Diagnóstico de depressões unipolares e bipolares e seus especificadores

Depression is a common, recurrent and chronic disease with a high prevalence in the world population. It is a disease that affects the individual organism as a whole, affecting, in addition to mood, cognitive, neuroendocrine and physiological functions, impairing personal, social and laboral well-being. Depression is multifactorial (intrinsic and extrinsic etiology) and heterogeneous, because in addition of being unipolar or bipolar, there are specifiers (subtypes) of depression, each containing particuliarities in symptomathology. This review aimed to present the unipolar and bipolar depressions, as well as some of their specifiers, with their characteristics, diagnostic criteria, epidemiology, associated comorbidities and etiology; also presenting the importance of being done and how we can make the differential diagnosis between unipolar and bipolar depressionsDepressão é um doença comum, recorrente e crônica, que acomete o organismo do indivíduo como um todo, afetando o humor, as funções cognitivas, neuroendócrinas e outros sistemas do organismo, prejudicando o bem-estar pessoal, social e laboral. A depressão é multifatorial (etiologia intrínseca e extrínseca) e heterogênea, pois, além de unipolar ou bipolar, existem especificadores (subtipos) de depressão, cada um contendo particulares em sua sintomatologia. A presente revisão visa abordar as depressões unipolares e bipolares, assim como alguns de seus especificadores, apresentando suas características, crité- rios diagnósticos, epidemiologia, comorbidades associadas e etiologia; também apresentando a importância de ser feito e como pode ser feito o diagnóstico diferencial entre as depressões unipolares e bipolare

Avaliação neuropsicológica de funções executivas e da variabilidade simpático/parassimpática cardíaca de pacientes com transtorno de estresse pós-traumático

O transtorno de estresse pós-traumático (TEPT) é um distúrbio psiquiátrico que desenvolve-se após a exposição do indivíduo a um evento extremamente estressante. Pacientes com esse transtorno tem um acentuado prejuízo em sua qualidade de vida, considerando os sintomas que incluem o prejuízo das funções executivas, assim como a hiper-reatividade simpático/parassimpática, somados ao possível desenvolvimento de outras comorbidades associadas ao TEPT. Ainda são raros os estudos que investiguem esses aspectos nos pacientes com TEPT na população brasileira. Visando conhecer as particularidades neuropsicológicas e psicofisiológicas presentes nesse transtorno para poder, futuramente, contribuir para desenvolvimento de tratamentos mais eficazes e específicos, o presente trabalho teve como objetivos gerais: a) avaliar características e habilidades neuropsicológicas de pacientes com TEPT e compará-las com as de indivíduos do grupo controle; e, b) estudar a variabilidade dos componentes simpático e parassimpático cardíacos de pacientes com TEPT e de indivíduos controle submetidos à percepção de expressões faciais com valências emocionais, de forma consciente e não-consciente. A amostra contou com indivíduos adultos, com idades entre 18 e 54 anos de idade de ambos os sexos. Não houve diferença entre os sujeitos do grupo TEPT e controle quanto ao sexo, idade e anos de escolaridade na etapa neuropsicológica do estudo. O grupo TEPT apresentou prejuízo cognitivo das funções executivas em quase todos os construtos avaliados pelos testes neuropsicológicos como flexibilidade cognitiva, atenção sustentada, inibição de impulsos, capacidade de formação de conceitos abstratos e velocidade de processamento de informações. Na etapa de variabilidade cardíaca, houve diferença entre o perfil dos grupos apenas quanto à idade. Quando avaliados os componentes simpático e parassimpático da variabilidade cardíaca frente a expressões faciais humanas foi possível observar uma maior variabilidade do grupo TEPT em relação ao grupo controle. O grupo TEPT apresentou variabilidade do componente cardíaco simpático já para a expressão facial neutra e nenhuma alteração significativa à expressão facial de alegria. Nesses pacientes, a percepção das expressões faciais de medo (consciente e não-consciente), raiva, tristeza e nojo (não-consciente) geraram maior variabilidade para o componente simpático cardíaco (LFnu). O componente parassimpático (HFnu) apresentou-se alterado para as expressões de nojo, raiva, tristeza, medo e nojo não-conscientes. O balanço simpatovagal (LF/HF) apresentou-se alterado para as expressões faciais de medo (consciente e não-consciente), nojo, raiva e tristeza. Esses resultados apontam que os sujeitos com TEPT já apresentam uma variabilidade cardíaca exacerbada principalmente em função do componente simpático, frente à maior parte das emoções primárias que estavam presentes nas expressões faciais expostas – o que já pôde ser observado quando houve variabilidade do componente simpático cardíaco significativa frente a expressão facial neutra. Os dados obtidos sugerem uma relação entre as alterações psicofisiológicas dos pacientes com TEPT e respostas exacerbadas simpática e parassimpática quando da percepção consciente e não-consciente de imagens com conteúdo emocional. Esses resultados podem contribuir para o melhor entendimento da fisiopatologia do TEPT, para a proposição de formas de avaliação da condição de resposta fisiológica dos pacientes diagnosticados com tal transtorno e para avaliação de resultados e progressão dos tratamentos empregados baseando-se em dados quantitativos adicionais aos que existem atualmente.Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed after exposure to an extremely stressful event. Patients with this disorder have a marked impairment in their quality of life, considering the symptoms that include deficits in executive functions, as well as hyperreactivity of sympathetic/parasympathetic system, associated to possible development of other comorbidities associated with PTSD. Still, there are few studies that investigate these aspects in PTSD patients in Brazilian population. In order to better understand the neuropsychological peculiarities of this disorder in order to contribute to the development of more effective and specific treatments, the general aims of the present study are: a) assess patients’ neuropsychological abilities and characteristics and compare them to those belonging to subjects of control group; and , b) study the variability of patients’ and controls’ cardiac sympathetic and parasympathetic components after they underwent perception of facial expressions with emotional valences, in conscious and non- conscious ways . The sample consisted of adults aged between 18 and 54 years-old, including both genders. There was no significant difference between PTSD and control groups regarding sex, age and years of schooling in the neuropsychological stage of the study. PTSD group showed cognitive impairment of executive functions in almost all constructs assessed by neuropsychological tests as cognitive flexibility, sustained attention, inhibiting impulses, ability to form abstract concepts and speed of information processing. In the stage of cardiac variability, there was difference between groups profiles concerning to age. When assessing the sympathetic and parasympathetic components of cardiac variability after exposure to human facial expressions was observed greater variability of PTSD group compared to control group. PTSD group showed significant variability of cardiac sympathetic component to neutral facial expression, but no significant change to facial expression of happiness. In these patients, the perception of facial expressions of fear (in conscious and non-conscious ways), anger, sadness, and disgust (in non-conscious way) produced higher variability for the component cardiac sympathetic (LFnu). The parasympathetic component (HFnu) was altered for expressions of anger, sadness, fear, and disgust (both when shown in non-conscious way). The sympathovagal balance (LF/HF) was altered after exposure to facial expressions of fear (in conscious and non-conscious ways), disgust, anger, and sadness. These results indicate that subjects with PTSD already have a heightened cardiac reactivity mainly due to the sympathetic component for almost all the basic emotions that were present in human facial expressions shown - which could already be observed when there was significant sympathetic reactivity after exposure to neutral facial expression. These data suggest a relationship between psychophysiological changes in patients with PTSD and sympathetic and parasympathetic exacerbated responses when conscious and non-conscious perception of pictures with emotional content occurs. These results may contribute to a better understanding of the pathophysiology of PTSD, to a propose of how to assess the physiological response condition of these patients, and to evaluate the results and prognostic of treatments based on quantitative data additional to that currently exist

