Diagnosis Of Current Major Depression Research Articles

The impact of traumatic childhood experiences on interoception: disregarding one’s own body

BackgroundDeficient interoception, the processing and perception of internal bodily signals, has been discussed as a mechanism underlying various mental disorders. First results indicate a mediating role of interoception in the interplay of traumatic childhood experiences and adult mental disorders. Traumatic childhood experiences may hinder the adequate processing, integration, and trust in bodily signals that are important in order to understand and regulate own needs and emotions, thereby increasing the vulnerability for mental disorders. However, an overarching study investigating alterations in different interoceptive measures and trauma-related disorders as well as their mediating role between early trauma and emotion dysregulation is still missing.MethodsOne hundred thirty-six individuals with varying levels of traumatic childhood experiences who either had a current diagnosis of major depression, posttraumatic stress disorder, or somatic symptom disorder, or no mental disorder, took part in a multidimensional assessment of interoceptive processes, including interoceptive accuracy, sensibility, and awareness. Kruskal–Wallis tests were used to compare groups regarding interoceptive processes and associations with traumatic childhood experiences and emotion dysregulation were analyzed with Spearman correlations. Furthermore, mediation analyses were computed to examine and compare interoceptive processes as potential mediators between traumatic childhood experiences and emotion dysregulation.ResultsOnly body dissociation, a measure for interoceptive sensibility, was significantly reduced in individuals with a current mental disorder. Body dissociation was also the only interoceptive measure significantly associated with traumatic childhood experiences and emotion dysregulation and the only significant mediator in the relationship between traumatic childhood experiences and emotion dysregulation across groups.ConclusionResults suggest body dissociation, but not other interoceptive measures, as an important feature linking traumatic childhood experiences to current emotion dysregulation, an important transdiagnostic feature. As body dissociation refers to a habitual non-attendance or disregard of interoceptive signals, integrative therapeutic interventions could help affected individuals to overcome difficulties in emotion perception and regulation.Trial registrationThe general study design was preregistered; see the German Clinical Trials Register (DRKS-ID: DRKS00015182). This study’s analysis plan was not preregistered.

Reducing worry and rumination in young adults via a mobile phone app: study protocol of the ECoWeB (Emotional Competence for Well-Being in Young Adults) randomised controlled trial focused on repetitive negative thinking

BackgroundPromoting well-being and preventing poor mental health in young people is a major global priority. Building emotional competence skills via a mobile app may be an effective, scalable and acceptable way to do this. A particular risk factor for anxiety and depression is elevated worry and rumination (repetitive negative thinking, RNT). An app designed to reduce RNT may prevent future incidence of depression and anxiety.Method/designThe Emotional Competence for Well-Being in Young Adults study developed an emotional competence app to be tested via randomised controlled trials in a longitudinal prospective cohort. This off-shoot study adapts the app to focus on targeting RNT (worry, rumination), known risk factors for poor mental health. In this study, 16–24 year olds in the UK, who report elevated worry and rumination on standardised questionnaires are randomised to (i) receive the RNT-targeting app immediately for 6 weeks (ii) a waiting list control who receive the app after 6 weeks. In total, the study will aim to recruit 204 participants, with no current diagnosis of major depression, bipolar disorder or psychosis, across the UK. Assessments take place at baseline (pre-randomisation), 6 and 12 weeks post-randomisation. Primary endpoint and outcome for the study is level of rumination assessed on the Rumination Response Styles Questionnaire at 6 weeks. Worry, depressive symptoms, anxiety symptoms and well-being are secondary outcomes. Compliance, adverse events and potentially mediating variables will be carefully monitored.DiscussionThis trial aims to better understand the benefits of tackling RNT via an mobile phone app intervention in young people. This prevention mechanism trial will establish whether targeting worry and rumination directly via an app provides a feasible approach to prevent depression and anxiety, with scope to become a widescale public health strategy for preventing poor mental health and promoting well-being in young people.Trial registrationClinicalTrials.gov, NCT04950257. Registered 6 July 2021 – Retrospectively registered.

