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Abstract Depressive and anxiety symptoms are prevalent among patients with various clinical conditions, resulting in diminished emotional well-being and impaired daily functioning. The neural mechanisms underlying these symptoms, particularly across different disorders, remain unclear, limiting the effectiveness of conventional treatments. Therefore, it is crucial to elucidate the neural underpinnings of depressive and anxiety symptoms and investigate novel, effective treatments across clinical conditions. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that can help understand the neural underpinnings of symptoms and facilitate the development of interventions, addressing the two research gaps at both neural and clinical levels. Thus, this systematic review and meta-analysis aims to evaluate the existing evidence regarding the therapeutic efficacy of tDCS in reducing depressive and anxiety symptoms among individuals with diverse clinical diagnoses. This review evaluated evidence from fifty-six randomized, sham-controlled trials that administered repeated tDCS sessions with a parallel design, applying a three-level meta-analytic model. tDCS targeting the left dorsolateral prefrontal cortex (DLPFC) at 2-mA intensity demonstrates moderate efficacy in alleviating depressive symptoms, identifying the left DLPFC as a transdiagnostic neural mechanism of depressive symptoms across clinical conditions. In comparison, the findings on anxiety symptoms demonstrate greater heterogeneity. tDCS over the left DLPFC is effective in reducing depressive symptoms and shows promising effects in alleviating anxiety symptoms among individuals with diverse diagnoses. These findings enhance our understanding of the neuropsychological basis of depressive and anxiety symptoms, laying the groundwork for the development of more effective tDCS interventions applicable across clinical conditions.

BackgroundThe fronto-cerebellar functional network has been proposed to subserve cognitive processing speed. This study aims to elucidate how the long-range frontal-to-cerebellar effective connectivity contributes to faster speed.MethodsIn total, 60 healthy participants were randomly allocated to three five-daily sessions of transcranial magnetic stimulation conditions, namely intermittent theta-burst stimulation (iTBS, excitatory), continuous theta-burst stimulation (CTBS, inhibitory), or a sham condition. The sites of the stimulations were the right pre-supplementary motor area (RpSMA), medial cerebellar vermis VI (MCV6), and vertex, respectively. Performances in two reaction time tasks were recorded at different time points.ResultsPost-stimulation speeds revealed marginal decreases in the simple but not complex task. Nevertheless, participants in the excitatory RpSMA and inhibitory MCV6 conditions showed direct and negative path effects on faster speeds compared to the sham condition in the simple reaction time (SRT) task (β = −0.320, p = 0.045 and β = −0.414, p = 0.007, respectively). These path effects were not observed in the SDMT task.DiscussionRpSMA and MCV6 were involved in promoting the path effects of faster reaction times on simple cognitive task. This study offers further evidence to support their roles within the long-range frontal-to-cerebellar connectivity subserving cognitive processing speed. The enhancement effects, however, are likely limited to simple rather than complex mental operations.

Abstract There is an emerging potential for digital assessment of depression. In this study, Chinese patients with major depressive disorder (MDD) and controls underwent a week of multimodal measurement including actigraphy and app-based measures (D-MOMO) to record rest-activity, facial expression, voice, and mood states. Seven machine-learning models (Random Forest [RF], Logistic regression [LR], Support vector machine [SVM], K-Nearest Neighbors [KNN], Decision tree [DT], Naive Bayes [NB], and Artificial Neural Networks [ANN]) with leave-one-out cross-validation were applied to detect lifetime diagnosis of MDD and non-remission status. Eighty MDD subjects and 76 age- and sex-matched controls completed the actigraphy, while 61 MDD subjects and 47 controls completed the app-based assessment. MDD subjects had lower mobile time (P = 0.006), later sleep midpoint (P = 0.047) and Acrophase (P = 0.024) than controls. For app measurement, MDD subjects had more frequent brow lowering (P = 0.023), less lip corner pulling (P = 0.007), higher pause variability (P = 0.046), more frequent self-reference (P = 0.024) and negative emotion words (P = 0.002), lower articulation rate (P

