Multiple mediation of the association between childhood emotional abuse and adult obesity by anxiety and bulimia - a sample from bariatric surgery candidates and healthy controls.

Bulimia, which means a person has episodes of eating a very large amount of food (bingeing) during which the person feels a loss of control over their eating, is the most primitive reason for being overweight and obese. The extended literature has indicated that childhood emotional abuse has a close relationship with adverse mood states, bulimia, and obesity. To comprehensively understand the potential links among these factors, we evaluated a multiple mediation model in which anxiety/depression and bulimia were mediators between childhood emotional abuse and body mass index (BMI). A set of self-report questionnaires, including the Childhood Trauma Questionnaire (CTQ), Beck Anxiety Inventory, Beck Depression Inventory (BDI), and Eating Disorder Inventory (EDI), was sent out. Clinical data from 37 obese patients (age: 29.65 ± 5.35, body mass index (BMI): 37.59 ± 6.34) and 37 demographically well-matched healthy people with normal body weight (age: 31.35 ± 10.84, BMI: 22.16 ± 3.69) were included in the investigation. We first performed an independent t-test to compare all scales or subscale scores between the two groups. Then, we conducted Pearson correlation analysis to test every two variables' pairwise correlation. Finally, multiple mediation analysis was performed with BMI as the outcome variable, and childhood emotional abuse as the predictive variable. Pairs of anxiety, bulimia, and depression, bulimia were selected as the mediating variables in different multiple mediation models separately. The results show that the obese group reported higher childhood emotional abuse (t = 2.157, p = 0.034), worse mood state (anxiety: t = 5.466, p < 0.001; depression: t = 2.220, p = 0.030), and higher bulimia (t = 3.400, p = 0.001) than the healthy control group. Positive correlations were found in every pairwise combination of BMI, childhood emotional abuse, anxiety, and bulimia. Multiple mediation analyses indicate that childhood emotional abuse is positively linked to BMI (ß = 1.312, 95% CI = 0.482-2.141). The model using anxiety and bulimia as the multiple mediating variables is attested to play roles in the relationship between childhood emotional abuse and obesity (indirect effect = 0.739, 95% CI = 0.261-1.608, 56.33% of the total effect). These findings confirm that childhood emotional abuse contributes to adulthood obesity through the multiple mediating effects of anxiety and bulimia. The present study adds another potential model to facilitate our understanding of the eating psychopathology of obesity.

Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features.

Deep brain stimulation (DBS) of structures in the brain's reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain's anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB-DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients' left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients' health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB-DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB-DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB-DBS for treatment-refractory mood disorders in a more rigorous fashion.

Pictures Library of Smoking Cravings: Development and Verification of Smokers and Non-smokers.

Background: The cue-induced craving by addiction related materials is commonly employed in addiction research; however, no existing standardized picture database based on the expectation model of craving has been developed. We prepared and validated a Pictures Library of Smoking Cravings (PLSC) in this study. Methods: We captured pictures 366 smoking and 406 control pictures (matched in content). We selected 109 smoking pictures and 115 control pictures and asked participants to provide ratings of craving, familiarity, valence, and arousal induced in them. Participants were divided into three groups: non-smokers (n = 211), light smokers (n = 504), and heavy smokers (n = 101). Results: The results showed that smoking pictures evoked a greater craving, familiarity, and arousal than control pictures in smokers (ps < 0.01). In addition, craving caused by smoking pictures was positively associated with the Fagerström test for nicotine dependence score in dependent smokers. Conclusions: Overall, the contemporary results showed that PLSC is effective and can be used in smoking-related studies.

Neuromodulation-Based Stem Cell Therapy in Brain Repair: Recent Advances and Future Perspectives.

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.

The effects of repetitive transcranial magnetic stimulation on cue-induced craving in male patients with heroin use disorder.

BACKGROUND: Craving is a central feature of addiction. Early evidence suggests that repetitive transcranial magnetic stimulation is effective in reducing cue induced craving for patients with opioid use disorder (OUD). However, trials in large populations of patients with OUDs are lacking. METHODS: We randomly assigned 118 male heroin patients into three groups (i.e., 10 Hz rTMS, 1 Hz rTMS and a wait-list control group) from two addiction rehabilitation centers. rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) for 20 daily consecutive sessions. FINDINGS: Results showed that 10 Hz rTMS and 1 Hz rTMS were both effective in reducing cue-induced craving scores in heroin users when compared to the wait list group. The treatment effects lasted for up to 60 days after rTMS treatment cessation. INTERPRETATION: Our results suggest that rTMS applied to the DLPFC is effective in reducing craving severity in heroin use disorder patients. Our results also suggest that such treatment effects can last for up to 60 days after treatment cessation.

