<p>Theory of mind (ToM) and empathic responding are thought to rely on the joint contribution of cognitive and affective processes, and the corresponding complex neural networks involved in these diverse cognitive and affective functions. Individuals with mood disorders demonstrate deficits in many of the same cognitive and affective processes thought to mediate ToM and empathy, and demonstrate structural and functional changes in the neural regions that subserve these social cognitive domains. We examined ToM and empathic responding in patients with major depressive disorder (MDD) and bipolar disorder (BD) using standardized measures of social cognitive responding. Patients with BD and MDD with sub-syndromal depressive symptoms showed deficits on a cognitively challenging task that required them to integrate two perspectives simultaneously (second-order ToM stimuli). Sub-syndromal patients with BD also showed a trend toward poor performance on a less demanding first-order ToM task; no such deficit was observed for sub-syndromal MDD patients. Patients with BD were also impaired at discriminating mental states from pictures of eyes and in making complex social judgments. Both patient groups reported reduced levels of cognitive empathy, but differed in response on affective empathy domains. Specifically, whereas the BD group reported higher levels of distress in response to others' negative experiences, the MDD group reported less feelings of care and concern in response to another’s emotional experience. Across the BD studies, impaired ToM and empathic responding were found to be associated with poor social functioning and increased depressive symptoms, but the influence of illness burden variables on performance was variable. Across the MDD studies, the associations between social cognitive performance, illness variables, and social functioning were inconsistent. Taken together, our findings indicate that patients with mood disorders demonstrate altered ToM and empathic responding that may contribute to the difficulties in social communication observed in these patient populations.</p> / Doctor of Philosophy (PhD)

Bipolar disorder (BD) and unipolar depression (UD) are two severe mood disorders, with BD often misdiagnosed as UD. Given their severity and high rates of misdiagnosis, it is of paramount importance to understand the psychological and neurobiological mechanisms underlying these disorders to enhance our ability to diagnose, treat, and prevent them effectively. Many neuroimaging studies have shown that mood disorders are associated with abnormal reward-related responses, particularly in the ventral striatum (VS). Yet, the link between mood disorders and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of mood disorders. To provide insights into the neurobiological underpinnings of reward processing dysfunction in mood disorders, two studies were conducted. Study 1 (Chapter 2) is a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder (MDD), and 803 healthy controls (HC). It aims to address inconsistencies in the literature by synthesizing the literature quantitatively. The findings of Study 1 indicate that MDD is associated with opposing abnormalities in the reward circuit: hypo-responses in the VS and hyper-responses in the orbitofrontal cortex (OFC). These findings provide a foundation for Study 2 (Chapter 3) and help to reconceptualize our understanding of reward processing abnormalities in UD by suggesting a role for dysregulated corticostriatal connectivity. Study 2 is the first fMRI study to employ region-of-interest (VS and OFC), whole-brain, activation, connectivity, and network analyses to examine the similarities and differences in reward-related brain activation patterns between 46 children with remitted bipolar I disorder, 48 children with remitted MDD, and 46 HC. The results of Study 2 revealed differential connectivity in corticostriatal circuitry during reward processing among BD, UD, and HC in pre-adolescence. Specifically, BD exhibited increases in OFC-VS connectivity during anticipation of larger reward, whereas UD and HC showed no changes in OFC-VS connectivity across anticipation conditions ranging from large loss to large reward. Furthermore, BD and UD generally showed more abnormal whole-brain responses to reward anticipation in accordance with the valence of the stimuli than HC. These findings suggest that pre-adolescents with BD and UD exhibit reward processing dysfunction during reward anticipation relative to HC even outside of acute periods of illness. Taken together, the dissertation provides novel insight into the nature of reward processing abnormalities in mood disorders in pre-adolescence. As early onset BD or UD often is associated with long treatment delays and a persistently pernicious illness course, this dissertation may aid efforts to ensure early accurate diagnosis, which may improve our ability to intervene with appropriate treatments and result in a more benign prognosis and course of illness over the lifespan. / Psychology