Abstract Background Subthreshold depression is a highly prevalent mood disorder in young adults. Mind–body exercises, such as Tai Chi, have been adopted as interventions for clinical depressive symptoms. However, the possible effect and underlying mechanism of Tai Chi on subthreshold depression of young individuals remain unclear. This randomized controlled study aimed to evaluate the effects of Tai Chi training and tested the combined stress and reward circuitry model for subthreshold depression. Results A total of 103 participants completed this trial, with 49 in the 12-week 24-style Tai Chi group and 54 participants in control group. Our results showed significantly lower scores on depressive symptoms (P = 0.002) and anxiety symptoms (P = 0.009) and higher scores on quality of life (P = 0.002) after Tai Chi training. There were significant reductions in salivary cortisol levels (P = 0.007) and putamen gray matter volume (P

Abstract Background People with mild cognitive impairment (MCI) experience a loss of cognitive functions, whose mechanism is characterized by aberrant structure‒function (SC-FC) coupling and topological attributes of multiple networks. This study aimed to reveal the network-level SC-FC coupling and internal topological changes triggered by computerized cognitive training (CCT) to explain the therapeutic effects of this training in individuals with MCI. Methods In this randomized block experiment, we recruited 60 MCI individuals and randomly divided them into an 8-week multidomain CCT group and a health education control group. The neuropsychological outcome measures were the Montreal Cognitive Assessment (MoCA), Chinese Auditory Verbal Learning Test (CAVLT), Chinese Stroop Color–Word Test (SCWT), and Rey–Osterrieth Complex Figure Test (Rey CFT). The brain imaging outcome measures were SC-FC coupling and topological attributes using functional MRI and diffusion tensor imaging methods. We applied linear model analysis to assess the differences in the outcome measures and identify the correspondence between the changes in the brain networks and cognitive functions before and after the CCT. Results Fifty participants were included in the analyses after the exclusion of three dropouts and seven participants with low-quality MRI scans. Significant group × time effects were found on the changes in the MoCA, CAVLT, and Rey CFT recall scores. The changes in the SC-FC coupling values of the default mode network (DMN) and somatomotor network (SOM) were higher in the CCT group than in the control group (P(unc.) = 0.033, P(unc.) = 0.019), but opposite effects were found on the coupling values of the visual network (VIS) (P(unc.) = 0.039). Increasing clustering coefficients in the functional DMN and SOM and subtle changes in the nodal degree centrality and nodal efficiency of the right dorsal medial prefrontal cortex, posterior cingulate cortex, left parietal lobe, somatomotor area, and visual cortex were observed in the CCT group (P

Abstract There has been a lack of high-quality evidence concerning the association between childhood maltreatment and psychiatric diagnoses particularly for Axis II disorders. This study aimed to examine the association between childhood maltreatment exposure and Axis I and Axis II psychiatry disorders using electronic health records. In this study, the exposed group (n = 7473) comprised patients aged 0 to 19 years with a first-time record of maltreatment episode between January 1, 2001 and December 31, 2010, whereas the unexposed group (n = 26,834) comprised individuals of the same gender and age who were admitted into the same hospital in the same calendar year and month but had no records of maltreatment in the Hong Kong Clinical Data Analysis and Reporting System (CDARS). Data on their psychiatric diagnoses recorded from the date of admission to January 31, 2019 were extracted. A Cox proportional hazard regression model was fitted to estimate the hazard ratio (HR, plus 95% CIs) between childhood maltreatment exposure and psychiatric diagnoses, adjusting for age at index visit, sex, and government welfare recipient status. Results showed that childhood maltreatment exposure was significantly associated with subsequent diagnosis of conduct disorder/ oppositional defiant disorder (adjusted HR, 10.99 [95% CI 6.36, 19.01]), attention deficit hyperactivity disorder (ADHD) (7.28 [5.49, 9.65]), and personality disorders (5.36 [3.78, 7.59]). The risk of psychiatric disorders following childhood maltreatment did not vary by history of childhood sexual abuse, age at maltreatment exposure, and gender. Individuals with a history of childhood maltreatment are vulnerable to psychiatric disorders. Findings support the provision of integrated care within the primary health care setting to address the long-term medical and psychosocial needs of individuals with a history of childhood maltreatment.

