Risk Factor For Affective Disorders Research Articles

Specific dysphoric disorders in epilepsy

To analyze affective-somatoform (dysphoric) disorders specific to epilepsy. Dysphoric disorders can be divided into 3 groups: “periictal” disorders, interictal dysphoric disorder and alternative affective-somatoform syndromes. There are 3 groups of risk factors for affective disorders in epilepsy including depressive and dysphoric: those associated with the disease, those associated with the treatment and those associated with psychosocial aspects. Treatment for depression in epilepsy includes medication and psychotherapy. At the first stage of drug therapy, anticonvulsants are corrected, and at the second, an antidepressant is added. Cognitive behavioral therapy is the most effective method of psychotherapy. Dysphoric disorders in epilepsy are presented by a wide range of conditions, both paroxysmal and non-paroxysmal, and have their own classification and development factors, which must be taken into account when choosing adequate therapy.

Interleukin-1β and TNF-α are elevated in the amygdala of adult rats prenatally exposed to ethanol.

Affective disorders, including anxiety and depression, developed in adult offspring of the mothers who consumed alcohol during pregnancy could be associated with an imbalance in neuroimmune factors in the amygdala (corpus amygdaloideum) resulted in impaired emotional stimulus processing. The aim of this study was to compare the content of cytokines TNF-α, IL-1α, IL-1β, IL-10, and IL-17 in the amygdala of adult female rats exposed to alcohol in utero and control rats. Cytokine levels were evaluated using a multiplex immunoassay system; mRNA expression was investigated using a real-time reverse transcription-polymerase chain reaction (RT-qPCR) assay. Prenatal alcohol exposure led to the increase in the content of TNF-α and IL-1β without significant changes in the mRNA expression level. Our data suggest that ethanol exposure to the fetus during pregnancy can result in long-term alterations in the content of the key neuroinflammatory factors in the amygdala, which in turn can be a risk factor for affective disorders in the adulthood.

Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability

Aberrant responses to frustration are central mechanisms of pediatric irritability, which is a common reason for psychiatric consultation and a risk factor for affective disorders and suicidality. This pilot study aimed to characterize brain network configuration during and after frustration and test whether characteristics of networks formed during or after frustration relate to irritability. During functional magnetic resonance imaging, a transdiagnostic sample enriched for irritability (N= 66, mean age= 14.0 years, 50% female participants) completed a frustration-induction task flanked by pretask and posttask resting-state scans. We first tested whether and how the organization of brain regions (ie, nodes) into networks (ie, modules) changes during and after frustration. Then, using a train/test/held-out procedure, we aimed to predict past-week irritability from global efficiency (Eglob) (ie, capacity for parallel information processing) of these modules. Two modules present in the baseline pretask resting-state scan (one encompassing anterior default mode and temporolimbic regions and one consisting of frontoparietal regions) contributed most to brain circuit reorganization during and after frustration. Only Eglob of modules in the posttask resting-state scans (ie, after frustration) predicted irritability symptoms. Self-reported irritability was predicted by Eglob of a frontotemporal-limbic module. Parent-reported irritability was predicted by Eglob of ventral-prefrontal-subcortical and somatomotor-parietal modules. These pilot results suggest the importance of the postfrustration recovery period in the pathophysiology of irritability. Eglob in 3 specific posttask modules, involved in emotion processing, reward processing, or motor function, predicted irritability. These findings, if replicated, could represent specific intervention targets for irritability.

