Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation.

Sleep loss robustly disrupts mood and emotion regulation in healthy individuals but can have a transient antidepressant effect in a subset of patients with depression. The neural mechanisms underlying this paradoxical effect remain unclear. Previous studies suggest that the amygdala and dorsal nexus (DN) play key roles in depressive mood regulation. Here, we used functional MRI to examine associations between amygdala- and DN-related resting-state connectivity alterations and mood changes after one night of total sleep deprivation (TSD) in both healthy adults and patients with major depressive disorder using strictly controlled in-laboratory studies. Behavioral data showed that TSD increased negative mood in healthy participants but reduced depressive symptoms in 43% of patients. Imaging data showed that TSD enhanced both amygdala- and DN-related connectivity in healthy participants. Moreover, enhanced amygdala connectivity to the anterior cingulate cortex (ACC) after TSD associated with better mood in healthy participants and antidepressant effects in depressed patients. These findings support the key role of the amygdala-cingulate circuit in mood regulation in both healthy and depressed populations and suggest that rapid antidepressant treatment may target the enhancement of amygdala-ACC connectivity.

Effects of Kinesio Taping for Chronic Nonspecific Low Back Pain: A Systematic Review and Meta-analysis.

Context: Chronic nonspecific low back pain (CNLBP) is a common musculoskeletal disorder that seriously affects patients' quality of life (QoL). Clinicians have used Kinesio Taping (KT) in the treatment of CNLBP patients, but evidence is still lacking on the benefits of KT for CNLBP. Objective: The study aimed to perform a systematic review and meta-analysis of the currently published randomized controlled trails (RCTs) to determine KT's efficacy for CNLBP patients. Design: The research team performed a literature search using five major electronic databases-PubMed, Embase, Web of science, Cochrane Library, MEDLINE and OpenGrey-and included studies form inception to January 2018. The search used the keywords "kinesio tap*", "kinesio*", and "chronic low back pain (CLBP)" or "CNLBP". Setting: The study took place in the 942 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army. Outcome Measures: The research team performed the meta-analysis using RevMan 5.3 software. The team selected studies that used pain intensity and disability as the primary outcome measures, and if the study used other outcomes, they had to be the secondary outcomes. Results: The systematic review included nine RCTs in the meta-analysis. KT can significantly reduce pain intensity between baseline and immediately postintervention (SMD = -0.47, 95% CI -0.93 to -0.02, P = .04) and between baseline and the short-term follow-up period (SMD = -0.67, 95% CI -0.44 to -0.20, P = .03). However, no significant differences existed between KT's ability to relieve other symptoms of CNLBP-disability, trunk flexion range of motion (ROM), change in status, fear of movement, isometric endurance of the trunk muscles, or extension-when compared to either sham taping or KT as an adjunct to physical therapy. Conclusions: KT can have immediate and short-term positive effects on reducing pain intensity, but existing evidence doesn't support KT's superiority to other interventions in improving functions for individuals with CNLBP.

Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£è€ å’ŒåŒ»åŠ¡äººå‘˜çš„å¿ƒç†ç¤¾ä¼šå±æœºå¹²é¢„ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

Cerebellum anatomy predicts individual risk-taking behavior and risk tolerance.

Human risk tolerance is highly idiosyncratic and individuals often show distinctive preferences when faced with similar risky situations. However, the neural underpinnings of individual differences in risk-taking remain unclear. Here we combined structural and perfusion MRI and examined the associations between brain anatomy and individual risk-taking behavior/risk tolerance in a sample of 115 healthy participants during the Balloon Analogue Risk Task, a well-established sequential risky decision paradigm. Both whole brain and region-of-interest analyses showed that the left cerebellum gray matter volume (GMV) has a strong association with individual risk-taking behavior and risk tolerance, outperforming the previously reported associations with the amygdala and right posterior parietal cortex (PPC) GMV. Left cerebellum GMV also accounted for risk tolerance and risk-taking behavior changes with aging. However, regional cerebral blood flow (CBF) provided no additional predictive power. These findings suggest a novel cerebellar anatomical contribution to individual differences in risk tolerance. Further studies are necessary to elucidate the underestimated important role of cerebellum in risk-taking.

MDH1-mediated malate-aspartate NADH shuttle maintains the activity levels of fetal liver hematopoietic stem cells.