A study on patients with major depressive disorder (MDD) suggests that a specific sadness-processing connection between the amygdala and pons appears to be dysfunctional among people with MDD and associated with severity of depression.

State rumination, unlike trait rumination which is described as a persistent and stable response style, is usually triggered by a specific stressful event and causes negative emotions within a short period of time. The measurement methods of trait rumination, such as the ruminative response scale (RRS), are therefore not fully applicable to state rumination. Recently, researchers have developed the brief state rumination inventory (BSRI) to characterize state rumination, addressing the gap in the field of accurate measurement of state rumination. To develop such an effective tool in the Chinese context, we developed a Chinese version of the BSRI and tested its psychometric properties. Two studies were conducted to address the research goal. In Study 1, we recruited 512 subjects, each of whom completed the Chinese version of the BSRI, RRS, emotional regulation questionnaire (ERQ), depression–anxiety–stress scale (DASS), and positive and negative affect scale (PANAS). Results showed that the scores of the BSRI were positively correlated with all other scale scores (ps < 0.001), and the correlation with the RRS was the highest, indicating that the BSRI showed good convergent validity. Additionally, the Cronbach's alpha coefficient for the Chinese version of the BSRI was 0.93. Study 2 aimed to examine the ecological validity of the Chinese version of the BSRI. We recruited another 54 subjects who were randomly divided into two groups, with 27 in the rumination induction group and 27 in the distraction group, and recorded the BSRI scores of the two groups before and after a specific experiment. We found there was a significant increase in BSRI scores after rumination induction (t = 3.91, p < 0.001), while there was no significant difference in the concrete distraction group before and after the experiment (t = 0.70, p = 0.48). In sum, the Chinese version of the BSRI showed good reliability and validity for assessing state rumination in the general Chinese population.

The counseling process involves attention, emotional perception, cognitive appraisal, and decision-making. This study aimed to investigate cognitive appraisal and the associated emotional processes when reading short therapists' statements of motivational interviewing (MI). Thirty participants with work injuries were classified into the pre-contemplation (PC, n = 15) or readiness stage of the change group (RD, n = 15). The participants viewed MI congruent (MI-C), MI incongruent (MI-INC), or control phrases during which their electroencephalograms were captured. The results indicated significant Group × Condition effects in the frontally oriented late positive complex (P600/LPC). The P600/LPC's amplitudes were more positive-going in the PC than in the RD group for the MI congruent statements. Within the PC group, the amplitudes of the N400 were significantly correlated (r = 0.607–0.649) with the participants' level of negative affect. Our findings suggest that the brief contents of MI statements alone can elicit late cognitive and emotional appraisal processes beyond semantic processing.

ObjectivePrevious studies have shown that the impairment of executive function is positively related to aggression in children and adolescents. What is worth investigating is the moderator of such a relationship so that aggressive behavior can be reduced effectively in those who have executive function problems. The present study examined the association between executive function and two major subtypes of aggression (proactive and reactive aggression) and whether their caregivers’ grit (perseverance) moderated such relationship.MethodExecutive function and reactive and proactive aggression were assessed in 254 children and adolescents aged 8–19 years old, and their caregivers’ grit was measured.ResultsResults show that caregivers’ grit plays a significant role in moderating the relationship between children’s executive function and proactive aggression after controlling for the covariates including the children’s age, gender, and family income. Specifically, children’s executive function became more negatively associated with proactive aggression when caregivers’ grit was high while the association was positive when it was low. On the other hand, the association between children’s executive function and reactive aggression did not vary across different levels of caregivers’ grit.ConclusionThese findings suggest that proactive aggression may be reduced in those who have better executive function by enhancing their caregivers’ grit, which inform the design of interventions in adjunct with the current approach (e.g., executive function training) to reduce aggression in children and adolescents in the community.