Relationship between body mass index and neuropsychiatric symptoms: Evidence and inflammatory correlates

ObjectiveNeuropsychiatric symptoms are frequent in obese individuals. Mounting evidence suggests that adiposity-related inflammation contributes to this effect. This study assessed the relationship between adiposity, neuropsychiatric symptom dimensions and systemic inflammation in subjects stratified by body-mass-index (BMI). MethodsThe study included 165 subjects, of whom 70 were very severely obese (BMI ≥ 40 kg/m2), 50 severely obese (BMI: 35–39.99 kg/m2), 21 overweight or moderately obese (BMI: 25–34.9 kg/m2), and 24 lean (BMI < 25 kg/m2). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mini-International Neuropsychiatric Interview (MINI). Fatigue and general neurobehavioral symptoms were assessed using the Multidimensional Fatigue Inventory (MFI) and Neurotoxicity Rating Scale (NRS) respectively. Serum levels of the inflammatory markers, high-sensitive (hs) CRP and hsIL-6, were determined by ELISA. ResultsSeverely obese subjects exhibited higher MADRS, MFI and NRS scores and were more frequently afflicted with current diagnosis of major depression than lean participants. Scores on psychometric scales were also increased in very severely obese subjects, although to a lesser extent. Alterations in neuropsychiatric dimensions were highly inter-related. HsCRP was significantly increased in subjects with severe or very severe obesity, while hsIL-6 was augmented in all obese groups. Overall, increased neuropsychiatric comorbidity was associated with greater systemic inflammation, notably hsCRP. ConclusionObesity is characterized by an increased prevalence of inter-related neuropsychiatric symptoms together with low-grade systemic inflammation augmenting with adiposity. The association between adiposity, systemic inflammation and neuropsychiatric alterations supports the contribution of adiposity-related inflammatory processes to neuropsychiatric comorbidities in obesity. These data suggest that consideration of adiposity characteristics may help identifying subjects at increased risk for neuropsychiatric comorbidity.

11β-Hydroxylase (CYP11B1) gene variants and new-onset depression in later life.

BackgroundCumulative exposure to high glucocorticoid levels is detrimental for the brain and may have particular implications in later life. A feature of late-life depression is increased cortisol secretion. Variants in the CYP11B1 gene, which codes for the enzyme responsible for cortisol synthesis, could influence risk of late-life depression, but this hypothesis has not been examined. We investigated the associations between variants in the CYP11B1 gene and late-life depression, taking into account history of depression and potential sex-specific effects.MethodsWe assessed depression in 1007 community-dwellers aged 65 years or older (60% women) at baseline and over a 14-year follow-up. A clinical level of depression was defined as a score of ≥ 16 on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). We examined incident and recurrent depression in participants without or with a history of major depression, respectively. We genotyped 5 single-nucleotide polymorphisms (SNPs) spanning CYP11B1. We used multivariable analyses to adjust for age, body mass index, cardiovascular ischemic pathologies, hypertension, cognitive impairment and anxiety.ResultsIn women, rs6471580 and rs7016924 were associated with a 50% lower rate of incident (new-onset) late-life depression, and rs11783855 was associated with a 2.4-fold higher rate of late-life depression. These associations remained after correction for multiple testing, but we found no associations for recurrent depression in women or men.LimitationsThis study focused on the major gene involved in corticosteroid biosynthesis, but other genes may also be implicated in this pathway.ConclusionVariants of the CYP11B1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner.

Late-Life Depression Is Associated With Reduced Cortical Amyloid Burden: Findings From the Alzheimer’s Disease Neuroimaging Initiative Depression Project

BackgroundWe evaluated the role of cortical amyloid deposition as a factor contributing to memory dysfunction and increased risk of dementia associated with late-life depression (LLD). MethodsA total of 119 older adult participants with a current diagnosis of major depression (LLD) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Depression Project study and 119 nondepressed (ND) cognitively unimpaired participants matched on age, sex, and APOE genotype were obtained from the ADNI database. ResultsThirty-three percent of LLD participants met ADNI criteria for mild cognitive impairment. Compared with ND individuals, the LLD group exhibited less global amyloid beta (Aβ) accumulation (p = .05). The proportion of amyloid positivity in the LLD group was 19.3% compared with 31.1% for the ND participants (p = .02). Among LLD participants, global Aβ was not associated with lifetime number of depressive episodes, lifetime length of depression, length of lifetime selective serotonin reuptake inhibitor use, or lifetime length of untreated depression (p > .21 for all). Global Aβ was associated with worse memory performance (p = .05). Similar results were found in secondary analyses restricting comparisons to the cognitively unimpaired LLD participants as well as when comparing the LLD group with an ND group that included participants with mild cognitive impairment. ConclusionsContrary to expectation, the LLD group showed less Aβ deposition than the ND group and Aβ deposition was not associated with depression history characteristics. Aβ was associated with memory, but this relationship did not differ between LLD and ND. Our results suggest that memory deficits and accelerated cognitive decline reported in previous studies of LLD are not due to greater cortical Aβ accumulation.