Multimodal treatment for spinal cord injury: a sword of neuroregeneration upon neuromodulation.

Spinal cord injury is linked to the interruption of neural pathways, which results in irreversible neural dysfunction. Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury, which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies. Besides the involvement of endogenous stem cells in neurogenesis and neural repair, exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases. However, to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury, appropriate interventional measures (e.g., neuromodulation) should be adopted. Neuromodulation techniques, such as noninvasive magnetic stimulation and electrical stimulation, have been safely applied in many neuropsychiatric diseases. There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system; namely, by exciting, inhibiting, or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury. Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth, encourages the formation of new synaptic connections to promote neural plasticity, and improves motor function recovery in patients with spinal cord injury. With the development of biomaterial technology and biomechanical engineering, several emerging treatments have been developed, such as robots, brain-computer interfaces, and nanomaterials. These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury. However, large-scale clinical trials need to be conducted to validate their efficacy. This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence, to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.

Neurosurgical treatment for addiction: lessons from an untold story in China and a path forward.

Addiction is a major public-health crisis associated with significant disability and mortality. Although various pharmacological and behavioral treatments are currently available, the clinical efficacy of these treatments is limited. Given this situation, there is a growing interest in finding an effective neurosurgical treatment for addiction. First, we discuss the use of ablative surgery in treating addiction. We focus on the rise and fall of nucleus accumbens ablation for addiction in China. Subsequently, we review recent studies that have explored the efficacy and safety of deep-brain-stimulation treatment for addiction. We conclude that neurosurgical procedures, particularly deep-brain stimulation, have a potentially valuable role in the management of otherwise intractable addictive disorders. Larger well-controlled clinical trials, however, are needed to assess clinical efficacy and safety. We end by discussing several key issues involved in this clinical field and identifying some areas of progress.

Enhancement of Hippocampal Plasticity by Physical Exercise as a Polypill for Stress and Depression: A Review.

Generation of newborn neurons that form functional synaptic connections in the dentate gyrus of adult mammals, known as adult hippocampal neurogenesis, has been suggested to play critical roles in regulating mood, as well as certain forms of hippocampus-dependent learning and memory. Environmental stress suppresses structural plasticity including adult neurogenesis and dendritic remodeling in the hippocampus, whereas physical exercise exerts opposite effects. Here, we review recent discoveries on the potential mechanisms concerning how physical exercise mitigates the stressrelated depressive disorders, with a focus on the perspective of modulation on hippocampal neurogenesis, dendritic remodeling and synaptic plasticity. Unmasking such mechanisms may help devise new drugs in the future for treating neuropsychiatric disorders involving impaired neural plasticity.

Fish oil treatment reduces chronic alcohol exposure induced synaptic changes.

Alcohol addiction is a chronic neuropsychiatric disorder that represents one of the most serious global public health problems. Yet, currently there still lacks an effective pharmacotherapy. Omega-3 polyunsaturated fatty acids (N-3 PUFAs) have exhibited beneficial effects in a variety of neurological disorders, particularly in reversing behavioral deficits and neurotoxicity induced by prenatal alcohol exposure and binge drinking. In the present study, we investigated if fish oil, which is rich in N-3 PUFAs, had beneficial effects on preventing relapse and alleviating withdrawal symptoms after chronic alcohol exposure. Our results demonstrated that fish oil significantly reduced the chronic alcohol exposure-induced aberrant dendritic morphologic changes of the medium-sized spiny neurons in the core and the shell of nucleus accumbens. This inhibited the expression of AMPAR2-lacking AMPARs and their accumulation on the post synaptic membranes of medium-sized spiny neurons and eventually alleviated withdrawal symptoms and alcohol dependence. Our study therefore suggests that N-3 PUFAs are promising for treating withdrawal symptoms and alcohol dependence.

Fish Oil Prevents Lipopolysaccharide-Induced Depressive-Like Behavior by Inhibiting Neuroinflammation.