Abstract The beneficial effects of meditation on preserving age-related changes in cognitive functioning are well established. Yet, the neural underpinnings of these positive effects have not been fully unveiled. This study employed a prospective longitudinal design, and graph-based analysis, to study how an eight-week meditation training vs. relaxation training shaped network configuration at global, intermediate, and local levels using graph theory in the elderly. At the intermediate level, meditation training lead to decreased intra-connectivity in the default mode network (DMN), salience network (SAN) and somatomotor network (SMN) modules post training. Also, there was decreased connectivity strength between the DMN and other modules. At a local level, meditation training lowered nodal strength in the left posterior cingulate gryus, bilateral paracentral lobule, and middle cingulate gyrus. According to previous literature, the direction of these changes is consistent with a movement towards a more self-detached viewpoint, as well as more efficient processing. Furthermore, our findings highlight the importance of considering brain network changes across organizational levels, as well as the pace at which these changes may occur. Overall, this study provides further support for short-term meditation as a potentially beneficial method of mental training for the elderly that warrants further investigation.

Robotic technologies offer a range of functions to augment clinical rehabilitation practice. However, compliance with robot-assisted rehabilitation techniques has not been optimally achieved. Traditional approaches to improving the treatment efficacy are focusing more on the system function, while psychological factors have not been integrated comprehensively. In this perspective paper, eight key factors reflecting three conceptions-robot design, function design, and patients’ expectations have been evaluated and analyzed. Clinical results with 28 therapists and 84 patients indicate that integrating psychological strategies into robot-assisted physiotherapy may promote better trust and acceptance of rehabilitation robots.

The dorsolateral prefrontal cortex (DLPFC) plays a key role in the modulation of affective processing. However, its specific role in the regulation of neurocognitive processes underlying the interplay of affective perception and visual awareness has remained largely unclear. Using a mixed factorial design, this study investigated effects of inhibitory continuous theta-burst stimulation (cTBS) of the right DLPFC (rDLPFC) compared to an Active Control condition on behavioral (N = 48) and electroencephalographic (N = 38) correlates of affective processing in healthy Chinese participants. Event-related potentials (ERPs) in response to passively viewed subliminal and supraliminal negative and neutral natural scenes were recorded before and after cTBS application. We applied minimum-norm approaches to estimate the corresponding neuronal sources. On a behavioral level, we found evidence for reduced emotional interference by, and less negative and aroused ratings of negative supraliminal stimuli following rDLPFC inhibition. We found no evidence for stimulation effects on self-reported mood or the behavioral discrimination of subliminal stimuli. On a neurophysiological level, rDLPFC inhibition relatively enhanced occipito-parietal brain activity for both subliminal and supraliminal negative compared to neutral images (112–268 ms; 320–380 ms). The early onset and localization of these effects suggests that rDLPFC inhibition boosts automatic processes of “emotional attention” independently of visual awareness. Further, our study reveals the first available evidence for a differential influence of rDLPFC inhibition on subliminal versus supraliminal neural emotion processing. Explicitly, our findings indicate that rDLPFC inhibition selectively enhances late (292–360 ms) activity in response to supraliminal negative images. We tentatively suggest that this differential frontal activity likely reflects enhanced awareness-dependent down-regulation of negative scene processing, eventually leading to facilitated disengagement from and less negative and aroused evaluations of negative supraliminal stimuli.