The aetiology of major depressive disorder (MDD) is poorly understood. Current evidence suggests immune activation and gut microbiota may play a role. Recent studies demonstrated that behavioural traits can be transferred through microbiota transplantation into germ-free (GF) mice. Here we study whether microbiota from patients with MDD can induce depressive-like behaviour. Methods: GF NIH Swiss mice were colonized with stool microbiota from a patient with MDD with elevated faecal β-defensin 2, or a healthy donor (HC). After three weeks, behaviour was assessed using standard tests. Expression of neuroimmune markers was assessed in the gut and brain using gene expression profiling and immunohistochemistry. Microbiota composition was assessed by 16S rRNA sequencing. Results: Microbiota profiles differed between the two groups of mice (p=0.001). Mice colonised with microbiota from a single characterised MDD patient (MDD1), exhibited lower preference for sucrose (p=0.002) and more emotionality (p=0.003) than mice with HC microbiota, however other MDD mice did not display abnormal behaviour. Abnormal MDD1 behaviour was associated with lower BDNF expression in the dentate gyrus of the hippocampus (p=0.02). Mice colonised with another characterised MDD patient (MDD4 mice) did not have differences in BDNF expression in the same region (p=0.20). MDD1 and MDD4 mice had altered hippocampal and gut gene expression for genes associated with the immune and nervous system. In summary, GF mice colonized with MDD1 microbiota exhibit depression-like behaviors. This appears to be accompanied by changes in intestinal permeability and neuroimmune function. These results suggest that gut microbiota has the capacity to influence the expression of MDD in some patients. / Thesis / Master of Science (MSc)

The brain has the capacity to modify itself structurally and functionally, to adapt to novel circumstances. Adaptive changes in neural circuitry that become intransigent, such as continued hypervigilance after resolution of a threat situation, become maladaptive and may facilitate development of psychiatric disorders such as Major Depressive Disorder (MDD). Although MDD pathogenesis is unclear, hypothalamic-pituitary-adrenal axis dysregulation may facilitate the neuroplastic changes observed in MDD. Whether these neuroplastic changes facilitate the development of MDD or develop due to MDD remains unclear. The characterization of neuroplastic changes in MDD has resulted in sometimes contradictory findings. There are gaps in understanding the timing of neuroplastic changes in MDD, and how and when they are affected by antidepressant treatment. Characterization of neuroplasticity in MDD may uncover different phenotypes and aid in the discovery of a predictive biomarker of antidepressant treatment response. This dissertation presents the results of a series of neuroimaging studies. Chapter 1 provides an introduction to neuroplasticity and MDD. In Chapter 2 results of a study examining hippocampal memory function in treatment naïve patients with MDD are presented. Chapter 3 exhibits findings from a study examining effects of an acute tryptophan depletion paradigm in midlife women receiving estrogen-based treatment on an emotional conflict task. Chapter 4 discusses results from an examination of unmedicated patients with MDD and healthy control participants on an emotional conflict task. Chapter 5 presents longitudinal data of the sample from Chapter 4, and the effect of 8 weeks of treatment with antidepressant escitalopram on performance on an emotional conflict task. In Chapter 6 a case study is presented of a patient with long-standing overt ventriculomegaly, whose chief complaint was of mood and cognitive impairments. Chapter 7 summarizes the findings and contributions of this body of research and discusses clinical implications and future directions. / Dissertation / Doctor of Philosophy (PhD) / The characterization of brain changes in Major Depressive Disorder (MDD) has resulted in contradictory findings, and gaps in understanding how the brain changes in response to antidepressant treatment. This dissertation aims to characterize brain changes in MDD through a series of neuroimaging studies. Chapter 1 provides an introduction to MDD and brain changes in MDD. Chapter 2 presents an examination of memory in treatment naïve patients with MDD. Chapter 3 presents a study of acute tryptophan depletion in midlife women receiving estrogen-based treatment on an emotional conflict task. Chapter 4 examines unmedicated patients with MDD and healthy control participants on an emotional conflict task. Chapter 5 examines the effects of antidepressant treatment on performance on an emotional conflict task. Chapter 6 presents a case study of a patient with ventriculomegaly with mood and cognitive impairments. Chapter 7 summarizes the contributions of this research and discusses implications and future directions.

