The Relationship Between Early Maladaptive Schemas,Depression, and Generalized Anxiety among Adults Seeking Residential Treatment for Substance Use Disorders

Abstract

Previous research has shown that early maladaptive schemas (EMS) play an important role in substance use, depression, and anxiety. However, few studies have examined the role of EMS within the context of all three concurrently. The goal of this study was to determine the role of EMS in predicting symptoms of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) among adults in residential treatment for substance dependence. We used pre-existing patient records of adults diagnosed with a substance use disorder from a residential substance use treatment facility (N = 122). The EMS domains of disconnection and rejection and impaired limits were associated with symptoms of MDD and the domain of impaired autonomy and performance was associated with symptoms of GAD, even after controlling for age, gender, years of education, alcohol use, drug use, and symptoms of MDD (when predicting GAD) and GAD (when predicting MDD). Findings suggest that EMS may play an important role in comorbid mental health problems among men and women in residential substance use treatment. Continued treatment outcome research is needed to examine whether modification of EMS results in improved mental health and substance use outcomes.     

Role of Immunity in Recovery from a Peripheral Nerve Injury

Motoneurons are large multipolar neurons with cell bodies located in the brainstem and spinal cord, and peripheral axons ending in neuromuscular junctions. Peripheral nerve damage, outside the blood-brain barrier (BBB), results in both retrograde changes centrally and anterograde changes along the length of the axon distal to the lesion site. Often, peripheral nerve damage is accompanied by motoneuron cell death, unless axon regrowth and target reconnection occur so that the target muscle can provide essential neurotrophic factors. It is essential that the motoneuron cell body survive during the process of reconnection so that the source for essential axon-rebuilding proteins is assure(of a fact)/ensured (results). A commonly used peripheral injury paradigm is that of facial nerve transection at its exit from the skull through the stylomastoid foramen so that nerve reconnection to the facial muscle tissue is permanently prevented. This model system allows for the study of the mechanisms responsible for maintaining facial motoneuron (FMN) cell body survival, without the complicating factor of axon regrowth. Injury to the nervous system results in an immune response that is either neuroprotective or neurodestructive. Findings suggest that FMN survival after facial nerve axotomy depends on the action of a CD4⁺ T cell that is initially activated peripherally and subsequently reactivated centrally. This review will summarize what is known about the neural-immune players involved in FMN survival and repair, so that the pharmacological manipulation of this interaction will one day become evident for the clinical management of neurological situations.     

The Role of Lymphocytes in the Pathogenesis of Asthma and COPD

Asthma and chronic obstructive pulmonary disease (COPD) are two different inflammatory disorders of the lungs which share a common functional abnormality, i.e. airflow limitation [1,2]. In asthma, airflow limitation is largely reversible, either spontaneously or with treatment, and does not progress in most cases [1]. On the other hand, airflow limitation in COPD is usually progressive and poorly reversible [2]. In asthma, the chronic inflammation causes an associated increase in airway responsiveness to a variety of stimuli, leading to recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly at night and in the early morning. Many cells are involved in the inflammatory response in asthma and, among these, CD4+ Type-2 lymphocytes, mast cells and eosinophils are thought to play a crucial role. In COPD, the poorly reversible airflow limitation is associated with an abnormal inflammatory response of the lungs to noxious particles or gases [2]. This chronic inflammation is characterized by an increased number of CD8+ Type-1 T-lymphocytes and macrophages in the lung tissue and neutrophils in the airway lumen. Lymphocytes, which are markedly different in the two inflammatory conditions, play a crucial role in the pathogenesis of asthma and COPD. In this review, we will discuss the current concepts on the recruitment, homing and activity of lymphocytes in these two respiratory diseases.     

Homeostasis and the Importance for a Balance Between AKT/mTOR Activity and Intracellular Signaling

The AKT family of serine threonine kinases is of critical importance with regard to growth factor signaling, cell proliferation, survival and oncogenesis. Engagement of signaling receptors induces the lipid kinase, phosphatidylinositol 3-kinase (PI3K), which enables the activation of AKT. Responsive to the PI3K/AKT pathway is the mammalian target of rapamycin (mTOR), a major effector that is specifically implicated in the regulation of cell growth as a result of nutrient availability and cellular bioenergetics. These kinases mediate the activity of a multitude of intracellular signaling molecules and intersect with multiple pathways that regulate cellular processes. Elucidating the role of AKT/mTOR in metabolism and in hallmark signaling pathways that are aberrantly affected in cancer has provided a solid foundation of discoveries. From this, new research directions are emerging with regard to the role of AKT/mTOR in diabetes and T cell-mediated immunity. As a result, a new perspective is developing in how AKT/mTOR functions within intracellular signaling pathways to maintain cellular homeostasis. An appreciation is emerging that altered equilibrium of AKT/mTOR pathways contributes to disease and malignancy. Such new insights may lead to novel intervention strategies that may be useful to reprogram or reset the balance of intracellular signaling.     

