Glucocorticoids exert profound effects on the brain and behavior, but cortisol concentrations are rarely linked to subjectively reported emotional states in humans. This study examined whether the link between cortisol and subjective anxiety varied by childhood maltreatment history. To do this, 97 individuals (60.8% female) participated in a standardized stress task in the laboratory (Trier Social Stress Test, TSST) while providing serial ratings of their feelings of anxiety as well as cortisol samples in blood. These measurements were collected nine times across the laboratory visit, from immediately before the TSST to 65 minutes after stress initiation. We estimated the within-person association between cortisol concentrations and momentary feelings of anxiety for individuals with and without exposure to childhood maltreatment, measured via self-report on the Childhood Trauma Questionnaire (CTQ). Individuals exposed to maltreatment during childhood reported the greatest feelings of anxiety when cortisol concentrations were lowest. This pattern was exaggerated among female participants, those with posttraumatic stress disorder (PTSD), and those exposed to emotional neglect relative to other forms of maltreatment. Early life adversity, such as parental maltreatment, may alter the role of cortisol in affective experiences. This observation may provide preliminary, translational evidence of a novel pathway through which stress may lead to and maintain internalizing symptoms in humans. More studies accounting for the moderating role of childhood maltreatment in biobehavioral pathways are needed.

Drawing upon Berry's (1980) bi-dimensional model of acculturation and using data from a community-based sample of adults in Miami-Dade, Florida, the current investigation compared various immigrant acculturation profiles in their levels of depressive symptoms and assessed the mediating role of social support in explaining mental health differences across these acculturation profiles. Latent class analysis specified separated, partial separated, bicultural and marginal profiles of acculturation among Latino immigrants. Notably, our findings identified a small, albeit significant, marginal class among Latino immigrants, and both bivariate and multivariate findings demonstrated that those in marginal class reported the poorest mental health. Our findings further revealed that the observed mental health disadvantage among the marginal class relative to other immigrants was due to their disadvantage in family support . Overall, this investigation further underscores the importance of family support as an element of immigrant acculturation experience and mental health. From a policy perspective, social support, specifically family support, is critical for immigrant mental health, and a lack of family support may increase the risk for developing a marginal experience and mental health problems among a growing population of Latino immigrants in the United States.

Background: Much work has documented hypothalamic pituitary adrenal (HPA) axis abnormalities in major depressive disorder (MDD), but inconsistencies leave this system's role in the illness unclear. Comparisons across studies are complicated by variation in co-morbidity (Posttraumatic Stress Disorder-PTSD, anxiety disorders), exposure to trauma, and timing of trauma (child vs. adult). Here, we examined the impact of these factors on HPA axis profiles in depression. Methods: We recruited 5 groups of participants: MDD (n = 14), comorbid MDD + PTSD following adulthood trauma (MDD + PTSD-Adult; n = 12), comorbid MDD + PTSD following childhood trauma (MDD + PTSDChild; n = 18), comorbid MDD + social anxiety disorder (MDD + SAD; n = 12), and non-depressed control participants who were sex and age matched to patients (combined total n = 36). HPA axis function was assessed using three challenges: stress reactivity via the Trier Social Stress Test (TSST), feedback sensitivity via a dexamethasone suppression test (DST), and central drive via a metyrapone challenge (MET). We compared hormonal responses between patient groups and their respective non-depressed controls. Results: MDD + PTSD-Child showed low cortisol levels at baseline, and reduced adrenocorticotropic hormone (ACTH) levels at baseline and throughout the TSST. MDD-only, MDD + PTSD-Adult, and MDD + SAD did not differ from non-depressed controls in HPA axis responses to the TSST. Controlling for childhood trauma severity, the reduced baseline levels in MDD + PTSD-Child were no longer significant and significantly reduced baseline cortisol levels emerged for MDD + PTSD-Adult. No diagnostic group effects were detected with DST and MET. Childhood maltreatment subtypes were associated with unique HPA axis responses to TSST and MET. Conclusion: Comorbidity and trauma exposure, as well as their timing and type, contribute to inconsistencies in the depression literature and must be included in efforts to clarify the role of the HPA axis in MDD.

