Serotonin Transporter-linked Promoter Region Research Articles

Interactions Between Serotonin Transporter Gene and Adverse Childhood Experience in a Generalized Additive Model: A Pilot Study.

While most people experience potentially traumatic events (PTEs), including Adverse Childhood Experiences (ACEs), the stress reactions to PTEs on mental health outcomes are highly heterogeneous. Resilience is influenced by a complex biopsychosocial ecological system, including gene serotonin transporter-linked promoter region or 5-HTTLPR /rs25531 by ACEs interactions. This pilot study investigated the gene-by-environment interactions on mental health outcomes in adults enrolled in a health care profession program using a generalized additive model (GAM). Seventy health care college students (mean age = 27.4 years, 67.1% women) participated in this cross-sectional study. Saliva samples were collected from students to analyze 5-HTTLPR/rs25531. Participants completed the ACE Questionnaire and the Mental Health Inventory. GAMs with different interaction terms were built adjusting for age, gender, and race. The value of the effective degree of freedom (EDF) quantifies the curvature of the relationship. Among participants with the long allele of 5-HTTLPR/rs25531, a linear pattern was found between the total ACE score and mental health outcomes (EDF = 1). Conversely, among participants with the short allele, EDF was approximately 2, indicating a curved association suggesting that mental health worsens in individuals exposed to up to four types of ACEs. The impact of up to four ACEs on mental health was stronger among individuals with the short allele of 5-HTTLPR/rs25531 than those with the long allele. Although this study does not claim to provide a definite approach to analyzing gene-by-environment interactions, we offer a different perspective to explore the relationship.

Association of 5-HTTLPR With Post-Traumatic Stress Disorder in US Service Members

Objective Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members. Methods Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44. Results Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, P = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers (P < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups (P > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal (P < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score (P < .001). Conclusion Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.

Structural brain alterations in older adults exposed to early-life adversity

BackgroundAdverse childhood events may have differential effects on the brain that persist into adulthood. Findings on structural brain alterations in older adults exposed to early-life adversity are inconsistent notably due to heterogeneity in imaging studies, population, psychiatric comorbidities, nature of adverse events, and genetic vulnerability. This study examines whether exposure related to physical or sexual maltreatment, emotional maltreatment, and global adverse environment during childhood are associated with specific alterations in grey matter volumes and if this varies according to sex and serotonin transporter-linked promoter region (5-HTTLPR) genotype. MethodStructural MRI was used to acquire anatomical scans from 398 community-dwelling older adults. Quantitative regional estimates of 23 subregional volumes were derived using FreeSurfer software. Retrospective reporting of childhood adversity was collected using structured self-reported questionnaire. Analyses adjusted for age, sex, brain volume, head injury, lifetime depression and anxiety disorder, psychiatric medication, and cardiovascular ischemic pathologies. ResultsExposure to adverse family environment was associated with smaller volumes of several frontal, cingulate, and parietal subregions and larger amygdala in the 5-HTTLPR SS genotype participants specifically but larger volumes of caudate, putamen, pallidum, and nucleus accumbens in the SL genotype participants. Highly significant differences were found with excessive sharing of parent problems with children, associated with larger grey-matter volumes in the thalamus and several frontal and parietal regions in 5-HTTLPR SL male participants specifically. ConclusionsEarly-life adversity is associated with grey-matter volume alterations in older adults and this varies according to the type of adversity experienced, sex, and serotonergic genetic vulnerability; 5-HTTLPR SS participants appearing most vulnerable and SL individuals most resilient.

Threat-Avoidance Tendencies Moderate the Link Between Serotonin Transporter Genetic Variation and Reactive Aggression.