Depression in patients receiving pharmacotherapy for epilepsy: An audit in a tertiary care centre

BackgroundThe association of depression and epilepsy is thought to be bidirectional. The present study aimed to evaluate the prevalence of depression in patients on antiepileptic drugs (AEDs) and factors affecting it.MethodsIn this preliminary cross sectional study, patients at epilepsy clinic of a tertiary care centre were studied for occurrence of depression, using Hospital Anxiety and Depression Scale (HADS-D) and Patient Health Questionnaire (PHQ-2) scales. Correlation analysis was carried out to determine the factors associated with presence of depression in these patients.ResultsA total of 12 AEDs (maximum 5 per patient including older and newer) were prescribed to 933 patients in different treatment regimens over a period of 3 years. The median age of the patients was 22 years (10–77) and among them 63.5% were men. Mild and clinically relevant depression occurred in 279 (29.9%) and 223 (23.9%) patients, respectively. Mean HADS-D and PHQ-2 score was significantly higher with polytherapy as compared to monotherapy (p < 0.001). Patients on levetiracetam exhibited significantly higher HADS-D score in comparison to phenytoin (p < 0.001), carbamazepine (p < 0.001) and sodium valproate (p < 0.05). However, there was no significant difference in PHQ score among patients on monotherapy of different AEDs. Multivariate regression analysis suggested correlation between depression and seizure frequency, total number of AEDs and their load (p < 0.001).ConclusionDepressive symptoms were found to be present in more than half of the patients with epilepsy which require detailed work up for depression. Levetiracetam was found to be associated with a higher incidence of subclinical depression which needs further investigation.     

Lymphocytes T and pharmacokinetics after a single oral dose of levamisole in healthy and cancer subjects

Levamisole, an anthelmintic drug with immunopotentiating activity, is shown to have variable effects on cell-mediated immunity. We have studied the effect of a single oral dose (2.5 mg/kg or 5 mg/kg) on early and spontaneous E rosettes percentages in healthy and cancer patients. Pharmacokinetic study of this compound was conducted in parallel. The results indicated that single administration of levamisole (2.5 mg/kg) in healthy men can promote an increase of early E rosettes with mean peak plasma level of 0.8 micrograms. ml-1. On the other hand, there was no change in the proportion of early E rosettes in cancer patients and in the proportion of spontaneous E rosettes in healthy and cancer subjects.     

Neurotransmitters as Regulators of Tumor Angiogenesis and Immunity: The Role of Catecholamines

The growing tumor employs various strategies to establish its growth, progression and spread in the host. Angiogenesis or formation of new blood vessels from existing ones and escape from immune surveillance are the two critical steps that ensure proper establishment and growth of the newly formed tumor. Thus understanding the novel pathways associated with tumor angiogenesis and immunity may lead to the development of newer therapeutic strategies using the regulators of these pathways to improve patient outcomes. These two pivotal steps in the process of tumorigenesis are governed by plethora of endogenous factors. The neuroendocrine molecules, which include the catecholamine neurotransmitters, dopamine, norepinephrine and epinephrine are of growing interest considering their varied and diverse regulatory roles both in the process of tumor angiogenesis and tumor immunity. This review focuses on the emerging roles of catecholamines in modulating tumor angiogenesis and immunity, and also discusses the probable molecular mechanisms of their actions. Understanding of this new group of endogenous regulators of tumor growth may lead to the development of newer therapeutic approaches for the treatment of cancer.     