SUSCEPTIBILITY TO COGNITIVE AND EMOTIONAL INTERFERENCE IN LATE-LIFE DEPRESSION

Introduction Susceptibility to cognitive interference is common in older adults with major depression. Traditionally susceptibility to cognitive interference is measured with “cold” cognitive tasks such as the Stroop Color Word test. Etkin and colleagues developed an emotional version of the classic Stroop test included as a condition of the Cognitive and Emotional Conflict Test. There are two conditions for this test where participants are presented with photographs of emotional faces portraying either fear or happiness: 1) the “non-emotional task,” where participants identify the gender of the face while trying to ignore congruent or incongruent gender labels displayed across the faces; and 2) the “emotional task,” where participants identify the facial expression as happy to fearful while trying to ignore congruent or incongruent emotion labels displayed across the faces. There is some functional neuroimaging evidence from younger adults to suggest that these two conditions may activate distinct cognitive and emotional control systems. However, little if any behavioral data is available for this task in older adults with major depression. The aim of the current study was to examine the effect of late-life major depression and chronic worry / emotional instability (neuroticism) on the Cognitive and Emotional Conflict Test. We first contrasted test performance in older adults with major depression compared to non-depressed elders and hypothesized that depressed patients would perform worse on both test conditions. We next contrasted test performance in older adults with major depression with either high or low in neuroticism. Considering that adults with depression and neuroticism exhibit worse performance on “cold” cognitive tests and heightened sensitivity to negative stimuli, we hypothesized that elders with depression and high neuroticism would perform worse on both test conditions compared to depressed elders with low neuroticism. Finally, we explored whether the emotion valence expressed by the face in the test stimuli influenced the results. Methods The sample included 118 adults age 60+ with a current diagnosis of major depression based on DSM-V criteria and 43 non-depressed cognitively normal older adults (NC). All participants completed a comprehensive evaluation including a clinical interview with a geriatric psychiatrist and detailed subjective and objective assessment of cognition and mood. The measures relevant to this study included the Montgomery Asberg Depression Rating Scale (MADRS), The Cognitive and Emotional Conflict Test, and the neuroticism subscale of the NEO-PI-R. The main outcomes were differences between congruent and incongruent trials on the two conditions of the Cognitive and Emotional Conflict Test. Congruent trials are defined as having the word and picture match, while incongruent is when it is when they do not match. Multivariate analyses of covariance (MANCOVA) controlling for age and sex were used to test the main hypotheses. Results When contrasting patients and controls, depressed patients exhibited a significantly slower reaction time when completing the non-emotional task (F (1,158) = 4.90, p = .028). No differences were found between groups for reaction time on the emotional task (F (1,158) = .312, p = .577. Contrary to our hypotheses, when these analyses were repeated contrasting depressed patients with high and low neuroticism based upon median split (NEO-PI-R Neuroticism Raw Score = 111), there were no significant group differences on either the non-emotional (F (1,148) = 1.76, p = .187) or emotional (F (1,148) = .104, p = .747) condition. Separating the outcomes based upon emotional expression did not result in significant group differences when contrasting controls versus patients or high and low neurotic patients. Conclusions Compared with non-depressed cognitively normal subjects, older adults with major depression performed slower on a “non-emotional”, but not a presumed “emotional”, interference test. This finding supports evidence suggesting weakness in “cold” response inhibition (presumably dependent on the cognitive control network mediated by the dorsal lateral prefrontal cortex) is a prominent deficit in late-life depression. To better understand this test, future studies may wish to examine the correlation with other “hot” (e.g., Iowa Gambling) and “cold” (e.g., Stroop) cognitive tests as well as structural and functional imaging correlates in older adults. This research was funded by: Research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under linked Award Numbers RL5GM118969, TL4GM118971, UL1GM118970; by National Institute of Mental Health grant R01 MH108578; and by the Leo and Anne Albert Charitable Trust.

Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression.

Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined. This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety. Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels. Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels.

Determinants of Suicide-related Ideation in Late Life Depression: Associations with Perceived Stress

ABSTRACTObjectives: Perceived stress is emerging as a potential contributing factor in suicide-related ideation in older adults. We hypothesized higher levels of perceived stress would be associated with increased self-reported suicidal ideation independent of depressive symptom severity.Methods: This study used data from community-dwelling older adults aged ≥65 with a current diagnosis of major depression. Eligible participants completed measures of depression symptom severity (Hamilton Depression Rating Scale-17 item), current suicidal ideation (Geriatric Suicide Ideation Scale), and perceived stress (Perceived Stress Scale).Results: Participants were 225 older adults with a mean age of 71.4 (SD = 5.6). Sixty-five percent of the sample was female. Fifteen percent of the variance in suicidal ideation was accounted for by lower education (p = .03), male sex (p = .03) and higher current perceived stress (p < .001). Specifically, stress accounted for 12% of the variance.Conclusions: Perceived stress is an important avenue to increase identification of individuals with a higher risk of suicide-related ideation among older adults with a current diagnosis of major depression.Clinical Implications: Screening for perceived stress may allow for improved screening and prevention of suicidal activity in depressed older adults.

Lower resting cardiac autonomic balance in young adults with current major depression.

Research on cardiac autonomic function in major depressive disorder (MDD) has predominantly examined cardiac vagal control and adopted a model of reciprocal autonomic balance. A proposed bivariate autonomic continuum uses cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) models, derived from normalized values of respiratory sinus arrhythmia and pre-ejection period, to more adequately index patterns of autonomic control. The purpose of this study was to assess resting levels of CAB and CAR among young adults with and without a current diagnosis of major depression. One hundred forty-two young adults (n=65 MDD, n=77 healthy controls; 20.8±2.6 years) completed a structured diagnostic interview, cardiovascular assessment, and a maximal aerobic fitness test. The findings revealed that CAB, but not CAR, significantly predicted current MDD status (OR=0.70, 95% CI [0.53, 0.93]), an effect that remained after controlling for aerobic fitness and body mass index. Although CAB was found to be a significant predictor of current MDD status among a sample of young adults, there remained substantial variation in autonomic control that was not captured by the traditional model of reciprocal autonomic balance.

Diagnostic, clinical, and personality correlates of food anxiety during a food exposure in patients diagnosed with an eating disorder.

Eating disorders are characterized by high levels of anxiety, especially while eating. However, little is known about anxiety experienced during meals and specifically what other variables may impact such anxiety. We sought to further quantify and understand the relationship between food anxiety, eating disorders, and related correlates (e.g., comorbid diagnoses, personality). In the current study [N = 42 participants diagnosed with an eating disorder (n = 36 participants with anorexia nervosa)], we quantified anxiety before, during, and after a meal using data from a food exposure session in a partial hospital eating disorder center. We examined diagnostic, personality, and clinical factors as correlates of food anxiety. Participants were more likely to experience higher food anxiety if they had a current diagnosis of major depression, obsessive-compulsive disorder, or post-traumatic stress disorder (PTSD). Concern over mistakes was the strongest and most consistent correlate of food anxiety regardless of time during the meal that anxiety was assessed. Other significant correlates were fear of positive evaluation, social appearance anxiety, BMI, and trust. These findings show how diagnoses, perfectionism (concern over mistakes), and other correlates relate to anxiety during meals. Food exposure interventions may benefit from personalizations that address these factors. IV Evidence from a randomized control trial, but from the first session before effects of the design would be present.

