Exploring social cognition in individuals with neuropsychiatric symptoms following acquired brain injury.

In this study, we explored the social cognitive skills of individuals with neuropsychiatric symptoms following acquired brain injury (ABI). To this end, a retrospective chart review was carried out. We examined scores on social cognition tests that were administered as part of routine neuropsychological assessment at a Dutch specialized care facility for patients with neuropsychiatric symptoms following ABI. In addition, correlations with time post injury were explored. Aspects of social cognition (emotion recognition, Theory of Mind (ToM) and empathy) were measured using the Emotion Recognition Task (n = 40), the Ekman 60-Faces Test of the Facial Expression of Emotion: Stimuli and Tests (n = 11) and the Faux Pas Test (n = 36). 72.5% to 81.8% of participants scored very low or low on emotion recognition. Participants' scores for ToM and empathy were lower than those reported recently for samples of Dutch stroke and traumatic brain injury patients. Correlations between social cognition scores and time since injury were non-significant or negative. While further research is necessary, our results indicate that social cognitive problems are prevalent and persistent in individuals who display neuropsychiatric symptoms after ABI. Future studies should employ a prospective approach in order to confirm our exploratory findings.

Factors Related to the Quality and Stability of Partner Relationships After Traumatic Brain Injury: A Systematic Literature Review.

OBJECTIVE: The latest literature review on partner relationships after traumatic brain injury (TBI), conducted a decade ago, discussed solely quantitative work and noted significant knowledge gaps. The current review updates and expands on this work by providing an overview of the current state of knowledge on factors related to relationship quality and stability after TBI. DATA SOURCES: Cumulative Index to Nursing and Allied Health, Embase, MEDLINE, Psychology and Behavioral Sciences Collection, APA PsycINFO, and PubMed were searched on April 23, 2020, for literature on factors associated with (1) relationship quality; and (2) relationship stability after TBI. STUDY SELECTION: English quantitative and qualitative studies investigating factors associated with relationship quality and/or stability after TBI were included. Two reviewers independently assessed eligibility. If consensus was not reached, a third reviewer's conclusion was decisive. Forty-three studies were included. DATA EXTRACTION: Information regarding study objectives and characteristics, participant demographics, independent and dependent variables, and main findings was extracted. Study quality was rated using the JBI Checklist for Analytical Cross-Sectional Studies and/or the CASP Checklist for Qualitative Research. Both were performed by the lead reviewer and checked by the second reviewer. DATA SYNTHESIS: Thirty-eight factors related to relationship quality and/or stability were identified, covering injury characteristics (eg, severity), body functions (eg, personality changes), activities (eg, communication), participation (eg, social dependence), environment (eg, children), and personal factors (eg, coping strategies). CONCLUSIONS: Relationship quality and stability after TBI are related to a multitude of factors, including newly identified factors such as personality changes and dependence. Future research may wish to quantitatively investigate factors thus far only identified in qualitative research, explore possible positive effects of TBI on relationships, study the experiences of same-sex couples, and include the perspectives of both partners with and without the injury.

Comment on Laratta et al. Marital Stability and Quality of Couple Relationships after Acquired Brain Injury: A Two-Year Follow-Up Clinical Study. Healthcare 2021, 9, 283.

We read with great interest the recent article by Laratta et al. [...].

Exploring Perceived Interactions Between Consequences of Traumatic Brain Injury.

OBJECTIVE: To explore the perceived interactions between consequences of traumatic brain injury (TBI). PARTICIPANTS: Fifteen clinicians experienced in working with patients with TBI. METHODS: Participating clinicians completed an online questionnaire in which they estimated the degree to which consequences of TBI (taken from the Brief ICF Core Set for Traumatic Brain Injury) causally relate to each other. Based on these perceived interactions, a visual network was constructed and centrality measures for this network were computed. RESULTS: The resulting network demonstrates various strong perceived causal relations between the consequences of TBI. Impairments in consciousness were perceived to most strongly cause other TBI consequences in the network. Difficulties with acquiring, keeping, and terminating a job were perceived to be most strongly caused by other TBI consequences. Difficulties in partaking in complex interpersonal interactions were also perceived to play a central role in the network. CONCLUSION: In the perception of clinicians, consequences of TBI interact with each other and are thus not solely a direct result of the injury. While more research is needed to map the interactions between consequences of TBI, our results could have important implications for the way we understand and treat the problems patients are faced with after TBI.

Aerobic Activity in the Healthy Elderly Is Associated with Larger Plasticity in Memory Related Brain Structures and Lower Systemic Inflammation.