Neurotrophins Role in Depression Neurobiology: A Review of Basic and Clinical Evidence

Depression is a neuropsychiatric disorder affecting a huge percentage of the active population especially in developed countries. Research has devoted much of its attention to this problematic and many drugs have been developed and are currently prescribed to treat this pathology. Yet, many patients are refractory to the available therapeutic drugs, which mainly act by increasing the levels of the monoamines serotonin and noradrenaline in the synaptic cleft. Even in the cases antidepressants are effective, it is usually observed a delay of a few weeks between the onset of treatment and remission of the clinical symptoms. Additionally, many of these patients who show remission with antidepressant therapy present a relapse of depression upon treatment cessation. Thus research has focused on other possible molecular targets, besides monoamines, underlying depression. Both basic and clinical evidence indicates that depression is associated with several structural and neurochemical changes where the levels of neurotrophins, particularly of brain-derived neurotrophic factor (BDNF), are altered. Antidepressants, as well as other therapeutic strategies, seem to restore these levels. Neuronal atrophy, mostly detected in limbic structures that regulate mood and cognition, like the hippocampus, is observed in depressed patients and in animal behavioural paradigms for depression. Moreover, chronic antidepressant treatment enhances adult hippocampal neurogenesis, supporting the notion that this event underlies antidepressants effects. Here we review some of the preclinical and clinical studies, aimed at disclosing the role of neurotrophins in the pathophysiological mechanisms of depression and the mode of action of antidepressants, which favour the neurotrophic/neurogenic hypothesis.     

Involving Stakeholders in the Evaluation of Community Alcohol Projects: Finding a Balance Between Subjective Insight and Objective Facts

The role played by key community representatives in the evaluation of community alcohol projects differs according to the evaluation paradigm adopted. In evaluations that adopt a positivist, experimental design they are cast in the role of independent informants. In post-positivist evaluations they are seen as having an interest in the evaluation and accordingly are considered active stakeholders. However, the degree to which stakeholders can be actively engaged in an evaluation varies considerably along a number of dimensions. Four dimensions of the stakeholder role—stakeholder inclusiveness, participation mode, participation frequency, and evaluation role—are examined in the context of eight evaluation theories. This is integrated into a model that links these dimensions to an object-subject continuum of stakeholder involvement. The model facilitates systematic consideration of these dimensions and will assist evaluators in achieving their desired balance of subjective insight and objective fact.     

Role of regulatory T cells in allergy: implications for therapeutic strategy

The interest in regulatory T cells (Tregs) has been revived following the discovery of developing multiorgan autoimmune diseases as a result of depleting CD4+CD25+ T cells from mice. The importance of Tregs is being recognized in various clinical fields such as tumor and microbial immunities, transplantation and allergy. Prevalence of allergic diseases such as asthma, atopic dermatitis and rhinitis is significantly increasing worldwide. A better understanding of the mechanisms of T-cell regulation in allergic diseases may help in developing more effective therapeutic strategies. The well-known role of Tregs in preventing autoimmune diseases indicates that these important cells might be involved in prevention of allergy, and allergic diseases are associated with a low frequency and/or an impaired function of Tregs. Recent data show that natural CD4+CD25+ Tregs and interleukin (IL)-10-producing Tregs are normally able to suppress Th2 responses to allergens, while such suppression is diminished in allergic conditions. In this review, I summarize the role of Tregs in allergic diseases and discuss the possibility of manipulating these cells for treating allergic diseases.     

Exploring Peers as a Mediator of the Association Between Depression and Smoking in Young Adolescents

Recent research has suggested that depression causes teens to begin smoking to elevate their mood. Other studies, however, have suggested the reverse causal direction: smoking causes depression. To gain a more complete understanding of the relationship between smoking and depression, potential mediators should be explored. This study explored how peer influences could mediate the relationship between depression and smoking. The methodology of Baron and Kenney was followed to test for mediation and moderation. Peers mediated the relationship between depression and smoking. Separate analyses by gender showed that depression remained significantly associated with smoking when peers were included in the model for girls only. Peer influence was related to depressed affect for both genders. These results provide evidence that peer influences are an important variable to take into consideration when addressing a depression smoking relationship.     

A Role for Corticosterone in Impaired Intestinal Immunity and Barrier Function in a Rodent Model of Acute Alcohol Intoxication and Burn Injury

Alcohol (EtOH) intoxication and burn injury independently activate hypothalamic-pituitary-adrenal (HPA) axis, and glucocorticoids, the end product of the HPA axis, play a role in shaping the immune response under those conditions. By utilizing a rat model of acute EtOH intoxication and burn injury, studies in our laboratory have investigated the role of corticosterone (i.e., glucocorticoids in rodents) in altered intestinal immunity and barrier function following a combined insult of EtOH and burn injury. Results from these studies suggest that EtOH intoxication prior to burn injury augments corticosterone release, which in turn suppresses intestinal T cell function by inhibiting mitogen-activated protein kinase (i.e., p38 and ERK) pathway. Furthermore, we found that corticosterone does not directly alter the intestinal barrier function; rather, it up-regulates interleukin-18, which then directly or indirectly contributes to impaired intestinal barrier function. The loss of intestinal immunity/barrier function may result in increased bacterial translocation and thereby contribute to postinjury pathogenesis, leading to sepsis and organ dysfunction in burn patients as well as in patients with a history of EtOH intoxication.     

