Brief Psychosocial Intervention to Address Poststroke Depression May Also Benefit Fatigue and Sleep-Wake Disturbance.

PURPOSE: This study aimed to determine if brief psychosocial/behavioral therapy directed to reduce poststroke depression would decrease fatigue and improve sleep-wake disturbance. DESIGN: A preplanned secondary data analysis from a completed clinical trial was conducted. METHODS: One hundred participants received usual care, in-person intervention, or telephone intervention. Depression, fatigue, and sleep-wake disturbance were measured at entry, 8 weeks, 21 weeks, and 12 months following the intervention. FINDINGS: Fatigue (within: p = .042, between: p = .394), sleep disturbance (within: p = .024, between: p = .102), and wake disturbance (within: p = .004, between: p = .508) decreased over the 12 months in the intervention groups, but not in the control group. This difference was clinically meaningful for wake disturbance and approached the clinically important difference for fatigue. CONCLUSIONS/CLINICAL RELEVANCE: Reduction in wake disturbance was consistent with clinically meaningful difference standards for patient-reported outcomes, warranting further research in larger samples.

Serotonin transporter gene polymorphisms and depressive symptoms in patients with chronic obstructive pulmonary disease.

Background: We examined the relationship between polymorphisms in the promoter region of the serotonin transport (SERT) gene (5-HTTLPR, short 'S' and long 'L' alleles) and in intron 2 variable number tandem repeat (STin2VNTR, 9, 10, or 12-repeat alleles) with depression or anxiety in patients with COPD.Methods: 302 patients with moderate to severe COPD participated in SERT study. History and number of prior depressive episodes were measured using the Structured Clinical Interview for Depression; Hospital Anxiety Depression Scale (HAD) depression ≥8 or a Patient Health Questionnaire-9 (PHQ-9) >,10.Results: 240 (80%) male sample had a mean age of 68.0 years. Current depression was 22% (HAD) or 21% (PHQ-9), anxiety was 25% (HAD), and suicidal ideation (6%). 5-HTTLPR or STin2 VNTR genotypes were not associated with current depressive or anxiety symptoms. The mean number of prior depressive episodes was higher for patients with the 5-HTTLPR genotype S/S or S/L compared with L/L (4.4 ± 6.1; 5.3 ± 6.8; 4.0 ± 6.1, p < 0.001) and with STin2VNTR high-risk genotype (9/12 or 12/12), medium risk (9/10 or 10/12) compared to low risk (10/10) genotypes (5.1 ± 6.8; 4.9 ± 6.7; 2.7 ± 4.5, p < 0.001).Conclusions: SERT 5-HTTLPR and STin2-VNTR polymorphisms were not associated with current depressive and anxiety symptoms, but the high-risk STin2-VNTR genotypes and S/L were associated with the number of prior depressive episodes.

Stroke impact symptoms are associated with sleep-related impairment.

BACKGROUND: Sleep-related impairment is a common but under-appreciated complication after stroke and may impede stroke recovery. Yet little is known about factors associated with sleep-related impairment after stroke. OBJECTIVE: The purpose of this analysis was to examine the relationship between stroke impact symptoms and sleep-related impairment among stroke survivors. METHODS: We conducted a cross-sectional secondary analysis of a baseline (entry) data in a completed clinical trial with 100 community-dwelling stroke survivors recruited within 4 months after stroke. Sleep-related impairment and stroke impact domain symptoms after stroke were assessed with the Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment scale and the Stroke Impact Scale, respectively. A multivariate regression was computed. RESULTS: Stroke impact domain-mood (B = -0.105, t = -3.263, p = .002) - and fatigue (B = 0.346, t = 3.997, p < .001) were associated with sleep-related impairment. CONCLUSIONS: Our findings suggest that ongoing stroke impact symptoms are closely related to sleep-related impairment. An intervention targeting both stroke impact symptoms and sleep-related impairment may be useful in improving neurologic recovery and quality of life in stroke survivors.

Randomized trial of telephone versus in-person delivery of a brief psychosocial intervention in post-stroke depression.

