Never-depressed Controls Research Articles

Script-driven imagery of socially salient autobiographical memories in major depressive disorder

Cues of social rejection and affiliation represent proximal risk and protective factors in the onset and maintenance of depression. Such cues are thought to activate an evolutionarily primed neuro-cognitive alarm system, alerting the agent to the benefits of inclusion or the risk of social exclusion within social hierarchies focused on ensuring continued access to resources. In tandem, autobiographical memory is thought to be over-general and negatively biased in Major Depressive Disorder (MDD) which can contribute to maintenance and relapse. How memories of social rejection and affiliation are experienced and processed in MDD remains unexplored. Eighteen participants with recurrent and chronic MDD and 18 never-depressed controls listened to and vividly revisited autobiographical social experiences in an ecologically valid script-driven imagery paradigm using naturalistic memory narratives in an fMRI paradigm. Memories of Social Inclusion and Social Rejection broadly activated a common network of regions including the bilateral insula, thalamus and pre/postcentral gyrus across both groups. However, having a diagnosis of MDD was associated with an increased activation of the right middle frontal gyrus irrespective of memory type. Changes in positive affect were associated with activity in the dorsal ACC in the MDD group and in the insular cortex of the Control group. Our findings add to the evidence for complex representations for both positive and negative social signals in MDD and suggest neural sensitivity in MDD towards any socially salient information as opposed to selective sensitivity towards negative social experiences.

Long-term stability of respiratory sinus arrhythmia among adults with and without a history of depression.

Respiratory sinus arrhythmia (RSA) is an index of parasympathetic nervous system activity reflecting respiratory influences on heart rate. This influence is typically measured as high frequency heart rate variability (HF-HRV) or root mean square of successive differences (RMSSD) of adjacent inter-beat intervals. Examining the long-term stability of its measurement is important as levels of resting RSA have been conceptualized as a marker of individual differences; in particular, of an individual's autonomic regulation and affect-related processes, including emotion regulation. At present, it is not known if resting RSA levels reflect stable differences over a long-term period (i.e., >1 year). Even less is known about how RSA stability differs as a function of depression history and whether it relates to depression risk trajectories. In the present study, we examined the 1.5-year test-retest reliability of resting RSA using the intraclass correlation coefficient (ICC) in 82 adults: n = 41 with a history of depression (ever-depressed); n = 41 controls with no depression history (never-depressed). HF-HRV was fairly stable in both groups (ever-depressed ICC = 0.55, never-depressed ICC = 0.54). RMSSD was also fairly stable in ever-depressed adults (ICC = 0.57) and never-depressed controls (ICC = 0.40). ICC values for both indices did not differ between groups per overlapping 95% confidence intervals. Therefore, RSA stability as assessed by both frequency (HF-HRV) and time domain (RMSSD) measures was not attenuated by a depression history. Implications and the need for future research are discussed.

Understanding and predicting future relapse in depression from resting state functional connectivity and self-referential processing

BackgroundThe recurrent nature of Major Depressive Disorder (MDD) asks for a better understanding of mechanisms underlying relapse. Previously, self-referential processing abnormalities have been linked to vulnerability for relapse. We investigated whether abnormalities in self-referential cognitions and functioning of associated brain-networks persist upon remission and predict relapse. MethodsRemitted recurrent MDD patients (n = 48) and never-depressed controls (n = 23) underwent resting-state fMRI scanning at baseline and were additionally assessed for their implicit depressed self-associations and ruminative behaviour. A template-based dual regression approach was used to investigate between-group differences in default mode, cingulo-opercular and frontoparietal network resting-state functional connectivity (RSFC). Additional prediction of relapse status at 18-month follow-up was investigated within patients using both regression analyses and machine learning classifiers. ResultsRemitted patients showed higher rumination, but no implicit depressed self-associations or RSFC abnormalities were observed between patients and controls. Nevertheless, relapse was related to i) baseline RSFC between the ventral default mode network and the precuneus, dorsomedial frontal gyrus, and inferior occipital lobe, ii) implicit self-associations, and iii) uncontrollability of ruminative thinking, when controlled for depressive symptomatology. Moreover, preliminary machine learning classifiers demonstrated that RSFC within the investigated networks predicted relapse on an individual basis. ConclusionsRemitted MDD patients seem to be commonly characterized by abnormal rumination, but not by implicit self-associations or abnormalities in relevant brain networks. Nevertheless, relapse was predicted by self-related cognitions and default mode RSFC during remission, suggesting that variations in self-relevant processing play a role in the complex dynamics associated with the vulnerability to developing recurrent depressive episodes. Clinical trial registrationNetherlands Trial Register, August 18, 2015, trial number NL53205.042.15.

