Marker Of Risk For Depression Research Articles

The Plasma Neurofilament Light Chain, Brain-Derived Neurotrophic Factor, and Risk of Depression in Chronic Hemodialysis Patients.

Depression is highly prevalent among hemodialysis patients. Understanding the relationship between the plasma neurofilament light chain (NfL) and brain-derived neurotrophic factor (BDNF) may help us to better understand the mechanisms of depression. This study determined their impact, alongside that of other factors, on the risk of depression in hemodialysis patients. The study enrolled 82 patients undergoing chronic hemodialysis. Serum NfL, BDNF, uric acid, urea, potassium, calcium, phosphorus, intact parathyroid hormone, and C-reactive protein (CRP) levels were measured. The patients completed the Beck Depression Inventory (BDI). Blood pressure values, body mass before and after hemodialysis, and weekly duration of hemodialysis in hours were assessed. For 19-month survival analysis, the patients were stratified according to baseline BDI scores. Based on the BDI score, 18.3% of the patients had an increased risk of depression. Lower scores were associated with significantly longer duration of hemodialysis treatment (37.5 (25-57) 24 (14-37) months, p = 0.01). Within the 19-month survival analysis, 31.7% of patients died. The patients with BDI scores above the median had significantly lower survival than those below the median (log-rank test p = 0.02). No significant differences in serum BDNF levels (192.7 [125.2-278.2]; 207.7 [142.8-265.8] pg/mL, p = 0.40), or NfL concentrations (1431.5 [1182.6-1625.7]; 1494.6 [1335.7-1667] kDa, p = 0.52) were found between patients with lower and higher risk of depression. Patients with BDI scores above the median had significantly higher levels of CRP (9.6 [4.4-14]) than those with scores below the median (3.6 [2.2-7.5], p = 0.01). A significant positive correlation was found between the BDI score and serum CRP level (r = 0.38, p = 0.01). A significant negative correlation was observed between the BDI score and URR% value (r = -0.36, p = 0.02). Patients with lower BDI scores had a longer dialysis duration, indicating a potential negative association between depression risk and length of dialysis treatment. Neither serum NfL nor BDNF levels can serve as markers of depression risk in the dialysis population.

Preschool Depression and Hippocampal Volume: The Moderating Role of Family Income.

Depression and low socioeconomic status have both been associated with hippocampal volume alterations. Whether these factors interact to predict neurobehavioral outcomes has not been adequately studied. The authors investigated family income as a moderator of the relationship between depression and hippocampal volume in a longitudinal sample. Longitudinal behavioral data, beginning at preschool age, and behavioral and neuroimaging data from school age to adolescence were used to assess the impact of preschool only and total preschool to adolescent depression symptoms on hippocampal volumes using family income as a moderator (N= 176). Depression severity during the preschool period interacted with family income to predict hippocampal volumes at the intercept (ie, age 13 years; B=-0.078, p= .003). Interaction decomposition revealed that only individuals with relatively high family income exhibited smaller hippocampal volume with increasing depression severity (B=-0.146, p= .005). Family income was associated with hippocampus volumes only in individuals with low to moderate preschool depression severity (B= 0.289, p= .007 and B= 0.169, p= .030, respectively). Preschool depression severity interacts with family income to predict hippocampal volume across development, such that the effects of early depression are evident only in those with higher income. These findings suggest that hippocampal volume may not be an effective marker of risk for depression at different levels of socioeconomic status, and emphasizes the importance of the environmental context when assessing risk markers for depression. Future research should explore how socioeconomic stress may eclipse the effects of depression on hippocampal development, setting alternative neurodevelopmental risk trajectories.

Neural and peripheral markers of reward during positive social evaluation are associated with less clinician-rated depression symptom severity in adolescence

Although blunted sensitivity to reward is thought to play a key role in promoting risk for depression, most research on this topic has utilized monetary reward paradigms and focused on currently depressed adults. To address this issue, we analyzed neural reward and β-endorphin data from the Psychobiology of Stress and Adolescent Depression (PSY SAD) Study, which recruited a well-characterized sample of adolescent girls at high vs. low risk for major depressive disorder (MDD) (N = 52, Mage = 14.90, SD = 1.35) based on their mothers’ lifetime history of MDD. As hypothesized, greater striatal activity while receiving positive (vs. neutral) social evaluation was associated with lower depression symptom severity as independently assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). This association was present for girls at high but not low risk for MDD, suggesting that this neural response may represent a pre-clinical marker of risk for depression. Consistent with these results, higher post-social evaluation levels of a peripheral marker of reward sensitivity, β-endorphin, were related to lower clinician-rated depression symptom severity. Together, these results indicate that neural and peripheral markers of responsivity to social reward are both related to depression severity, which may have implications for understanding the pathophysiology of depression.