Bakgrund: Postpartumdepression definieras som en episod av egentlig depression(måttlig till svår) hos en nybliven förälder som har sin debut upp till ett år efter enförlossning. Forskning om nyblivna pappors upplevelser av att insjukna ipostpartumdepression är närapå obefintlig. Förståelse för pappors upplevelser avpostpartumdepression bland sjuksköterskor kan bidra till ett gott bemötande av dennapatientgrupp. Syfte: Syftet var att beskriva nyblivna pappors erfarenheter av att insjukna ipostpartumdepression. Metod: En litteraturstudie av åtta vetenskapliga artiklar genomfördes. Databassökningägde rum i Cinahl, Pubmed, PsychInfo samt PubMed. Analys genomfördes med inspirationav kvalitativ innehållsanalys. Resultat: Analysen resulterade i tre huvudkategorier och sju subkategorier. Huvudkategorierna var ”behöva tolka och hantera ansträngande symtom”, ”behöva stöd” samt ”negativt påverkade familjerelationer”. Konklusion: Litteraturstudiens resultat visade att pappor beskrev upplevelser avbristande stöd från vården i form av kunskapsbrist. En kartläggning av kunskapsläget ompostpartumdepression hos pappor bland sjukvårdspersonal skulle kunna motiverakunskapshöjande interventioner eller införande av rutinmässig screening. I mötet mednyblivna pappor kan sjuksköterskan med kunskap om symtombilden vidpostpartumdepression bistå med att detektera depressionssymtom samt erbjuda stöd för att tillgodose pappors grundläggande behov. / Background: Postpartum depression is defined as an episode of major depressivedisorder within a year postpartum. There is to this point almost no research about fathers’experiences with onset of postpartum depression. Understanding of such experiencesamong nurses could facilitate better treatment of depressed fathers in interactions with thehealthcare system. Aim: The aim was to describe new fathers experiences with onset of postpartumdepression. Methods: A literature study consisting of eight scientific articles was conducted. Database search was conducted in Cinahl, PubMed, PsychInfo and Scopus. To analyze thestudies, qualitative content analysis was used. Results: The analysis resulted in three main categories and seven sub categories. Themain categories consisted in “Interpreting and Handling Exhausting Symptoms”, “Needfor Support”, and “Negatively Influenced Family Relationships”. Conclusion: Fathers describe lack of knowledge among healthcare providers. Futureresearch about healthcare professionals knowledge about postpartum depression could,depending on results, motivate awareness raising interventions or screening routines.With further knowledge about symptoms of postpartum depression in new fathers, nursescan help detecting such symptoms and offer support in accommodate fathers’ basal needs.

