A preliminary study on brain developmental features of bipolar disorder familial risk and subthreshold symptoms.

BACKGROUND: Risk for Bipolar disorder (BD) is increased among individuals with family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remained unknown. METHODS: This longitudinal cohort study examined the brain grey matter volume (GMV) developmental features of familial and symptomatic risks for BD, and their associations with participants' global function levels. We recruited unaffected BD offspring with (N=26, age=14.9±2.9 years, 14 females) or without (N=35, age=15.3±2.7 years, 19 females) subthreshold manic or depressive symptoms, and unaffected non-BD offspring with (N=49, age=14.5±2.2 years, 30 females) or without (N=68, age=15.0±2.3 years, 37 females) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63±1.63 years. RESULTS: We found at baseline, significant interactive effects of familial risk and subthreshold symptoms indicated the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and non-symptomatic) displayed accelerated GMV decrease than BD non-offspring, in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and non-offspring) displayed slower GMV decrease than non-symptomatic participants, in the ventromedial prefrontal cortex. Larger GMV at baseline, and accelerated GMV decrease during follow-up, prospectively and longitudinally predicted positive global function changes. All results survived multiple-testing correction. CONCLUSIONS: These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments, and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.

Common neural deficits across reward functions in major depression: a meta-analysis of fMRI studies.

Major depressive disorder (MDD) is characterized by deficient reward functions in the brain. However, existing findings on functional alterations during reward anticipation, reward processing, and learning among MDD patients are inconsistent, and it was unclear whether a common reward system implicated in multiple reward functions is altered in MDD. Here we meta-analyzed 18 past studies that compared brain reward functions between adult MDD patients (N = 477, mean age = 26.50 years, female = 59.40%) and healthy controls (N = 506, mean age = 28.11 years, females = 55.58%), and particularly examined group differences across multiple reward functions. Jack-knife sensitivity and subgroup meta-analyses were conducted to test robustness of findings across patient comorbidity, task paradigm, and reward nature. Meta-regression analyses assessed the moderating effect of patient symptom severity and anhedonia scores. We found during reward anticipation, MDD patients showed lower activities in the lateral prefrontal-thalamus circuitry. During reward processing, patients displayed reduced activities in the right striatum and prefrontal cortex, but increased activities in the left temporal cortex. During reward learning, patients showed reduced activity in the lateral prefrontal-thalamic-striatal circuitry and the right parahippocampal-occipital circuitry but higher activities in bilateral cerebellum and the left visual cortex. MDD patients showed decreased activity in the right thalamus during both reward anticipation and learning, and in the right caudate during both reward processing and learning. Larger functional changes in MDD were observed among patients with more severe symptoms and higher anhedonia levels. The thalamic-striatal circuitry functional alterations could be the key neural mechanism underlying MDD patients overarching reward function deficiencies.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202409000-00036/figure1/v/2024-01-16T170235Z/r/image-tiff Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses. Moreover, anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms. Lycium barbarum polysaccharide (LBP), derived from Goji berries, exhibits notable antioxidative and anti-inflammatory properties. In our recent double-blinded randomized placebo-controlled trial, we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression. It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines. In the double-blinded randomized controlled trial, we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group. In the LBP group, adolescents were given 300 mg/d LBP. A 6-week follow up was completed by 24 adolescents, comprising 14 adolescents from the LBP group (15.36 ± 2.06 years, 3 men and 11 women) and 10 adolescents from the placebo group (14.9 ± 1.6 years, 2 men and 8 women). Our results showed that after 6 weeks of treatment, the interleukin-17A level in the LBP group was lower than that in the placebo group. Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors, which were associated with the improvement in depressive symptoms. These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level, thereby exerting an antidepressant effect.

Leveraging History to Predict Infrequent Abnormal Transfers in Distributed Workflows.

Scientific computing heavily relies on data shared by the community, especially in distributed data-intensive applications. This research focuses on predicting slow connections that create bottlenecks in distributed workflows. In this study, we analyze network traffic logs collected between January 2021 and August 2022 at the National Energy Research Scientific Computing Center (NERSC). Based on the observed patterns, we define a set of features primarily based on history for identifying low-performing data transfers. Typically, there are far fewer slow connections on well-maintained networks, which creates difficulty in learning to identify these abnormally slow connections from the normal ones. We devise several stratified sampling techniques to address the class-imbalance challenge and study how they affect the machine learning approaches. Our tests show that a relatively simple technique that undersamples the normal cases to balance the number of samples in two classes (normal and slow) is very effective for model training. This model predicts slow connections with an F1 score of 0.926.

Exercise effect on the gut microbiota in young adolescents with subthreshold depression: A randomized psychoeducation-controlled Trial.

This 3-month randomized psychoeducation-controlled trial (RCT) of exercise was undertaken in young adolescents with subthreshold depression to examine the impact on gut microbiota. Participants (aged 12-14 years) were randomly assigned to an exercise or a psychoeducation-controlled group. The exercise intervention arm took moderate-intensity exercise, comprised of 30 min of running per day, 4 days a week for 3 months. Psychoeducation intervention consisted of 6 sessions of group activity including gaming, reading, and singing. The gut microbiota was assessed by metagenomic sequencing. After 3-month moderate-intensity exercise, the intervention group increased the relative abundance of Coprococcus, Blautia, Dorea, Tyzzerella at the genus level, as well as Tyzzerella nexilis, Ruminococcus obeum at species level when compared to the psychoeducation-controlled group. Moreover, EggNOG analyses showed that the defense and signal transduction mechanism were highly enriched after the active intervention, and changes were correlated with improvements in depressive symptoms measured by Chinese Patient Depression Questionnaire 9. The KEGG pathway of neurodegenerative diseases was depleted in the microbiome in young adolescents with subthreshold depression after exercise intervention. This 3-month RCT suggests that at both the genus and species levels, aerobic group exercise intervention improved in depressive symptoms and revealed changes in gut microbiota suggesting beneficial effects.

Multi-systemic evaluation of biological and emotional responses to the Trier Social Stress Test: A meta-analysis and systematic review.

Humans experience multiple biological and emotional changes under acute stress. Adopting a multi-systemic approach, we summarized 61 studies on healthy people's endocrinological, physiological, immunological and emotional responses to the Trier Social Stress Test. We found salivary cortisol and negative mood states were the most sensitive markers to acute stress and recovery. Biomarkers such as heart rate and salivary alpha-amylase also showed sensitivity to acute stress, but the numbers of studies were small. Other endocrinological (e.g., dehydroepiandrosterone), inflammatory (C-Reactive Protein, Interleukin-6) and physiological (e.g., skin conductance level) measures received modest support as acute stress markers. Salivary cortisol showed some associations with mood measures (e.g., state anxiety) during acute stress and recovery, and heart rate showed preliminary positive relationship with calmness ratings during response to TSST, but the overall evidence was mixed. While further research is needed, these findings provide updated and comprehensive knowledge on the integrated psychobiological response profiles to TSST.

The positive and negative emotion functions related to loneliness: a systematic review of behavioural and neuroimaging studies.

Loneliness is associated with high prevalences of major psychiatric illnesses such as major depression. However, the underlying emotional mechanisms of loneliness remained unclear. We hypothesized that loneliness originates from both decreases in positive emotional processing and increases in negative emotion processing. To test this, we conducted a systematic review of 29 previous studies (total participants n = 19 560, mean age = 37.16 years, female proportion = 59.7%), including 18 studies that included questionnaire measures of emotions only, and 11 studies that examined the brain correlates of emotions. The main findings were that loneliness was negatively correlated with general positive emotions and positively correlated with general negative emotions. Furthermore, limited evidence indicates loneliness exhibited negative and positive correlations with the brain positive (e.g. the striatum) and negative (e.g. insula) emotion systems, respectively, but the sign of correlation was not entirely consistent. Additionally, loneliness was associated with the structure and function of the brain emotion regulation systems, particularly the prefrontal cortex, but the direction of this relationship remained ambiguous. We concluded that the existing evidence supported a bivalence model of loneliness, but several critical gaps existed that could be addressed by future studies that include adolescent and middle-aged samples, use both questionnaire and task measures of emotions, distinguish between general emotion and social emotion as well as between positive and negative emotion regulation, and adopt a longitudinal design that allows us to ascertain the causal relationships between loneliness and emotion dysfunction. Our findings provide new insights into the underlying emotion mechanisms of loneliness that can inform interventions for lonely individuals.

Global hippocampus functional connectivity as a predictive neural marker for conversion to future mood disorder in unaffected offspring of bipolar disorder parents.

OBJECTIVES: Hippocampus-related functional alteration in genetically at-risk individuals may reflect an endophenotype of a mood disorder. Herein, we performed a prospective study to investigate whether baseline hippocampus functional connectivity (FC) in offspring of patients with bipolar disorder (BD) would predict subsequent conversion to mood disorder. METHODS: Eighty bipolar offspring and 40 matched normal controls (NC) underwent resting state functional MRI (rsfMRI) scanning on a 3.0 Tesla MR scanner. The offspring were subdivided into asymptomatic offspring (AO) (n = 41) and symptomatic offspring (SO) (n = 39) according to whether they manifested subthreshold mood symptoms. After identifying the different hippocampus FCs between the AO and SO, a logistic regression analysis was conducted to investigate whether the baseline hippocampus FCs predicted a future mood disorder during a 6-year follow-up. RESULTS: We identified seven baseline para/hippocampus FCs that showed differences between AO and SO, which were entered as predictive features in the logistic regressive model. Of the 80 bipolar offspring entering the analysis, the FCs between left hippocampus and left precuneus, and between right hippocampus and left posterior cingulate, showed a discriminative capacity for predicting future mood disorder (area-under-curve, or AUC=75.76 % and 75.00 % respectively), and for predicting BD onset (AUC=77.46 % and 81.63 %, respectively). CONCLUSIONS: The present findings revealed high predictive utility of the hippocampus resting state FCs for future mood disorder and BD onset in individuals at familial risk. These neural markers can potentially improve early detection of individuals carrying particularly high risk for future mood disorder.

Differential Relationships Among C-Reactive Protein, Attention Functioning, and Brain Structure in Bipolar Offspring With and Without Subthreshold Mood Symptoms.

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and premorbid period of BD. Also, the differential inflammation-brain relationship may be identified as biological markers for BD pathology or resilience.Methods: The present data were collected between March 2013 and June 2016. Sixty-four offspring of BD patients were recruited and subdivided into asymptomatic (n = 33, mean age = 17.8 years) and symptomatic (n = 31, mean age = 16.2 years) groups according to whether they manifested subthreshold mood symptoms. The diagnosis of BD was confirmed according to DSM-IV criteria. C-reactive protein (CRP) level, attention functioning, and GMV data were measured by ELISA, the Continuous Performance Test-Identical Pair test (CPT-IP), and 3.0 T magnetic resonance imaging, respectively. Their relationships were examined with mediation and moderation analyses.Results: We observed a higher level of CRP and poorer attention in the symptomatic group than the asymptomatic group and found a significant group × CRP interactive effect on GMV in regions spanning right precentral and postcentral gyri (P = .043). CRP levels negatively mediated the relationship between the group and CPT-IP scores, and the group marginally moderated the relationship between pre/postcentral gyri volumes and CPT-IP scores (P = .05).Conclusions: Symptomatic and asymptomatic bipolar offspring manifested differential inflammation-GMV-attention relationships, which may represent, respectively, an endophenotype or a resilience process for BD.

Multimodal Neural Evidence on the Corticostriatal Underpinning of Suicidality in Late-Life Depression.

BACKGROUND: Suicidality involves thoughts (ideations and plans) and actions related to self-inflicted death. To improve management and prevention of suicidality, it is essential to understand the key neural mechanisms underlying suicidal thoughts and actions. Following empirically informed neural framework, we hypothesized that suicidal thoughts would be primarily characterized by alterations in the default mode network indicating disrupted self-related processing, whereas suicidal actions would be characterized by changes in the lateral prefrontal corticostriatal circuitries implicating compromised action control. METHODS: We analyzed the gray matter volume and resting-state functional connectivity of 113 individuals with late-life depression, including 45 nonsuicidal patients, 33 with suicidal thoughts but no action, and 35 with past suicidal action. Between-group analyses revealed key neural features associated with suicidality. The functional directionality of the identified resting-state functional connectivity was examined using dynamic causal modeling to further elucidate its mechanistic nature. Post hoc classification analysis examined the contribution of the neural measures to suicide classification. RESULTS: As expected, reduced gray matter volumes in the default mode network and lateral prefrontal regions characterized patients with suicidal thoughts and those with past suicidal actions compared with nonsuicidal patients. Furthermore, region-of-interest analyses revealed that the directionality and strength of the ventrolateral prefrontal cortex-caudate resting-state functional connectivity were related to suicidal thoughts and actions. The neural features significantly improved classification of suicidal thoughts and actions over that based on clinical and suicide questionnaire variables. CONCLUSIONS: Gray matter reductions in the default mode network and lateral prefrontal regions and the ventrolateral prefrontal cortex-caudate connectivity alterations characterized suicidal thoughts and actions in patients with late-life depression.