Trying to name what doesn't change: Neural nonresponse to Cognitive Therapy for depression.

Theoretical models of neural mechanisms underlying Cognitive Behavior Therapy (CBT) for major depressive disorder (MDD) propose that psychotherapy changes neural functioning of prefrontal cortical structures associated with cognitive-control processes (DeRubeis, Siegle, & Hollon, ); however, MDD is persistent and characterized by long-lasting vulnerabilities to recurrence after intervention, suggesting that underlying neural mechanisms of MDD remain despite treatment. It follows that identification of treatment-resistant aberrant neural processes in MDD may inform clinical and research efforts targeting sustained remission. Thus, we sought to identify brain regions showing aberrant neural functioning in MDD that either (1) fail to exhibit substantive change (nonresponse) or (2) exhibit functional changes (response) following CBT. To identify treatment-resistant neural processes (as well as neural processes exhibiting change after treatment), we collected functional magnetic resonance imaging (fMRI) data of MDD patients (n = 58) before and after CBT as well as never-depressed controls (n = 35) before and after a similar amount of time. We evaluated fMRI data using conjunction analyses, which utilized several contrast-based criteria to characterize brain regions showing both differences between patients and controls at baseline and nonresponse or response to CBT. Findings revealed nonresponse in a cerebellar region and response in prefrontal and parietal regions. Results are consistent with prior theoretical models of CBT's direct effect on cortical regulatory processes but expand on them with identification of additional regions (and associated neural systems) of response and nonresponse to CBT.

Effects of current and past depressive episodes on behavioral performance and subjective experience during an N-back task

Background and objectivesDepression impairs working memory (WM). And, while many studies have documented impairment in WM during depression remission, those using the N-back task did not find differences between individuals with remitted depression and healthy controls. One reason for these findings may be that certain depression phenotypes, such as the childhood-onset form, which is likely to be associated with persistent WM problems, are underrepresented or unevenly represented in the studies. Because childhood-onset depression (COD) affects individuals while cognitive development is still ongoing, it is more likely to have lasting detrimental effects, as evidenced in residual memory impairment, than depression that onsets later in life. Further, it is unclear if depression episodes have cumulative effects on WM when measured via the N-back. MethodsWe examined the effects of depression on WM performance (response time, accuracy, signal detection d’) and subjective experience (difficulty, mental effort required) during a four-level N-back task among 112 adults with COD (42 currently depressed; 70 remitted depressed) and 80 never-depressed controls. ResultsCompared to never-depressed controls, there was minimal evidence of impaired WM performance among participants with remitted or current depression; the groups also reported overall similar subjective experiences during the N-back. Notably, number of lifetime depressive episodes had a detrimental cumulative effect on response accuracy and d’. LimitationsWM was assessed only in regard to verbal memory. The sample size of currently depressed cases was smaller than that of the other groups. ConclusionsWM remains largely intact among adults with remitted COD, but increased number of depression episodes worsens WM performance.

The impact of personality traits on the course of frailty

ABSTRACT Objectives Determinants of frailty are generally explored within context of somatic healthcare and/or lifestyle characteristics. To examine the impact of personality traits on change in frailty and the potential role of depression. Methods A 2-year follow-up study including 285 patients with a depressive disorder and 116 never-depressed controls. Multiple linear regression analyses were conducted to regress the Big Five personality traits (independent variables) on different frailty measures (dependent variables), including the Frailty Index, Frailty phenotype, gait speed, and handgrip strength. Analyses were adjusted for confounders (with and without depressive disorder) and baseline frailty severity. Interactions between personality traits and depressive disorder were examined. Results All personality traits were associated with change in at least one frailty marker over time. Over time, a higher level of neuroticism was associated with an accelerated increase of frailty, whereas a higher level of extraversion, agreeableness, conscientiousness and openness were associated with an attenuated increase of frailty. None of the associations were moderated by depression. Additional adjustment for depression decreased the strength of the association of neuroticism, extraversion and conscientiousness with frailty. Conclusions Personality traits have impact on frailty trajectories in later life. Clinical implications Underlying pathways and potential modification by psychotherapy merit further study.