Insomnia is a key risk factor for persistent anxiety and depressive symptoms: A 12-month longitudinal cohort study during the COVID-19 pandemic

BackgroundInsomnia is a risk factor for affective disorders. This study examined whether individuals with insomnia symptoms early in the pandemic, either pre-existing or new-onset, were more vulnerable to anxiety and depressive symptoms over time than those who maintained normal sleep. Additionally, sleep-related factors such as pre-sleep arousal were assessed for their influence on clinically significant anxiety and depression risk. MethodsUsing a global online survey with 3-, 6-, and 12-month follow-ups between April 2020 and May 2021, data from 2069 participants (M = 46.16 ± 13.42 years; 75.3 % female) with pre-existing, new-onset, or no insomnia symptoms was examined using mixed-effects and logistic regression models. ResultsNew-onset and pre-existing insomnia predicted persistent anxiety and depressive symptoms longitudinally (p's < 0.001), over other known risk factors, including age, sex, and previous psychiatric diagnoses. Anxiety and depressive symptoms in both insomnia groups remained above clinically significant thresholds at most time points, whereas normal sleepers remained subclinical. Pre-sleep arousal was found to increase the risk of clinically significant anxiety (OR = 1.05) and depressive symptoms (OR = 1.09) at 12-months. Sleep effort contributed to anxiety (OR = 1.06), whereas dysfunctional sleep-related beliefs and attitudes predicted clinically significant depression (OR = 1.22). LimitationsInsomnia group categorization was based on self-report at baseline supported by a validated measure. High participant attrition was observed at 3-months (53 %; n = 971), but retention remained steady till 12-months (63 %, n = 779). ConclusionsInsomnia is a modifiable risk factor for persistent anxiety and depressive symptoms that needs to be addressed in mental healthcare. Additionally, pre-sleep arousal may be an important transdiagnostic process linking insomnia with affective disorders.

Appraisal Bias and Emotion Dispositions Are Risk Factors for Depression and Generalized Anxiety: Empirical Evidence.

Appraisal theory of emotion predicts that appraisal biases may generate stable emotion dispositions, which can ultimately lead to affective disorders. One example is the habitual underestimation of one’s potential to cope with adverse events, which favors frequent experiences of sadness and worry and therefore increases the risk for development of depression and generalized anxiety disorders. To examine the relationships between these variables as potential risk factors, in Study 1, we used appraisal and emotion questions in the Swiss Household Panel (SHP), a nationwide representative sample, and analyzed data for N = 4,859 participants in one annual survey wave (Wave 14, SHP 2012) via theory-based hierarchical regressions. Path analysis of the nomological network linking frequent experiences of depression and anxiety to the emotion dispositions of sadness and worry, and measures of perceived coping potential (appraisal bias) supports the theoretical predictions and further identifies the effects of important background variables such as personality, motivation, and life events. Discriminant analysis shows that these predictors allow correct classification of close to 70% of the participants with elevated risk. In Study 2, we used established validated instruments to assess the risk for depression and anxiety disorders, as well as a recently validated scenario method to assess appraisal bias and emotion disposition in a survey with N = 152 students. The results correspond to the theoretical predictions and largely confirm the findings with the household survey. The results of both studies demonstrate the utility of using current emotion theory to provide new vistas for research on risk factors for affective disorders and to inform the development of appropriate interventions to reduce the level of risk.

Developmental Antecedents of Adult Macaque Neurogenesis: Early-Life Adversity, 5-HTTLPR Polymorphisms, and Adolescent Hippocampal Volume

Introduction: Attenuated adult hippocampal neurogenesis may manifest in affective symptomatology and/or resistance to antidepressant treatment. While early-life adversity and the short variant (‘s’) of the serotonin transporter gene's long polymorphic region (5-HTTLPR) are suggested as interacting risk factors for affective disorders, no studies have examined whether their superposed risk effectuates neurogenic changes into adulthood. Similarly, it is not established whether reduced hippocampal volume in adolescence, variously identified as a marker and antecedent of affective disorders, anticipates diminished adult neurogenesis. We investigate these potential developmental precursors of neurogenic alterations using a bonnet macaque model.Methods: Twenty-five male infant bonnet macaques were randomized to stressed [variable foraging demand (VFD)] or normative [low foraging demand (LFD)] rearing protocols and genotyped for 5-HTTLPR polymorphisms. Adolescent MRI brain scans (mean age 4.2y) were available for 14 subjects. Adult-born neurons were detected post-mortem (mean age 8.6y) via immunohistochemistry targeting the microtubule protein doublecortin (DCX). Models were adjusted for age and weight.Results: A putative vulnerability group (VG) of VFD-reared ‘s’-carriers (all ‘s/l’) exhibited reduced neurogenesis compared to non-VG subjects. Neurogenesis levels were positively predicted by ipsilateral hippocampal volume normalized for total brain volume, but not by contralateral or raw hippocampal volume.Limitations: No ‘s’-carriers were identified in LFD-reared subjects, precluding a 2×2 factorial analysis.Conclusion: The ‘s’ allele (with adverse rearing) and low adolescent hippocampal volume portend a neurogenic deficit in adult macaques, suggesting persistent alterations in hippocampal plasticity may contribute to these developmental factors’ affective risk in humans.