Rumination is a trait that includes two subcomponents, namely brooding and reflective pondering, respectively construed as maladaptive and adaptive response styles to negative experiences. Existing evidence indicates that rumination in general is associated with structural and functional differences in the anterior cingulate cortex (ACC) and the dorsal lateral prefrontal cortex (DLPFC). However, conclusive evidence on the specific neural structural basis of each of the two subcomponents is lacking. In this voxel-based morphometry study, we investigated the independent and specific neural structural basis of brooding and reflective pondering in 30 healthy young adults, who belonged to high or low brooding or reflective pondering groups. Consistent with past research, modest but significant positive correlation was found between brooding and reflective pondering. When controlling for reflective pondering, high-brooding group showed increased gray matter volumes in the left DLPFC and ACC. Further analysis on extracted gray matter values showed that gray matter of the same DLPFC and ACC regions also showed significant negative effects of reflective pondering. Taken together, our findings indicate that the two subcomponents of rumination might share some common processes yet also have distinct neural basis. In view of the significant roles of the left DLPFC and ACC in attention and self-related emotional processing/regulation, our findings provide insight into how the potentially shared and distinct cognitive, affective and neural processes of brooding and reflective pondering can be extended to clinical populations to further elucidate the neurobehavioral relationships between rumination and prefrontal abnormality.

Gaze direction is a common social cue implying potential interpersonal interaction. However, little is known about the neural processing of social decision making influenced by perceived gaze direction. Here, we employed functional magnetic resonance imaging (fMRI) method to investigate 27 females when they were engaging in an economic exchange game task during which photos of direct or averted eye gaze were shown. We found that, when averted but not direct gaze was presented, prosocial vs. selfish choices were associated with stronger activations in the right superior temporal gyrus (STG) as well as larger functional couplings between right STG and the posterior cingulate cortex (PCC). Moreover, stronger activations in right STG was associated with quicker actions for making prosocial choice accompanied with averted gaze. The findings suggest that, when the cue implying social contact is absent, the processing of understanding others’ intention and the relationship between self and others is more involved for making prosocial than selfish decisions. These findings could advance our understanding of the roles of subtle cues in influencing prosocial decision making, as well as shedding lights on deficient social cue processing and functioning among individuals with autism spectrum disorder (ASD).

Brain structural abnormalities in the orbitofrontal cortex (OFC) and striatum (caudate and putamen) have been observed in violent individuals. However, a uni-modal neuroimaging perspective has been used and prior findings have been mixed. The present study takes the multimodal structural brain imaging approaches to investigate the differential gray matter volumes (GMV) and cortical thickness (CTh) in the OFC and striatum between violent (accused of homicide) and non-violent (not accused of any violent crimes) individuals with different levels of psychopathic traits (interpersonal and unemotional qualities, factor 1 psychopathy and the expressions of antisocial disposition and impulsivity, factor 2 psychopathy). Structural Magnetic Resonance Imaging data, psychopathy and demographic information were assessed in sixty seven non-violent or violent adults. The results showed that the relationship between violence and the GMV in the right lateral OFC varied across different levels of the factor 1 psychopathy. At the subcortical level, the psychopathy level (the factor 1 psychopathy) moderated the positive relationship of violence with both left and right putamen GMV as well as left caudate GMV. Although the CTh findings were not significant, overall findings suggested that psychopathic traits moderated the relationship between violence and the brain structural morphology in the OFC and striatum. In conclusion, psychopathy takes upon a significant role in moderating violent behavior which gives insight to design and implement prevention measures targeting violent acts, thereby possibly mitigating their occurrence within the society.

Cortisol homeostasis is important for healthy brain and cognitive aging. The aim of the current study is to investigate the role of serum cortisol levels in the relationship between regional brain volumes and cognitive processing speed in a group of cognitively normal elderly subjects. Forty-one healthy elderly participants were from a parallel longitudinal study. The reported data in this study reflects baseline measurements. Whole-brain anatomical scanning was performed using a 3.0 Tesla Philips Medical Systems Achieva scanner. Cognitive processing speed was assessed by the digit-symbol and symbol search tests, from the Chinese version of the Wechsler Adult Intelligence Scale—third edition (WAIS-III). Serum cortisol levels (sampled in the late morning) were measured by ELISA kits. Whole-brain regression analysis revealed that serum cortisol levels positively predicted the white matter volumes (WMV) of the right thalamus, the gray matter volumes (GMV) of the left thalamus and right cerebellar tonsil, and negatively predicted the WMV and GMV of the left middle temporal gyrus (MTG) in 41 healthy elderly participants. Furthermore, serum cortisol significantly moderated the relationship between the GMV of the left MTG and processing speed, as well as the GMV of the left thalamus and processing speed. This study provided the first piece of evidence supporting serum cortisol levels in moderating the relationship between regional brain volumes and processing speed in healthy elderly subjects. This observation enriches our understanding of the role of cortisol in brain morphology and cognitive functioning.