The connections between energy metabolism and stemness of hematopoietic stem cells (HSCs) at different developmental stages remain largely unknown. We generated a transgenic mouse line for the genetically encoded NADH/NAD+ sensor (SoNar) and demonstrate that there are 3 distinct fetal liver hematopoietic cell populations according to the ratios of SoNar fluorescence. SoNar-low cells had an enhanced level of mitochondrial respiration but a glycolytic level similar to that of SoNar-high cells. Interestingly, 10% of SoNar-low cells were enriched for 65% of total immunophenotypic fetal liver HSCs (FL-HSCs) and contained approximately fivefold more functional HSCs than their SoNar-high counterparts. SoNar was able to monitor sensitively the dynamic changes of energy metabolism in HSCs both in vitro and in vivo. Mechanistically, STAT3 transactivated MDH1 to sustain the malate-aspartate NADH shuttle activity and HSC self-renewal and differentiation. We reveal an unexpected metabolic program of FL-HSCs and provide a powerful genetic tool for metabolic studies of HSCs or other types of stem cells.

Decision-making biases in suicide attempters with major depressive disorder: A computational modeling study using the balloon analog risk task (BART).

BACKGROUND: In the last decade, suicidality has been increasingly theorized as a distinct phenomenon from major depressive disorder (MDD), with unique psychological and neural mechanisms, rather than being mostly a severe symptom of MDD. Although decision-making biases have been widely reported in suicide attempters with MDD, little is known regarding what components of these biases can be distinguished from depressiveness itself. METHODS: Ninety-three patients with current MDD (40 with suicide attempts [SA group] and 53 without suicide attempts [NS group]) and 65 healthy controls (HCs) completed psychometric assessments and the balloon analog risk task (BART). To analyze and compare decision-making components among the three groups, we applied a five-parameter Bayesian computational modeling. RESULTS: Psychological assessments showed that the SA group had greater suicidal ideation and psychological pain avoidance than the NS group. Computational modeling showed that both MDD groups had higher risk preference and lower ability to learn and adapt from within-task observations than HCs, without differences between the SA and NS patient groups. The SA group also had higher loss aversion than the NS and HC groups, which had similar loss aversion. CONCLUSIONS: Our BART and computational modeling findings suggest that psychological pain avoidance and loss aversion may be important suicide risk factor that are distinguishable from depression illness itself.

Test-retest reliability of brain responses to risk-taking during the balloon analogue risk task.

The Balloon Analogue Risk Task (BART) provides a reliable and ecologically valid model for the assessment of individual risk-taking propensity and is frequently used in neuroimaging and developmental research. Although the test-retest reliability of risk-taking behavior during the BART is well established, the reliability of brain activation patterns in response to risk-taking during the BART remains elusive. In this study, we used functional magnetic resonance imaging (fMRI) and evaluated the test-retest reliability of brain responses in 34 healthy adults during a modified BART by calculating the intraclass correlation coefficients (ICC) and Dice's similarity coefficients (DSC). Analyses revealed that risk-induced brain activation patterns showed good test-retest reliability (median ICC â€‹= â€‹0.62) and moderate to high spatial consistency, while brain activation patterns associated with win or loss outcomes only had poor to fair reliability (median ICC â€‹= â€‹0.33 for win and 0.42 for loss). These findings have important implications for future utility of the BART in fMRI to examine brain responses to risk-taking and decision-making.

Altered spontaneous brain activity in obsessive-compulsive personality disorder.

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is one of the most prevalent personality disorders in general population. However, neural mechanisms underlying OCPD remain elusive. The aim of this study is to use functional magnetic resonance imaging (fMRI) to examine whether OCPD patients will exhibit altered spontaneous brain activity as compared to healthy controls (HC). METHODS: Resting-state fMRI data were acquired in 37 OCPD patients and 37 matched HC. Amplitudes of low-frequency fluctuation (ALFF) were calculated and compared between the two groups. Correlation analysis was performed between regional ALFF values and OCPD severity scores. RESULTS: Significant group differences in regional ALFF were found in multiple brain regions. Compared to HCs, OCPD subjects had increased ALFF in bilateral caudate, left precuneus, left insula, and left medial superior frontal gyrus, and decreased ALFF in the right fusiform gyrus and left lingual gyrus. The ALFF values in the left precuneus correlated with OCPD severity scores. LIMITATIONS: We excluded patients with comorbidity and did not conduct cognitive function assessments. Our findings are also limited to cross-sectional analysis. CONCLUSIONS: OCPD patients exhibit altered spontaneous neural activity as compared to healthy controls in multiple brain regions, which may reflect different characteristic symptoms of OCPD pathophysiology, including cognitive inflexibility, excessive self-control, lower empathy, and visual attention bias.