Background: Successful correction of hindfoot alignment in adult acquired flatfoot deformity (AAFD) is likely influenced by the degree of medializing calcaneal osteotomy (MCO) performed, but it is not known if other reconstruction procedures significantly contribute as well. The purpose of this study was to evaluate the correlation between common preoperative and postoperative variables and hindfoot alignment. Methods: Thirty patients with stage II AAFD undergoing flatfoot reconstruction were followed prospectively. Preoperative and postoperative radiographs were reviewed to assess for correction in hindfoot alignment as measured by the change in hindfoot moment arm. Nineteen variables were analyzed, including age, gender, height, weight, body mass index (BMI), medial cuneiform-fifth metatarsal height, anteroposterior (AP) talonavicular coverage, AP talus-first metatarsal, lateral talus-first metatarsal and calcaneal pitch angles as well as intraoperative use of the MCO, lateral column lengthening (LCL), Cotton osteotomy, first tarsometatarsal fusion, flexor digitorum longus transfer, spring ligament reconstruction, and gastrocnemius recession or Achilles lengthening. Mean age was 57.3 years (range, 22-77). Final radiographs were obtained at a mean of 47 weeks (range, 25-78) postoperatively. Results: Seven variables were found to significantly affect hindfoot moment arm. These were gender (P < .05), the amount of MCO performed (P < .001), LCL (P < .01), first tarsometatarsal fusion (P < .01), spring ligament reconstruction (P < .01), medial cuneiform-fifth metatarsal height (P < .001), and calcaneal pitch angle (P < .05). Multivariate regression analysis revealed that MCO was the only significant predictor of hindfoot moment arm. The final regression model for MCO showed a good fit (R2 = .93, P < .001). Conclusion: Correction of hindfoot valgus alignment obtained in flatfoot reconstruction is primarily determined by the MCO procedure and can be modeled linearly. We believe that the hindfoot alignment view can serve as a valuable preoperative measurement to help surgeons adjust the proper amount of correction intraoperatively. Level of Evidence: Level IV, prospective case series.

BACKGROUND:Surgical treatment of multiplanar (varus and dorsal angulation) second toe deformities due to degenerative instability can lead to recurrence, stiffness, and pain. The goal of this study was to evaluate the short-term outcomes associated with a new technique using an extensor digitorum brevis (EDB) tendon reconstruction to correct such deviation of the second metatarsophalangeal (MTP) joint.METHODS:Ten patients (10 female, 0 male) with 11 operated second toes having undergone correction with a reconstruction using the EDB tendon were assessed at an average of 18.5 months (range, 12-34) after surgery. The technique was indicated when MTP and medial partial plantar plate release alone were not sufficient to correct multiplanar deformity. Radiographic parameters (AP and lateral metatarsal-proximal phalanx angles), physical exam (MTP joint range of motion), and subjective outcomes (the Foot and Ankle Outcome Score [FAOS]) were assessed. A toe-specific survey captured more detailed subjective information, including patient satisfaction.RESULTS:Preoperatively, the average MTP joint angle was 4.5 degrees in the varus direction, which changed to 14.2 degrees in the valgus direction postoperatively. On exam, the average MTP joint range of motion was 60.9 ± 11.6 degrees dorsiflexion and 11.1 ± 2.5 degrees plantarflexion. Postoperative FAOS scores demonstrated an average of 89.9 ± 9.8 for the symptoms domain. In all, 9 of 11 patients were either highly satisfied or moderately satisfied (none dissatisfied).CONCLUSION:With the stated limitations, the EDB tendon reconstruction technique described in conjunction with collateral ligament and partial plantar plate release provided powerful correction. Minimal release of the medial plantar plate and not overtightening the reconstruction are recommended to avoid shifting the toe in the opposite direction.LEVEL OF EVIDENCE:Level IV, retrospective study.

Background: Patient-reported outcome questionnaires such as the Foot and Ankle Outcome Score (FAOS) are useful in evaluating results after orthopedic interventions. However, despite being frequently used in the literature, its validity has not been established for forefoot disorders. Our study aimed to validate the FAOS for use in assessing outcomes of hallux valgus surgery. Methods: From 2006 to 2009, 195 patients with nonarthritic hallux valgus were included in the construct validity portion of the study. Patients had a SF-36 and a FAOS completed. Forty additional patients, both preoperative and postoperative, were given questionnaires to assess the relevance of each of the FAOS questions as it pertained to their bunions. Patients were also given the FAOS 1 month after the first to assess FAOS reliability. Responsiveness of the FAOS was included with 40 patients who had both preoperative and postoperative FAOS scores. Results: Four out of five FAOS subscales demonstrated acceptable correlation with the SF-36. The FAOS symptoms subscale showed the least correlation with SF-36, demonstrating the foot-specific nature of the questions. Both preoperative and postoperative patients rated the FAOS quality of life questions as the most relevant. All five subscales achieved acceptable test-retest reliability. The FAOS sports and recreation subscale was the least responsive. Conclusion: Patient-based assessments have become increasingly important in evaluating treatment effectiveness. This study has shown that the FAOS has acceptable construct validity, reliability, and responsiveness in hallux valgus patients and is a useful patient-based tool in assessing these patients.

