Abstract Introduction and Background Many people in the pediatric population are be brushed off and misdiagnosed when it comes to depression. I decided to research into pediatric depression and how the effects of their peers, parents, and exposure to violence correspond with depression and how it effects their daily life. Purpose Statement The purpose of this literature review is to systematically and critically appraise current literature to examine the associations between pediatric depression and sleep issues, exposure to violence, peer relationships, and parental criticism. Literature Review For this literature review I gathered a total of 5 articles which are included in this review. All the 5 articles are academic journals. These articles all come from CINAHL complete from the ETSU library database. Findings When the pediatric population is exposed to emotional abuse, emotional neglect, physical abuse, physical neglect, peer victimization and peer fighting, they were reported to have significantly greater depressive symptoms and hopelessness than the pediatric population who did not experience as much violence and neglect (Benton et al. 2020). Children who had preschool-onset major depressive disorder, after receiving parent-child interactive therapy with a focus on emotional development were found to experience a significant reduction in insomnia, daytime fatigue, and total sleeping problems (Hoyniak et al., 2020). There was also a strong correlation that the more parental criticism an adolescence receives, the higher the risk for major depression there is (Nelemans et al., 2020). The CLPM model indicated that depressive symptoms increased the risk for subsequent peer rejection consistently and peer acceptance mainly before eighth grade (Yang et al., 2020). And in the patients who came to the ER with non-psychiatric complaints, after screening for depression many of their results indicated a moderately-severe depression score which presents a need for additional help from a mental health care provider (Arrojo and Hooshmand, 2021). Conclusions Overall, there is a strong correlation between pediatric depression and sleep issues, exposure to violence, peer relationships, and parental criticism. The studies proved that the more parental criticism a child received, the more depressive symptoms they faced, as well as the more sleeping issues they experienced. The data also proved that in adolescence the influence of peers is strong and peer relationships have heavy influence on the depressive symptoms shown by adolescence. When children are exposed to a ‘web of violence’ they are also more inclined to experience depression and many children try to internalize their mental health issues to please their parents. There needs to be more general education about pediatric depression and more implementations of mandatory screenings added to the EHR. For many of these studies, if they were to be performed again, they would benefit from more diversity as well as larger sample sizes. This would provide a more generalizable set of data that could be applied in more places.

Major depressive disorder (MDD) is rapidly growing and one of the most common causes of disability and mortality worldwide. People with MDD often display brain changes such as adisrupted balance in neurotransmitters, impaired neurogenesis and neuroplasticity. Traditionally has MDD been treated with medications and talking therapies (psychotherapy). Studies have shown that just around 50 % of people with MDD get improvements from common traditional treatments.Therefore is there a great need for a better understanding of MDD and new treatments. There is now an emerging field of research that indicates that the gut microbiota plays a crucial role in disturbing normal brain functioning in MDD. This connection between the gut and the brain is called the gutbrain axis.The thesis aims to investigate if there is a connection between gut microbiota disruption and MDD and if gut microbiota restoration can be a potential effective future treatment for MDD. Key findings of the thesis were, studies show that people with MDD often display gut microbiota disruption and chronic low grade inflammation. Studies also indicate that this inflammation can cause the specific brain change often displayed in people with MDD. One of the most critical findings in the thesis was that gut brain treatments affect tryptophan metabolism, which affects the risk of MDD. The research area of the gut brain axis is still new and many more studies are needed,particularly in humans.

Background: Major depressive disorder is one of the leading diseases in the world. While anti-depressive medication is the most commonly used treatment, studies shows conflicting results of its benefits, where other alternative treatments are getting more attention such as psychological treatment and physical activity. Aim: The study aimed to illuminate the meaning of physical activity for adult patients suffering from major depressive disorder. Method: The method used is a literature review of nine original scientific articles, published in Cinahl, PubMed and PsycArticles databases between 2010-2020, limited to peer-review and English language. Results: The result showed a decrease in depressive symptoms as shown in rating scales such as HDRS, BDI and MADRS, in patients treated with physical activity. Patients suffering from severe major depressive disorder showed paramount difference pre-post intervention, despite their initial state of disability. Conclusion: Regardless of the severity of disease, physical activity shows a valid effect as an adjunct treatment in adults suffering from major depressive disorder. The result shows that while the use of physical activity as therapy is warranted in patients with major depressive disorder, adherence to treatment is of outmost importance, and the support from health professionals is mandatory.