Cognitive abilities decline over the time course of our life, a process, which may be mediated by brain atrophy and enhanced inflammatory processes. Lifestyle factors, such as regular physical activities have been shown to counteract those noxious processes and are assumed to delay or possibly even prevent pathological states, such as dementing disorders. Whereas the impact of lifestyle and immunological factors and their interactions on cognitive aging have been frequently studied, their effects on neural parameters as brain activation and functional connectivity are less well studied. Therefore, we investigated 32 healthy elderly individuals (60.4 ± 5.0 SD; range 52-71 years) with low or high level of self-reported aerobic physical activity at the time of testing. A higher compared to a lower level in aerobic physical activity was associated with an increased encoding related functional connectivity in an episodic memory network comprising mPFC, thalamus, hippocampus precuneus, and insula. Moreover, encoding related functional connectivity of this network was associated with decreased systemic inflammation, as measured by systemic levels of interleukin 6.

Association between serum brain-derived neurotrophic factor and plasma interleukin-6 in major depressive disorder with melancholic features.

Inflammatory processes as well as attenuation of brain-derived neurotrophic factor (BDNF) availability are involved in the pathophysiology of major depressive disorder (MDD). Although it is generally presumed that these two systems interact negatively in the brain, preclinical and human in vitro studies have shown synergistic rather than antagonistic interactions in the periphery. We therefore examined the association between serum levels of BDNF and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in patients with MDD (n=1070) and non-depressed controls (n=379) from the Netherlands Study of Depression and Anxiety. We used multiple regression analyses with serum BDNF as the dependent variable and we specifically tested the presence of BDNF-cytokine associations in DSM-IV-assigned melancholic MDD patients, identified by the Inventory of Depressive Symptomatology. After adjustment for sociodemographics, sampling variability, lifestyle indicators, somatic diseases and medication use, BDNF levels were predicted by the interaction between MDD diagnosis and IL-6 (p-interaction=.006). Stratified analyses showed that BDNF levels are indeed positively associated with IL-6 levels in MDD patients (ß=.07, p=.02), but not in non-depressed controls (ß=-.07, p=.23). When further stratified for melancholic and non-melancholic MDD (p-interaction=.005), IL-6 emerged as a robust positive predictor of BDNF only in the melancholic sample (ß=.21, p=.01), wherein serum BDNF levels were accordingly enhanced. Post-hoc exploratory analyses verified an accentuated positive association of BDNF levels with leucocyte counts in melancholia. No significant associations emerged between BDNF and TNF-α. Overall, our cross-sectional approach may have disclosed an allostatic, BDNF-inducing component of peripheral immunity and/or an immunotrophic function of peripheral BDNF. Both scenarios may warrant further exploration, as they could inform new research concepts towards immune-based antidepressive treatment strategies.

Atherosclerosis decreases the impact of neuroticism in late-life depression: hypothesis of vascular apathy.

OBJECTIVE: To examine the interplay between subclinical atherosclerotic disease and neuroticism in explaining variance in late-life depressive symptoms. METHODS: This study was part of the Nijmegen Biomedical Study, a population-based survey; 1,517 participants aged 50-70 years were included. Depressive symptoms were measured by the Beck Depression Inventory (BDI). Principal components analysis of the BDI items yielded two factors, representing a cognitive-affective symptom cluster and a somatic-affective symptom cluster. Atherosclerotic disease was measured by the intima media thickness (IMT) of the carotid arteries and neuroticism by the revised Eysenck Personality Questionnaire. RESULTS: Multiple linear regression analyses using different measures of depressive symptoms as the dependent variable showed that neuroticism was strongly and significantly associated with the sum score of the BDI and with the two depressive symptom clusters. IMT, however, was only significantly associated with the somatic-affective symptom cluster but not with the cognitive-affective symptom cluster. Interestingly, we found a significant negative interaction between neuroticism and IMT in explaining the severity of the cognitive-affective symptom cluster but not with respect to the somatic-affective symptom cluster. CONCLUSION: The negative interaction between neuroticism and atherosclerosis indicates that neuroticism is less strongly associated with cognitive-depressive symptoms in the presence of more severe atherosclerosis. This may be explained by apathy due to cerebrovascular disease and fits with a hypothesis of vascular apathy.

Serum BDNF concentrations show strong seasonal variation and correlations with the amount of ambient sunlight.

Earlier findings show seasonality in processes and behaviors such as brain plasticity and depression that in part are regulated by Brain-Derived Neurotrophic Factor (BDNF). Based on this we investigated seasonal variation in serum BDNF concentrations in 2,851 persons who took part in the Netherlands Study of Depression and Anxiety (NESDA). Analyses by month of sampling (monthly n's >196) showed pronounced seasonal variation in serum BDNF concentrations (P<.0001) with increasing concentrations in the spring-summer period (standardized regression weight (ß) = 0.19, P<.0001) and decreasing concentrations in the autumn-winter period (ß = -0.17, P<.0001). Effect sizes [Cohen's d] ranged from 0.27 to 0.66 for monthly significant differences. We found similar seasonal variation for both sexes and for persons with a DSM-IV depression diagnosis and healthy control subjects. In explorative analyses we found that the number of sunshine hours (a major trigger to entrain seasonality) in the week of blood withdrawal and the 10 weeks prior to this event positively correlated with serum BDNF concentrations (Pearson's correlation coefficients ranged: 0.05-0.18) and this could partly explain the observed monthly variation. These results provide strong evidence that serum BDNF concentrations systematically vary over the year. This finding is important for our understanding of those factors that regulate BDNF expression and may provide novel avenues to understand seasonal dependent changes in behavior and illness such as depression. Finally, the findings reported here should be taken into account when designing and interpreting studies on BDNF.