Brain Response of Major Depressive Disorder Patients to Emotionally Positive and Negative Music.

Depression is characterized by poor emotion regulation that makes it difficult to escape the effects of emotional pain, but the neuromodulation behind these symptoms is still unclear. This study investigated the neural mechanism of emotional state-related responses during music stimuli in participants with major depressive disorder (MDD) compared to never-depressed (ND) controls. A novel two-level feature selection method, integrating recursive feature elimination based on support vector machine (SVM-RFE) and random forest algorithm (RF), was proposed to screen emotional recognition brain regions (ERBRs). On this basis, the differences of functional connectivity (FC) were systematically analyzed by two-sample t-test. The results demonstrate that ND participants show eight pairs of FCs with a significant difference between positive emotional music stimuli (pEMS) versus negative emotional music stimuli (nEMS) in 15 ERBRs of MDD, but the participants with MDD show one pair of significant difference in FC. The decreased number reflects the fuzzy response to positive and negative emotions in MDD, which appears to arise from obstacle to emotional cognition and regulation. Furthermore, there was no significant difference in FC between MDDs and NDs under pEMS, but a significant difference was detected between the two groups under nEMS (p < 0.01), revealing a 'bias' against the negative state in MDD. The current study may help to better comprehend the abnormal evolution from normal to depression and inform the utilization of pEMS in formal treatment for depression.

Economic Choice and Heart Rate Fractal Scaling Indicate That Cognitive Effort Is Reduced by Depression and Boosted by Sad Mood

BackgroundPeople with depression typically exhibit diminished cognitive control. Control is subjectively costly, prompting speculation that control deficits reflect reduced cognitive effort. Evidence that people with depression exert less cognitive effort is mixed, however, and motivation may depend on state affect. MethodsWe used a cognitive effort discounting task to measure propensity to expend cognitive effort and fractal structure in the temporal dynamics of interbeat intervals to assess on-task effort exertion for 49 healthy control subjects, 36 people with current depression, and 67 people with remitted depression. ResultsPeople with depression discounted more steeply, indicating that they were less willing to exert cognitive effort than people with remitted depression and never-depressed control subjects. Also, steeper discounting predicted worse functioning in daily life. Surprisingly, a sad mood induction selectively boosted motivation among participants with depression, erasing differences between them and control subjects. During task performance, depressed participants with the lowest cognitive motivation showed blunted autonomic reactivity as a function of load. ConclusionsDiscounting patterns supported the hypothesis that people with current depression would be less willing to exert cognitive effort, and steeper discounting predicted lower global functioning in daily life. Heart rate fractal scaling proved to be a highly sensitive index of cognitive load, and data implied that people with lower motivation for cognitive effort had a diminished physiological capacity to respond to rising cognitive demands. State affect appeared to influence motivation among people with current depression given that they were more willing to exert cognitive effort following a sad mood induction.