The Emotion Regulation Questionnaire: Psychometric Properties and Relations with Affective Symptoms in a United States General Community Sample

BackgroundDifficulties in emotion regulation are a key risk factor for affective disorders. The Emotion Regulation Questionnaire (ERQ) is a 10-item measure of two emotion regulation strategies, cognitive reappraisal and expressive suppression. It is widely used tool in the United States, however, most psychometric studies of the ERQ have so far been conducted with college students and some researchers have recently questioned its factorial validity in non-student samples. In this study, we conducted the first confirmatory factor analysis study of the ERQ in a United States general community sample. MethodWe examined the ERQ's factor structure, measurement invariance across age, education and gender categories, internal consistency reliability, and concurrent validity with a sample of 508 adults. ResultsThe intended two-factor model (cognitive reappraisal, expressive suppression) was an excellent fit to the data, and this structure was invariant across different age, education, and gender categories. Both ERQ scale scores had good omega and alpha reliabilities, and correlated as expected with depression and anxiety symptoms. Cognitive reappraisal was negatively correlated with these symptoms, whereas expressive suppression was positively correlated with these symptoms. LimitationsWe did not include a clinical sample and future psychometric studies of the ERQ in specialised clinical populations would be useful. ConclusionsThe ERQ appears to have strong psychometric properties when used with general community members from the United States. ERQ scores can be confidently used and compared across adults of different ages, genders, and educational backgrounds.

The BDNF Val66Met polymorphism regulates vulnerability to chronic stress and phantom perception.

Auditory phantom percepts, such as tinnitus, are a heterogeneous condition with great interindividual variations regarding both the percept itself and its concomitants. Tinnitus causes a considerable amount of distress, with as many as 25% of affected people reporting that it interferes with their daily lives. Although previous research gives an idea about the neural correlates of tinnitus-related distress, it cannot explain why some tinnitus patients develop distress and while others are not bothered by their tinnitus. BDNF Val66Met polymorphism (rs6265) is a known risk factor for affective disorders due to its common frequency and established functionality. To elucidate, we explore the neural activation pattern of tinnitus associated with the BDNF Val66Met polymorphism using electrophysiological data to assess activity and connectivity changes. A total of 110 participants (55 tinnitus and 55 matched control subjects) were included. In this study, we validate that the BDNF Val66Met polymorphism plays an important role in the susceptibility to the clinical manifestation of tinnitus-related distress. We demonstrate that Val/Met carriers have increased alpha power in the subgenual anterior cingulate cortex that correlates with distress levels. Furthermore, distress mediates the relationship between BDNF Val66Met polymorphism and tinnitus loudness. In other words, for Val/Met carriers, the subgenual anterior cingulate cortex sends distress-related information to the parahippocampus, which likely integrates the loudness and distress of the tinnitus percept.