DETERMINANTS OF SUICIDAL IDEATION IN OLDER ADULTS WITH MAJOR DEPRESSION – ASSOCIATIONS WITH PERCEIVED STRESS

Introduction Depression has been strongly linked to suicide ideation in older adults. However, the role of other factors is less clear. Perceived stress is a factor that is emerging as a potential contributing factor in suicide ideation in older adults. We hypothesized higher levels of perceived stress would be associated with increased self-reported suicidal ideation independent of depressive symptom severity in older adults with LLD. Methods This study used data from community-dwelling older adults aged 65 with current diagnosis of major depression. Eligible participants completed measures of depression symptom severity (Hamilton Depression Rating Scale-17 item), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and perceived stress (Perceived Stress Scale; PSS). Statistical analyses were conducted using SPSS version 20. Descriptive statistics, including demographic and clinical characteristics of the participants were obtained. A linear regression analysis was then conducted, assessing the relationship of perceived stress to suicidal ideation, controlling for the effects of age, education, gender, and depression symptom severity. R2 were then calculated based on standardized beta values in the final model. Results Participants were 225 older adults with a mean age of 71.4 (SD = 5.6), who were 64.9% female. Sixteen percent of the variance in suicidality (GSIS total score) was accounted for by the variables assessed. In particular, lower education (B = −.13, p = .04), male gender (B = −.13, p = .04), greater depression severity (B = .15, p = .02) and higher current perceived stress (B = .32, p Conclusions Our findings suggest that increased perceived stress might be a particularly important factor of those more likely to think about suicide. Perceive stress may thus be a useful factor that could improve early identification and intervention of suicide ideation among late life depression patients at a high risk for suicidal behaviors. Mechanisms and coping strategies to reduce perceived stress could be directly implemented in depressed patients with suicidal ideation. Further research is warranted on perceived stress in relation to suicidal ideation. This research was funded by This work was supported by R01 MH0977669: (PI:Mackin), R01 MH101472 (PI:Mackin); UCSF Epstein Endowment Fund

Psychological Symptoms of Sexually Victimized Children and Adolescents Compared With Other Maltreatment Subtypes

ABSTRACTThe differential effects of sexual victimization and other forms of maltreatment on psychological functioning are not well understood. A sample of sexually victimized children and adolescents (N = 70; 6.3–17.9 years) and a group of youth with a history of nonsexual maltreatment (N = 108; 6.7–16.9 years) were compared using measures of mental health and psychosocial functioning. Assessments included standardized clinical interviews on individual maltreatment history and current psychopathology as well as questionnaires on behavioral and emotional symptoms, including posttraumatic stress symptoms. The results from this study suggest that the risk of experiencing any current mental disorders was independent of type of maltreatment. The risk of meeting the criteria for a current diagnosis of major depression, however, is greater among youth with a history of maltreatment that includes sexual victimization. The significant impact of sexual victimization on posttraumatic stress symptoms was found to be nonsignificant after controlling for age and gender effects. The results indicate that the outcomes of child maltreatment depend on type of maltreatment, but age and gender must be taken into account.

Patterns and correlates of attempted suicide amongst heroin users: 11-year follow-up of the Australian treatment outcome study cohort

Lifetime and recent rates of attempted suicide and suicidal ideation amongst the Australian Treatment Outcome Study cohort of heroin users at 11-year follow-up were examined. The mean elapsed time since heroin initiation was 20.4 years. At 11-year follow-up, 42.2% of the cohort reported ever having made a suicide attempt, 11.1% having made a first attempt subsequent to baseline. In the year preceding 11-year follow-up, 1.6% had made an attempt, suicidal ideation was reported by 10.4%, and 4.2% had a current suicide plan. After controlling for other variables, past 12 month attempts, current ideation or plans were independently associated with a current diagnosis of Major Depression (odds ratios (OR) 1.67) and more extensive polydrug use (OR 1.39), while each standard deviation higher on the SF12 physical health scale (reflecting better health) was associated with reduced odds (OR 0.66). Suicide and suicidal ideation remained a significant clinical issue for heroin users, some 20 years after their heroin use commenced.