0199 Iris color predicts melanopsin-driven retinal responses in older but not younger individuals

Abstract Introduction The retina contains melanopsin-containing retinal ganglion cells, which underlie non-image forming responses to light. The Post-Illumination Pupil Response (PIPR) can assess melanopsin cell responsivity, with applications for sleep disorders, mood disorders, and circadian entrainment. Lighter pigmented irises allow more light to pass through the retina. The present study tested an association between the PIPR and iris pigmentation. Methods Participants (N=49) included seasonal depression (n=26) and never-depressed controls (n=23). Photos of participants’ irises were rated using both the Franssen (2008) scale, a set of 24 standardized iris photos, and the Mackey (2011) scale, a 9-category rating system. Red and blue stimuli 13.5 log photons/cm2/s were presented, and infrared pupillometry measured pupil diameter for 40 seconds. We used multilevel regression with a random intercept of participant to predict the PIPR from each iris rating system separately, controlling for age, gender, and circadian time of testing determined from Dim Light Melatonin Onset. Results Agreement between raters, calculated using Cohen's κ, was moderate for both scales (Franssen, κ=0.57, 95% CI: 0.42 to 0.71, p&amp;lt;0.001; Mackey, κ=0.67, 95% CI: 0.53 to 0.81, p&amp;lt;0.001). Bivariate correlations showed age was inversely associated with iris color: older individuals had lighter iris pigmentation. Analyses were therefore stratified by age (older &amp;gt;=31 years: n=24; younger &amp;lt;31 years, n=25). Greater retinal responsivity was associated with lighter iris pigmentation in the older sample (Mackey: unstandardized b=-0.016; SE=0.005; p=0.002; Franssen: unstandardized b=-0.006; SE=0.002, p=0.002), but not the younger sample (Mackey: unstandardized b=-0.0008; SE=0.003; p=0.770; Franssen: unstandardized b=-0.0009; SE=0.002, p=0.619). There was no effect of iris color on PIPR in the whole sample (p’s &amp;gt;0.13). Conclusion Iris color explained ~8% of variance in the PIPR, indicating that PIPR studies should recruit samples with similar distributions of iris pigmentation across conditions and ages, as this finding was only seen in the older sample with more individuals with lighter iris pigmentation. Future studies will test iris pigmentation by light exposure interactions on the PIPR. Light stimuli focused to a point on the pupil (i.e., Maxwellian) would eliminate variation in the amount of light incident on the retina due to iris pigmentation. Support (If Any) NIMH K.A.R. MH103303

Ecological momentary assessment of affect in depression-prone and control samples: Survey compliance and affective yield

BackgroundEcological momentary assessment (EMA) is a high-frequency ambulatory data collection approach that has come to be widely used in emotion research. It therefore is timely to examine two features of EMA needed for a successful study: compliance with survey prompts and high affective yield (survey prompts that capture affect experience). We posit that compliance may be subject to temporal variation (time-of-day, days in study) and individual differences (depression history), and that affective yield may also differ by social context. MethodsWe examined these issues in a sample of 318 young adults (Mage = 24.7 years, SD = 2.7), including those with current depression (n = 28), remitted depression (n = 168) and never-depressed controls (n = 122) who participated in a 7-day EMA protocol of negative and positive affect (NA and PA, respectively). ResultsThe overall compliance rate was 91% and remained stable across the survey week. However, subjects were significantly less likely to respond to the first daily prompt compared to those that followed. The likelihood of capturing NA and PA decreased with each EMA protocol day, and affective yield across social contexts differed by participants' depression status. LimitationsThe sample was largely comprised of White young adults. Relative to the remitted and control groups, the sample size for the currently depressed was unbalanced. ConclusionResearchers can optimize compliance and affective yield within EMA by considering depression, time-of-day, study duration, and social context. Clinicians using EMA to monitor affect may benefit from considering these parameters.

Suicidal ideation in remitted major depressive disorder predicts recurrence

IntroductionEach year almost 800.000 people die from suicide, of which up to 87% are affected by major depressive disorder (MDD). Despite the strong association between suicidality and MDD, it remains unknown if suicidal symptoms during remission put remitted recurrent MDD patients (rrMDD) at risk for recurrence. MethodsAt baseline we compared sociodemographic characteristics and suicidal symptoms in un-medicated rrMDD participants to matched never-depressed controls. We used the HDRS17 and IDS-SR30 to assess suicidal symptoms and depressive symptomatology. Next, we studied the longitudinal association between baseline suicidal symptoms and time to recurrence(s) in rrMDD during a 2.5-year follow-up period using cox regression analyses. Further, we studied with longitudinal data whether suicidal symptoms and depressive symptomatology were cross-sectionally associated using mixed model analysis. ResultsAt baseline, rrMDD participants (N = 73) had higher self-reported suicidal symptoms than matched never-depressed controls (N = 45) (χ2 = 12.09 p < .002). Self-reported suicidal symptoms were almost four times higher (27.9% versus 6.9%) compared to clinician-rated suicidal symptoms in rrMDD at baseline. Self-reported baseline suicidal symptoms, but not clinician-rated symptoms, predicted earlier MDD-recurrence during follow-up, independent of other residual depressive symptoms (χ2 = 7.26, p < .026). Higher suicidal symptoms were longitudinally related to higher depressive symptoms (HDRS17; F = 49.87, p < .001), IDS-SR30; (F = 22.36, p < .001). ConclusionThis study showed that self-reported – but not clinician-rated - suicidal symptoms persist during remission in rrMDD and predict recurrence, independent from residual symptoms. We recommend to monitor both suicidal and depressive symptomatology during remission in rrMDD, preferably also including self-reported questionnaires apart from clinician-rated. It would be beneficial for future research to assess suicidality using questionnaires primarily designed for measuring suicidal ideation.