Hypertension is a risk factor for cognitive impairment in older age. However, evidence of the neural basis of the relationship between the deterioration of cognitive function and elevated blood pressure is sparse. Based on previous research, we speculate that variations in brain connectivity are closely related to elevated blood pressure even before the onset of clinical conditions and apparent cognitive decline in individuals over 60 years of age. Forty cognitively healthy adults were recruited. Each received a blood pressure test before and after the cognitive assessment in various domains. Diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) data were collected. Our findings confirm that elevated blood pressure is associated with brain connectivity variations in cognitively healthy individuals. The integrity of the splenium of the corpus callosum is closely related to individual differences in systolic blood pressure. In particular, elevated systolic blood pressure is related to resting-state ventral attention network (VAN) and information processing speed. Serial mediation analyses have further revealed that lower integrity of the splenium statistically predicts elevated systolic blood pressure, which in turn predicts weakened functional connectivity (FC) within the VAN and eventually poorer processing speed. The current study sheds light on how neural correlates are involved in the impact of elevated blood pressure on cognitive functioning.

Adult neurogenesis within the dentate gyrus (DG) of the hippocampus can be increased by voluntary exercise but is suppressed under stress, such as with corticosterone (CORT). However, the effects of exercise and CORT on the cell proliferation of the other traditional neurogenic site, the subventricular zone (SVZ), have been reported with controversial results. In addition, the cotreatment effects of voluntary exercise and CORT have not been investigated. This study aims to determine whether CORT can suppress cell proliferation in the SVZ and whether this can be reversed by voluntary exercise. In the present study, the effect of chronic (4 weeks) CORT treatment and wheel running simultaneously on the SVZ cell proliferation of adult Sprague–Dawley rats was examined. The results showed that cell proliferation indicated by bromodeoxyuridine (BrdU) was increased by voluntary wheel running, whereas it was decreased by CORT treatment within the SVZ of the rats without running. For the rats with both CORT treatment and wheel running, it was found that the number of BrdU-labeled cells was approximately at the same level as the vehicle control group. Furthermore, these proliferating cells expressed doublecortin (DCX), a migrating neuroblast marker. Wheel running increased the percentage of BrdU-labeled cells expressing DCX in the SVZ, whereas CORT treatment decreased this percentage. Thus, chronic injection of CORT can decrease the number of proliferating cells, while wheel running can reverse the decrease in cell proliferation within the SVZ to normal levels. In addition, CORT can suppress the cell differentiation within the SVZ, and this was alleviated by wheel running as indicated by the double labeling of BrdU and DCX.

Background. The rising public health concern regarding traumatic brain injury (TBI) implies a growing need for rehabilitation services for patients surviving TBI. Methods. To this end, this paper reviews the practices and research on TBI rehabilitation in Hong Kong so as to inform future developments in this area. This paper begins by introducing the general situation of TBI patients in Hong Kong and the need for rehabilitation. Next, the trauma system in Hong Kong is introduced. Following that is a detailed description of the rehabilitation services for TBI patients in Hong Kong, as exemplified by a rehabilitation hospital in Hong Kong. This paper will also review intervention studies on rehabilitating brain-injured populations in Hong Kong with respect to various rehabilitation goals. Lastly, the implications of culture-related issues will be discussed in relation to TBI. Results/Conclusions. The intervention studies conducted in Hong Kong are generally successful in achieving various rehabilitative outcomes. Additionally, certain cultural-related issues, such as the stigma associated with TBI, may impede the rehabilitative process and lead to various psychosocial problems.

Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n=109) and the Active Control Group (n=100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

The case of a 67-year-old right-handed Chinese man with Central Pontine Myelinolysis [CPM] is described to illustrate the resulting cognitive and emotional disturbances. A comparison of the data in this report with that in published studies suggests that ethnicity does not seem to have much effect on the symptoms of CPM. Possible underlying neural-pathological mechanisms are discussed. This case further substantiates the speculation that the brainstem plays a role in higher cognitive processes and emotional regulation.

We have previously shown that voluntary running acts as an anxiolytic and ameliorates deficits in hippocampal neurogenesis and spatial learning. It also reduces depression-like behaviors that are normally observed in rats that were administered either low (30 mg/kg) or moderate (40 mg/kg) doses of corticosterone (CORT). However, the protective effects of running were absent in rats treated with a high (50 mg/kg) dose of CORT. We examined whether allowing animals to exercise for 2 weeks prior and/or concurrently with the administration of 50 mg/kg CORT treatment could have similar protective effects. We examined hippocampal neurogenesis using immuno-histochemical staining of proliferative and survival cells with the thymidine analogs (BrdU, CIdU, and IdU). In addition, we monitored synaptic protein expression and quantified the levels of neurotrophic factors in these animals as well as performing behavioral analyses (forced swim test and sucrose preference test). Our results indicate that the depressive phenotype and reductions in neurogenesis that normally accompany high CORT administration could only be prevented by allowing animals to exercise both prior to and concurrently with the CORT administration period. These animals also showed increases in both synaptophysin and PSD-95 protein levels, but surprisingly, neither brain-derived neurotrophic factor (BDNF) nor insulin-like growth factor 1 (IGF-1) levels were increased in these animals. The results suggest that persistent exercise can strengthen resilience to stress by promoting hippocampal neurogenesis and increasing synaptic protein levels, thereby reducing the deleterious effects of stress.

Depression is a life-threatening psychiatric disorder characterized with a long-term hypercortisolemia in depressed patients. Based on this clinical feature, hypercortisolemia was mimicked in experimental animals to understand the neuropathogy of depression and to explore new therapeutic strategies. Wolfberry, also known as Lycium barbarum , is a type of common fruit produced in mainland China. Accumulated evidence has shown that the extracts from Lycium barbarum (LBP) had a wide range of neuroprotective effects in various neurogenerative models. However, the antidepressant effect of LBP on depression and its mechanism has not yet been explored. In the present study, we investigated the effects of LBP on counteracting depression using an animal model injected with moderate dose (40 mg/kg) or severe dose (50 mg/kg) of corticosterone (CORT) treatments for 14 days. The results showed that CORT significantly increased immobility time and decreased hippocampal cell proliferation. LBP treatment significantly decreased the immobility time in forced swimming test, a test for the intensity of depressive behaviors, both in 40 and 50 mg/kg CORT stressed rats. Moreover, LBP treatment restored the reduced proliferation of neuroprogentior cells in the hippocampus in 40 mg/kg CORT stressed rats and the neuronal differentiation but not the proliferation in 50 mg/kg CORT stressed rats. After ablation of adult neurogenesis with Ara-c infusion, the beneficial effect of LBP treatment in reducing immobility time was not affected in 40 and 50 mg/kg CORT stressed rats. Golgi staining and Western blotting detection showed that LBP treatment restored the reduced spine density and the decreased level of PSD-95 in the hippocampus caused by 40 and 50 mg/kg CORT, respectively, indicating enhanced synaptic plasticity in the hippocampus. The data showed a novel effect of LBP on reducing depression-like behavior and its antidepressant effect may be mediated by enhanced synaptic plasticity, but not hippocampal neurogenesis.