BACKGROUND: A psychosocial behavioral intervention delivered in-person by advanced practice nurses has been shown effective in substantially reducing post-stroke depression (PSD). This follow-up trial compared the effectiveness of a shortened intervention delivered by either telephone or in-person to usual care. To our knowledge, this is the first of current behavioral therapy trials to expand the protocol in a new clinical sample. 100 people with Geriatric Depression Scores ≥ 11 were randomized within 4 months of stroke to usual care (N = 28), telephone intervention (N = 37), or in-person intervention (N = 35). Primary outcome was response [percent reduction in the Hamilton Depression Rating Scale (HDRS)] and remission (HDRS score < 10) at 8 weeks and 12 months post treatment. RESULTS: Intervention groups were combined for the primary analysis (pre-planned). The mean response in HDRS scores was 39% reduction for the combined intervention group (40% in-person; 38% telephone groups) versus 33% for the usual care group at 8 weeks (p = 0.3). Remission occurred in 37% in the combined intervention groups at 8 weeks versus 27% in the control group (p = 0.3) and 44% intervention versus 36% control at 12 months (p = 0.5). While favouring the intervention, these differences were not statistically significant. CONCLUSIONS: A brief psychosocial intervention for PSD delivered by telephone or in-person did not reduce depression significantly more than usual care. However, the comparable effectiveness of telephone and in-person follow-up for treatment of depression found is important given greater accessibility by telephone and mandated post-hospital follow-up for comprehensive stroke centers. Clinical Trial Registration URL: https://register.clinicaltrials.gov , unique identifier: NCT01133106, Registered 5/26/2010.

COMT Val158Met Polymorphism and Symptom Improvement Following a Cognitively Focused Intervention for Irritable Bowel Syndrome.

BACKGROUND: Our nurse-delivered comprehensive self-management (CSM) program, a cognitive behavioral therapy intervention, is effective in reducing gastrointestinal and psychological distress symptoms in patients with irritable bowel syndrome (IBS). Findings from non-IBS studies indicate that the catechol-O-methyltransferase (COMT) Val158Met polymorphism may moderate the efficacy of cognitive behavioral therapy. It is unknown whether this COMT polymorphism is associated with symptom improvements in patients with IBS. OBJECTIVE: We tested whether this COMT Val158Met polymorphism influences the efficacy of our 2-month CSM intervention. METHODS: We analyzed data from two published randomized controlled trials of CSM. The combined European American sample included 149 women and 23 men with IBS (CSM, n = 111; usual care [UC], n = 61). The primary outcomes were daily reports of abdominal pain, depression, anxiety, and feeling stressed measured 3 and 6 months after randomization. Secondary outcomes were additional daily symptoms, retrospective psychological distress, IBS quality of life, and cognitive beliefs about IBS. The interaction between COMT Val158Met polymorphism and treatment group (CSM vs. UC) in a generalized estimating equation model tested the main objective. RESULTS: At 3 months, participants with at least one Val allele benefited more from CSM than did those with the Met/Met genotype (p = .01 for anxiety and feeling stressed, and p < .16 for abdominal pain and depression). The moderating effect of genotype was weaker at 6 months. DISCUSSION: Persons with at least one Val allele may benefit more from CSM than those homozygous for the Met allele. Future studies with larger and more racially diverse samples are needed to confirm these findings. RCT REGISTRATION: Parent studies were registered at ClinicalTrials.gov (NCT00167635 and NCT00907790).

Symptom profiles and inflammatory markers in moderate to severe COPD.