Major depressive disorder (MDD) is considered the current leading cause of disability worldwide (Friedrich, 2017), yet the recovery process in MDD, including neurobiological underpinnings, clinical features and optimal approaches to treatment remains ambiguous. Current definitions of recovery are disputed and involve measures considered subjective in nature, such as thresholds for questionnaires and clinical interviews of symptoms and their duration (De Zwart and Jeronimus, 2019; Fava et al., 2007; Keller, 2003, 2004). Symptom-based measures, although informative of clinical presentation, are not informative of neurobiological underpinnings that may persist even when symptoms are reduced. Indeed, even after treatment, persistent residual symptoms, impairments in quality of life, and vulnerabilities for future return to more severe psychopathology persist (Gotlib and Hammen, 2008; IsHak et al., 2011; Judd et al., 1998a; Kennedy et al., 2004; Kennedy and Foy, 2005; Kennedy and Paykel, 2004). Without assessment of neural mechanisms of recovery in MDD, efforts toward developing novel treatment approaches that are able to address neural processes of illness and to provide sustained remission are slowed. The following collection of studies provide neural and clinical insights into MDD recovery and relate findings to potential treatment approaches that are optimized to individual differences in symptoms and neural functioning and able to address neural vulnerabilities to provide sustained remission. In pursuit of individualized treatment selection in MDD, study one involved a meta-analysis of prior prognostic fMRI studies of response to cognitive behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI) in MDD. Study one also reported on the application of resulting meta-analytic regions (subgenual and perigenual anterior cingulate cortex) in a confirmatory MDD sample. Although regions showed some predictive potential in the confirmatory sample, when predicting SSRI response, effects were inconsistent with prior studies, suggesting methodological confounds may hinder ready translation. In an assessment of the course of MDD, the second study documented depression symptoms and quality of life across 9-14 years after acute treatment (CBT or SSRI) and found that persistent residual depression symptoms and quality of life deficits were common. In light of the normality of chronic symptoms and impairment, the third study evaluated neural features of treatment (CBT) resistance in MDD within the context of neural mechanisms of change. The third study found a vermis-centered cerebellar cluster that was unresponsive to CBT, whereas prefrontal and parietal cortical regions were responsive, providing support of prior theories that CBT directly affects cognitive control and cortical regulatory processes in contrast to salience-driven subcortical functioning (Clark and Beck, 2010; DeRubeis et al., 2008; Frewen et al., 2008; Mayberg, 2003). In consideration of findings, clinical recommendations that pertain to treating residual symptoms and associated neural features toward asymptomatic remission are provided. Future research directions are also provided regarding neuroscience informed precision medicine, current therapy and medication practices, and the larger picture of MDD chronicity broadly. / Doctor of Philosophy / Major depressive disorder (MDD) is considered the leading cause of disability worldwide (Friedrich, 2017), yet there are many aspects of MDD recovery that are unclear such as neural and clinical features and optimal treatment approaches. Current definitions of recovery involve questionnaires and interviews, which may not accurately represent all aspects of recovery (De Zwart and Jeronimus, 2019; Fava et al., 2007; Keller, 2003, 2004). For example, they do not assess neural or biological features of recovery that may continue even if symptoms improve. Indeed, even after treatment, often some minimal depression symptoms, impairments in quality of life, and risks for future more severe symptoms continue (Gotlib and Hammen, 2008; IsHak et al., 2011; Judd et al., 1998a; Kennedy et al., 2004; Kennedy and Foy, 2005; Kennedy and Paykel, 2004). Without assessing neural features of MDD and recovery, developing treatments that can address illness- related neural features and provide sustained recovery are slowed. The following studies report on neural and clinical features of MDD recovery to approach treatment and sustained recovery with consideration of individual differences in symptoms and neural functioning. Pursuing neuroimaging measures of individual differences to inform treatment selection, study one involved a statistical review of prior neuroimaging prediction studies of MDD treatment. Study one also reported on whether the regions suggested by the statistical review to inform treatment selection would be useful when applied to a prior MDD treatment study. Findings suggested functioning of the identified brain regions can help inform treatment selection, but method differences among studies included in the review hinder application of resulting regions. In an assessment of the course of MDD, the second study documented depression symptoms and quality of life across 9-14 years after treatment and found at least minimal depression symptoms as well as impairments in quality life commonly continued after treatment. In light of persistent symptoms and impairment, the third study aimed to identify neural features of MDD that did not respond to treatment, as well as neural features that were responsive to treatment. The third study found that therapy directly affects cognitive control processes, but may not affect brain regions associated more with emotion-driven processes. Clinical recommendations pertain to treating depression symptoms that continue after treatment toward asymptomatic recovery. Future research directions pertain to neuroscience informed treatment selection, current therapy and medication practices, and the larger picture of persistent depression symptoms broadly.