Associations between heart rate variability, peripheral inflammatory markers and major depressive disorder

Background: Measures for the irregularity of the heartbeat, for example respiratory sinus arrhythmia, have been implicated as a measure for restorative functions of the vegetative nervous system. Methods: In the current observational study, we investigated 265 subjects, 70 of whom had a lifetime history of major depression, with a plethysmographic heartbeat monitor, blood sampling, as well as a range of psychiatric questionnaires. Results: Subjects with a history of MDE had significantly reduced respiratory sinus arrhythmia (RSA) as compared to never-depressed controls; in the whole sample, higher RSA went with lower anxiety/fear variables, especially in subscores related to cardiac symptoms as well as being afraid of dying. A reduced RSA was also associated with an increased concentration of cytokines (TNFa, IL1a, IL6, IFNg) and thyroid-stimulating hormone in the serum, pointing to a possible triangular relationship between immune system, vegetative nervous system, and emotional dysregulation. Limitations: We used a plethysmographic device for the measurement of heartbeat instead of an electrocardiogram, and had a single time point only. Conclusions: This data corroborate the idea that a disequilibrium of the vegetative nervous, especially if accompanied by a dysregulation system in immune function, can increase the risk for depression. Conversely, vagal stimulation and anti-inflammatory treatments may support the treatment with antidepressants.

Attentional Bias, Autonomic Reactivity and Depression

Attentional deficits as well as attentional biases towards negative material are related to major depression and might maintain chronicity. However, studies investigating attentional deficits and attentional biases in chronic, treatment-resistant depressed are lacking. The aim of the current study was to compare measures of attentional deficits and attentional bias between chronic, treatment-resistant depressed outpatients and never-depressed control participants. Attentional deficits were assessed with the attentional control scale (ACS) and the Stroop Color naming task. Attentional bias was measured with the exogenous cueing task (ECT) and an emotional Stroop task. Chronic, treatment-resistant depressed patients (n = 80) showed significantly more attentional deficits than never-depressed controls (n = 113) on the ACS and Stroop color-naming task. However, in contrast with hypotheses, no differences were found between chronic, treatment-resistant depressed patients and never-depressed individuals on the ECT or emotional Stroop task. The current findings indicate that chronic, treatment-resistant depressed patients present attentional deficits. The results however question whether this patient group shows attentional biases for negative material. Future research should include comparisons of chronic, treatment-resistant and non-chronically depressed patients. If replicated, these current results might indicate that focusing on improving attentional deficits could be a more promising target for treatment than addressing attentional biases.

Elusive hypersomnolence in seasonal affective disorder: actigraphic and self-reported sleep in and out of depressive episodes.