Online behavioural activation during the COVID-19 pandemic decreases depression and negative affective bias.

The COVID-19 pandemic highlighted the need for mental health interventions that can be easily disseminated during a crisis. Behavioural activation (BA) is a cost-effective treatment that can be administered by non-specialists; however, it is unclear whether it is still effective during a time of lockdown and social distancing, when opportunities for positive activity are significantly constrained. Between May and October 2020, we randomised 68 UK participants with mild to moderate low mood to either a 4-week online programme of non-specialist administered BA or to a passive control group. Before and after the intervention, we collected self-report data on mood and COVID-related disruption, as well as measuring emotional cognition as an objective marker of risk for depression. In comparison to the control group, the BA group showed a significant decrease in depression, anxiety and anhedonia after the intervention, as well as an increase in self-reported activation and social support. Benefits persisted at 1-month follow-up. BA also decreased negative affective bias on several measures of the Facial Emotion Recognition Task and early change in bias was associated with later therapeutic gain. Participants rated the intervention as highly acceptable. This study highlights the benefits of online BA that can be administered by non-specialists after brief training. These findings can help inform the policy response towards the rising incidence of mental health problems during a crisis situation such as a pandemic. They also highlight the use of objective cognitive markers of risk across different treatment modalities.

Motivated attention and family risk for depression: Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal blunted emotional responsivity.

Behavioral and electrophysiologic evidence suggests that major depression (MDD) involves right parietotemporal dysfunction, a region activated by arousing affective stimuli. Building on prior event-related potential (ERP) findings (Kayser et al. 2016 NeuroImage 142:337–350), this study examined whether these abnormalities also characterize individuals at clinical high risk for MDD. We systematically explored the impact of family risk status and personal history of depression and anxiety on three distinct stages of emotional processing comprising the late positive potential (LPP). ERPs (72 channels) were recorded from 74 high and 53 low risk individuals (age 13–59 years, 58 male) during a visual half-field paradigm using highly-controlled pictures of cosmetic surgery patients showing disordered (negative) or healed (neutral) facial areas before or after treatment. Reference-free current source density (CSD) transformations of ERP waveforms were quantified by temporal principal components analysis (tPCA). Component scores of prominent CSD-tPCA factors sensitive to emotional content were analyzed via permutation tests and repeated measures ANOVA for mixed factorial designs with unstructured covariance matrix, including gender, age and clinical covariates. Factor-based distributed inverse solutions provided descriptive estimates of emotional brain activations at group level corresponding to hierarchical activations along ventral visual processing stream. Risk status affected emotional responsivity (increased positivity to negative-than-neutral stimuli) overlapping early N2 sink (peak latency 212 ms), P3 source (385 ms), and a late centroparietal source (630 ms). High risk individuals had reduced right-greater-than-left emotional lateralization involving occipitotemporal cortex (N2 sink) and bilaterally reduced emotional effects involving posterior cingulate (P3 source) and inferior temporal cortex (630 ms) when compared to those at low risk. While the early emotional effects were enhanced for left hemifield (right hemisphere) presentations, hemifield modulations did not differ between risk groups, suggesting top-down rather than bottom-up effects of risk. Groups did not differ in their stimulus valence or arousal ratings. Similar effects were seen for individuals with a lifetime history of depression or anxiety disorder in comparison to those without. However, there was no evidence that risk status and history of MDD or anxiety disorder interacted in their impact on emotional responsivity, suggesting largely independent attenuation of attentional resource allocation to enhance perceptual processing of motivationally salient stimuli. These findings further suggest that a deficit in motivated attention preceding conscious awareness may be a marker of risk for depression.

Ruminative brooding is associated with salience network coherence in early pubertal youth.

