between the 5-HTT-linked polymorphic region (5-HTTLPR) and depression. The present study is to investigate the association between the polymorphisms in the promoter of the 5-HTT gene (including 5-HTTLPR and rs25531), which determine either a higher or lower 5-HT uptake, and risk for depression of PD. Three hundred six idiopathic PD patients were recruited randomly from hospital clinic and the Center for Epidemiological Studies Depression Scale (CES-D) was used as the diagnosis or rating scale for depression. Polymerase Chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used and the patients’ genotypes were divided as L_A, L_G, S_A, and S_G. We found no evidence for an association between variants of 5-HTTLPR and rs25531 alleles, and depressive symptoms in Chinese PD patients.     

Serotonin transporter polymorphism and borderline or antisocial traits among low-income young adults

OBJECTIVES: The short allele of the serotonin transporter linked polymorphic region, 5HTTLPR has been associated with anxiety, major depressive disorder and suicidality. The impulsive self- and other-damaging behaviors seen in borderline personality disorder and antisocial personality disorder also have substantial comorbidity with depression but are associated with more severe environmental stressors. This study tested the hypothesis of an association between the short allele of the 5HTTLPR and borderline or antisocial traits in young adulthood. METHODS: The 5HTTLPR was genotyped among 96 young adults from low to moderate income families (62 adults without and 34 adults with borderline personality disorder or antisocial personality disorder traits). Traits of borderline and antisocial personality disorders were assessed with the Structured Clinical Interview for Diagnosis-Axis II. RESULTS: The number of short 5HTTLPR alleles were significantly related to incidence of borderline personality disorder or antisocial personality disorder traits and also to each set of traits independently. Male sex and quality of care in infancy were also associated with incidence of borderline personality disorder and antisocial personality disorder traits but did not account for the association with the short allele. Depressive disorders were not associated with the short allele in this sample. CONCLUSIONS: Young adults of lower socioeconomic status who carry the short 5HTTLPR allele may be especially vulnerable to developing antisocial or borderline traits by young adulthood.     

REM sleep and depressive symptoms in a population‐based study of middle‐aged and elderly persons

Alterations in rapid eye movement sleep have been consistently related to depression in clinical studies. So far, there is limited evidence from population‐based studies for this association of rapid eye movement sleep alterations with depressive symptoms. In 489 participants of the Rotterdam Study, we assessed rapid eye movement sleep latency, rapid eye movement sleep duration and rapid eye movement density with ambulant polysomnography, and depressive symptoms with the Center of Epidemiologic Studies‐Depression Scale. A longer rapid eye movement sleep latency (B = 0.002, P = 0.025) and higher rapid eye movement density (B = 0.015, P = 0.046) were related to depressive symptoms after age–sex adjustment. When we excluded persons who used sleep medication or medication for the nervous system (n = 124), only rapid eye movement density remained related to depressive symptoms (B = 0.018, P = 0.027). Our results suggest that rapid eye movement density is a marker of depressive symptoms in the general population, and that associations of rapid eye movement sleep with depressive symptoms are modified by the use of medication.     

Family‐based association study of 5‐HTTLPR,TPH, MAO‐A,and DRD4 polymorphisms in mood disorders

Variants of the functional polymorphism in the serotonin transporter (upstream regulatory region: 5‐HTTLPR), the tryptophan hydroxylase (TPH), the monoamine oxidase A (MAO‐A), and the dopamine receptor D4 (DRD4) genes have all been associated with mood disorders. The aim of this study was to test those hypotheses by using a family‐based association approach. Both diagnoses and psychopathology were used for phenotype definitions. A total of 134 nuclear families with mood disorders, with probands affected by bipolar (n = 103) or major depressive (n = 58) disorders, were included in the study. All subjects were typed for the above‐mentioned gene variants using polymerase chain reaction (PCR) technique. No significant transmission disequilibrium was found in the overall sample for any polymorphism. A separate analysis of bipolar subjects only, or the use of continuous psychopathologic traits as affectation status did not influence the observed results. Our study did not support the involvement of 5‐HTTLPR, TPH, MAO‐A, or DRD4 polymorphisms in mood disorders. © 2002 Wiley‐Liss, Inc.     

Testing the diathesis‐stress model: 5‐HTTLPR,childhood emotional maltreatment,and vulnerability to social anxiety disorder

Regarding the development of social anxiety disorder (SAD), a diathesis‐stress paradigm including biological vulnerabilities and environmental stressors can be assumed. However, studies dealing with the etiology of SAD did not integrate both aspects so far. We examined a particular diathesis‐stress model for SAD in which we included a functional polymorphism of the serotonin transporter (5‐HTTLPR) as a genetic vulnerability factor and childhood emotional maltreatment (CEM) as an environmental stressor. Current analyses were based on individuals who participated in the Study of Health in Pomerania. Psychiatric disorders were assessed with diagnostic interviews according to DSM‐IV criteria. The triallelic genotype of 5‐HTTLPR was determined. Statistical analyses were performed in 78 individuals with SAD and 1,035 without an axis I disorder. Logistic regression analysis revealed that the experience of CEM (odds ratio [OR] 4.56; 95% confidence interval [CI] 2.65–7.84), the l/l genotype of 5‐HTTLPR (OR 2.13; 95% CI 1.31–3.48), female gender (OR 3.03; 95% CI 1.80–5.08) and younger age (OR 1.04; 95% CI 1.02–1.06) increased the odds for SAD. The data suggest that CEM, the l/l genotype of 5‐HTTLPR, female gender and younger age are risk factors for SAD. This is in favor of the tested diathesis‐stress model. © 2013 Wiley Periodicals, Inc.     

Association study of serotonin transporter gene regulatory region polymorphism and alcoholism

Previous studies have indicated associations between a functional biallelic repetitive element in the 5′ regulatory region of the serotonin transporter gene (5‐HTTLPR) and alcoholic subjects who have either dissocial personality disorder or severe withdrawal symptoms. To replicate these associations under the hypothesis that genetic polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcoholics, the associations between alcoholic subjects' genetic polymorphisms, clinical characteristics, and personality traits were examined. This case control study comprised 697 alcoholic and 270 control subjects. A questionnaire focusing on family and social background, history of drinking and alcohol withdrawal, DSM‐III‐R criteria for the evaluation of psychiatric conditions, and Feighner's criteria for the lifetime diagnosis and assessment of overall severity of alcoholism was administered to 373 alcoholic subjects. Temperament and Character Inventory (TCI) and Sensation Seeking Scale (SSS) were used to evaluate the other 324 alcoholics. The frequency of the homozygous short allele was significantly higher in alcoholic binge drinkers than in nonbinge drinking alcoholics. There were no significant differences in the frequencies of either the 5‐HTTLPR genotype or the short vs. long allele in alcoholic and control subjects. The alcoholics' 5‐HTTLPR genotype and allele frequencies did not differ significantly by the severity of withdrawal symptoms or by the number of positive Feighner's diagnostic criteria. Although these results indicate an association between 5‐HTTLPR and a subgroup of alcoholics characterized by binge drinking, the authors found no differences in SSS and TCI subscale scores for alcoholics with different 5‐HTTLPR genotypes. Future studies of the association in other alcoholic population should take into account personality traits. © 2001 Wiley‐Liss, Inc.     

Sleep problems and depressive symptoms in toddlers and 8‐year‐old children: A longitudinal study

Sleep and depression are interlinked throughout the lifespan, but very few studies have examined the directionality of the sleep–depression link in children. The aim of the current study was to prospectively examine the bidirectional association between sleep problems and internalizing problems and depressive symptoms in toddlers and children aged 1.5 and 8 years. Data stem from the large ongoing population‐based longitudinal study, the Norwegian Mother, Father and Child Cohort Study, recruited from October 1999 to July 2009. A total of 35,075 children were included. Information on sleep duration, nocturnal awakenings and internalizing problems (Child Behaviour Checklist) was provided by the mothers at 1.5 years, whereas data on sleep duration and depressive symptoms (Short Mood and Feelings Questionnaire) were provided by the mothers when the children were 8 years old. Odds ratios (ORs) were calculated using logistic regression analyses. After accounting for previous internalizing problems, short sleep duration (≤10 hr) and frequent (≥3) nightly awakenings at 1.5 years predicted the development of depressive symptoms at 8 years of age (adjusted OR = 1.28; 95% confidence interval [CI] 1.08–1.51, and adjusted OR = 1.27, 95% CI 1.08–1.50, respectively). Also, internalizing problems at 1.5 years predicted onset of later short sleep duration (adjusted OR = 1.83, 95% CI 1.32–2.54) after accounting for early sleep problems. This prospective study demonstrated a bidirectional association between sleep and internalizing/depressive symptoms from toddlerhood to middle childhood. Intervention studies are needed to examine whether targeting either of these problems at this early age may prevent onset of the other.     

Serotonin transporter gene polymorphisms are associated with anxiety‐related personality traits in women

Several studies have reported an association between anxiety‐related personality traits and a promoter polymorphism in the human serotonin transporter (5‐HTT) gene (5‐HTT gene‐linked polymorphic region, 5‐HTTLPR). In the present study, a population of 251 subjects was assessed with the Karolinska Scales of Personality (KSP) and genotyped both for the 5‐HTTLPR and for a variable number of tandem repeats polymorphism in the second intron of the same gene. The interpretation of previous studies has to some extent been confounded by the studied subjects differing with respect to ethnicity, sex, and age. To circumvent this problem, all included subjects were Caucasians, women, and born in the same year (1956). Associations were found between the 5‐HTTLPR and four of the five anxiety‐related KSP scales (psychic anxiety, muscular tension, psychasthenia, and lack of assertiveness), subjects being homozygous for the short allele displaying higher anxiety scores than those of the long/long or long/short genotype. In addition, an association was found between the intron 2 polymorphism and one anxiety‐related personality trait (somatic anxiety). © 2001 Wiley‐Liss, Inc.     

Brief school‐based interventions to assist adolescents’ sleep‐onset latency: Comparing mindfulness and constructive worry versus controls

Difficulties falling asleep are common among adolescents, especially during times of stress. Adolescents may thus benefit from brief techniques (15 min) that decrease pre‐sleep cognitive‐emotional arousal and sleep‐onset latency. The present study used a 3 (intervention: mindfulness bodyscan mp3, constructive worry, control) by 3 (time: baseline, week 1, week 2) mixed‐model design on a school‐based sample of adolescents (N = 232; M_age = 15.9 ± 0.8 years, range = 14–18 years; 19% male), and a sub‐sample of adolescents with prolonged sleep‐onset latency (i.e. ≥30 min; N = 119; M_age = 16.9 ± 0.9 years; 21% male). It was expected that the 15‐min pre‐recorded breath‐based mindfulness bodyscan, and constructive worry, would decrease sleep‐onset latency and pre‐sleep arousal similarly over time, relative to the control condition. A significant interaction was observed among adolescents with prolonged sleep‐onset latency, who completed ≥3 days for at least 1 week (p = .001), where mindfulness decreased sleep‐onset latency relative to constructive worry and the control. Neither technique changed pre‐sleep worry or cognitive‐emotional arousal, or associated daytime functioning (both the whole sample and sub‐sample). A pre‐recorded mp3 breath‐based mindfulness bodyscan technique is a promising means by which adolescents with prolonged sleep‐onset latency can decrease sleep‐onset latency. This simple tool has potential for scalable dissemination by stakeholders (e.g. teachers), unqualified to treat adolescent sleep difficulties. Future studies are needed to determine whether benefits may extend to academic performance and mental health, if performed for a longer time period with increased compliance.     