Dysregulation of the hypothalamic-pituitary-adrenal axis is hypothesized to be an important pathway linking socioeconomic position and chronic disease.This paper tests the association between education and the diurnal rhythm of salivary cortisol.Up to eight measures of cortisol (mean of 5.38 per respondent) over 2 days were obtained from 311 respondents, aged 18-70, drawn from the 2001-2002 Chicago Community Adult Health Study. Multi-level models with linear splines were used to estimate waking level, rates of cortisol decline, and area-under-the-curve over the day, by categories of education.Lower education (0-11 years) was associated with lower waking levels of cortisol, but not the rate of decline of cortisol, resulting in a higher area-under-the-curve for more educated respondents throughout the day.This study found evidence of lower cortisol exposure among individuals with less education and thus does not support the hypothesis that less education is associated with chronic over-exposure to cortisol.

Objective: The purpose of this study was to determine whether there are differences in depression characteristics among premenopausal, perimenopausal, and postmenopausal women with major depressive disorder. This study also evaluated these differences between postmenopausal women with major depressive disorder who are taking and not taking hormone therapy.Methods: Analyses conducted with data from the Sequenced Treatment Alternatives to Relieve Depression study focused on female outpatients with nonpsychotic major depressive disorder seeking treatment in 41 primary or psychiatric care settings across the United States. Baseline demographic and clinical characteristics were compared among women not taking hormone therapy who were premenopausal (n = 950), perimenopausal (n = 380), or postmenopausal (n = 562). These comparisons were also made between postmenopausal women (n = 768) taking (n = 171) or not taking (n = 562) hormone therapy.Results: After adjusting for sociodemographic and clinical baseline differences, premenopausal women were more likely to present with irritability than were either perimenopausal or postmenopausal women and were more likely to have decreased appetite and less likely to have early-morning insomnia than were perimenopausal women. Postmenopausal women were more likely to have suicidal ideation and poorer physical functioning than were either of the other groups and were more likely to have sympathetic arousal and gastrointestinal symptoms than were premenopausal women. After adjusting for baseline differences, postmenopausal women taking hormone therapy had better physical functioning, fewer melancholic features, less sympathetic arousal, and more lack of involvement in activities than did women not taking hormone therapy.Conclusions: Menopause status and postmenopausal use of hormone therapy may influence the clinical presentation of major depressive episodes in women.

Background: The hypothalamic-pituitary adrenal (HPA) axis is critical for biobehavioral adaptation to challenge and appears dysregulated in a range of psychiatric disorders. Its precise rote in psychopathology remains unclear and discrepant and difficult to explain findings abound in the clinical literature. Basic research suggests this system is sensitive to psychosocial cues, but psychosocial milieu factors are rarely controlled or examined in psychiatric studies using biological probes of the HPA axis. To test the hypothesis that psychological factors might complicate HPA study results even in direct, pharmacological challenge paradigms, endocrine responses to corticotropin-releasing hormone (CRH) were examined under two different cognitive preparation conditions.Methods: Healthy subjects (n = 32) received standard instructions or a cognitive intervention (CI) prior to injection with CRH and placebo, given on separate days in random order. The CI combined access to control over drug exposure with novelty reduction and coping enhancement. Blood samples were obtained via intravenous catheter before and after CRHResults: Cognitive intervention reduced corticotropin (ACTH) levels, but only when CRH was given first (intervention by order interaction). It did not reduce cortisol response. The CI and visit (1st or 2nd) both impacted cortisol levels on placebo day.Conclusions: Modifiable psychological factors may amplify or inhibit HPA axis activity in pharmacological activation paradigms, including CRH stimulation tests. The factors manipulated by the CI (novelty/familiarity, control and coping) may have particular salience to the HPA axis. Differential sensitivity to such factors could impact results in studies applying biological HPA probes to psychiatric populations. (c) 2009 Elsevier Ltd. All rights reserved.