Disrupted emotion processes are central features of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), which are linked to altered neural response patterns. However, inconsistent results have led to questions about the reliability of such findings. Heterogeneous clinical presentations across individuals with PTSD and MDD are likely to be associated with heterogeneous neurobehavioral changes which may differ depending on the emotion process studied. Similarly, neurobehavioral signatures of treatment response prediction may vary based on the task or context probed. In these studies, we examined how neuroimaging of emotion processes may shed light on mechanisms underlying symptom heterogeneity in PTSD (Study 1) and how similar neuroimaging signatures may be useful for predicting response to MDD treatment (Study 2). Results showed re-experiencing and hyperarousal symptoms had opponent effects on neural habituation to negative images, such that while increasing severity of hyperarousal symptoms was related to diminished habituation, increasing severity of re-experiencing symptoms was associated with enhanced habituation. Additionally, across MDD studies, two regions of the brain, the right anterior insula and the subgenual anterior cingulate cortex, exhibited pretreatment responses to negative emotional stimuli that were predictive of clinical response to treatment. Considered together, this work demonstrates the translational utility of neuroimaging of negative emotion processes to enhance our understanding of symptomatology and treatment prediction in PTSD and MDD. / Ph.D. / People who have posttraumatic stress disorder (PTSD) or depression often notice changes in the intensity and range of emotions they experience. These changes are thought to be related to differences in how the brain processes emotional information. Using neuroimaging to visualize changes that occur in the brains of individuals with PTSD or depression when they are experiencing negative emotions, we may gain a better understanding of how their symptoms are impacting them and how they may respond to different types of treatments. In these studies, I used brain imaging to measure responses to emotional images of people with and without PTSD. I found that certain PTSD symptoms affected the way people's brains responded over time to negative and neutral images. More several arousal symptoms were linked to less decreases of brain responses over time or less habituation. More severe symptoms of intrusive memories or distress when exposed to reminders of trauma were associated with greater decreases of brain responses to negative images. In a second study, I found that across studies of people with depression, two regions of the brain that are involved in emotion processing and stress responsivity, show pretreatment responses to negative emotional stimuli that are related to how they are likely to respond to treatment for depression. Overall, my research demonstrates how brain responses to negative emotions may be useful for understanding symptoms of mental health disorders and may help with predicting how individuals will respond to treatment.

Background and Aims: Executive dysfunction is pervasive in substance-dependent individuals (Verdejo-García, Bechara, Recknor, & Perez-Garcia, 2006). As many as four-fifths of individuals in treatment for substance use disorders (SUDs) have co-existing lifetime psychopathology. Executive function deficits are tied to markers of decreased quality of life including increases in negative life events (Green, Kern, Braff, & Mintz, 2000), maladaptive social functioning (Kurtz, Moberg, Ragland, Gur, & Gur, 2005) and worsened treatment outcomes (Czuchry & Dansereau, 2003). Despite evidence of executive dysfunction across several mental disorders, few studies investigate how the co-occurrence of psychopathologies in SUDs impacts executive functioning. Methods: Here, we compare measures of executive function (i.e., the Iowa Gambling Test, Letter Number Sequencing Test, Stroop Test, Wisconsin Card Sorting Test, Continuous Performance Test, Towers Test, and Delay Discounting Test) in individuals with a) substance use disorder, b) substance use disorder and co-occurring major depressive disorder, c) substance use disorder and co-occurring antisocial personality disorder, d) substance use disorder and co-occurring major depressive disorder and antisocial personality disorder and e) no substance use disorder or co-occurring psychopathology. Results: Regression models of respective executive function measure outcomes as a function of education, income, age, and group membership indicated that the Delay Discounting Test and Continuous Performance Test were the only significant overall models (F(4, 313) = 12.699, p < 0.001 and F(4, 307) = 2.659, p = 0.033, respectively). Conclusions: Overall the Delay Discounting Test and Continuous Performance Test were the most sensitive to differences between substance use and psychopathology profiles assessed. / Master of Science