A systematic review and meta-analysis on the association between BDNF val(66)met and hippocampal volume--a genuine effect or a winners curse?

Inconsistenties have been reported with regard to an association between val(66)met, a polymorphism on the BDNF gene, and hippocampal volume. We performed a systematic review and a meta-analysis to determine the magnitude and direction of this putative association and estimated the potential influence of demographic, clinical, and methodological characteristics of studies. Tests of publication bias and time-related trends were performed and statistical power of the included studies was calculated. The literature search for MRI studies on differences in total hippocampal volume as a function of BDNF val(66)met returned 25 records that fulfilled our criteria (total N = 3,620). Meta-analysis showed that carriers of a met allele had lower hippocampal volumes relative to val/val homozygotes (d = 0.13, P = 0.02). Between-study heterogeneity in effect size estimates was substantial (Q = 54.47, P < .001) and this could not be explained by demographic, clinical, and methodological differences across studies. Funnel plot inspection and trim-and-fill estimations suggested evidence for publication bias and effect sizes decreased substantially over the years (Pearson's r = -0.54, P < .01). All included studies were underpowered. This meta-analysis shows that carriers of a met allele have lower total hippocampal volumes relative to val/val homozygotes. However, effect sizes converged closer to null with virtually each attempt at replication and were based on underpowered studies. Altogether, this may call into question whether the observed effect is a genuine biological effect of the met allele or whether it is subject to a winners curse, with large effect sizes found in a few early studies and increasingly smaller effect sizes in later studies.

Increase in serum brain-derived neurotrophic factor in met allele carriers of the BDNF Val66Met polymorphism is specific to males.

BACKGROUND: Association studies of the Val66Met polymorphism and serum brain-derived neurotrophic factor (BDNF) levels have yielded conflicting results. Recently, sex-specific differences in BDNF levels were demonstrated. As these might explain the reported inconsistencies, we tested sex interactions with the Val66Met genotype on serum BDNF level. METHODS: Participants (n = 548, age range 50-72 years; mean 62.8 ± 5.4 years, 267 males) were tested for rs6265 genotype and serum BDNF levels [Hardy-Weinberg equilibrium (HWE), p = 0.04]. A regression analysis with BDNF level as the dependent variable and BDNF Val66Met genotype as an independent variable was used to test the sex interaction corrected for age, smoking and depressive symptoms. Subsequently, we examined the effect of genotype on BDNF levels stratified for sex. RESULTS: We found a significant interaction between sex and genotype on BDNF levels (p = 0.02). Male Met carriers had significantly higher BDNF levels than Val/Val homozygotes (ß = 0.17, p = 0.013), while in females no effect of Val66Met genotype was found (ß = -0.07, p = 0.28). CONCLUSION: Our findings may partly explain the inconsistent findings of earlier studies where results were influenced by male-female ratios. Replication is warranted, however, as our sample was not in HWE.

Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety.

OBJECTIVES: Whereas animal models indicate that brain-derived neurotrophic factor (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in patients with an anxiety disorder. We tested the hypothesis that serum BDNF levels are low in patients with an anxiety disorder as compared to healthy controls. We further examined the associations of gender and some of the clinical characteristics of anxiety with BDNF levels. METHODS: Serum BDNF levels were determined in 393 unmedicated, non-depressed patients with social anxiety disorder, panic disorder, agoraphobia, and generalised anxiety disorder (66.7% females) and in 382 healthy controls (62.0% females). RESULTS: Overall, there were no differences in BDNF levels among patients and controls, regardless of type of anxiety disorder. Analyses stratified by gender revealed that female patients had lower levels of BDNF relative to female controls (P < 0.05, d = 0.19), which was stronger in female patients with > 1 anxiety disorder (P < 0.01, d = 0.32). BDNF levels were similar among male patients and controls and unrelated to the clinical characteristics of anxiety. CONCLUSION: Our results mirror preclinical findings indicating that gender plays a role in the association between BDNF and anxiety and suggest that BDNF might play a role in the pathophysiology of anxiety in women.