Therapeutic Options for Treating Major Depression,and the Role of Venlafaxine

Major depression is a debilitating disorder that is often undertreated. Psychotherapy, electroconvulsive therapy, and pharmacotherapy are options for management. Tricyclic antidepressants and selective serotonin reuptake inhibitors are the cornerstones of drug therapy. Venlafaxine, a phenylethylamine antidepressant that primarily inhibits reuptake of norepinephrine and serotonin, is an alternative to those agents. It has been studied in short-term and continuation studies and appears to have efficacy similar to that of imipramine, trazodone, and fluoxetine. Moreover, venlafaxine is effective in approximately one-third of patients with treatment-resistant depression. Venlafaxine is metabolized by the P-450 enzyme system to an active metabolite O-desmethyl-venlafaxine, which is excreted renally. Nausea, somnolence, and dizziness are dose-related adverse effects that often occur with initiation of therapy. Increases in blood pressure, particularly with high dosages, also may occur. Drug-drug interactions appear to be minimal.     

女性抑郁症与代谢综合征的相关研究

目的探讨女性抑郁症与代谢综合征的相关性。方法入组90例女性单相抑郁症患者和148例正常女性对照,检测两组人群代谢综合征的各项指标。结果女性抑郁症患者组的代谢综合征患病率与对照组比较,存在显著性差异,抑郁症与代谢综合征存在显著相关性(P<0.01);患者组和对照组各项代谢综合征指标比较,两组身体质量指数、血压无显著性差异(P均>0.05)。患者组的空腹血糖和三酰甘油高于对照组,高密度脂蛋白低于对照组,存在统计学差异(P<0.05或0.01)。结论女性抑郁症与代谢综合征存在关联性。抑郁症的早期治疗对患者身体代谢状况十分重要。另一方面,需要对抑郁症患者的健康状况进行监测。     

宫颈癌患者外周血T淋巴细胞NK细胞的检测及临床意义

目的探讨宫颈癌患者外周血T淋巴细胞NK细胞的检测及临床意义。方法 2008年1月至2010年月1月收治的宫颈癌患者140例,选取同期健康体检140例进行外周血T淋巴细胞NK细胞的检测。结果正常组与宫颈癌组各期对比P〈0.05有显著差异性。结论宫颈癌患者免疫状态与TNM分期呈负相关,免疫功能越低下,提示病期越晚、预后越差,外周血T淋巴细胞NK细胞的检测可间接提示患者预后。     

Role of Aspirin and Dexamethasone against Experimentally Induced Depression in Rats

A large number of current studies indicate that inflammatory mediators may contribute to depression in experimental models as well as in human beings. Nevertheless, the subject, whether anti‐inflammatory treatments can prevent depression still remains controversial. In the present study, a chronic mild stress (CMS) model of male Sprague Dawley rats was used to investigate the role of anti‐inflammatory drugs in the treatment of depression. All the animals in different groups, except the normal control group, were exposed to CMS procedure for 28 days and concurrently treated with aspirin (10 mg/kg, p.o.), dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o., reference standard), respectively. Amitriptyline was also used in combination with aspirin and dexamethasone to inspect any synergistic effects. Tests performed towards the end of the study included sucrose preference test, behavioural tests like forced swim test, elevated plus‐maze, light/dark box, locomotor activity and biochemical estimations like serum cortisol and brain neurotransmitters. Disease control group (CMS‐treated) produced significant depressive behaviour in rats. The animals treated with aspirin showed increased sucrose preference, decreased immobility time in forced swim test, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was aggravation of depressive behaviour in rats treated with dexamethasone. Together, these findings suggest that aspirin can serve as a potential antidepressant both individually and as adjunctive agent in the treatment of depression. Inhibition of the inflammatory mediators during stress procedures or any other potential physiological and biochemical mechanisms may be involved in its antidepressant effect.