A depressão é o mais comum dos distúrbios afetivos. Afeta ao menos 10% da população idosa do Brasil. Nos idosos, alguns fatores ligados ao metabolismo parecem estar bastante relacionados a esse transtorno, como uma menor concentração de noradrenalina e serotonina (5-HT) e uma maior atividade da monoaminooxidase em relação a adultos jovens. Os inibidores seletivos da recaptação da serotonina (ISRS), principalmente a sertralina, são a primeira opção no tratamento da fase aguda e manutenção dos episódios depressivos em idosos. As plaquetas vêm sendo amplamente utilizadas como modelo para estudar na periferia alterações que ocorrem no sistema nervoso central. A 5-HT apesar de ser primordialmente expressa no cérebro, também pode ser encontrada em plaquetas. Este neurotransmissor está envolvido em inúmeros aspectos do funcionamento normal do cérebro desde a regulação do humor até a regulação hormonal. A deficiência nos níveis de 5-HT pode estar intimamente ligada a alguma anormalidade na atividade da glicogênio sintase quinase 3B(GSK3B). Esta enzima exerce funções no metabolismo celular que vão desde sobrevivência celular, metabolismo e processamento de proteínas, até processos cognitivos. A atividade da GSK3B é estreitamente regulada pela fosforilação. Fosforilação no sítio ser9 inativa a enzima, enquanto que a desfosforilação neste mesmo sítio ativa a enzima. Diversos estudos têm mostrado que a forma inativa da enzima exerce um efeito neuroprotetor. O objetivo do presente estudo foi verificar a influência do tratamento com sertralina, em pacientes idosos com diagnóstico de depressão maior, sobre a 5- HT e GSK3B após 3 e 12 meses de tratamento. A quantificação da 5-HT foi realizada por HPLC e da GSK3B plaquetária, pelos métodos de ELISA e blotting, que se revelaram equivalentes. Após um ano de tratamento encontramos uma diminuição da 5-HT plaquetária nos pacientes com depressão maior com relação aos níveis basais, bem como um aumento da forma total da enzima GSK3B (GSKT), uma diminuição da forma fosforilada (pGSK) e da razão entre pGSK e GSKT (rGSK). Quando comparados os níveis de GSK3B de pacientes tratados por um ano e controles, observamos uma maior expressão de GSKT em pacientes; enquanto a pGSK e rGSK se mostraram equivalentes. Pudemos observar, portanto, uma modulação da 5-HT e da GSK3B pelo uso de sertralina. Essa modulação pode indicar que a ação antidepressiva deste fármaco pode estar associada a essas vias de sinalização / Depression is the most common affective disorders. It affects at least 10% of the elderly population of Brazil. In the elderly, some factors related to metabolism appear to be closely related to this disorder, such as lower concentration of noradrenaline and serotonin (5-HT) and increased monoamine oxidase activity in relation to young adults. The selective serotonin reuptake inhibitors (SSRI), especially sertraline are the first choice in treating acute and maintenance of depressive episodes in the elderly. Platelets have been widely used as a model to study in peripheral changes that occur in Central Nervous System. Although 5-HT is primarily expressed in the brain, it can also be found in platelets. This neurotransmitter is involved in numerous aspects of normal brain function since the regulation of mood to the hormonal regulation. A deficiency in 5-HT levels may be closely related to an abnormality in glycogen synthase kinase 3B (GSK3B) activity. This enzyme plays several functions in cell metabolism, ranging from cell survival, metabolism and protein processing, to cognitive processes. The GSK3B activity is tightly regulated by phosphorylation. Phosphorylation on Ser9 site inactives the enzyme, whereas dephosphorylation in the same site actives the enzyme. Several studies have shown that the inactive form of the enzyme plays a neuroprotective effect. The objective of this study was to investigate the influence of sertraline in elderly patients diagnosed with major depression, on platelet 5-HT and GSK3B after 3 and 12 months of treatment. Quantification of 5-HT was performed by HPLC and GSK3B by ELISA and western blotting. The methods for platelet GSK3B determination showed to be equivalent. After one year of treatment we found a decrease of platelet 5-HT in patients with major depression relative to their baseline levels, as well as an increase in the total form of GSK3B enzyme (GSKT), a decrease in phosphorylated form (pGSK) and the ratio between pGSK and GSKT (rGSK). Comparing the levels of GSK3B of patients with one year of treatment and controls, we found a higher GSKT expression in patients; while pGSK and rGSK showed to be equivalent. Therefore we observed a modulation of 5-HT and GSK3B by sertraline. This modulation may indicate that the antidepressant action of this drug may be associated with these signaling pathways