The short (S) allele of the serotonin transporter-linked promoter region (5-HTTLPR) polymorphism has been linked to reactive aggression in men, but this association is less consistent in females. Reactive aggression has been particularly described as a result of fear-driven defense to threat, but how this interaction between defensive behavior and aggression is expressed in S-allele carriers remains unknown. In order to explore this interplay between 5-HTTLPR genotype, defensive behavior and reactive aggression, we combined genotyping with objective measures of action tendencies toward angry faces in an approach-avoidance task (AAT) and reactive aggression in the Taylor aggression paradigm (TAP) in healthy females, N = 95. This study shows that female S-allele carriers in general display increased implicit reactive aggression (administering aversive white noise) toward opponents. Furthermore, we found that threat-avoidance tendencies moderate the association between 5-HTTLPR genotype and aggression displayed on the TAP. Together, these findings indicate a positive correlation between avoidance of angry faces in the AAT and reactive aggression in the TAP exclusively present in S-allele carriers.

Lifetime major depression and grey-matter volume

There is evidence of structural brain alterations in major depressive disorder (MDD), but little is known about how these alterations might be affected by age at onset or genetic vulnerability. This study examines whether lifetime episodes of MDD are associated with specific alterations in grey-matter volume, and whether those alterations vary according to sex or serotonin transporter-linked promoter region (5-HTTLPR) genotype (LL, SL or SS). We used structural MRI to acquire anatomic scans from 610 community-dwelling participants. We derived quantitative regional estimates of grey-matter volume in 16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV criteria. We adjusted analyses for age, sex, total brain volume, education level, head injury and comorbidities. Lifetime MDD was associated with a smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens and with a larger pericalcarine region in both men and women. These associations remained after adjustment for false discovery rate. Lifetime MDD was also associated with a smaller caudate nucleus and amygdala in men and with a larger rostral anterior cingulate cortex in women. Late-onset first episodes of MDD (after age 50 years) were associated with a larger rostral anterior cingulate cortex and lingual and pericalcarine regions; early-onset MDD was associated with a smaller ventral diencephalon and nucleus accumbens. Some associations differed according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD and the LL genotype; pericalcarine and lingual volumes were higher in those with the SL genotype. This study was limited by its cross-sectional design. Major depressive disorder was associated with persistent volume reductions in the deep nuclei and insula and with enlargements in visual cortex subregions; alterations varied according to age of onset and genotype.

Polymorphism of rs3813034 in Serotonin Transporter Gene SLC6A4 Is Associated With the Selective Serotonin and Serotonin-Norepinephrine Reuptake Inhibitor Response in Depressive Disorder: Sequencing Analysis of SLC6A4.

Selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRI/SNRI) are commonly used for treating major depression. Regretfully, significant heterogeneity exists regarding the benefits of SSRI/SNRI in individual cases. We previously reported that a polymorphism located in the serotonin transporter linked promoter region (5-HTT LPR) is associated with an interindividual difference in SSRI treatment efficacy. However, this explains only a small part of the variation of this complex phenotype. Other 5-HTT variants in the coding regions, 3' untranslated region (3' UTR), and introns adjacent to each exon could also contribute to treatment response. Therefore, we performed a sequencing analysis of the SLC6A4 gene (coding for 5-HTT) and investigated the association between variants detected in this study and the antidepressant response to SSRI/SNRI in 201 Japanese depressive patients. Seventeen novel mutations were identified by sequencing analysis. We found that the polymorphism G2563T (rs3813034) as a tag single-nucleotide polymorphism of IVS9 A-90G (rs140701), G2356T (rs1042173), and A3641C (rs7224199) is associated with interindividual variability of SSRI/SNRI efficacy at week 6, independent from clinical variables and effect of 5-HTT LPR (P < 0.001 by multiple regression analysis). This polymorphism could help determine individualized SSRI/SNRI treatments for depressive patients in combination with 5-HTT LPR.