BACKGROUND: Major Depressive Disorder (MDD) is a common mental health illness, characterized by persistent feelings of sadness, diminished interests, guilt, low-self esteem, and disturbances in sleep and appetite. A significant percentage of patients with MDD are treatment resistant. Electroconvulsive Therapy (ECT) is a biological procedure utilized for treatment resistant illnesses. Diagnosis and clinical conditions primarily dictate when ECT is the appropriate treatment modality for an individual. Circumstances requiring rapid clinical response, risks affiliated with alternative treatments, resistance to pharmacotherapy, and medical history are all factors that designate ECT as the treatment of choice. METHODS: The objective of this systematic review was to examine how different anesthetics or combinations of agents affect ECT’s therapeutic efficacy in depressed, adult patients. Electroencephalography (EEG) and motor seizure durations and Hamilton Depression Rating Scale (HDRS) scores were used as primary measures of clinical outcomes. Two rounds of literature searches were conducted in the PubMed, Web of Science, and Google Scholar databases to identify randomized controlled trials and crossover trials that examined the effects of different intravenous sedatives and hypnotic agents on ECT. Two reviewers independently evaluated the internal validity and quality of studies, extracted data, and analyzed statistics. Utilizing all relevant data, standardized mean differences (SMD) with 95% confidence intervals (CIs), and heterogeneity measures were calculated. Ten studies with 373 participants were included. RESULTS: Thiopental only anesthesia was associated with longer EEG seizure duration when compared to propofol only treatment. The pooled effect size from studies with propofol anesthesia also suggests that this agent is associated with shorter seizure durations. If assessed individually with thiopental, the combination of ketamine and thiopental is correlated with increased motor as well as EEG seizure durations. When pooled; however, studies with patient groups assigned to anesthesia consisting of ketamine and another primary agent do not show significant differences either in EEG or motor seizure durations. Additionally, no difference exists in HDRS score reductions between propofol and methohexital. Of note; however, ketamine combined with either propofol or thiopental had significantly greater decreases in HDRS scores. CONCLUSION: Choice of anesthetic should be determined based on anticipated clinical outcome, adverse effect profile, reemergence, and patient preference. If long seizures are preferred, thiopental may be a reasonable option. However, if significantly larger decreases in depression score are preferred, then the combinations of ketamine and propofol or ketamine and thiopental appear to be the therapies of choice. Small sample sizes and insufficient clinical data limit the interpretations of these variables that determine therapeutic efficacy. Larger randomized control trials and crossover trials would provide greater insight into the optimal use of intravenous anesthetic agents with minimal adverse effects.

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a lifetime prevalence rate of approximately 20%. Inadequate pharmacological treatment methods for MDD are a significant debilitating factor. Patient estimates suggest that the treatment resistance rate for pharmacological interventions is over 30%. Postmortem analyses of human tissue of individuals diagnosed with MDD have shown an increase in Poly (ADP-ribose) polymerase 1 (PARP-1) mRNA gene expression in prefrontal cortical white matter when compared to psychiatrically normal brain tissue. In order to further investigate this issue, the present study used the social defeat stress/chronic unpredictable stress (SDS + CUS) rodent model of depression to induce a state of chronic psychological distress. Rats were treated with either the PARP-inhibitor, 3-aminobenzamide (3-AB); a common selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), or saline. During the stress manipulation we conducted the sucrose preference test, results revealed that saline-treated rats which had undergone SDS + CUS showed significant reductions in sucrose preference compared to all other groups. In addition, a social interaction test was conducted one day after the stress manipulation, and saline-treated stressed animals demonstrated less social interaction compared to all other groups, indicating the stress manipulation was effective. Neurobiological assays were conducted to examine PARP expression, microglial morphology, and proinflammatory cytokine expression. Though we expected to find a decrease, results from immunofluorescence studies of tissue sections revealed an elevation of PARP-1 protein expression in prefrontal cortical gray matter in the FLX/Stress group compared with SAL/Stress group. Microglial morphological changes indicated that the SAL/Stress group had significantly more prolate microglia when compared to all other treatment groups, suggesting early activation of microglia, an indicator of neuroinflammation. Increases in IL-1β and TNF-⍺ expression was observed in the hippocampus of the SAL/Stress group when compared to all other treatment groups. Interestingly, IL-6 expression was significantly elevated in the SAL/Stress group when compared to the FLX/Stress group and the CTRL/No stress group but did not significantly differ from the 3-AB/Stress group. This study revealed therapeutic potential of 3-AB for the treatment of stress-related disorders, as well as the neuroinflammatory mechanisms associated with chronic stress.

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Mindfulness-based cognitive therapy (MBCT) is a meditation-based psychotherapeutic intervention suggested to be equally effective as antidepressant medication for preventing depressive relapse. A lot of patients with major depressive disorder (MDD) have preference for psychotherapeutic intervention compared to antidepressant medication, currently being the most common treatment for preventing depressive relapse. The aim of this systematic review was to examine the effectiveness of MBCT compared to antidepressant medication for preventing depressive relapse in individuals with MDD, treatment-resistant depression, or suicidal ideation. After a literature search in the databases Scopus and Web of Science, 16 articles were included in this systematic review. Results were mixed. While two studies demonstrated that MBCT is equally effective as antidepressant medication in preventing depressive relapse, four studies showed evidence of reduced relapse rates after MBCT treatment alone. Further, four studies suggested that MBCT is inferior to antidepressant medication in preventing depressive relapse. Future studies should focus on comparing MBCT alone to specific antidepressant medication in order to further evaluate the effectiveness of MBCT vs antidepressant medication.

Early life stress has been found to be a strong predictor of depression severity, with genetic risk factors such as the serotonin transporter promotor (5-HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms moderating depression development. Our investigation aims to extend these findings to examine the impact of depression severity, genetic risk factors, and childhood maltreatment on neuronal connectivity changes using tract based spatial statistics (TBSS) and probabilistic tractography. Fifty-five medication-free patients with major depressive disorder (MDD) [x̅ age: 36.4, M/F: 22/33] and 18 controls [x̅ age: 33.2, M/F: 8/10] underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionairre. Corrected TBSS findings revealed trends toward significantly reduced FA in the right anterior internal capsule [p=0.051], fornix [p=0.085] and right anterior corona radiata [p=0.084] in the MDD group. Probabilistic tractography analysis examined fractional anisotropy (FA) in the cingulum bundle, uncinate fasciculus and superior longitudinal fasciculus. Individuals scoring high in depression severity and who experienced severe childhood physical neglect (PN) and emotional neglect (EN) had higher FA in the uncinate [PN: p=0.003, EN: p=0.029] and superior longitudinal fasciculus [PN: p=0.0748], with BDNF and 5-HTTLPR moderating these associations. BDNF polymorphisms also exhibited a stronger impact on uncinate FA in individuals with high depression severity, with val-BDNF exhibiting higher FA than met carriers [p=0.021]. In conclusion, MDD patients exhibit widespread decreases in FA across many neural regions. Furthermore, the impact that depression severity has on FA is considerably influenced by early life neglect. / Thesis / Master of Science (MSc)

A major challenge in the treatment of major depressive disorder (MDD) is relapse, which is defined as the return of depressive symptoms during a period of remission. Relapse rates in MDD are high, with approximately 50% of individuals relapsing following treatment of their first depressive episode, therefore early intervention to prevent relapse is crucial. Evidence suggests that immune dysregulation may be linked to longitudinal changes in depressive severity. However, it is currently unknown whether inflammation can predict future relapse in MDD. The objective of this project was to identify potential immune predictors of relapse in participants that responded to a treatment or a combination of treatments for MDD. A secondary objective was to investigate immune composition in efforts to stratify MDD individuals into more homogenous groups and further explore these groups in relation to clinical symptoms. This project is part of the Wellness Monitoring for Major Depressive Disorder longitudinal study (NCT02934334) of responders to antidepressant treatment conducted at 6 clinical sites across Canada. Montgomery Asberg Depression Rating Scale (MADRS) scores were used to assess depression severity and to categorize participants into ultrastable, unstable, and relapse groups. Plasma immune profiles were generated using the LEGENDplex Human Th Cytokine Panel immunoassay. Principal Component Analysis and Kruskal-Wallis tests of individual immune cytokines did not show differences between ultrastable, unstable, or relapse groups. Principal Component Analysis did reveal two cytokine clusters. Hierarchical Clustering analysis identified three distinct immune biotypes characterized by differing levels of Th cytokines and validated the presence of the cytokine clusters. Neither of these outcomes was predictive of relapse in this cohort. Our findings have shown that immune composition may serve as an important factor in parsing heterogeneity that is observed in this disorder through identification of distinct immune biotypes and highly interconnected cytokine subnetworks in major depression. The potential for immune biotypes for optimizing treatment regimens and relapse prevention necessitates further investigation and replication. / Thesis / Master of Science (MSc)