BACKGROUND: Physical and psychological symptoms are the hallmark of patients' subjective perception of their illness. The purpose of this analysis was to determine if patients with COPD have distinctive symptom profiles and to examine the association of symptom profiles with systemic biomarkers of inflammation. METHODS: We conducted latent class analyses of three physical (dyspnea, fatigue, and pain) and two psychological symptoms (depression and anxiety) in 302 patients with moderate to severe COPD using baseline data from a longitudinal observational study of depression in COPD. Systemic inflammatory markers included IL1, IL8, IL10, IL12, IL13, INF, GM-CSF, TNF-α (levels >75thcentile was considered high); and CRP (levels >3 mg/L was considered high). Multinominal logistic regression models were used to examine the association between symptom classes and inflammation while adjusting for key socio-demographic and disease characteristics. RESULTS: We found that a 4-class model best fit the data: 1) low physical and psychological symptoms (26%, Low-Phys/Low-Psych), 2) low physical but moderate psychological symptoms (18%, Low-Phys/Mod Psych), 3) high physical but moderate psychological symptoms (25%, High-Phys/Mod Psych), and 4) high physical and psychological symptoms (30%, High-Phys/High Psych). Unadjusted analyses showed associations between symptom class with high levels of IL7, IL-8 (p ≤ .10) and CRP (p < .01). In the adjusted model, those with a high CRP level were less likely to be in the High-Phys/Mod-Psych class compared to the Low-Phys/Low-Psych (OR: 0.41, 95%CI 0.19, 0.90) and Low-Phys/Mod-Psych classes (OR: 0.35, 95%CI 0.16, 0.78); elevated CRP was associated with in increased odds of being in the High-Phys/High-Psych compared to the High-Phys/Mod-Psych class (OR: 2.22, 95%CI 1.08, 4.58). Younger age, having at least a college education, oxygen use and depression history were more prominent predictors of membership in the higher symptom classes. CONCLUSIONS: Patients with COPD can be classified into four distinct symptom classes based on five commonly co-occurring physical and psychological symptoms. Systemic biomarkers of inflammation were not associated with symptom class. Additional work to test the reliability of these symptom classes, their biological drivers and their validity for prognostication and tailoring therapy in larger and more diverse samples is needed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01074515 .

Rare Variants of the Serotonin Transporter Are Associated With Psychiatric Comorbidity in Irritable Bowel Syndrome.

Alterations in serotonin signaling are suspected in the pathophysiology of irritable bowel syndrome (IBS). By modulating the extracellular reuptake of serotonin, the serotonin transporter (SERT) acts as a key regulator of the bioavailability of serotonin. This study is the first to investigate the impact of rare SERT variants (i.e., those with a minor allele frequency of < 1%) on the risk for IBS, gastrointestinal (GI) symptom level, response to cognitive-behavioral treatment, and psychiatric comorbidity. We sequenced a 0.19 megabase chromosomal stretch containing the SERT gene and surrounding regions in a community sample of 304 IBS patients and 83 controls. We found no significant associations between rare variants in and around the SERT gene and IBS risk, GI symptom profile, or response to treatment. We found preliminary evidence, however, that IBS subjects with a history of either depression or anxiety were significantly more likely to carry multiple rare likely functional variant alleles than IBS patients without psychiatric comorbidity.

Examining gene-environment interactions in comorbid depressive and disruptive behavior disorders using a Bayesian approach.

OBJECTIVE: The objective of this study was to apply a Bayesian statistical analytic approach that minimizes multiple testing problems to explore the combined effects of chronic low familial support and variants in 12 candidate genes on risk for a common and debilitating childhood mental health condition. METHOD: Bayesian mixture modeling was used to examine gene by environment interactions among genetic variants and environmental factors (family support) associated in previous studies with the occurrence of comorbid depression and disruptive behavior disorders youth, using a sample of 255 children. RESULTS: One main effect, variants in the oxytocin receptor (OXTR, rs53576) was associated with increased risk for comorbid disorders. Two significant gene × environment and one signification gene × gene interactions emerged. Variants in the nicotinic acetylcholine receptor α5 subunit (CHRNA5, rs16969968) and in the glucocorticoid receptor chaperone protein FK506 binding protein 5 (FKBP5, rs4713902) interacted with chronic low family support in association with child mental health status. One gene × gene interaction, 5-HTTLPR variant of the serotonin transporter (SERT/SLC6A4) in combination with µ opioid receptor (OPRM1, rs1799971) was associated with comorbid depression and conduct problems. CONCLUSIONS: Results indicate that Bayesian modeling is a feasible strategy for conducting behavioral genetics research. This approach, combined with an optimized genetic selection strategy (Vrieze et al., 2012), revealed genetic variants involved in stress regulation (FKBP5, SERT × OPMR), social bonding (OXTR), and nicotine responsivity (CHRNA5) in predicting comorbid status.

Prevalence and correlates of suicide ideation in patients with COPD: a mixed methods study.