Made available in DSpace on 2016-03-22T17:27:35Z (GMT). No. of bitstreams: 1 SharonMFerreir.pdf: 2163870 bytes, checksum: d5e466194ea4c397ec8640eb900fa160 (MD5) Previous issue date: 2014-10-27 / % Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders that affect approximately 17% of the population in a lifetime. Neurotrophins (NGF) are a group of structurally related proteins, which control the development and differentiation of nerve cells that play a role in cellular migration proliferation, differentiation and phenotypic maintenance central nervous system development. Thus, the role of NGF in neuronal plasticity and support, may suggests that these NGF plays an important action in the etiology and pathophysiology of suicide individuals. Therefore, the aim of this study was to evaluate serum levels of NGF in healthy and depressed person with and without suicide risk in a population-based sample of individuals. This study was performed 47 individuals with current depressive episode and suicide risk without a history of mania, and allocated to major depression and suicide risk groups. Two groups of 47 individuals each, were matched by sex and age: the active control group was composed of those with current depressive episode without risk of suicide; while the population control group included individuals with no history of affective disorder.This study was conducted by a questionnaire with demographic questions (gender, ethnicity, age and education level). After the diagnostic interview, a collection of blood from each individual was performed. Measurement of serum levels of NGF by ELISA. The comparison between the levels of NGF with the group of depressed individuals at risk for suicide without a depressed suicide risk and healthy control was performed by ANOVA with Bonferroni through post-hoc test.. NGF levels were significantly lower (p <0.001) in the groups with major depression and major depression with suicide risk (92.39 ± 41.21ng / mL and 100.99 ± 35.08ng / mL, 40 respectively) compared to the control group (149.81 ± 65.94 ng / ml). In conclusion, our study demonstrates that reducing the levels of NGF can be used as a marker TDM, compared with healthy individuals / O transtorno depressivo maior (TDM) é um dos distúrbios psiquiátricos de maior prevalência que acomete em aproximadamente 17% da população geral ao longo da vida. As neurotrofinas, dentre elas o fator de crescimento neural (NGF), são um grupo de proteínas relacionadas estruturalmente, as quais controlam o desenvolvimento e a diferenciação das células nervosas que desempenham um papel importante na proliferação celular, migração, diferenciação fenotípica e manutenção do sistema nervoso central em desenvolvimento. Devido ao importante papel das NGF na plasticidade e suporte neuronal, sugere-se que o NGF desempenha um importante papel na etiologia e fisiopatologia do suicídio. Portanto o objetivo deste estudo foi avaliar os níveis séricos de NGF em indivíduos saudáveis e deprimidos com e sem risco de suicídio de uma amostra de base populacional. O estudo envolveu 47 indivíduos para compor o grupo com depressão maior e risco de suicídio. Outros dois grupos, de 47 indivíduos cada, foram pareados por sexo e idade: o grupo controle ativo foi composto por aqueles que apresentaram episódio depressivo atual, sem risco de suicídio; enquanto o grupo controle populacional contemplou os indivíduos sem história de transtorno afetivo. O estudo foi realizado por um questionário com questões sociodemográficas (sexo, etnia, idade e escolaridade). Os níveis séricos de NGF foram analisados através da técnica de ELISA. A comparação entre os níveis de NGF com o grupo de indivíduos deprimidos com risco de suicídio, deprimidos sem risco de suicídio e controle populacional foi realizada por ANOVA, com post-hoc através do teste Bonferroni. Os níveis de NGF foram significativamente menores (p<0.001) nos grupos com depressão maior e depressão maior com risco de suicídio 38 (92.39±41.21ng/mL e 100.99±35.08ng/mL, respectivamente) quando comparados ao grupo controle (149.81±65.94ng/mL).Concluimos que a redução dos níveis de NGF podem ser utilizados como um marcador de estado em TDM, em comparação com os de indivíduos saudáveis