Objectives Desensitization of serotonin 1A (HTR1A) and 1B (HTR1B) autoreceptors has been proposed to be involved in the delayed onset of response to selective serotonin reuptake inhibitors (SSRIs). Variations in gene expression in these genes may thus affect SSRI response. Methods Here, we test this hypothesis in two samples from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), and show evidence for involvement of several genetic variants alone and in interaction. Initially, three functional single nucleotide polymorphisms (SNPs) in the HTR1B gene and in the HTR1A gene were analyzed in 153 depressed patients treated with citalopram. The 16-item Quick Inventory of Depressive Symptomatology Clinician scores were evaluated over time with respect to genetic variation. Results Individuals homozygous for the −1019 G allele (rs6295) in HTR1A showed the higher baseline 16-item Quick Inventory of Depressive Symptomatology Clinician scores (P=0.033), and by 12 weeks had a significantly lower response rate (P=0.005). HTR1B haplotypes were estimated according to the previously reported in-vitro expression levels. Individuals who were homozygous for the high-expression haplotype showed significantly slower response to citalopram (P=0.034). We then analyzed more SNPs in the extended overall STAR*D sample. Although we could not directly test the same functional SNPs, we found that homozygotes for the G allele at rs1364043 in HTR1A (P=0.045) and the C allele of rs6298 in HTR1B showed better response to citalopram over time (P=0.022). Test for interaction between rs6298 in HTR1B and rs1364043 in HTR1A was significant (overall P=0.032). Conclusion Our data suggest that an enhanced capacity of HTR1B or HTR1A transcriptional activity may impair desensitization of the autoreceptors during SSRI treatment.

Objective: Controversy exists as to whether women with depression respond better to selective serotonin reuptake inhibitors (SSRIs) than men. The purpose of this report was to determine whether men and women differ in their responses to treatment with the SSRI citalopram using a large sample of real world patients from primary and psychiatric specialty care settings.Method: As part of the sequenced treatment alternatives to relieve depression (STAR D) study, 2876 participants were treated with citalopram for up to 12-14 weeks. Baseline demographic and clinical characteristics and outcomes were gathered and compared between men and women.Results: At baseline, women were Younger, had more severe depressive symptoms and were more likely to have: early onset; previous suicide attempt(s); a family history of depression, alcohol abuse or drug abuse: atypical symptom features; and one or more of several concurrent psychiatric disorders. Despite greater baseline severity and more Axis I comorbidities, women were more likely to reach remission and response with citalopram than men.Conclusions: Women have a better response to the SSRI citalopram than men, which may be due to sex-specific biological differences particularly in serotonergic systems. (C) 2008 Elsevier Ltd. All rights reserved.

OBJECTIVE:Examine the diurnal variation of salivary cortisol in adults with spinal cord injury (SCI) and the effect of stressors on cortisol and mood.METHOD:Ecological momentary assessment (EMA) to capture cortisol, stress, and mood from 25 persons with SCI and 26 without SCI. Data were analyzed using linear mixed models.RESULTS:There were no systematic differences between groups on missing data. Diurnal variation of cortisol of participants with SCI reflected an expected pattern. No significant group differences for cortisol diurnal pattern, stress, or mood; when group interactions were significant, results indicated lower cortisol reactivity to stress in participants with SCI. Stress had a significant impact on positive, negative and agitated moods.CONCLUSIONS:Stress in daily life and its association with cortisol and mood were largely similar between persons with and without SCI. A key methodological contribution is the demonstration of using EMA to collect biological and behavioral data in the field from participants with SCI. The use of EMA in rehabilitation psychology research has great potential to advance our understanding of the dynamics of daily life with disability.

A variety of hypothalamic–pituitary–adrenal axis abnormalities have been described in depressed patients: cortisol hypersecretion, insensitivity to dexamethasone negative feedback, blunted corticotroph response to corticotropin-releasing hormone, increased adrenal response to ACTH infusion, and decreased sensitivity to glucocorticoid fast feedback. The overall picture suggests that depression generally shows both increased activity in circadian activational elements of the system and reduced feedback inhibition. Whether all of these abnormalities are present in the same individual or whether they represent different stages of the illness or different subgroups of patients remains an area for future research.

Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43% (medication augmentation); 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes.