Impact of data extraction errors in meta-analyses on the association between depression and peripheral inflammatory biomarkers: an umbrella review.

BACKGROUND: Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-ß (IL-1ß), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof. RESULTS: Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1ß, are associated with depression. CONCLUSIONS: These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

Theory of mind and hair cortisol in healthy young adults: the moderating effects of childhood trauma.

Background: Experiences of negative social interactions and childhood trauma (CT) can lead to aberrant hypothalamic-pituitary-adrenal functions. Poor theory of mind (ToM) ability is related to increased social stress levels; however, studies on the relationship between ToM and cortisol remain scarce. Objective: This study aimed to evaluate the relationship between ToM and the hair cortisol concentration (HCC) in healthy young adults considering the moderating role of CT. Method: A total of 206 healthy young adults were divided into two groups based on an experience of moderate-to-severe childhood trauma (CT+ and CT-). To determine whether CT moderated the relationship between ToM and HCC, moderation analysis was conducted controlling for age, sex, years of education, and scores of perceived stress, depression, and anxiety. Results: CT+ individuals reported higher subjective stress perception and depressive symptoms than CT- individuals, whereas anxiety-related symptoms, ToM, and HCC were not different between the groups. The experience of CT significantly moderated the relationship between ToM and HCC. The association between poorer ToM ability and higher HCC was significant only in CT+ group. Conclusion: CT is a moderator of the association between ToM and HCC, indicating the importance of CT in social cognition and the stress response.

Antecedentes: Las experiencias de interacciones sociales negativas y el trauma infantil (CT por sus siglas en inglés) pueden conducir a funciones hipotalámicas-pituitarias-adrenales aberrantes. La pobre capacidad de teoría de la mente (ToM por sus siglas en inglés) está relacionada con mayores niveles de estrés social; sin embargo, los estudios sobre la relación entre ToM y cortisol siguen siendo escasos.Objetivo: Este estudio tuvo como objetivo evaluar la relación entre ToM y concentración de cortisol en el cabello (HCC por sus siglas en inglés) en adultos jóvenes sanos considerando el papel moderador del CT.Método: Un total de 206 adultos jóvenes sanos se dividieron en dos grupos en función de una experiencia de trauma infantil de moderada a severa (CT+ y CT­). Para determinar si el CT moderaba la relación entre ToM y HCC, se realizó un análisis de moderación controlando la edad, sexo, años de educación y las puntuaciones de estrés percibido, depresión y ansiedad.Resultados: Individuos CT+ informaron una mayor percepción subjetiva de estrés y síntomas depresivos que los individuos CT­, mientras que los síntomas relacionados con ansiedad, ToM y HCC no fueron diferentes entre los grupos. La experiencia de CT moderó significativamente la relación entre ToM y HCC. La asociación entre una capacidad de ToM más pobre y un HCC más alto fue significativa solo en el grupo CT+.Conclusión: CT es un moderador de la asociación entre ToM y HCC, lo que indica la importancia del CT en la cognición social y la respuesta al estrés.

Altered Functional Connectivity of the Salience Network in Problematic Smartphone Users.

Smartphones provide convenience in everyday life. Smartphones, however, can elicit adverse effects when used excessively. The purpose of this study was to examine the underlying neurobiological alterations that arise from problematic smartphone use. We performed resting state seed-based functional connectivity (FC) analysis of 44 problematic smartphone users and 54 healthy controls. This analysis assessed the salience, central executive, default mode, and affective networks. Compared to controls, problematic smartphone users showed enhanced FC within the salience network and between the salience and default mode network. Moreover, we observed decreased FC between the salience and central executive network in problematic smartphone users, compared to controls. These results imply that problematic smartphone use is associated with aberrant FC in key brain networks. Our results suggest that changes in FC of key networks centered around the salience network might be associated with problematic smartphone use.

Increased resting-state cerebellar-cortical connectivity in breast cancer survivors with cognitive complaints after chemotherapy.

Cognitive complaints after chemotherapy are common in breast cancer patients, but the neural bases for these complaints remain unclear. This pilot study explored resting-state functional connectivity (FC) as a marker of subtle cognitive changes in breast cancer patients who experience cognitive complaints. Chemotherapy-treated (n = 20, at least 6 months off therapy) and untreated (n = 17, disease-control) female breast cancer patients with cognitive complaints and healthy controls (n = 20) were recruited. The FC of the right dorsolateral prefrontal cortex was calculated, and any correlations between this FC and neuropsychological assessments were determined. Chemotherapy-treated patients with cognitive complaints displayed increased FC between the right dorsolateral prefrontal cortex and both the contralateral cerebellar lobule VII and the cerebellar vermis XI, compared to the disease-control and healthy-control groups, despite unimpaired neuropsychological performance. The increased FC was negatively correlated with executive function and attention in breast cancer survivors with cognitive complaints. Our pilot study findings provide evidence that cerebellar-cortical FC changes may be a pathophysiological basis for chemotherapy-related cognitive complaints. In addition, the FC changes have the potential to reflect minor or compensated cognitive function impairment in breast cancer patients.

Altered functional connectivity of the dorsal attention network among problematic social network users.

Many smartphone users spend excessive amounts of time online and cannot control their behavior, and the addictive overuse of social-networking services has been shown to be associated with diminished executive control. Attentional control is a cognitive process crucial to exerting executive functions. The purpose of this study was to investigate functional connectivity (FC) characteristics of attention networks in problematic social-network users. We performed seed-based resting-state FC analyses for 29 males and 10 females with excessive social network use and 32 healthy males and 17 healthy females. The right intraparietal sulcus and frontal eye fields were considered seeds of the dorsal attention network (DAN), and the right temporoparietal junction and ventral frontal cortex were considered seeds of the ventral attention network (VAN). Clinical characteristics predictive of FC findings in problematic social network users were identified through hierarchical multiple regression analysis. In FC analysis with DAN seeds, FC between the right intraparietal sulcus and the right middle occipital gyrus was stronger in problematic social network users than in controls, and FC between the right frontal eye field and the right dorsolateral prefrontal cortex was weaker than that in controls. There was no significant difference between the groups in FC analysis with VAN seeds. Hierarchical regression analyses showed that usage times on social networking platforms significantly predicted the negative effects on the strength of FC between the intraparietal sulcus and the dorsolateral prefrontal cortex. These findings indicated that problematic social network use reflects changes in the neural circuits underlying attentional control. Weaking of prefrontal control for attention networks would have a significant impact on failure to control one's time spent on social networks.

Diminished cognitive control in Internet gaming disorder: A multimodal approach with magnetic resonance imaging and real-time heart rate variability.

OBJECTIVE: Recently, the addiction to online games, classified as Internet gaming disorder (IGD) on DSM-V, has emerged as an important mental health problem. The loss of control over gaming in IGD is associated with diminished cognitive control. This study aimed to link the neurobiological mechanism reflected by brain imaging and the diminished cognitive control reflected by heart rate variability (HRV) measurements during real-time gameplay. METHODS: HRV was assessed in 33 young males with IGD and 29 controls while playing their favorite games. Seed-based functional connectivity (FC) was evaluated in the dorsolateral prefrontal cortex, anterior cingulate cortex, and dorsal striatum. Associations between HRV and alterations in FC were tested. RESULTS: Individuals with IGD showed a reduction of high-frequency HRV during real-time gaming, which is correlated with self-reported severity of IGD. Subjects with IGD showed decreased FC between the right dorsolateral prefrontal cortex and the right inferior frontal gyrus, corresponding to the cognitive control network. They showed decreased FC between the right anterior cingulate cortex and the superior parietal lobule. They also showed increased FC between the left dorsal putamen and the postcentral gyrus, corresponding to the sensorimotor network. Game-related high-frequency HRV was correlated with dorsolateral prefrontal cortex-inferior frontal gyrus connectivity. CONCLUSION: The diminished cognitive control reflected by HRV measurements during real-time gameplay was associated with FC alterations, involving a weak FC in the cognitive control network. Individuals with IGD may have less cognitive control, particularly when playing games, and consequently end up playing games in a habitual manner rather than in a goal-oriented manner.

Dorsal striatal functional connectivity changes in Internet gaming disorder: A longitudinal magnetic resonance imaging study.

Internet gaming disorder (IGD) is a behavioral addiction involving excessive online game use despite negative psychosocial consequences. Unrestricted online gaming may lead to changes in striatal activity and the relationship between the striatum and other cortical regions. This study investigated structural and functional abnormalities involving the striatum through longitudinal follow-up magnetic resonance imaging (MRI) assessments. Eighteen young males with IGD (mean age: 23.8 ± 2.0 years) and 18 controls (mean age: 23.9 ± 2.7 years) were evaluated. Subjects were reassessed ≥1 year after the first visit (mean follow-up duration: 22.8 ± 6.7 months), using voxel-based morphometry and seed-based resting-state functional connectivity (FC) analyses in seed regions of the dorsal and ventral striatum. Subjects with IGD had smaller gray matter volume (GMV) in the anterior/middle cingulate cortex compared with controls during initial and follow-up assessments. They exhibited decreased FC between the left dorsal putamen and left medial prefrontal cortex (mPFC) compared with controls. They exhibited increased FC strength between the right dorsal putamen and right middle occipital gyrus (MOG) during follow-up. Subjects with IGD showed a significant correlation between changes in the dorsal putamen-MOG FC and gaming time per day. Young males with IGD showed an altered FC pattern in the dorsal striatum during follow-up. FC of the dorsal striatum in IGD increased in the mPFC and decreased in the MOG. These findings showed that IGD was accompanied by weakening of prefrontal control and strengthening of the sensorimotor network, suggesting that uncontrolled gaming may be related with functional neural changes in the dorsal striatum.

Aberrant posterior superior temporal sulcus functional connectivity and executive dysfunction in adolescents with internet gaming disorder.

BACKGROUND AND AIMS: The clinical significance of Internet gaming disorder (IGD) is spreading worldwide, but its underlying neural mechanism still remains unclear. Moreover, the prevalence of IGD seems to be the highest in adolescents whose brains are in development. This study investigated the functional connectivity between large-scale intrinsic networks including default mode network, executive control network, and salience network. We hypothesized that adolescents with IGD would demonstrate different functional connectivity patterns among large-scale intrinsic networks, implying neurodevelopmental alterations, which might be associated with executive dysfunction. METHODS: This study included 17 male adolescents with Internet gaming disorder, and 18 age-matched male adolescents as healthy controls. Functional connectivity was examined using seed-to-voxel analysis and seed-to-seed analysis, with the nodes of large-scale intrinsic networks used as region of interests. Group independent component analysis was performed to investigate spatially independent network. RESULTS: We identified aberrant functional connectivity of salience network and default mode network with the left posterior superior temporal sulcus (pSTS) in adolescents with IGD. Furthermore, functional connectivity between salience network and pSTS correlated with proneness to Internet addiction and self-reported cognitive problems. Independent component analysis revealed that pSTS was involved in social brain network. DISCUSSION AND CONCLUSIONS: The results imply that aberrant functional connectivity of social brain network with default mode network and salience network was identified in IGD that may be associated with executive dysfunction. Our results suggest that inordinate social stimuli during excessive online gaming leads to altered connections among large-scale networks during neurodevelopment of adolescents.

Deactivation of anterior cingulate cortex during virtual social interaction in obsessive-compulsive disorder.

Studies about social functioning in obsessive-compulsive disorder (OCD) are lacking, even though neuroimaging studies and metacognition evaluation results suggest abnormal neural responses during social interactions. This study examined neural responses of OCD patients during handshakes with a virtual avatar. Because of the nature of the handshaking task, we expected that OCD patients with predominantly contamination/washing symptoms (CON) would show different neural responses compared to healthy controls (HCs) and to disease-controlled (NCON) patients. Thirteen CON, 13 NCON, and 18 HC participants performed handshake tasks with clean or dirty virtual avatars while undergoing functional magnetic resonance imaging. During handshakes with a clean avatar, deactivation in the left anterior cingulate cortex was found in CON patients compared to NCON and HC subjects. This cortical deactivation also occurred with dirty-avatar handshakes, but the difference was significant only between the two OCD groups and HC patients. Deactivation in the left anterior cingulate cortex was correlated with both OCD symptom severity and social anxiety traits. This cortical deactivation in OCD, especially in CON patients, suggests that social dysfunction in OCD may be due to interactions between OCD symptoms and impairment in social cognition, including emotional processing.

Changes in resting-state brain connectivity following computerized cognitive behavioral therapy for insomnia in dialysis patients: A pilot study.

OBJECTIVE: Insomnia is prevalent among dialysis patients and affects their mortality. Although cognitive behavioral therapy for insomnia (CBTi) is recommended, attending regular face-to-face CBTi sessions is a major challenge for patients. We evaluated the effectiveness of a self-directed computerized CBTi (cCBTi) in dialysis patients, and investigated changes in resting-state brain connectivity and inflammatory cytokines following cCBTi. METHOD: Thirty-five patients undergoing maintenance hemodialysis or peritoneal dialysis who had insomnia were screened for participation in the study, with 17 participants included in the final analyses. A self-directed cCBTi protocol accessed via tablet computer during dialysis or at home was developed and applied. Information about sleep, anxiety, depression, laboratory data, and resting-state functional magnetic resonance imaging data was obtained 3-5 days before and after cCBTi. RESULTS: cCBTi improved sleep quality, and this was correlated with increased resting-state brain connectivity between the default-mode network and the premotor/dorsolateral prefrontal cortex. The decrement of interleukin-1ß levels were correlated with improved sleep quality and increased brain connectivity after cCBTi. CONCLUSION: Our pilot study findings suggest that cCBTi is effective for dialysis patients with insomnia, and the therapeutic effects of cCBTi are related to changes in brain functional connectivity and inflammatory cytokines.