Individual differences in fear acquisition: multivariate analyses of different emotional negativity scales, physiological responding, subjective measures, and neural activation

Negative emotionality is a well-established and stable risk factor for affective disorders. Individual differences in negative emotionality have been linked to associative learning processes which can be captured experimentally by computing CS-discrimination values in fear conditioning paradigms. Literature suffers from underpowered samples, suboptimal methods, and an isolated focus on single questionnaires and single outcome measures. First, the specific and shared variance across three commonly employed questionnaires [STAI-T, NEO-FFI-Neuroticism, Intolerance of Uncertainty (IU) Scale] in relation to CS-discrimination during fear-acquisition in multiple analysis units (ratings, skin conductance, startle) is addressed (NStudy1 = 356). A specific significant negative association between STAI-T and CS-discrimination in SCRs and between IU and CS-discrimination in startle responding was identified in multimodal and dimensional analyses, but also between latent factors negative emotionality and fear learning, which capture shared variance across questionnaires/scales and across outcome measures. Second, STAI-T was positively associated with CS-discrimination in a number of brain areas linked to conditioned fear (amygdala, putamen, thalamus), but not to SCRs or ratings (NStudy2 = 113). Importantly, we replicate potential sampling biases between fMRI and behavioral studies regarding anxiety levels. Future studies are needed to target wide sampling distributions for STAI-T and verify whether current findings are generalizable to other samples.

Repetitive negative thinking following exposure to a natural stressor prospectively predicts altered stress responding and decision-making in the laboratory

Repetitive negative thinking (RNT) represents a transdiagnostic risk factor for affective disorders, and stress is theorized to exacerbate this vulnerability. One mechanism by which stress may influence individual differences in psychiatric symptoms is through altered decision-making, and loss aversion in particular. The present study uses multiple methods to investigate the relationships between RNT, stress, and decision-making. We measured RNT in young adults (N = 90) recently exposed to a natural stressor, Hurricane Irma, and tested the influence of RNT on changes in affect, cortisol, and decision-making during a laboratory stress induction two months later. Post-hurricane RNT predicted greater increases in loss averse decision-making (β = 0.30 [0.14, 0.47], p < .001; rp2 = 0.079) and negative affect (β = 0.59 [0.37, 0.81], p < .001; rp2 = 0.319) during the early-phase response to the laboratory stressor, as well as poorer cortisol recovery (β = 0.32, [0.10, 0.54], p = .005; rp2 = 0.095) in the late-phase stress response. Results highlight the role of loss aversion and stress in understanding RNT as an affective vulnerability factor.

EEG cross-frequency correlations as a marker of predisposition to affective disorders

EEG cross-frequency amplitude-amplitude correlation (CF-AAC) has been considered as a potential marker of social anxiety and other affective disturbances. Functional significance of this phenomenon remains unclear, partly because the majority of studies used channel-level analysis, which precluded the spatial localization of observed effects. It is not also clear whether CF-AAC may serve as a marker of specific pathological conditions and specific states, or a more general predisposition to affective disturbances. We used source-level analysis of EEG data obtained in resting conditions in a nonclinical sample and patients with major depressive disorder (MDD) and investigated associations of CF-AAC measures with a broad range of known risk factors for affective disorders, including age, gender, genotype, stress exposure, personality, and self-reported ‘neurotic’ symptomatology. A consistent pattern of associations showed that all investigated risk factors were associated with an enhancement of CF-AAC in cortical regions associated with emotional and self-referential processing. It could be concluded that CF-AAC is a promising candidate marker of a general predisposition to affective disorders at preclinical stages.

F200. Too Tired to Care: A Combination of Sleepiness and Poor Sleep Continuity Attenuate Reward-Related Brain Activation

Insomnia, characterized by sleep continuity complaints and daytime symptoms (e.g., sleepiness, fatigue), is a well-replicated risk factor for affective disorders. We examined the independent and combined effects of sleep continuity and sleepiness on reward-related brain function as a putative neural pathway linking insomnia and depression.