Effects of BDNF Val66Met polymorphisms on brain structures and behaviors in adolescents with conduct disorder.

Accumulating evidence suggests that neural abnormalities in conduct disorder (CD) may be subject to genetic influences, but few imaging studies have taken genetic variants into consideration. The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) has emerged as a high-interest genetic variant due to its importance in cortical maturation, and several studies have implicated its involvement in neurodevelopmental disorders. Thus, it is unclear how this polymorphism may influence brain anatomy and aberrant behaviors in CD. A total of 65 male adolescents with CD and 69 gender-, IQ- and socioeconomic status-matched healthy controls (HCs) (age range 13-17 years) were enrolled in this study. Analyses of variance (ANOVAs) were used to assess the main effects of CD diagnosis, BDNF genotype, and diagnosis-genotype interactions on brain anatomy and behaviors. We detected a significant main effect of BDNF genotype on temporal gyrification and antisocial behaviors, but not on CD symptoms. Diagnosis-genotype interactive effects were found for cortical thickness of the superior temporal and adjacent areas. These results suggest that the BDNF Val66Met polymorphism may exert its influence both on neural alterations and delinquent behaviors in CD patients. This initial evidence highlights the importance of elucidating potentially different pathways between BDNF genotype and cortical alterations or delinquent behaviors in CD patients.

Synthesis and evaluation of photo-activatable ß-diarylsydnone-l-alanines for fluorogenic photo-click cyclization of peptides.

Herein, we design and synthesize a series of photoactivatable ß-diarylsydnone-l-alanines (DASAs), which have excellent photo-reactivity with high fluorescence turn-on toward alkenes in a biocompatible environment. The environmental sensing properties of the resulting fluorescent pyrazoline-alanine facilitate its probing capability. By introducing the DASA residue on the side chain of linear peptides, the macrocyclic peptides resulting from the in situ photo-cyclization toward the alkene residue exhibited fluorogenic translocation through live cell membranes.

Discovery of Fluorogenic Diarylsydnone-Alkene Photoligation: Conversion of ortho-Dual-Twisted Diarylsydnones into Planar Pyrazolines.

A small library of diarylsydnones (DASyds) was constructed based on aryl-pairing combinations and subjected to click reaction toward alkenes under photoirradiation with high efficiency. We were able to demonstrate the utility of DASyds for highly fluorescent turn-on ligation targeting the trans-cyclooct-4-en-1-ol moieties on protein.

Psychometric properties of the Chinese version of Arthritis Self-Efficacy Scale-8 (ASES-8) in a rheumatoid arthritis population.

The Arthritis Self-Efficacy Scale-8 (ASES-8) is a valid tool to measure patients' arthritis-specific self-efficacy. However, evidence about reliability and validity of the ASES-8 in Chinese arthritis patients is lacking. This study aimed to culturally adapt and test the psychometric properties of the Chinese version of the ASES-8. Chinese ASES-8 was translated from original English version using translation and back-translation procedures. Validation survey was then conducted in a university-affiliated hospital by a set of questionnaires comprised Chinese ASES-8, pain-VAS, The Hospital Anxiety and Depression Scale (HADS), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), and Short Form 36-Item Health Survey (SF-36) physical functioning subscale. A convenience sample of 134 patients with rheumatoid arthritis was recruited from the department of rheumatology. Validity was assessed by Pearson's correlation analysis and exploratory factor analysis. Reliability was assessed using the intra-class correlation coefficient (ICC) and Cronbach's alpha. Exploratory factor analysis extracted one dimension that explained of the 71.35% variation. Significant negative correlations were found between the ASES-8 and pain-VAS, HADS-D, HADS-A scores (r -0.487 to -0.656, p < 0.01), while positive correlations were found between the ASES-8 and SF-36 PH (r = 0.561, p < 0.01), FACIT-F (r = 0.660, p < 0.01). Excellent test-retest reliability (ICC = 0.98) and internal consistency (Cronbach's alpha = 0.942) were demonstrated. The Chinese version of the ASES-8 had statistically acceptable levels of reliability and validity for assessing self-efficacy in patients with rheumatoid arthritis. This disease-specific scale is particularly valuable for use among patients with rheumatoid arthritis from the Chinese population.

Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

[Grey matter concentration revealed by voxel-based morphometry in individuals with cognitive vulnerability to depression].

OBJECTIVE: To explore the grey matter concentration in individuals with cognitive vulnerability to depression.
 Methods: Thirty individuals with cognitive vulnerability to depression and thirty age- and gender-matched healthy controls were enrolled in this study, and they were subjected to magnetic resonance imaging (MRI) examination. The grey matter concentration differences were compared between the two groups by using voxel-based morphometry (VBM) following MRI.
 Results: Individuals with cognitive vulnerability to depression showed significantly lower grey matter density in bilateral insular, left cerebellum, right supplementary motor area, and left precentral gyrus than those in the healthy controls, while the healthy controls showed significantly lower grey density in the right inferior frontal gyrus, right middle frontal gyrus, and left cuneus than those in the individuals with cognitive vulnerability to depression.
 Conclusion: Structural brain abnormalities in individuals with cognitive vulnerability to depression might be the neural basis for cognitive vulnerability to depression.

Icariin regulates RANKL-induced osteoclast differentiation via the ERα/c-Src/RANK signaling.

Osteoporosis (OP) is a common metabolic bone disease. Excessive osteoclastic activity significantly contributes to the development of OP. Icariin (ICA) is a flavonol glycoside derived from herbal plants and possesses curative effects on postmenopausal OP and bone fracture. This study aimed to investigate the effects of ICA on osteoclast differentiation induced by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) and the involvement of estrogen receptorα(ERα) and RANK signaling cascade in this process. RANKL was used to induce the differentiation of RAW264.7 cells to into osteoclasts. Small interfering RNA technique was used to knockdown ERαin cells. Cell counting kit-8 assay was performed to determine the cytotoxicity of ICA. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells was quantified by TRAP staining. RANKL induced the differentiation of RAW264.7 cells into osteoclasts, while ICA abolished the pro-osteoporotic effect of RANKL. Moreover, ERαknockdown abolished the effects of ICA on RANKL-induced osteoclastogenesis. Further exploration revealed that ICA inhibited the phosphorylation ofc-Src in osteoclasts via regulating ERα, while inactivation ofc-Src reversed ERαknockdown-promoted osteoclastogenesis. Lastly, ICA inhibited the activation of the mitogen-activated protein kinase signaling pathway and downregulated the expressions of target osteoclastogenic proteins in RANKL-treated RAW 264.7 cells, while ERαknockdown almost completely diminished the effects of ICA. ICA inhibited RANKL-induced osteoclast differentiation via regulating the ERα/c-Src/RANK signaling. These findings elucidated a novel mechanism by which ICA exerts an anti-osteoporotic effect.

Relationships among self-esteem, depression and self-injury in adolescents: a longitudinal study.

Objective: Non-suicidal self-injury is a widespread mental health concern among adolescents. This study aimed to examine the relationship between self-esteem, depression, and self-injury among adolescents using a longitudinal research design. Methods: The Self-Esteem Scale (SES), Child Depression Inventory (CDI), and Adolescent Self-Injury Scale (ASIS) were used to follow up 1,265 junior middle school students on three occasions with six-month intervals. Results: At all three time points, there were significant gender differences in self-esteem, depression, and self-injury. Self-esteem was negatively correlated with depression and self-injury at all three time points, while depression and self-injury were significantly positively correlated. Cross-lagged analysis revealed that self-esteem at Time 1 (T1) did not significantly predict self-injury at Time 2 (T2), but self-esteem (T2) significantly predicted self-injury at Time 3 (T3; ß = -0.079, p < 0.05). Similarly, self-injury (T1) significantly predicted self-esteem (T2; ß = -0.140, p < 0.001), and self-injury (T2) significantly predicted self-esteem (T3; ß = -0.071, p < 0.01). Horizontal and longitudinal mediating analysis showed that depression served as a complete mediator in both the pathway from self-esteem to self-injury and from self-injury to self-esteem. Cross-lagged analysis showed that self-esteem (T1) significantly predicts depression (T2; ß = -0.070, p < 0.05), which in turn predict self-injury (T3; ß = 0.126, p < 0.001). Similarly, self-injury (T1) predicted depression (T2; ß = 0.055, p < 0.05), which further predicted self-esteem (T3; ß = -0.218, p < 0.001). Conclusion: The self-esteem, depression, and self-injury of adolescents are closely related; self-esteem and self-injury predict each other; self-esteem indirectly affects self-injury through depression; and self-injury indirectly affects self-esteem through depression. Based on the relationship of bi-directional prediction of self-esteem and self-injury mediated by depression, this study proposes a theoretical model of depression-mediated self-esteem and self-injury cycle.