Hypersomnolence has been considered a prominent feature of seasonal affective disorder (SAD) despite mixed research findings. In the largest multi-season study conducted to date, we aimed to clarify the nature and extent of hypersomnolence in SAD using multiple measurements during winter depressive episodes and summer remission. Sleep measurements assessed in individuals with SAD and nonseasonal, never-depressed controls included actigraphy, daily sleep diaries, retrospective self-report questionnaires, and self-reported hypersomnia assessed via clinical interviews. To characterize hypersomnolence in SAD we (1) compared sleep between diagnostic groups and seasons, (2) examined correlates of self-reported hypersomnia in SAD, and (3) assessed agreement between commonly used measurement modalities. In winter compared to summer, individuals with SAD (n = 64) reported sleeping 72 min longer based on clinical interviews (p < 0.001) and 23 min longer based on actigraphy (p = 0.011). Controls (n = 80) did not differ across seasons. There were no seasonal or group differences on total sleep time when assessed by sleep diaries or retrospective self-reports (p's > 0.05). Endorsement of winter hypersomnia in SAD participants was predicted by greater fatigue, total sleep time, time in bed, naps, and later sleep midpoints (p's < 0.05). Despite a winter increase in total sleep time and year-round elevated daytime sleepiness, the average total sleep time (7 h) suggest hypersomnolence is a poor characterization of SAD. Importantly, self-reported hypersomnia captures multiple sleep disruptions, not solely lengthened sleep duration. We recommend using a multimodal assessment of hypersomnolence in mood disorders prior to sleep intervention.

Converging evidence for enduring perceptions of low social status in individuals in remission from depression

Background: The risk of depressive relapse and recurrence is associated with social risk factors that may be amplified by a submissive socio-cognitive profile. Methods: In Study 1 we aimed to identify perceptions of low social status in a community sample (N = 613) with a self-reported history of mental health difficulties (n = 232) and, more specifically in Study 2 (N = 122), in individuals in clinical remission from depression (n = 18), relative to a never-depressed control group (n = 64), and relative to a group experiencing a current depressive episode (n = 40). Results: In Study 1, a total of 225 of the 232 participants in the self-reported mental health difficulties group opted to provide further information regarding their mental health history, of whom 153 (68%) reported a history of anxiety, 168 (74.7%) reported a history of depression, and 13 (5.8%) reported an unspecified mental health history. Elevated depressive symptoms were associated with perceptions of low social status which significantly differed between individuals with and without a self-reported history of mental health difficulties. In Study 2 we found enduring perceptions of low social status in remitted depressed individuals. Limitations: We were unable to discern between historical or current clinical diagnosis in the community sample of Study 1, as we were reliant on self-report. We were unable to explore the effects of medication or causal relationships between depressive symptoms and social status as the studies were cross-sectional in nature. Conclusions: These findings suggest that evolutionarily rooted socio-cognitive profiles could impact affiliative processes and may confer increased vulnerability to future depressive episodes.

A 6-year prospective clinical cohort study on the bidirectional association between frailty and depressive disorder.

IntroductionDepressive disorder has been conceptualised as a condition of accelerated biological ageing. We operationalised a frailty index (FI) as marker for biological ageing aimed to explore the bidirectional, longitudinal association between frailty and either depressive symptoms or depressive disorder.MethodsA cohort study with 6‐year follow‐up including 377 older (≥60 years) outpatients with a DSM‐IV‐defined depressive disorder and 132 never‐depressed controls. Site visits at baseline, 2 and 6‐year follow‐up were conducted and included the CIDI 2.0 to assess depressive disorder and relevant covariates. Depressive symptom severity and mortality were assessed every 6 months by mail and telephone. A 41‐item FI was operationalised and validated against the 6‐year morality rate by Cox regression (HRFI = 1.04 [95% CI: 1.02–1.06]).ResultsCox regression showed that a higher FI was associated with a lower chance of remission among depressed patients (HRFI = 0.98 [95% CI: 0.97–0.99]). Nonetheless, this latter effect disappeared after adjustment for baseline depressive symptom severity. Linear mixed models showed that the FI increased over time in the whole sample (B[SE] = 0.94 (0.12), p < .001) with a differential impact of depressive symptom severity and depressive disorder. Higher baseline depressive symptom severity was associated with an attenuated and depressive disorder with an accelerated increase of the FI over time.ConclusionsThe sum score of depression rating scales is likely confounded by frailty. Depressive disorder, according to DSM‐IV criteria, is associated with accelerated biological ageing. This argues for the development of multidisciplinary geriatric care models incorporating frailty to improve the overall outcome of late‐life depression.