P.4.08 Metabolic syndrome, inflammation and oxidative stress as potential risk factors for affective disorders – a twin study

UVB radiation results in the formation of potentially mutagenic photoproducts in the DNA of epidermal skin cells. In vitro approaches have demonstrated that the nucleotide excision repair (NER) machinery removes UV photoproducts from DNA in the form of small (∼30-nt-long), excised, damage-containing DNA oligonucleotides (sedDNAs). Though this process presumably takes place in human skin exposed to UVB radiation, sedDNAs have not previously been detected in human skin. Using surgically discarded human skin, we have optimized the detection of the sedDNA products of NER from small amounts of human epidermal tissue ex vivo within minutes of UVB exposure and after UVB doses that normally lead to minimal erythema. Moreover, sedDNA generation was inhibited by treatment of skin explants with spironolactone, which depletes the epidermis of the essential NER protein XPB to mimic the skin of xeroderma pigmentosum patients. Time course experiments revealed that a partially degraded form of the sedDNAs could be readily detected even 12 hours following UVB exposure, which indicates that these repair products are relatively stable in human skin epidermis. Together, these data suggest that sedDNA detection may be a useful assay for determining how genetic, environmental, and other factors influence NER activity in human skin epidermis and whether abnormal sedDNA processing contributes to photosensitive skin disorders.

The predictive value of Approach and Avoidance tendencies on the onset and course of depression and anxiety disorders.

BackgroundTrait and automatic approach‐avoidance (AA) tendencies are central concepts in research on affective disorders. We longitudinally examined the associations of trait and automatic AA tendencies with the risk of onset and chronicity of anxiety and depressive disorders.MethodsParticipants were subdivided into those with (n = 766) versus without (n = 1,636) a current anxiety or depression diagnosis at baseline. Clinical diagnoses were reassessed after 2‐year follow‐up. Automatic AA tendencies in reaction to facial expressions were assessed using the Approach‐Avoidance Task, whereas self‐reported trait AA tendencies were assessed using the Behavioral Inhibition System and the Behavioral Activation System scales. Analyses were adjusted for socio‐demographics (basic adjustment) and for severity and history of psychopathology (full adjustment).ResultsStronger trait avoidance tendencies predicted both increased risk of onset and increased risk of a chronic course of anxiety disorders after full adjustment (Odds ratioonset = 1.55, P < .001, and Odds ratiochronicity = 1.31, P = .03). The associations between stronger trait avoidance tendencies and increased risk of onset and chronicity of depressive disorders were no longer significant after full adjustment. In contrast, trait approach tendencies and automatic AA tendencies were not related to onset or chronicity of disorders.ConclusionsIncreased trait avoidance tendencies are a risk factor for affective disorders in general, with possibly a slightly more pronounced role in anxiety than depressive disorders. This underlines the importance of addressing trait avoidance tendencies in both the treatment and aftercare of affective disorders.

ADHD symptoms in healthy adults are associated with stressful life events and negative memory bias

Stressful life events, especially Childhood Trauma, predict ADHD symptoms. Childhood Trauma and negatively biased memory are risk factors for affective disorders. The association of life events and bias with ADHD symptoms may inform about the etiology of ADHD. Memory bias was tested using a computer task in N = 675 healthy adults. Life events and ADHD symptoms were assessed using questionnaires. The mediation of the association between life events and ADHD symptoms by memory bias was examined. We explored the roles of different types of life events and of ADHD symptom clusters. Life events and memory bias were associated with overall ADHD symptoms as well as inattention and hyperactivity/impulsivity symptom clusters. Memory bias mediated the association of Lifetime Life Events, specifically Childhood Trauma, with ADHD symptoms. Negatively biased memory may be a cognitive marker of the effects of Childhood Trauma on the development and/or persistence of ADHD symptoms.