Network analysis of the relationship between non-suicidal self-injury, depression, and childhood trauma in adolescents.

BACKGROUND: Non-suicidal self-injury seriously harm the physical and mental health of adolescents. The aim of the current study was to explore the relationship between non-suicide self-injury, depression, and childhood trauma from the perspective of symptoms in adolescents. METHODS: A cross-sectional survey was conducted in four junior high middle schools and collected 2640 valid questionnaires. There were 1329 male students and 1311 female students. The age of the participants ranged from 11 to 17 years old, with a mean age of 13.3 (± 0.94) years. Non-suicidal self-injury (NSSI), depressive symptoms, and childhood trauma were assessed using the Adolescent Self-Harm Scale, the Childhood Depression Scale, and the Childhood Trauma Questionnaire, respectively. A network analysis was performed. RESULTS: In the network, NSSI, depressive symptoms, and childhood trauma were closely related. Negative self-esteem in the depressive symptoms and emotional abuse in childhood were the most central nodes. Negative self-esteem and negative mood were directly connected to NSSI, other nodes of depressive symptoms appeared to be indirectly connected to NSSI through these two nodes. Emotional abuse was the only node in childhood trauma categories directly connected to NSSI. Nodes of other categories of childhood trauma (physical neglect, physical abuse, emotional neglect, and sexual abuse) were indirectly connected to NSSI through emotional abuse. CONCLUSIONS: NSSI, depression, and childhood trauma of teenagers were closely related. Individuals who have suffered emotional abuse in childhood were more likely to have depressive symptoms and NSSI. Improving negative self-esteem and negative emotions and reducing emotional abuse may be beneficial in alleviating depression and reducing NSSI in adolescents.

Sex-specific resting state brain network dynamics in patients with major depressive disorder.

Sex-specific neurobiological changes have been implicated in Major Depressive Disorder (MDD). Dysfunctions of the default mode network (DMN), salience network (SN) and frontoparietal network (FPN) are critical neural characteristics of MDD, however, the potential moderating role of sex on resting-state network dynamics in MDD has not been sufficiently evaluated. Thus, resting-state functional magnetic resonance imaging (fMRI) data were collected from 138 unmedicated patients with first-episode MDD (55 males) and 243 healthy controls (HCs; 106 males). Recurring functional network co-activation patterns (CAPs) were extracted, and time spent in each CAP (the total amount of volumes associated to a CAP), persistence (the average number of consecutive volumes linked to a CAP), and transitions across CAPs involving the SN, DMN and FPN were quantified. Relative to HCs, MDD patients exhibited greater persistence in a CAP involving activation of the DMN and deactivation of the FPN (DMN + FPN-). In addition, relative to the sex-matched HCs, the male MDD group spent more time in two CAPs involving the SN and DMN (i.e., DMN + SN- and DMN-SN + ) and transitioned more frequently from the DMN + FPN- CAP to the DMN + SN- CAP relative to the male HC group. Conversely, the female MDD group showed less persistence in the DMN + SN- CAP relative to the female HC group. Our findings highlight that the imbalance between SN and DMN could be a neurobiological marker supporting sex differences in MDD. Moreover, the dominance of the DMN accompanied by the deactivation of the FPN could be a sex-independent neurobiological correlate related to depression.

Regulation and function of the RSK family of protein kinases.

The RSK (90 kDa ribosomal S6 kinase) family comprises a group of highly related serine/threonine kinases that regulate diverse cellular processes, including cell growth, proliferation, survival and motility. This family includes four vertebrate isoforms (RSK1, RSK2, RSK3 and RSK4), and single family member orthologues are also present in Drosophila and Caenorhabditis elegans. The RSK isoforms are downstream effectors of the Ras/ERK (extracellular-signal-regulated kinase) signalling pathway. Significant advances in the field of RSK signalling have occurred in the past few years, including several new functions ascribed to the RSK isoforms, the discovery of novel protein substrates and the implication of different RSK isoforms in cancer. Collectively, these new findings increase the diversity of biological functions regulated by RSK, and highlight potential new directions of research. In the present paper, we review the structure, expression and activation mechanisms of the RSK isoforms, and discuss their physiological roles on the basis of established substrates and recent discoveries.