PURPOSE: The purpose of this study was to examine the prevalence and correlates of suicidal ideation (SI) in patients with stable moderate to very severe chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We conducted an exploratory mixed methods analysis of data from participants in a longitudinal observational study of depression in COPD. We measured depression with the Patient Health Questionnaire-9 (PHQ-9), which includes an item on SI. We compared participants with and without SI in relation to sociodemographics, symptoms, anxiety, and healthcare resource use with independent t-tests and chi-square tests. Content analysis was performed on qualitative data gathered during a structured SI safety assessment. RESULTS: Of 202 participants, 121 (60%) had depressive symptoms (PHQ ≥6); 51 (25%) had a PHQ-9 ≥10, indicating a high likelihood of current major depression; and 22 (11%) reported SI. Compared to the 99 depressed participants without SI, those with SI were more likely to be female (59% vs 27%, P=0.004); had worse dyspnea (P=0.009), depression (P<0.001), and anxiety (P=0.003); and were also more likely to have received treatment for depression and/or anxiety (82% vs 40%, P<0.001) and more hospitalizations for COPD exacerbations (P=0.03) but had similar levels of airflow obstruction and functioning than participants without SI. Themes from the qualitative analysis among those with SI included current or prior adverse life situations, untreated or partially treated complex depression, loss of a key relationship, experience of illness and disability, and poor communication with providers. CONCLUSION: Our findings suggest that current SI is common in COPD, may occur disproportionately in women, can persist despite mental health treatment, and has complex relationships with both health and life events. Adequate management of SI in COPD may therefore require tailored, comprehensive treatment approaches that integrate medical and mental health objectives.

Poststroke fatigue: hints to a biological mechanism.

BACKGROUND: Poststroke fatigue (PSF) is common, but the biological basis of this fatigue is unknown. We explored the possibility that PSF is related to systemic inflammation by investigating polymorphisms in 2 genes that affect the immune response. METHODS: In a substudy of a larger trial that evaluated the role of the immune response on stroke outcome, fatigue was assessed at 30, 90, 180, and 365 days after ischemic stroke using the Fatigue Assessment Scale. Subjects were genotyped for 3 single nucleotide polymorphisms, one in the interleukin-1 receptor antagonist gene (IL1RN; rs4251961, a T/C substitution) and two in the in toll-like receptor-4 (TLR4) gene (1063 A/G [Asp299Gly] rs4986790 and 1363 C/T [Thr399Ile] rs4986791). RESULTS: Of the 39 participants, 22 (56%) endorsed fatigue during the study. The degree of fatigue was remarkably constant over time and independent of stroke outcome. The C allele of the rs4251961 single nucleotide polymorphism (SNP) in IL1RN was associated with self-reported fatigue (P = .03), whereas the cosegregating polymorphisms in TLR4 were associated with lower levels of fatigue (P= .04). CONCLUSIONS: SNPs in 2 genes with opposing effects on inflammatory immune responses were significantly, but differentially, associated with PSF. These findings suggest a direct link between immune signaling dysregulation and PSF.

A pilot investigation of the association of genetic polymorphisms regulating corticotrophin-releasing hormone with posttraumatic stress and depressive symptoms in medical-surgical intensive care unit survivors.

PURPOSE: To determine if single nucleotide polymorphisms of the corticotrophin-releasing hormone binding protein (CRHBP, rs10055255) and CRH receptor type 1 (CRHR1, rs1876831) were associated with posttraumatic stress disorder (PTSD) and depressive symptoms following medical-surgical intensive care unit (ICU) hospitalization. MATERIALS AND METHODS: We extracted DNA for genotyping from saliva samples of 93 ICU patients enrolled in a prospective cohort investigation. Follow-up interviews conducted 3 and 12-months post-ICU included assessment of PTSD symptoms with the PTSD Checklist-Civilian Version and depressive symptoms with the Patient Health Questionnaire-9. RESULTS: Homozygosity for the CRHBP rs10055255 T allele was associated with significantly fewer post-ICU PTSD (ß = -10.8, 95% confidence interval [95% CI], -17.7 to -3.9; P = .002) and depressive symptoms (ß = -3.7, 95% CI, -6.7 to -0.7; P = .02). Carrying a CRHR1 rs1876831 C allele was associated with significantly more post-ICU depressive symptoms compared to T/T homozygotes (C/T heterozygtes: ß = 6.9, 95% CI, 1.2-12.6; P = .02; C/C homozygotes: ß = 5.8; 95% CI: 0.2-11.3; P = .04). These associations remained significant after adjustment for age, race, illness severity, and in-ICU steroid exposure. CONCLUSIONS: Despite a small sample size, our findings suggest a potential role for genetic variants of CRHBP and CRHR1 in the development of post-ICU psychiatric morbidity.