Associations between seasonal variations in day length (photoperiod), sleep timing, sleep quality and mood: a comparison between Ghana (5°) and Norway (69°)

The hypothesis of whether day length (photoperiod) is an important zeitgeber (time‐giver) for keeping the circadian rhythm entrained to a 24‐hour cycle was examined, as was its association with sleep patterns and mood problems. Data were collected prospectively from a site with very large differences in daylight duration across seasons (Tromsø in Norway, 69°39′N) and a site with very small seasonal differences in daylight duration (Ghana in Accra, 5°32′N). Two hundred subjects were recruited from both sites in January. At the follow‐up in August, 180 and 150 subjects in Ghana and Norway participated, respectively. Use of a weekly sleep diary indicated low to moderately strong seasonal changes in rise‐ and bedtime, sleep efficiency and sleep onset latency only in the northern latitude. No seasonal changes in sleep duration or night awakenings were observed. The self‐report measures indicated moderate to strong seasonal differences in insomnia and fatigue, and weaker differences in depressed mood in Norway, but small to non‐existing seasonal differences in Ghana. Lack of daylight was related to phase‐delayed rise‐ and bedtimes, increased problems falling asleep, daytime fatigue and depressive mood. However, total sleep duration and sleep quality appeared unaffected.     

Psychological distress following marital separation interacts with a polymorphism in the serotonin transporter gene to predict cardiac vagal control in the laboratory

Marital separation is linked to negative mental and physical health; however, the strength of this link may vary across people. This study examined changes in respiratory sinus arrhythmia (RSA), used to assess cardiac vagal control, in recently separated adults (N = 79; M time since separation = 3.5 months). When reflecting on the separation, self‐reported psychological distress following the separation interacted with a polymorphism in the serotonin transporter gene (5‐HTTLPR) and a relevant single nucleotide polymorphism (SNP), rs25531, to predict RSA. Among people reporting emotional difficulties after the separation, those who were homozygous for the short allele had lower RSA levels while reflecting on their relationship than other genotypes. The findings, although limited by the relatively small sample size, are discussed in terms of how higher‐sensitivity genotypes may interact with psychological responses to stress to alter physiology.     

Psychosocial work characteristics,sleep disturbances and risk of subsequent depressive symptoms: a study of time‐varying effect modification

Job strain and low social support at work are recognized risk factors for depression. However, people with poor sleep may represent a high‐risk group more likely to benefit from interventions against work stress. The present study examined whether the associations between these work stressors and depressive symptoms differed by strata of sleep disturbances (effect modification/effect moderation) considering repeat measures of work characteristics and sleep. The study was based on five biennial measurements of the Swedish Longitudinal Occupational Survey of Health, including 1537 respondents recurrently in paid work, from an originally representative sample of the Swedish working population. High work demands, low decision authority and low social support were measured waves 2 and 4, sleep disturbances (putative moderator/modifier) waves 1 and 3, and depressive symptoms (outcome) wave 5. Causal effect modification, whether the effect of working conditions differed by strata of sleep disturbances, was analysed by structural nested mean modelling estimated using a regression‐with‐residuals with inverse‐probability‐of‐treatment weighting approach. High demands and low social support, but not low decision authority, influenced subsequent depressive symptoms. The relationship between social support and depressive symptoms was not apparently modified by sleep disturbances. However, disturbed sleep wave 3 modified the effect of high demands wave 4 (coefficient 1.77, P < 0.05) on depressive symptoms wave 5. The results indicate that high job demands is a stronger risk factor for depressive symptoms in people with pre‐existing sleep disturbances, suggesting that targeted workplace interventions may be more effective when it comes to preventing negative effects of job demands.