Childhood-onset depression and arterial stiffness in young adulthood

ObjectivesThe literature on childhood-onset depression and future compromised vascular function is suggestive but limited. The objective of this study was to determine if arterial stiffness, a predictor of future cardiovascular disease (CVD), measured in young adulthood, is associated with childhood-onset depression. MethodsCardiometabolic risk factors and pulse wave velocity (PWV), a measure of arterial stiffness, were cross-sectionally assessed in young adults with a history of childhood-onset depression (clinical diagnosis of major depressive episode or dysthymic disorder; N = 294 probands; initially recruited via child mental health facilities across Hungary; mean age of first depressive episode = 10.4 years), their never-depressed full biological siblings (N = 269), and never-depressed controls (N = 169). The mean ages of probands, siblings, and controls at the PWV visit were 25.6, 25.0, and 21.7 years, respectively, and 8.8% of the probands were in a current depressive episode. ResultsControlling for age, sex, age*sex, education, and family clusters, PWV (m/s) did not statistically differ across the groups (probands = 7.01; siblings = 6.98; controls = 6.81). However, after adjusting for key covariates, there were several across-group differences in CVD risk factors: compared to controls, probands and siblings had higher diastolic blood pressure and lower high-density lipoprotein cholesterol, probands had higher triglycerides, and siblings had higher body mass index (all p < 0.05). ConclusionWe found limited evidence of an association between a history of childhood-onset depression and young adulthood arterial stiffness. However, our findings of elevated cardiovascular risk factors in those with childhood-onset depression suggest that pediatric depression may predispose to increased CVD risk later in life and warrants further investigation.

A multi-method assessment of attentional processes in chronic, treatment-resistant depression

Attentional deficits as well as attentional biases towards negative material are related to major depression and might maintain chronicity. However, studies investigating attentional deficits and attentional biases in chronic, treatment-resistant depressed are lacking. The aim of the current study was to compare measures of attentional deficits and attentional bias between chronic, treatment-resistant depressed outpatients and never-depressed control participants. Attentional deficits were assessed with the attentional control scale (ACS) and the Stroop Color naming task. Attentional bias was measured with the exogenous cueing task (ECT) and an emotional Stroop task. Chronic, treatment-resistant depressed patients (n = 80) showed significantly more attentional deficits than never-depressed controls (n = 113) on the ACS and Stroop color-naming task. However, in contrast with hypotheses, no differences were found between chronic, treatment-resistant depressed patients and never-depressed individuals on the ECT or emotional Stroop task. The current findings indicate that chronic, treatment-resistant depressed patients present attentional deficits. The results however question whether this patient group shows attentional biases for negative material. Future research should include comparisons of chronic, treatment-resistant and non-chronically depressed patients. If replicated, these current results might indicate that focusing on improving attentional deficits could be a more promising target for treatment than addressing attentional biases.

Late-life depression and increased risk of dementia: a longitudinal cohort study

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.

Eyeing ambiguity: Pupillary reactivity during early automatic interpretations in major depressive disorder

Automatic interpretation biases (AIB) are theorized to be a risk factor for depression. However, documenting AIB in depressed persons has been challenging and the source (affective vs cognitive) of AIB remains unclear. We conducted a psychophysiological investigation of AIB in a sample of 25 clinical interview assessed individuals experiencing a current major depressive episode and 28 never-depressed control individuals. Participants completed the Word Sentence Association Paradigm for Depression while their pupil size was recorded. Repeated measures ANOVAs were used to examine behavioral response data and multilevel modeling was used to examine pupillary reactivity (change from trial baseline). Compared to controls, the depressed group was both more likely to endorse negative AIB (p = .001, d = 1.01) and less likely to endorse benign AIB (p = .011, d = 0.72). Further, the depressed group exhibited significantly increased pupil size while processing negative words when they endorsed a negative interpretation compared with controls (ps = .010–.037, ds = 0.69–0.87), but did not differ during other AIB trial types. Within group comparisons revealed greater differentiation between interpretations in the healthy control group in both reaction time and pupillary reactivity AIB measures. This depression-related pupillary reactivity pattern fits with an emotional salience-based explanation better than a cognitive effort-based hypothesis of negative AIB, while pupillary reactivity pattern within the control group is consistent with a benign bias. People with depression lack benign AIB and may be more emotionally engaged during negative AIB than healthy controls.