HAM/TSP and major depression: the role of age

ObjectiveTo investigate the role of demographic variables in the relationship between the presence of HAM/TSP and current major depression. MethodsIt is a cross-sectional study of 108 HTLV-1 infected patients (47 with TSP/HAM) resident of Salvador, Brazil. The Mini International Neuropsychiatric Interview, Brazilian Version 5 was used to evaluate the presence of depression. Prevalence ratios were used to describe relationship between HAM/TSP and depression. The HAM/TSP classification was carried out according to the criteria proposed by Castro-Costa et al. ResultsPrevalence of depression was 37.96%. No association was observed between presence of HAM/TSP and diagnosis of current major depression in the global analysis of patients (PR: 0.94; CI 95%: 0.57–1.55). In the stratified analysis, however, greater prevalence of depression was observed amongst individuals with HAM/TSP in the 18–39 age group (PR: 2.59; CI 95%: 1.36–4.95). ConclusionOur findings suggest that age is an effect modifier in the relationship between HAM/TSP and depression, and this aspect should be considered in future studies on the topic.

C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression.

Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression

Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic–pituitary–adrenocortical (HPA) axis, which shows hyperactivity in depressed patients. ACE could thus be a promising candidate gene for late-life depression but this has not been examined previously. Depression was assessed in 1005 persons aged at least 65 years, at baseline and over the 10-year follow-up. A clinical level of depression (DEP) was defined as having a score of ⩾16 on the Centre for Epidemiology Studies-Depression scale or a diagnosis of current major depression based on the Mini International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) in the ACE gene were genotyped and diurnal cortisol secretion, as an index of HPA axis activity, was measured. Multivariable analyses were adjusted for socio-demographic and vascular factors, cognitive impairment, and apolipoprotein E. Strong significant associations were found between all seven SNPs and DEP and, in particular, first-onset DEP in persons without a past history of depression (P-values ranging from 0.005 to 0.0004). These associations remained significant after correction for multiple testing. The genotypes that were associated with an increased risk of DEP were also significantly associated with an increase in cortisol secretion under stress conditions. Variants of the ACE gene influence cortisol secretion and appear as susceptibility factors for late-life depression in the elderly population. Whether this could represent a common pathophysiological mechanism linking HPA axis and late-life depression remains to be explored.

A Longitudinal Study of Nonsuicidal Self-Injury in Offspring at High Risk for Mood Disorder

To determine the demographic and clinical predictors of nonsuicidal self-injury and to examine the longitudinal relationship between nonsuicidal self-injury and suicide attempt. This was a longitudinal cohort study of the familial transmission of suicidal behavior. The sample consisted of probands with DSM-IV mood disorder (n = 212), 54.2% of whom were suicide attempters, and their offspring aged at least 10 years (n = 352), followed for a mean of 3.8 years. Personal, parental, and familial characteristics were assessed annually to identify the most parsimonious subset of these variables associated with nonsuicidal self-injury, the primary outcome. Data were collected between August 1998 and August 2007. Of 352 offspring, 7.4% (n = 26) engaged in nonsuicidal self-injury during follow-up. In the final model examining predictors at baseline, the most severe time point, and the time point prior to nonsuicidal self-injury, only predictors from the most proximal time point were significant, namely younger age (odds ratio [OR] = 0.75, P = .002), diagnosis of current major depression (OR = 5.09, P < .001), and suicidal ideation (OR = 1.46, P = .02). In 2 of the 3 single time point models, baseline nonsuicidal self-injury was the most significant predictor of nonsuicidal self-injury during follow-up. Suicide attempt was predicted by both baseline nonsuicidal self-injury and suicide attempt, but when both were included in the model, nonsuicidal self-injury was a significant predictor (OR = 7.50, P = .009), but suicide attempter was not (OR = 3.78, P = .08); offspring aggression (OR = 1.11, P = .01) predicted suicide attempt but not nonsuicidal self-injury. Parental histories of nonsuicidal self-injury, suicide attempt, and abuse were not predictive of nonsuicidal self-injury. Nonsuicidal self-injury may be an earlier manifestation of a shared diathesis with suicide attempt, consisting of depression and suicidal ideation, and that diathesis may lead to suicidal behavior in the face of greater offspring aggression and family pathology. The apparent bidirectional temporal relationship between nonsuicidal self-injury and suicide attempt may be explained by this shared diathesis.