Differential susceptibility in longitudinal models of gene–environment interaction for adolescent depression

Although family support reliably predicts the development of adolescent depression and suicidal behaviors, relatively little is known about the interplay of family support with potential genetic factors. We tested the association of the 44 base pair polymorphism in the serotonin transporter linked promoter region gene (5-HTTLPR), family support (i.e., cohesion, communication, and warmth), and their interaction with self-reported depression symptoms and risk for suicide in 1,030 Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health. High-quality family support predicted fewer symptoms of depression and reduced risk for suicidality. There was also a significant interaction between 5-HTTLPR and family support for boys and a marginally significant interaction for girls. Among boys with poor family support, youth with at least one short allele had more symptoms of depression and a higher risk for suicide attempts relative to boys homozygous for the long allele. However, in the presence of high family support, boys with the short allele had the fewest depression symptoms (but not suicide attempts). Results suggest that the short allele may increase reactivity to both negative and positive family influences in the development of depression. We discuss the potential role of interactive exchanges between family support and offspring genotype in the development of adolescent depression and suicidal behaviors.

Pharmacogenetic polymorphisms and response to escitalopram and venlafaxine over 8 weeks in major depression

The objective of this study is to investigate the influence of the 5-HTTLPR (serotonin transporter-linked promoter region), cytochrome P450 2C19, and cytochrome P450 2D6 polymorphisms on escitalopram (ESC) and venlafaxine (VEN) responses in major depressive disorder. A prospective multi-site study of 106 patients (Caucasian and Han Chinese ethnicities) with major depressive disorder treated with either ESC or VEN was conducted. The 17-item Hamilton Depression scale (HDRS), Clinical Global Impression Scale, and an adverse events scale (UKU) were assessed over 8 weeks, blind to genotype. At the 8-week end point, a significant HDRS reduction for both ESC and VEN occurred (p < 0.0001). The 5-HTTLPR l/l genotype was associated with significantly greater score reductions on the HDRS compared with s/s carriers (p = 0.016) among Caucasian subjects receiving ESC (n = 47). Response rates were significantly higher for l/l (92%) compared with l/s (61%) and s/s (46%) variants (p = 0.042). For every l allele a participant carried, there was a 3.33 (95% confidence interval 1.25, 8.84; p = 0.02) times greater odds of ESC response. No significant associations between any of the genotypes and adverse effects were found. Ethnicity may have differential effects on the 5-HTTLPR genotype-efficacy relationship. Results suggest that l/l allele for 5-HTTLPR is associated with a robust treatment response to ESC in Caucasian subjects only.

Serotonin transporter genotype impacts amygdala habituation in youth with autism spectrum disorders

Failure of the amygdala to habituate, or decrease response intensity, to repeatedly presented faces may be one mechanism by which individuals with autism spectrum disorders (ASD) develop and maintain social symptoms. However, genetic influences on habituation in ASD have not been examined. We hypothesized that serotonin transporter-linked promoter region (5-HTTLPR) genotype affects change in amygdala response to repeated sad faces differently in individuals with ASD vs healthy controls. Forty-four youth with ASD and 65 controls aged 8-19 years were genotyped and underwent an event-related functional magnetic resonance imaging scan where they identified the gender of emotional faces presented for 250 ms. The first half of the run was compared with the second half to assess habituation. 5-HTTLPR genotype influences amygdala habituation to sad faces differently for individuals with ASD vs controls. The genotype-by-diagnosis-by-run half interaction was driven by individuals with ASD and low expressing genotypes (S/S, S/L(G) and L(G)/L(G)), who trended toward sensitization (increase in amygdala activation) and whose habituation scores significantly differed from individuals with ASD and higher expressing genotypes (L(A)/L(A), S/L(A) and L(A)/L(G)) as well as controls with low expressing genotypes. Our results show that amygdala response to social stimuli in ASD, which may contribute to social symptoms, is genetically influenced.

Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study

Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Västmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R2=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.

5HTTLPR: White Knight or Dark Blight?

In over 100 neuroscience genetics reports on SLC6A4 published in the first part of 2012, >40% reported data from genotyping only the serotonin transporter-linked promoter region [5HTTLPR] indel, omitting genotyping of two nearby SNPs that substantially alter 5HTTLPR allele frequencies and functionality. And 25% of these papers did not report ethnicity of the subjects genotyped, another factor that alters allele frequencies. This field thus seems stultified. Improved science for the present and future will be better served by attention to more complete methods for genotyping and subject sample reporting.

P-799 - Effects of the COMT x 5--HTTLPR genetic interaction on brain gray matter volume of healthy individuals

Genetic polymorphisms of the catechol-O-methyltransferase gene (COMT Val158Met) and the serotonin transporter linked promoter region (5-HTTLPR) have been reported to influence the gray matter volumes of amygdala and hippocampus, but the studies have been inconsistent. To elucidate the effects of COMT and 5-HTTLPR on regional gray matter volumes in the same sample of healthy individuals. We conducted a diffeomorphic anatomic registration through exponentiated Lie algebra (DARTEL) voxel-based morphometry (VBM) study of the effects of COMT and 5-HTTLPR polymorphisms and their interaction on the gray matter volumes of 91 healthy controls. A small increase of gray matter volume in right angular gyrus was detected in carriers of the Met allele of COMT, and no main effects of 5-HTTLPR on gray matter volume were detected. The effects of the interaction between COMT and 5-HTTLPR on gray matter volume were large and mainly involved bilateral amygdala and hippocampus. [COMT × 5-HTTLPR effects on gray matter volume]. The effects of the genetic interaction found in this study might explain the relative inconsistency in the results from previous studies, and suggest further research into genetic interactions.

Interaction of catechol O-methyltransferase and serotonin transporter genes modulates effective connectivity in a facial emotion-processing circuitry

Imaging genetic studies showed exaggerated blood oxygenation level-dependent response in limbic structures in carriers of low activity alleles of serotonin transporter-linked promoter region (5-HTTLPR) as well as catechol O-methyltransferase (COMT) genes. This was suggested to underlie the vulnerability to mood disorders. To better understand the mechanisms of vulnerability, it is important to investigate the genetic modulation of frontal-limbic connectivity that underlies emotional regulation and control. In this study, we have examined the interaction of 5-HTTLPR and COMT genetic markers on effective connectivity within neural circuitry for emotional facial expressions. A total of 91 healthy Caucasian adults underwent functional magnetic resonance imaging experiments with a task presenting dynamic emotional facial expressions of fear, sadness, happiness and anger. The effective connectivity within the facial processing circuitry was assessed with Granger causality method. We have demonstrated that in fear processing condition, an interaction between 5-HTTLPR (S) and COMT (met) low activity alleles was associated with reduced reciprocal connectivity within the circuitry including bilateral fusiform/inferior occipital regions, right superior temporal gyrus/superior temporal sulcus, bilateral inferior/middle prefrontal cortex and right amygdala. We suggest that the epistatic effect of reduced effective connectivity may underlie an inefficient emotion regulation that places these individuals at greater risk for depressive disorders.

Body image, sexual function and depression in Korean patients with breast cancer: modification by 5-HTT polymorphism

Nearly 50% of women with breast cancer show depressive symptoms after diagnosis and treatment. The purpose of this study was to clarify how psychosocial factors (body image, sexuality, and social relationships) and genetic factors (functional polymorphism of the serotonin transporter-linked promoter region) influence depression. The participants were categorized by DSM-IV diagnoses; scored according to their depressive symptoms, body image and social and sexual function (BIRS), self-esteem, and quality of life; and genotyped by functional polymorphism of the serotonin transporter promoter. Patients with depressive symptoms showed low self-esteem, poor body image, relationship problems, and low quality of life. Genotype frequencies did not differ between two groups categorized by the presence or absence of depressive symptoms. However, the patients with the short allele of the 5-HTTLPR had significantly higher HAM-D scores (F = 7.59, p = 0.047). The results suggest that psychosocial factors related to breast cancer treatment such as body image, self-esteem, and interpersonal relationship influence the development of depressive symptoms. The 5-HTTLPR may be associated with the severity of depressive symptoms rather than susceptibility to the development of depressive symptoms.

The Effects of Serotonin Transporter Promoter and Monoamine Oxidase A Gene Polymorphisms on Trait Emotional Intelligence

Objective: The purpose of this study was to evaluate the influences of major serotonin-related genetic variants of the serotonin transporter-linked promoter region (5-HTTLPR), tryptophan hydroxylase 1 gene (TPH1) and monoamine oxidase A gene (MAOA-EcoRV) on trait emotional intelligence (EI). Methods: The Trait Meta-Mood Scale (TMMS) measuring trait EI and genotyping were performed in 336 healthy Korean college students (204 males, 132 females). Results: Among the male participants, those with the T genotype of MAOA (lower MAOA activity) had significantly lower subscale scores on the TMMS than those with the C genotype (higher MAOA activity) did. Additionally, male participants with the s/s genotype of the 5-HTTLPR gene had significantly lower attention subscale scores and total TMMS scores than those with the non-s/s (l/l + l/s) genotypes did. Among the female participants, there were no associations between any of the 5-HTTLPR, TPH1 or MAOA-EcoRV polymorphisms and any of the TMMS scores. Conclusion: These findings suggest a potential genetic basis of EI with regard to attention to one’s own feelings involving the serotonin system in males.

How the serotonin transporter 5-HTTLPR polymorphism influences amygdala function: the roles of in vivo serotonin transporter expression and amygdala structure

The serotonin transporter-linked promoter region (5-HTTLPR) polymorphism of the serotonin transporter gene is associated with amygdala response during negative emotion. The aim of this study was to investigate whether this genotype effect on amygdala function is mediated by current serotonin transporter (5-HTT) levels or rather by genetically induced influences during neurodevelopment, shaping brain structure. A total of 54 healthy subjects underwent functional and structural magnetic resonance imaging, [11C]DASB positron emission tomography and 5-HTTLPR genotyping to analyze the interrelationships between amygdala activation during processing of unpleasant stimuli, 5-HTTLPR genotype, amygdala volumes and 5-HTT levels in the midbrain and in other brain regions. In line with previous research, carriers of the short allele (S) showed increased amygdala activation. Path analysis demonstrated that this genotype effect was not procured by current 5-HTT availability but by amygdala structure, with smaller amygdala volumes in the S than in the LL genotype, as well as smaller volumes being associated with increased amygdala activation. Our findings stress the role of genetic effects during neurodevelopment.

Val1483Ile polymorphism in the fatty acid synthase gene was associated with depressive symptoms under the influence of psychological stress

To study the association between lipid-metabolism and depressive symptoms, genetic polymorphisms in serotonin transporter linked promoter region (5-HTTLPR) and fatty acid synthase gene (FASN) were investigated. A cross-sectional study was conducted on 177 women (n = 166) and men (n = 15) recruited from workers in a hospital and nursing homes in Japan. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale and perceived psychological stress was measured using visual analogue scale (VAS). The genotypes of 5-HTTLPR (insertion/deletion; L/S), and FASN (Val1483Ile) were determined by the PCR methods. Linear regression analysis was performed, in which CES-D scores served as a dependent variable, and VAS scores, gene polymorphism, and confounders as independent variables. Under the influence of perceived stress, S/S carriers of the 5-HTTLPR gene showed significantly higher CES-D scores in comparison with L/L+L/S carriers (F = 8.2, standardised β = 0.15, p < 0.05). Regression analysis also confirmed that CES-D scores in participants with Ile/Ile+Val/Ile genotypes of the FASN gene were significantly higher than those with Val/Val genotype (F = 8.4, standardised β = 0.16, p<0.05). In relation to physical features, BMI among participants with S/S genotype of 5-HTTLPR was significantly lower compared with those with L/L+L/S genotypes. The Val1483Ile polymorphism in the FASN was associated with depressive symptoms under the influence of psychological stress. The S variant of 5-HTTLPR was related with less obese.

Children's genotypes interact with maternal responsive care in predicting children's competence: Diathesis–stress or differential susceptibility?

We examined Genotype × Environment (G × E) interactions between children's genotypes (the serotonin transporter linked promoter region [5-HTTLPR] gene) and maternal responsive care observed at 15, 25, 38, and 52 months on three aspects of children's competence at 67 months: academic skills and school engagement, social functioning with peers, and moral internalization that encompassed prosocial moral cognition and the moral self. Academic and social competence outcomes were reported by both parents, and moral internalization was observed in children's narratives elicited by hypothetical stories and in a puppet interview. Analyses revealed robust G × E interactions, such that children's genotype moderated the effects of maternal responsive care on all aspects of children's competence. Among children with a short 5-HTTLPR allele (ss/sl), those whose mothers were more responsive were significantly more competent than those whose mothers were less responsive. Responsiveness had no effect for children with two long alleles (ll). For academic and social competence, the G × E interactions resembled the diathesis-stress model: ss/sl children of unresponsive mothers had particularly unfavorable outcomes, but ss/sl children of responsive mothers had no worse outcomes than ll children. For moral internalization, the G × E interaction reflected the differential susceptibility model: whereas ss/sl children of unresponsive mothers again had particularly unfavorable outcomes, ss/sl children of responsive mothers had significantly better outcomes than ll children.

The effects of child maltreatment and polymorphisms of the serotonin transporter and dopamine D4 receptor genes on infant attachment and intervention efficacy

This investigation examined the extent to which polymorphisms of the serotonin transporter linked promoter region (5-HTTLPR) and the dopamine receptor D4 (DRD4) genes differentially influenced the development of attachment security and disorganization in maltreated and nonmaltreated infants at age 13 months, and the extent to which the efficacy of preventive interventions to promote attachment security were influenced by genetic variation. The sample consisted of 106 infants from maltreating families, participating in a randomized control trial evaluating the efficacy of two interventions, child-parent psychotherapy and psychoeducational parenting intervention, and 47 infants from nonmaltreating families. DNA samples were genotyped for polymorphisms of 5-HTTLPR, DRD4 exon III variable number tandem repeat, and DRD4-521. Attachment organization at age 1 and at age 2 was assessed with the Strange Situation for all participants, prior to and following the completion of the interventions. High rates of disorganized attachment were observed in the maltreatment compared to the nonmaltreatment group, and both interventions resulted in increased rates of attachment security at age 2. Genetic variation did not influence improvement in attachment organization among maltreated infants. Among maltreated infants, genetic variation had minimal effect on attachment organization. In contrast, among nonmaltreated infants, 5-HTTLPR and DRD4 polymorphisms influenced attachment security and disorganization at age 2 and the stability of attachment disorganization over time.

Serotonin Transporter Gene Polymorphism in Chinese Patients With Poststroke Depression

We sought to compare the distribution of the serotonin transporter gene SLC6A4 polymorphism between depressed and nondepressed poststroke patients. Patients with cerebral stroke admitted to hospital during a 1-year period were enrolled in a 1:1 case-control study. All cases and controls were genotyped for polymorphism of the serotonin transporter-linked promoter region and the single-nucleotide polymorphism rs25531. Among 367 patients with cerebral stroke, 57 (15.5%) were diagnosed with poststroke depression at 1 month after stroke. In the patients with poststroke depression, 7 genotypes of the serotonin transporter gene SLC6A4 were detected, and the frequency of S/S homozygotes was significantly higher (P=0.049) than that in controls. S/S homozygosity may be positively associated with the occurrence of poststroke depression in Chinese patients.