TPH gene polymorphisms are associated with disease perception and quality of life in women with irritable bowel syndrome.

The aims of this exploratory study were to examine whether tryptophan hydroxylase (TPH) gene polymorphisms are associated with psychosocial factors in women with irritable bowel syndrome (IBS). TPH is the rate-limiting enzyme in the biosynthesis of serotonin and has two isoforms, TPH1 and TPH2. Four single nucleotide polymorphisms (SNPs) in the TPH1 gene and one SNP in the TPH2 gene were selected based on previous studies investigating associations between these SNPs and psychiatric or behavioral disorders. One hundred ninety-nine Caucasian women with IBS were included. Results of univariate analysis showed no association between TPH1and TPH2 gene SNPs and current level of psychological distress or psychiatric illness. However, TPH1 gene SNPs were associated with IBS-related cognitions (rs4537731 and rs21105) and quality of life (rs684302 and rs1800532), in particular the mental health and energy subscales. These associations were independent of the subjects' levels of gastrointestinal symptoms. These results suggest that patients' perception of their illness, and of the impact it has on their lives, may be subject to genetic influences, in this case sequence variants in TPH1. However, caution should be used in interpreting these results given the large number of hypothesis tests performed in this exploratory hypothesis-generating study, and the results should be considered tentative until confirmed in an independent sample.

Depression persistence and serotonin transporter genotype in adolescents under usual care conditions.

OBJECTIVES: Polymorphisms of the serotonin transporter (SERT) gene have been shown to influence the risk for depression. The goal of this study was to investigate a possible effect of SERT polymorphisms on severity and course of depression symptoms in a community sample of adolescents. METHODS: Community-dwelling adolescents (n=192) ages 13-17 years, who were at risk for depression, were followed for a period of 6 months. Subjects donated a saliva sample for genotyping of the 5-HTTLPR and STin2 VNTR polymorphisms of SERT. RESULTS: We found no associations between SERT genotype and severity of depressive symptoms at baseline. Depression symptom severity markedly decreased over time. For 5-HTTLPR, we observed a significant interaction between time and genotype, indicating the possibility that heterozygote genotype carriers (s/l) might experience a greater reduction in depression symptoms over time compared with adolescents with the 5-HTTLPR l/l genotype. CONCLUSIONS: Our study shows that for most community-dwelling adolescents, depressive symptoms decrease over time. A possible interaction effect of time and SERT genotype will require confirmation in larger studies.

Patients with COPD with higher levels of anxiety are more physically active.

BACKGROUND: Physical activity (PA) has been found to be an excellent predictor of mortality beyond traditional measures in COPD. We aimed to determine the association between depression and anxiety with accelerometry-based PA in patients with COPD. METHODS: We performed a cross-sectional analysis of baseline data from 148 stable patients with COPD enrolled in an ongoing, longitudinal, observational study. We measured PA (total daily step count) with a Stepwatch Activity Monitor over 7 days, depression and anxiety with the Hospital Anxiety and Depression Scales (HADSs), dyspnea with the Shortness of Breath Questionnaire, and functional capacity with the 6-min walk test. RESULTS: Increased anxiety was associated with higher levels of PA such that for every one-point increase in the HADS-Anxiety score there was a corresponding increase of 288 step counts per day (ß=288 steps, P<.001), after adjusting for all other variables. Higher levels of depressive symptoms were associated with lower PA (ß=-176 steps, P=.02) only when anxiety was in the model. The interaction term for anxiety and depression approached significance (ß=26, P=.10), suggesting that higher levels of anxiety mitigate the negative effects of depression on PA. CONCLUSIONS: The increased PA associated with anxiety in COPD is, to our knowledge, a novel finding. However, it is unclear whether anxious patients with COPD are more restless, and use increased psychomotor activity as a coping mechanism, or whether those with COPD who push themselves to be more physically active experience more anxiety symptoms. Future studies should evaluate for anxiety and PA to better inform how to improve clinical outcomes. TRIAL REGISTRY: Clinicaltrials.gov; No.: NCT01074515; URL: www.clinicaltrials.gov.

Recreational physical activity in postmenopausal women is stable over 8 years of follow-up.

BACKGROUND: The goals of this study were to examine 1) longitudinal trajectories of energy expenditure from recreational physical activity (PA) in postmenopausal women, 2) whether women who belong to different PA trajectories engage in different types of PA, and 3) whether baseline sociodemographic, health, psychosocial, and lifestyle characteristics predict membership in PA trajectories. METHODS: Women from the Women's Health Initiative Observational Study with baseline PA data (n = 92,629) were included. Physical activity, measured via self-report 6 times over 8 years, was converted to MET hr/wk for analysis. Latent growth curve mixture models and latent profile models were used to analyze longitudinal PA trajectories and cross-sectional PA composition, respectively. RESULTS: Three distinct, stable PA trajectories (highly, moderately, and minimally active) were identified with nearly 75% of the women classified as minimally active (≤ 8 MET-hr/wk). The majority of women who were at least moderately active engaged in a balanced combination of walking, moderate, and vigorous PA. Sociodemographic characteristics such as income, education, and past vigorous PA were predictive of PA trajectory, as were some health status indicators (eg, body mass index), but not health related quality of life. CONCLUSIONS: Self-reported PA is largely stable across nearly a decade of follow-up in postmenopausal women.

Response to psychosocial treatment in poststroke depression is associated with serotonin transporter polymorphisms.

BACKGROUND AND PURPOSE: The Living Well With Stroke study has demonstrated effectiveness of a brief psychosocial treatment in reducing depressive symptoms after stroke. The purpose of this analysis was to determine whether key variables associated with prevalence of poststroke depression also predicted treatment response. METHODS: Response to a brief psychosocial/behavioral intervention for poststroke depression was measured with the Hamilton Rating Scale for Depression. Analysis of covariance models tested for interaction of potential predictor variables with treatment group on percent change in Hamilton Rating Scale for Depression from pre- to post-treatment as an outcome. RESULTS: Initial depression severity, hemispheric location, level of social support, age, gender, and antidepressant adherence did not interact with the treatment with respect to percent change in Hamilton Rating Scale for Depression when considered 1 at a time. Participants who carried 1 or 2 s-alleles at the 5-HTTLPR serotonin transporterpolymorphism or 1 or 2 9- or 12-repeats of the STin2 VNTR polymorphism had significantly better response to psychosocial treatment than those with no s-alleles or no 9- or 12-repeats. CONCLUSIONS: Opposite to the effects of antidepressant drug treatment with selective serotonin reuptake inhibitors, the Living Well With Stroke psychotherapy intervention was most effective in 5-HTTLPR s-allele carriers and STin2VNTR 9- or 12-repeat carriers. CLINICAL TRIAL REGISTRATION: URL: www.clinicaltrials.gov/ct/show/NCT00194454?order_1. Unique identifier: NCT00194454.

Genetics and gastrointestinal symptoms.

Gastrointestinal (GI) symptoms including nausea, vomiting, diarrhea, constipation, abdominal discomfort/pain, and heartburn are ubiquitous and as such are often the focus of nursing interventions. The etiologies of these symptoms include GI pathology (e.g., cancer, inflammation), dietary factors (e.g., lactose intolerance), infection, stress, autonomic nervous system dysregulation, medications, as well as a host of diseases outside the GI tract. This review focuses on a common condition (irritable bowel syndrome [IBS]) that is linked with both bowel pattern and abdominal discomfort/pain symptoms. Family and twin studies give evidence for a role of genetic factors in IBS. Whether genes are directly associated with IBS or influence disease risk indirectly by modulating the response to environmental factors remains unknown at this time. Given the multifactorial nature of IBS, it is unlikely that a single genetic factor is responsible for IBS. In addition, gene-gene (epistatic) interactions are also likely to play a role. Four genes coding for proteins involved in neurotransmission (i.e., the serotonin reuptake transporter [SERT], tryptophan hydroxylase [TPH], alpha2-adrenergic receptor [alpha2-ADR], catechol-o-methyl transferase [COMT]) and their potential relevance to GI symptoms and IBS will be reviewed. Further research using genome-wide association approaches with samples well characterized by ethnicity and standardized symptom subgrouping is needed.