FC23-02 - Gender and genotype modulation of the association between lipid levels and depressive symptomatology in community-dwelling elderly

BackgroundLipids appear to mediate depressive vulnerability in the elderly, however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies.MethodsDepression was assessed in a population of 1040 women and 752 men aged 65 years and over at baseline and after 7-year follow-up. Clinical level of depression (DEP) was defined as having either a score of 16 and above on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini International Neuropsychiatric Interview. Lipid levels, apolipoprotein E and serotonin transporter linked promoter region (5-HTTLPR) genotypes were evaluated at baseline.ResultsMultivariate analyses adjusted by socio-demographic and behavioral variables, measures of physical health including ischemic pathologies, and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP, independent of the use of lipid lowering agents or apolipoprotein E status. Men with low LDL-cholesterol levels had twice the risk of prevalent and incident DEP whereas in women low HDL-cholesterol levels were found to be significantly associated with increased prevalent DEP (OR = 1.5) only. A significant interaction was observed between low LDL-cholesterol and 5-HTTLPR genotype, men with s/s or s/l genotype being at increased risk of DEP (OR = 6.0 and 2.7, respectively). No significant gene-environment interaction was observed for women.ConclusionsDEP is associated with higher atherogenic risk in women (low HDL-cholesterol), whereas the reverse is observed in men (low LDL-cholesterol). Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men.

The cortisol awakening response predicts subclinical depressive symptomatology in Mexican American adults

While childhood trauma appears to be a risk factor for the onset of depression and subclinical depressive symptomatology in Mexican Americans, the specific physiological mechanisms contributing to this relationship remain to be clarified. Stress-induced dysregulation of the Hypothalamic–Pituitary–Adrenal (HPA) axis is associated with depressive symptomatology in non-Hispanics. The current study assessed the extent to which the cortisol awakening response (CAR) predicts subclinical depressive symptomatology beyond the influence of childhood trauma in a sample of 55 Mexican American males and females ages 18–38 years, without a diagnosis of clinical depression. Participants were assessed for exposure to early trauma and current depressive symptomatology. Salivary cortisol samples were collected on two consecutive days at awakening, 30, 45, and 60 min thereafter, and again at 3 p.m., 6 p.m. and 9 p.m. Data were analyzed using general linear models with repeated measures at four morning time points, and again, at three afternoon and evening time points. Results indicated a significant Symptoms × Time interaction for the CAR( p < 0.05). The Symptom × Time interaction was not significant for afternoon and evening cortisol concentrations. Moreover, subclinical symptomatology was associated with attenuation of the initial rise in CAR, after controlling for the total frequency of exposure to childhood traumas. Hierarchical analyses show attenuation of the initial rise in the CAR was the best predictor of greater subclinical depressive symptomatology beyond the influence of trauma, and independent of a current diagnosis of major depression in a sample of adult Mexican Americans.

Gender and Genotype Modulation of the Association Between Lipid Levels and Depressive Symptomatology in Community-Dwelling Elderly (The ESPRIT Study)

Lipids appear to mediate depressive vulnerability in the elderly; however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies. Depression was assessed in a population of 1040 women and 752 men aged 65 years and older at baseline and after 7-year follow-up. Clinical level of depression (DEP) was defined as having either a score of 16 or higher on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini-International Neuropsychiatric Interview. Lipid levels, apolipoprotein E, and serotonin transporter linked promoter region (5-serotonin transporter gene linked promoter region) genotypes were evaluated at baseline. Multivariate analyses adjusted by sociodemographic and behavioral variables, measures of physical health including ischemic pathologies, and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP, independent of the use of lipid-lowering agents or apolipoprotein E status. Men with low low-density lipoprotein cholesterol levels had twice the risk of prevalent and incident DEP, whereas in women low high-density lipoprotein cholesterol levels were found to be significantly associated with increased prevalent DEP (odds ratio = 1.5) only. A significant interaction was observed between low low-density lipoprotein-cholesterol and 5-serotonin transporter gene linked promoter region genotype, men with s/s or s/l genotype being at increased risk of DEP (odds ratio = 6.0 and 2.7, respectively). No significant gene-environment interaction was observed for women. DEP is associated with higher atherogenic risk in women (low high-density lipoprotein cholesterol), whereas the reverse is observed in men (low low-density lipoprotein cholesterol). Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men.