Serum brain-derived neurotrophic factor: determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) is involved in major depressive disorder and neurodegenerative diseases. Clinical studies, showing decreased serum BDNF levels, are difficult to interpret due to limited knowledge of potential confounders and mixed results for age and sex effects. We explored potential determinants of serum BDNF levels in a community sample of 1230 subjects. METHODS: Multiple linear regression analyses with serum BDNF level as the dependent variable were conducted to explore the effect of four categories of potential BDNF determinants (sampling characteristics, sociodemographic variables, lifestyle factors and somatic diseases) and of self-reported depressive symptoms (Beck's Depression Inventory (BDI). RESULTS: Our results show that BDNF levels decline with age in women, whereas in men levels remain stable. Moreover, after controlling for age and gender, the assays still showed lower serum BDNF levels with higher BDI sum scores. Effects remained significant after correction for two main confounders (time of sampling and smoking), suggesting that they serve as molecular trait factors independent of lifestyle factors. CONCLUSIONS: Given the age-sex interaction on serum BDNF levels and the known association between BDNF and gonadal hormones, research is warranted to delineate the effects of the latter interaction on the risk of psychiatric and neurodegenerative diseases.

Prevalence of depression in Parkinson's disease: effects of disease stage, motor subtype and gender.

Depression is one of the most common non-motor symptoms of Parkinson's disease (PD) with a large negative impact on the quality of life. Factors such as disease stage, subtype of PD and gender might play an important role in the prevalence of depression, but a large study investigating all these factors in a within-subject design is lacking. Therefore we studied a homogeneous group of 256 Dutch PD patients (60% men, mean age=65.12 (±9.6) years). In total, 36.3% of the subjects had a BDI-score indicative for a minor depression, while 12.9% had a major depression. Notably, only 8.6% of the minor depressed patients and 30.3% of the major depressed patients were taking antidepressants. A higher prevalence of depression was observed in the later stages of the disease. However, this finding was absent in a smaller subsample after correction for cognitive impairment. Our data did not show a difference in the prevalence of depression between the motor subtypes and showed a trend towards higher prevalence of depression in the tremor dominant group. There was no significant difference in the prevalence of depression between men and women. We will discuss the relevance of these results in relation to the findings of other studies.

Depressive symptom clusters are differentially associated with general and visceral obesity.

OBJECTIVES: To examine the relationship between obesity and depressive symptoms taking into account different measures for obesity (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) and different depressive symptom clusters. DESIGN: Cross-sectional population-based survey. SETTING: Baseline data of the Nijmegen Biomedical Study. PARTICIPANTS: One thousand two hundred eighty-four persons aged 50 to 70. MEASUREMENTS: Obesity (BMI, WC, and WHR) and depressive symptoms were measured, the latter using the Beck Depression Inventory (BDI). Principal components analysis of the BDI items yielded two factors, one representing a cognitive-affective symptom cluster and the other a somatic-affective symptom cluster. Multiple regression analyses corrected for confounders were conducted for each measure of obesity, with separate models testing the BDI sum score and the depression symptom clusters. RESULTS: BMI was significantly associated with BDI sum score (ß=0.12, P<.001) and the cognitive- (ß=0.08, P=.008) and somatic-affective symptom clusters (ß=0.10, P=.001). WC (ß=0.11, P<.001) and WHR (ß=0.07, P=.004) were specifically associated with the somatic-affective symptom cluster. CONCLUSION: Visceral obesity, which is more indicative of vascular risk than BMI, is specifically associated with somatic-affective depressive symptom cluster, which might suggest that these symptoms are primarily due to a (subclinical) somatic condition.

The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met.

RATIONALE: Recent findings show lowered brain-derived neurotrophic factor (BDNF) levels in major depressive disorder (MDD). Exposure to stressful life events may (partly) underlie these BDNF reductions, but little is known about the effects of early or recent life stress on BDNF levels. Moreover, the effects of stressful events on BDNF levels may in part be conditional upon a common variant on the BDNF gene (Val(66)Met; RS6265), with the Met allele being associated with a decrease in activity-dependent secretion of BDNF compared to the Val allele. METHODS: We investigated cross-sectionally in 1,435 individuals with lifetime MDD the impact of childhood abuse (CA) and recent life events on serum BDNF levels and assessed whether the impact of these events was moderated by the BDNF Val(66)Met polymorphism. RESULTS: Overall, BDNF Met carriers had reduced serum BDNF levels when exposed to CA in a dose-dependent way. Moreover, exposure to recent life events was also associated with decreases in BDNF levels, but this was independent of BDNF Val(66)Met. Moreover, when not exposed to CA, Met carriers had higher BDNF levels than the Val/Val individuals, who did not show decreases in BDNF associated with CA. Finally, these findings were only apparent in the MDD group without comorbid anxiety. CONCLUSIONS: These gene-environment interactions on serum BDNF levels suggest that Met carriers are particularly sensitive to (early) stressful life events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events.