Depression is associated with somatic immune changes, and neuroinflammation is now recognized as hallmark for depressive disorders. N-3 (or omega-3) polyunsaturated fatty acids (PUFAs) are well known to suppress neuroinflammation, reduce oxidative stress, and protect neuron from injury. We pretreated animals with fish oil and induced acute depression-like behaviors with systemic lipopolysaccharide (LPS) injection. The levels of cytokines and stress hormones were determined from plasma and different brain areas. The results showed that fish oil treatment prevent LPS-induce depressive behavior by suppression of neuroinflammation. LPS induced acute neuroinflammation in different brain regions, which were prevented in fish oil fed mice. However, neither LPS administration nor fish oil treatment has strong effect on stress hormone secretion in the hypothalamus and adrenal. Fish oil might provide a useful therapy against inflammation-associated depression.

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis.

The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking.

Transcranial direct current stimulation of the frontal-parietal-temporal area attenuates cue-induced craving for heroin.

BACKGROUND: Transcranial direct current stimulation (tDCS) is an effective approach to modulate brain region functions. We assessed if a single tDCS session over the bilateral frontal-parietal-temporal (FPT) areas would reduce cue induced craving in heroin addicts. METHODS: Twenty non-treated, long-term heroin-addicted subjects were randomly assigned to receive either real tDCS (1.5 mA, cathodal over bilateral FPT for 20 min) or control tDCS stimulation (turning off the stimulation after 30 s). The participants received heroin cue exposure (containing both injection and inhalation procedures) before and after stimulation and rated their craving after each block of cue presentation. RESULTS: Stimulation of the bilateral FPT with real tDCS for 20 min reduced craving scores significantly (68 ± 8.4 pre-stimulation vs. 43 ± 7.6 post-stimulation, p = 0.003), while the control stimulation group showed no significant changes. No side effects of tDCS were reported. CONCLUSIONS: One session of tDCS over bilateral FPT area significantly reduced subjective craving score induced by heroin cues in heroin addicted subjects.

Working memory dysfunction in insomniac adults: a systematic metanalytical review / Disfunção da memória de trabalho em adultos insones: uma revisão sistemática

BACKGROUND: Insomnia is the most commonly occurring sleep disorder: recent reports estimate that 25-30% of adults in the general population occasional instances of experience insomnia, while 10% suffer from disturbances severe enough to meet diagnostic criteria for insomnia. Little is known about the mechanisms, causes, clinical course, and consequences of this condition. Over 30 studies have been published on the matter but only a small proportion has found differences in the working memory of individuals with vs. without insomnia. OBJECTIVE: To summarize evidence regarding the differences in working memory performance between insomniac vs. normal adult sleepers. METHODS: The survey was conducted using an advanced search in the ISI Web of Science and MEDLINE/PubMed with the terms "sleep", "insomnia" and "working memory" as major descriptors; these were crossed with the following keywords: "psychological tests", "neuropsychology" and "performance". RESULTS: A total of 112 articles were identified in the search conducted in PubMed and Web of Science. After the screening, 102 articles unrelated to the proposed theme were excluded. Thus, 10 articles were analyzed by the eligibility and exclusion criteria, and included in this systematic review. CONCLUSION: The information resulting from the analysis of the reviewed articles suggests that mild, but not definitive deficits in cognitive performance might be masked by insignificant disparities in studies comparing insomniac individuals with normal sleepers. This shortcoming can be circumvented by larger and better-characterized samples, together with optimized methodological control of factors which might otherwise result in confounding variations among participants.

INTRODUÇÃO: A insônia é o distúrbio do sono mais comum: relatórios recentes estimam que 25-30% dos adultos sofrem episódios de insônia, enquanto 10% sofrem de distúrbio do sono suficientemente grave para cumprir os critérios de diagnóstico para insônia. Além disso, pouco se sabe sobre os mecanismos, causas, evolução clínica, e consequências desta doença crónica altamente prevalente. Mais de 30 estudos foram publicados sobre o assunto, mas apenas uma pequena proporção encontrou diferenças entre os indivíduos com e sem insônia, por exemplo, na memória de trabalho. OBJETIVO: Examinar as evidências sobre as diferenças entre adultos insones e normais no desempenho da memória de trabalho. MÉTODOS: A pesquisa foi realizada usando uma pesquisa avançada no ISI Web of Science e MEDLINE/PubMed com os termos "sleep", "insônia" e "memória de trabalho" como os principais descritores, que foram cruzados com as seguintes palavras-chave: "testes psicológicos", "neuropsicologia" e "performance". RESULTADOS: Um total de 132 artigos foram identificados na pesquisa realizada no PubMed e Web of Science; 20 duplicações foram excluídas. Após a triagem, 102 artigos foram excluídos, que não estavam relacionadas com o tema proposto. Assim, 10 artigos foram selecionados por critérios de elegibilidade e de exclusão, e incluídos na revisão sistemática. CONCLUSÃO: As descobertas relatadas em nosso estudo sugerem que os deficits leves mas não permanentes de desempenho cognitivo podem ser mascarados por disparidades insignificantes em estudos que comparam indivíduos com insônia com pessoas com sono normal. Tal deficiência pode ser contornada pela análise de amostras maiores e mais bem caracterizadas, em conjunto com o controle metodológico otimizado de fatores que potencialmente podem incorrer em variações entre os participantes.

Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.

Advances in cancer pain from bone metastasis.

With the technological advances in cancer diagnosis and treatment, the survival rates for patients with cancer are prolonged. The issue of figuring out how to improve the life quality of patients with cancer has become increasingly prominent. Pain, especially bone pain, is the most common symptom in malignancy patients, which seriously affects the life quality of patients with cancer. The research of cancer pain has a breakthrough due to the development of the animal models of cancer pain in recent years, such as the animal models of mouse femur, humerus, calcaneus, and rat tibia. The establishment of several kinds of animal models related to cancer pain provides a new platform in vivo to investigate the molecular mechanisms of cancer pain. In this review, we focus on the advances of cancer pain from bone metastasis, the mechanisms involved in cancer pain, and the drug treatment of cancer pain in the animal models.

Local proliferation is the main source of rod microglia after optic nerve transection.

Microglia are the resident phagocytic cells with various functions in the central nervous system, and the morphologies of microglia imply the different stages and functions. In optical nerve transection (ONT) model in the retina, the retrograde degeneration of retinal ganglion cells (RGCs) induces microglial activations to a unique morphology termed "rod" microglia. A few studies described the "rod" microglia in the cortex and retina; however, the function and origin of "rod" microglia are largely unknown. In the present study, we firstly studied the temporal appearance of "rod" microglia after ONT, and found the "rod" microglia emerge at approximately 7 days after ONT and peak during 14 to 21 days. Interestingly, the number of "rod" microglia remarkably decays after 6 weeks. Secondly, the "rod" microglia eliminate the degenerating RGC debris by phagocytosis. Moreover, we found the major source of "rod" microgliosis is local proliferation rather than the infiltration of peripheral monocytes/hematopoietic stem cells. We for the first time described the appearance of "rod" retinal microglia following optic nerve transection.

Specialized vasculature in the rostral migratory stream as a neurogenic niche and scaffold for neuroblast migration.

Neurovascular niches serve as the hosts for adult neural stem cells in both the hippocampus and subventricular zone. The rostral migratory stream (RMS) vasculature has been found to be important for neuroblast migration, while its roles in hosting putative neural stem cells have not been investigated. Here we investigated the organization of RMS vasculature and its contribution to the production of new neurons. A single pulse of bromodeoxyuridine (BrdU) administration revealed locally formed new neurons within RMS were located adjacent to blood vessels. In addition, BrdU label-retaining cells that are putative neural stem cells were also found close to the vasculature. Sodium fluorescein perfusion assay demonstrated that the blood-brain barrier (BBB) organization was especially "leaky" in the neurogenic niches. Immunohistochemical visualization of some BBB component molecules indicated a thinner BBB in the RMS region, compared to that in the frontal cortex of adult rats. Finally, the expression of vascular endothelial growth factor was strong and specialized in the RMS region, implying that the region was active in cell proliferation and migration. Here we show that the RMS vasculature associated with surrounding astrocytes provides a highly organized neurovascular niche for adult neural stem cell proliferation, in addition to the function of neuroblast migration support. This result points to a new vasculature supporting neurogenic region in the brain.

Adult neurogenesis in the hypothalamus: evidence, functions, and implications.

Neurogenesis occurs in the adult brain in a constitutive manner under physiological circumstances within two regions: the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. In contrast to these two so-called neurogenic areas, other regions of the brain were considered to be primarily non-neurogenic in nature, implying that no new neurons were formed there under normal conditions. Recently, low proliferative activity was reported in the hypothalamus and the cell layers surrounding the third ventricle. This review summarizes recent evidence for adult neurogenesis in the hypothalamus, and points out the potential contributions of these new neurons to neural processing. We also discussed some technical considerations in investigating neurogenesis in the adult hypothalamus. It is believed that the hypothalamus could serve as a new source and target for stem cell transplantation.