Efficacy of Lycium barbarum polysaccharide in adolescents with subthreshold depression: interim analysis of a randomized controlled study.

Subthreshold depression is a highly prevalent condition in adolescents who are at high risk for developing major depressive disorder. In preclinical models of neurological and psychiatric diseases, Lycium barbarum polysaccharide (LBP) extracted from Goji berries had anti-depressant effects including but not limited to anti-oxidative and anti-inflammatory properties. However, the effect of LBP on subthreshold depression is unclear. To investigate the clinical efficacy and safety of LBP for treating subthreshold depression in adolescents, we conducted a randomized, double-blind, placebo-controlled trial (RCT) with 29 adolescents with subthreshold depression recruited at The Fifth Affiliated Hospital of Guangzhou Medical University. The participants were randomly assigned to groups where they received either 300 mg LBP (LBP group, n = 15, 3 boys and 12 girls aged 15.13 ± 2.17 years) or a placebo (placebo group, n = 14, 2 boys and 12 girls aged 15 ± 1.71 years) for 6 successive weeks. Interim analyses revealed that the LBP group exhibited a greater change in Hamilton Depression Scale (HAMD-24) scores relative to the baseline and a higher remission rate (HAMD-24 total score ≤ 7) at 6 weeks compared with the placebo group. Scores on the Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), Kessler Psychological Distress Scale (Kessler), and Screen for Child Anxiety-Related Emotional Disorders (SCARED) were similar between the LBP and placebo groups. No side effects related to the intervention were reported in either group. These results indicate that LBP administration reduced depressive symptoms in adolescents with subthreshold depression. Furthermore, LBP was well tolerated with no treatment-limiting adverse events. Clinical trials involving a larger sample size are needed to further confirm the anti-depressive effects of LBP in adolescents with subthreshold depression. This study was approved by the Medical Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University (Guangzhou, China; approval No. L2019-08) on April 4, 2019 and was registered on ClinicalTrials.gov (identifier: NCT04032795) on July 25, 2019.

Qigong exercise enhances cognitive functions in the elderly via an interleukin-6-hippocampus pathway: A randomized active-controlled trial.

BACKGROUND: Evidence has suggested that exercise protects against cognitive decline in aging, but the recent lockdown measures associated with the COVID-19 pandemic have limited the opportunity for outdoor exercise. Herein we tested the effects of an indoor exercise, Qigong, on neurocognitive functioning as well as its potential neuro-immune pathway. METHODS: We conducted a 12-week randomized active-controlled trial with two study arms in cognitively healthy older people. We applied Wu Xing Ping Heng Gong (Qigong), which was designed by an experienced Daoist Qigong master, to the experimental group, whereas we applied the physical stretching exercise to the control group. The Qigong exercise consisted of a range of movements involving the stretching of arms and legs, the turning of the torso, and relaxing, which would follow the fundamental principles of Daoism and traditional Chinese medicine (e.g., Qi). We measured aging-sensitive neurocognitive abilities, serum interleukin-6 (IL-6) levels, and brain structural volumes in the experimental (Qigong, n = 22) and control groups (stretching, n = 26) before and after the 12-week training. RESULTS: We observed that Qigong caused significant improvement in processing speed (t (46) = 2.03, p = 0.048) and sustained attention (t (46) = -2.34, p = 0.023), increased hippocampal volume (t (41) = 3.94, p < 0.001), and reduced peripheral IL-6 levels (t (46) = -3.17, p = 0.003). Moreover, following Qigong training, greater reduction of peripheral IL-6 levels was associated with a greater increase of processing speed performance (bootstrapping CI: [0.16, 3.30]) and a more significant training-induced effect of hippocampal volume on the improvement in sustained attention (bootstrapping CI: [-0.35, -0.004]). CONCLUSION: Overall, these findings offer significant insight into the mechanistic role of peripheral IL-6-and its intricate interplay with neural processes-in the beneficial neurocognitive effects of Qigong. The findings have profound implications for early identification and intervention of older individuals vulnerable to cognitive decline, focusing on the neuro-immune pathway. The trial was registered at clinicaltrials.gov (identifier: NCT04641429).