Rumination, and particularly ruminative brooding, perpetuates dysphoric mood states and contributes to the emergence of depression. Studies of adults and older adolescents have characterized the association between rumination and intrinsic functional connectivity within default mode (DMN), salience (SN) and executive control (ECN) networks; we know little, however, about the brain network basis of rumination during early puberty, a sensitive period for network reorganization. 112 early puberty boys and girls completed resting-state scans, the Ruminative Response Scale, and the Youth Self-Report questionnaire. Using independent components analysis and dual regression, we quantified coherence for each individual in networks of interest (SN, ECN, DMN) and in non-relevant networks (motor, visual) in which we predicted no correlations with behavioral measures. Boys and girls did not differ in levels of rumination or internalizing symptoms, or in coherence for any network. The relation between SN network coherence and rumination; however, and specifically ruminative brooding, was moderated by sex: greater SN coherence was associated with higher levels of brooding in girls but not in boys. Further, in girls, brooding mediated the relation between SN coherence and internalizing symptoms. These results point to coherence within the SN as a potential neurodevelopmental marker of risk for depression in early pubertal girls.

The Interpersonal Toxicity of Excessive Reassurance-Seeking: Evidence From a Longitudinal Study of Romantic Relationships

Interpersonal rejection is associated with a number of marked negative psychological sequelae, including the development of depression. Interpersonal theories (e.g., Coyne, 1976) propose that excessive reassurance-seeking (ERS) may be particularly linked to rejection, but this hypothesis has yet to be tested using an objective, behavioral indicator of interpersonal rejection. Using a sample of 118 women and their romantic partners, we examined whether women's baseline ERS was associated with partner-initiated break-ups over a 1-year follow-up period. Secondarily, we explored whether this effect was moderated by the reassurance-seeker's initial depressive symptoms. Results revealed that ERS was associated with a more rapid time to partner rejection, but not to general relationship dissolutions. Further, the effect of ERS was not moderated by women's dysphoria at baseline. These results suggest that ERS is interpersonally toxic in and of itself, and may thus be an important behavioral marker of risk for depression and other psychiatric problems.

Parental depression and child cognitive vulnerability predict children's cortisol reactivity.

Risk for depression is expressed across multiple levels of analysis. For example, parental depression and cognitive vulnerability are known markers of depression risk, but no study has examined their interactive effects on children's cortisol reactivity, a likely mediator of early depression risk. We examined relations across these different levels of vulnerability using cross-sectional and longitudinal methods in two community samples of children. Children were assessed for cognitive vulnerability using self-reports (Study 1; n = 244) and tasks tapping memory and attentional bias (Study 2; n = 205), and their parents were assessed for depression history using structured clinical interviews. In both samples, children participated in standardized stress tasks and cortisol reactivity was assessed. Cross-sectionally and longitudinally, parental depression history and child cognitive vulnerability interacted to predict children's cortisol reactivity; associations between parent depression and elevated child cortisol activity were found when children also showed elevated depressotypic attributions as well as attentional and memory biases. Findings indicate that models of children's emerging depression risk may benefit from the examination of the interactive effects of multiple sources of vulnerability across levels of analysis.

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

Activity of the hypothalamic–pituitary–adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls' cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent–child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps < .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations.

Reduced reward anticipation in youth at high-risk for unipolar depression: A preliminary study

Offspring of depressed parents are at risk for depression and recent evidence suggests that reduced positive affect (PA) may be a marker of risk. We investigated whether self-reports of PA and fMRI-measured striatal response to reward, a neural correlate of PA, are reduced in adolescent youth at high familial risk for depression (HR) relative to youth at low familial risk for depression (LR). Functional magnetic resonance imaging assessments were conducted with 14 HR and 12 LR youth. All youth completed an ecological momentary assessment protocol to measure PA in natural settings and a self-report measure of depression symptomatology. Analyses found that HR youth demonstrated lower striatal response than LR youth during both reward anticipation and outcome. However, after controlling for youth self-reports of depression, HR youth demonstrated lower striatal response than LR youth only during reward anticipation. No significant differences were found between HR and LR youth on subjective ratings of PA or depressive symptoms. Results are consistent with previous findings that reduced reward response is a marker of risk for depression, particularly during reward anticipation, even in the absence of (or accounting for) disrupted subjective mood. Further examinations of prospective associations between reward response and depression onset are needed.