The heritability of postpartum depression.

Postpartum depression (PPD) is a serious mood disorder that may carry life-long consequences for a woman and her family. Multiple risk factors for PPD have been identified, including psychosocial, situational, and biological stimuli, several of which are experienced by most, if not all, postpartum women. Given the commonality of these risk factors, it is unclear why fewer than 20% of postpartum women actually develop PPD. In this review, we suggest that different susceptibility to PPD among postpartum women may be explained by the presence or absence of genetic variants that confer increased risk. We review three categories of genes known to code for proteins associated with depression in the general population or proteins known to be affected by childbirth for their possible association with PPD, including genes related to central nervous system monoamine availability, proinflammatory cytokines, and brain neuropeptides. Only two studies are available in the literature to date specifically looking at polymorphisms in postpartum women as related to PPD; both are concerned with monoamine availability. These are discussed in further depth. Conclusions regarding the contribution of genetic polymorphisms to the development of PPD are mixed. Ultimately, the complexity of the disorder and the interrelationships among different genes thought to contribute to depression suggest that much more research is required to understand the heritability of PPD. The complexity of the disorder also suggests that epigenetic influences must be considered as well when discussing susceptibility.

The serotonin transporter polymorphism rs25531 is associated with irritable bowel syndrome.

Irritable bowel syndrome is a frequent gastrointestinal disorder of unknown etiology. The serotonin transporter regulates the intensity and duration of serotonin signaling in the gut and is, therefore, an attractive candidate gene for irritable bowel syndrome. Previous studies investigating the 5-HTTLPR and Stin2 VNTR polymorphisms of the serotonin transporter have proved inconclusive. In this exploratory study we therefore expanded the search for a possible association of the serotonin transporter with irritable bowel syndrome to include not only the 5-HTTLPR and Stin2 VNTR length polymorphisms, but also the functional single nucleotide polymorphism rs25531. We genotyped 186 patients with irritable bowel syndrome and 50 healthy control subjects raging in age from 18 to 70 years. Carriers of the rare G allele of rs25531 had approximately threefold increased odds of irritable bowel syndrome compared with healthy controls (OR 3.3, 95% CI 1.1-9.6). Our findings suggest that further investigation of the possible role of the serotonin transporter in the etiology of IBS is warranted.

Association of serotonin transporter gene polymorphisms with poststroke depression.

CONTEXT: Polymorphisms of the serotonin transporter gene (SERT) have been associated with mental illness. In people with long-term medical conditions, variants of the 5-HTTLPR and STin2 VNTR polymorphisms of SERT have been shown to confer a heightened vulnerability to comorbid depression. OBJECTIVE: To determine whether the 5-HTTLPR, STin2 VNTR, and rs25531 polymorphisms of SERT are associated with poststroke depression (PSD) in stroke survivors. DESIGN: A case-control study in which stroke survivors were screened for depressive symptoms and assigned to either a depressed group or a nondepressed group. SETTING: Outpatient clinic. PARTICIPANTS: Seventy-five stroke survivors with PSD and 75 nondepressed stroke survivors. INTERVENTIONS: Blood or saliva samples were collected from each participant for DNA extraction and genotyping. MAIN OUTCOME MEASURES: The associations between the 5-HTTLPR, STin2 VNTR, and rs25531 polymorphisms and PSD. RESULTS: Individuals with the 5-HTTLPR s/s genotype had 3-fold higher odds of PSD compared with l/l or l/xl genotype carriers (odds ratio, 3.1; 95% confidence interval, 1.2-8.3). Participants with the STin2 9/12 or 12/12 genotype had 4-fold higher odds of PSD compared with STin2 10/10 genotype carriers (odds ratio, 4.1; 95% confidence interval, 1.2-13.6). An association of rs25531 with PSD was not shown. CONCLUSIONS: The 5-HTTLPR and the STin2 VNTR, but not the rs25531, polymorphisms of SERT are associated with PSD in stroke survivors. This gives further evidence of a role of SERT polymorphisms in mediating resilience to biopsychosocial stress.