Integrity of the uncinate fasciculus is associated with the onset of bipolar disorder: a 6-year followed-up study.

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049-0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

The executive control correlate of loneliness in healthy older people.

Perceived loneliness has implications in both cognitive and affective domains. High loneliness is considered to be a major risk factor for major depressive disorder. Loneliness is also associated with impaired executive control functioning (ECF) including multiple cognitive subdomains, such as working memory, planning, response inhibition, and attention control. However, little knowledge exists as to whether perceived loneliness is associated with impaired functioning of specific ECF components. The relationship between perceived loneliness and the latent dimensions capturing multiple measures across different ECF paradigms has not been established. In this study, we first investigated the latent dimensions of ECF processes across a comprehensive range of paradigms using exploratory factor analysis. We then examined the association of perceived loneliness and the resulted ECF components in older adults while simultaneously controlling for other demographic and affective measures. Four components emerged from the factor analysis: social cognition and processing speed, planning and working memory, selective, divided attention and inhibition control, and sustained attention and motor inhibition. We observed that the second ECF component, planning and working memory, was a significant predictor of perceived loneliness even after controlling for depressive characteristics measured by the Geriatric Depression Scale. Our findings have potential clinical significance in the older population, by showing that planning and working memory functions may predict perceived loneliness, which is also associated with higher risk for major depression. Thus, older individuals who have lower planning and working memory functions may be specifically targeted for possible early prevention of chronic loneliness and depression.

Connectome-based models can predict processing speed in older adults.

Decrement in processing speed (PS) is a primary cognitive morbidity in clinical populations and could significantly influence other cognitive functions, such as attention and memory. Verifying the usefulness of connectome-based models for predicting neurocognitive abilities has significant translational implications on clinical and aging research. In this study, we verified that resting-state functional connectivity could be used to predict PS in 99 older adults by using connectome-based predictive modeling (CPM). We identified two distinct connectome patterns across the whole brain: the fast-PS and slow-PS networks. Relative to the slow-PS network, the fast-PS network showed more within-network connectivity in the motor and visual networks and less between-network connectivity in the motor-visual, motor-subcortical/cerebellum and motor-frontoparietal networks. We further verified that the connectivity patterns for prediction of PS were also useful for predicting attention and memory in the same sample. To test the generalizability and specificity of the connectome-based predictive models, we applied these two connectome models to an independent sample of three age groups (101 younger adults, 103 middle-aged adults and 91 older adults) and confirmed these models could specifically be generalized to predict PS of the older adults, but not the younger and middle-aged adults. Taking all the findings together, the identified connectome-based predictive models are strong for predicting PS in older adults. The application of CPM to predict neurocognitive abilities can complement conventional neurocognitive assessments, bring significant clinical benefits to patient management and aid the clinical diagnoses, prognoses and management of people undergoing the aging process.

The relationship between loneliness and working-memory-related frontoparietal network connectivity in people with major depressive disorder.

Loneliness affects up to 40 % of middle-aged and older adults, and is closely associated with major depressive disorder (MDD). However, the relationship between loneliness and neural network functioning during executive cognitive processes, such as working memory, in MDD is still unclear. To address this gap, our study recruited 21 medicated MDD patients (mean age = 52.0 ± 5 years) and 24 matched healthy controls (HC) (mean age = 48.7 ± 6 years) who completed an n-back fMRI task. For behavioural performance, we observed no significant moderating effect of MDD or loneliness on the task condition effect. However, loneliness was positively associated, and MDD was negatively associated, with the functional connectivity between the inferior parietal cortex and the rostral dorsomedial prefrontal cortex (DMPFC) during task performance. Furthermore, an interactive effect of loneliness and MDD was observed on the functional connectivity between the supplementary motor area and the caudal DMPFC during the n-back task, with loneliness showing a positive relationship in the HC group but a negative relationship in the MDD group with the connectivity. Our results indicated that loneliness may be associated with altered neural regulatory functioning on self-referential processing and action control, which may further depend on the individual's depressive state. These findings can form the theoretical basis for devising intervention programme aimed at improving the mental wellness of the healthy and depressed lonely individuals.

Inflammation, brain structure and cognition interrelations among individuals with differential risks for bipolar disorder.