High intelligence: A risk factor for psychological and physiological overexcitabilities

High intelligence is touted as being predictive of positive outcomes including educational success and income level. However, little is known about the difficulties experienced among this population. Specifically, those with a high intellectual capacity (hyper brain) possess overexcitabilities in various domains that may predispose them to certain psychological disorders as well as physiological conditions involving elevated sensory, and altered immune and inflammatory responses (hyper body). The present study surveyed members of American Mensa, Ltd. (n=3715) in order to explore psychoneuroimmunological (PNI) processes among those at or above the 98th percentile of intelligence. Participants were asked to self-report prevalence of both diagnosed and/or suspected mood and anxiety disorders, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and physiological diseases that include environmental and food allergies, asthma, and autoimmune disease. High statistical significance and a remarkably high relative risk ratio of diagnoses for all examined conditions were confirmed among the Mensa group 2015 data when compared to the national average statistics. This implicates high IQ as being a potential risk factor for affective disorders, ADHD, ASD, and for increased incidence of disease related to immune dysregulation. Preliminary findings strongly support a hyper brain/hyper body association which may have substantial individual and societal implications and warrants further investigation to best identify and serve this at-risk population.

Neuroticism Associates with Cerebral in Vivo Serotonin Transporter Binding Differently in Males and Females.

BackgroundNeuroticism is a major risk factor for affective disorders. This personality trait has been hypothesized to associate with synaptic availability of the serotonin transporter, which critically controls serotonergic tone in the brain. However, earlier studies linking neuroticism and serotonin transporter have failed to produce converging findings. Because sex affects both the serotonergic system and the risk that neuroticism poses to the individual, sex may modify the association between neuroticism and serotonin transporter, but this question has not been investigated by previous studies.MethodsHere, we combined data from 4 different positron emission tomography imaging centers to address whether neuroticism is related to serotonin transporter binding in vivo. The data set included serotonin transporter binding potential values from the thalamus and striatum and personality scores from 91 healthy males and 56 healthy females. We specifically tested if the association between neuroticism and serotonin transporter is different in females and males.ResultsWe found that neuroticism and thalamic serotonin transporter binding potentials were associated in both males and females, but with opposite directionality. Higher neuroticism associated with higher serotonin transporter binding potential in males (standardized beta 0.292, P=.008), whereas in females, higher neuroticism associated with lower serotonin transporter binding potential (standardized beta -0.288, P=.014).ConclusionsThe finding is in agreement with recent studies showing that the serotonergic system is involved in affective disorders differently in males and females and suggests that contribution of thalamic serotonin transporter to the risk of affective disorders depends on sex.

Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress.

While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR) protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT), increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

Filling the Gap: Relationship Between the Serotonin-Transporter-Linked Polymorphic Region and Amygdala Activation

The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis showed that this association is statistically significant (Hedges’s g = 0.35) but warned that estimates might be distorted because of publication bias. Here, we report a replication study of this relationship in 120 participants. We failed to find an association of 5-HTTLPR variation with amygdala activation during a widely used emotional-face-matching paradigm. Moreover, when we conducted a meta-analysis that included unpublished studies and data from the current study, the pooled meta-analytic effect size was no longer significant (g = 0.20, p = .06). These findings cast doubt on previously reported substantial effects, suggesting that the 5-HTTLPR–amygdala association is either much smaller than previously thought, conditional on other factors, or nonexistent.

Temperament as a risk factor for obesity and affective disorders in obese patients in a Polish sample.

The main purpose of the study was to investigate temperament traits postulated in the Regulative Theory of Temperament that may contribute as risk factors to obesity and, potentially, to affective disorders in obese patients. A cross-sectional design was applied in this study. The study was conducted on a group of 163 obese patients (BMI>35) that included 59 men and 104 women compared with a control group that included 89 men and 113 women who were non-obese. Temperament was assessed using the formal characteristics of behaviour-temperament inventory (FCB-TI). Obese patients compared with a control group scored lower in briskness, endurance and activity, and higher in perseveration. When compared with obese men, obese women had higher levels of perseveration and emotional reactivity, and showed lower levels of activity. Temperament traits, including low levels of briskness, endurance and activity, may serve as risk factors for the development of obesity. Low levels of these traits with accompanying high levels of perseveration may potentially contribute as risk factors for affective disorders in obese patients. The findings suggest that obese women are at somewhat greater risk than obese men for the development of affective disorders.