Specific Parental Depression Symptoms as Risk Markers for New-Onset Depression in High-Risk Offspring

To disaggregate the depression construct and investigate whether specific depression symptoms in parents with a history of recurrent depression are clinical risk markers for future depression in their high-risk offspring. Our hypothesis was that parental symptoms of the type that might impact offspring would most likely be of greatest importance. Data were drawn from a longitudinal high-risk family study. Families were mainly recruited from primary care and included 337 parent-child dyads. Parents had a history of recurrent DSM-IV unipolar depression and were aged 26-55 years. Their offspring (197 female and 140 male) were aged 9-17 years. Three assessments were conducted between April 2007 and April 2011. Ninety-one percent of families (n = 305) provided full interview data at baseline and at least 1 follow-up, of which 291 were included in the primary analysis. The main outcome measure was new-onset DSM-IV mood disorder in the offspring, which was assessed using the Child and Adolescent Psychiatric Assessment. Of the 9 DSM-IV depression symptoms, parental change in appetite or weight, specifically loss of appetite or weight, most strongly predicted new-onset mood disorder (odds ratio [OR] = 4.47; 95% CI, 2.04-9.79; P < .001) and future depression symptoms in the offspring (β = 0.12; B = 0.21; 95% CI, 0.00-0.42; P = .050). The cross-generational association was not accounted for by measures of parental depression severity (total depression symptom score, episode recurrence, age at onset, and past impairment or hospitalization) or other potential confounds (parent physical health, eating disorder, or medication). Findings from this study suggest that loss of appetite or weight in parents with a history of recurrent depression is a marker of risk for depression in their offspring. The findings highlight the importance of examining depression heterogeneity. The biological and environmental mechanisms underlying this finding require investigation.

Frontal EEG asymmetry during emotional challenge differentiates individuals with and without lifetime major depressive disorder

Background Although it has been argued that frontal electroencephalographic (EEG) asymmetry at rest may be a risk marker for major depressive disorder (MDD), it is unclear whether a pattern of relatively less left than right activity characterizes depressed individuals during emotional challenges. Examination of frontal asymmetry during emotion task manipulations could provide an assessment of the function of systems relevant for MDD, and test the limits of frontal EEG asymmetry as a marker of risk for depression. Methods EEG data were assessed during a facial emotion task, wherein 306 individuals age 18–34 (31% male) with ( n = 143) and without ( n = 163) DSM-IV defined lifetime MDD made directed facial actions of approach (angry and happy) and withdrawal (afraid and sad) expressions. Results Lifetime depressed individuals displayed less relative left frontal activity than never-depressed individuals during all facial expressions across four EEG reference montages, findings that were not due to emotional experience, facial expression quality, electromyographic (EMG) activity, or current depression status. Limitations Although this was a sizable sample, only one emotion task was utilized. Conclusions Results provide further support for frontal EEG asymmetry as a risk marker for MDD.

Risk markers for depression in adolescents: sleep and HPA measures.

Previous work has demonstrated reliable electroencephalographic (EEG) sleep and hypothalamic-pituitary-adrenal (HPA) changes associated with adult major depressive disorder. These changes might be evident before clinical manifestation of the illness in at-risk persons. The aim of the study was to identify depression-related EEG sleep and HPA changes in healthy adolescents at high-risk for depression, and to examine the relationship between EEG sleep (or HPA) changes and the onset of depression. Forty-eight adolescent volunteers with no personal history of a psychiatric illness, including depression, but who were at high-risk for developing depression by virtue of parental depression (high-risk group), and 48 adolescent volunteers with no personal or family history of a psychiatric disorder (normal controls) were recruited. EEG sleep and HPA measures were collected on three consecutive evenings and nights at baseline. Clinical follow-up evaluations were conducted at regular intervals over a 5-year period. Compared with normal controls, adolescents at high-risk for depression had shorter latency to rapid eye movement (REM) sleep, increased phasic REM sleep, more REM sleep and elevated nocturnal urinary free cortisol (NUFC) excretion at baseline. Shorter REM latency, higher REM density and elevated NUFC (measured at baseline) were associated with the development of depression during follow-up. The findings that REM sleep abnormalities and elevated HPA activity occur prior to the onset of depression in at-risk adolescents suggest that these variables serve as vulnerability markers for the illness.