Neuro-inflammation might impact on clinical manifestations and cognition function via changing the volumes of key brain structures such as the anterior cingulate cortex (ACC) in bipolar disorder (BD). In this study, we investigated the interrelations among interleukin (IL)-6 cytokine level, grey matter (GM) volume of the anterior cingulated cortex (ACC), and attention function among offspring of parents diagnosed with BD. The offspring were categorized as being either asymptomatic or symptomatic based on whether they manifested pre-defined sub-threshold mood symptoms. We found that the symptomatic offspring showed significantly higher serum levels of IL-6 than the asymptomatic offspring (F(1, 59) = 67.65, p < 0.001). On the brain level, we obtained significant interactive effect of group and IL6 level on the ACC GM (PFWE = 0.017). Specifically, the GM volume of the rostral ACC was negatively associated with the levels of IL-6 in the asymptomatic offspring (PFWE = 0.021), but not the symptomatic offspring (PFWE > 0.05). Mediation analyses revealed that the GM volume of the rostral ACC significantly mediated the negative association between the IL-6 levels and attention performance in the asymptomatic offspring (bootstrapping Confidence Interval (CI) = -6.0432 to -0.0731) but not the symptomatic offspring (bootstrapping CI = -0.3197 to 1.3423). Our data suggest that the asymptomatic and symptomatic bipolar offspring may exhibit different neurocognitive-inflammatory profiles, which could be further validated as viable biosignatures for BD risk and resilience.

Loneliness and depression dissociated on parietal-centered networks in cognitive and resting states.

BACKGROUND: Perceived loneliness, an increasingly prevalent social issue, is closely associated with major depressive disorder (MDD). However, the neural mechanisms previously implicated in key cognitive and affective processes in loneliness and MDD still remain unclear. Such understanding is critical for delineating the psychobiological basis of the relationship between loneliness and MDD. METHODS: We isolated the unique and interactive cognitive and neural substrates of loneliness and MDD among 27 MDD patients (mean age = 51.85 years, 20 females), and 25 matched healthy controls (HCs; mean age = 48.72 years, 19 females). We assessed participants' behavioral performance and neural regional and network functions on a Stroop color-word task, and their resting-state neural connectivity. RESULTS: Behaviorally, we found greater incongruence-related accuracy cost in MDD patients, but reduced incongruence effect on reaction time in lonelier individuals. When performing the Stroop task, loneliness positively predicted prefrontal-anterior cingulate-parietal connectivity across all participants, whereas MDD patients showed a decrease in connectivity compared to controls. Furthermore, loneliness negatively predicted parietal and cerebellar activities in MDD patients, but positively predicted the same activities in HCs. During resting state, MDD patients showed reduced parietal-anterior cingulate connectivity, which again positively correlated with loneliness in this group. CONCLUSIONS: We speculate the distinct neurocognitive profile of loneliness might indicate increase in both bottom-up attention and top-down executive control functions. However, the upregulated cognitive control processes in lonely individuals may eventually become exhausted, which may in turn predispose to MDD onset.

Multi-Session Anodal Prefrontal Transcranial Direct Current Stimulation does not Improve Executive Functions among Older Adults.

OBJECTIVE: Findings from single-session online studies highlighted the potential of using anodal prefrontal transcranial direct current stimulation (tDCS) to enhance executive functions (EF) in the context of aging. However, tDCS must be executed as a multi-session offline intervention to ascertain its viability in this context. Relatedly, findings from multi-session studies remained inconclusive. To this end, we examined the effects of multi-session anodal prefrontal tDCS on EF in an intervention. METHOD: The intervention consisted of 15 sessions; in each, healthy older participants (Agemean = 66.7) received either 15 min of 1.5 mA tDCS (Ncompleted = 35) or sham stimulation (Ncompleted = 33) while performing EF training tasks. EF measures were assessed at baseline, post-intervention, and 1-month follow-up. Hierarchical linear models were used to examine the effect of tDCS on EF outcomes. RESULTS: Both groups of participants did not differ significantly in side effect ratings and attendance. There were no significant tDCS-associated gains in any EF outcomes in the intervention. CONCLUSIONS: Multi-session prefrontal tDCS did not lead to any significant gains in EF in the current intervention. More research is needed to optimize the use of tDCS before it can be effectively used to enhance EF among older adults.