Major depressive disorder and bipolar disorder: differentiation by genetic and hormonal factors, and exposure to early-life stress

Ainda são escassos estudos que avaliem biomarcadores para diferenciação de transtorno depressivo maior (TDM) e transtorno bipolar (TB), principalmente relativo à etiologia desses transtornos e sua relação com os receptores glicocorticoides (GR) e, principalmente, com os receptores mineralocorticoides (MR). Objetivo: Encontrar biomarcadores genéticos e/ou hormonais e observar sua associação entre si e/ou a fatores externos (estresse precoce - EP) para compreender melhor sua fisiopatogenia e auxiliar no diagnóstico diferencial entre TDM e TB. Material e Métodos: Participaram deste estudo N=273 sujeitos, sendo n=113 controles, n=78 unipolares e n=82 bipolares. A triagem diagnóstica de todos os sujeitos foi realizada por meio do MINI PLUS, checagem de história de trauma na infância pela CTQ, avaliação de sintomas depressivos pela GRID-HAM-D21, e demais comorbidades pela BAI, BHS e BSI. Na busca de biomarcador genético, observou-se as frequências genotípicas e alélicas de 3 polimorfismos de receptor de glicocorticoide (GR) (N363S, R22/23K e BclI) e de 2 polimorfismos de MR (MI180V e -2G/C) após realizada a discriminação alélica por reação em cadeia da polimerase quantitativa (qPCR). Foram avaliados de forma intragrupo as variáveis genéticas e endócrinas (e combinadas) e o efeito do EP sobre tais variáveis. Também, as variáveis polimorfismos, níveis hormonais e exposição a EP foram comparadas entre grupos para avaliar se havia diferença de prevalência, de perfil endócrino, ou se havia suscetibilidade maior por parte dos unipolares ou bipolares para alteração dos níveis hormonais e/ou intensidade do quadro depressivo frente a EP ou a determinado genótipo. Resultados: Todos os sujeitos unipolares e bipolares mostraram piora de seus sintomas depressivos frente a EP e seus subtipos, sendo eles unipolares ou bipolares. Como biomarcador hormonal, comparando-se controles x unipolares x bipolares, ou apenas unipolares x\' bipolares, foi possível observar que os níveis de cortisol e os níveis de aldosterona apresentaram-se os altos em unipolares e os baixos mais em bipolares, quando estes pacientes estavam com depressão grave ou gravíssima. Também, bipolares expostos a EP global, abuso físico e emocional mostraram níveis mais baixos de aldosterona que bipolares que não foram expostos. Frente a exposição a esses EP global e abuso físico, os bipolares tenderam a se mostrar mais suscetíveis que os unipolares a alteração dos níveis de aldosterona. Para biomarcador genético, frequência de genótipos ou alelos não diferenciaram unipolares de bipolares. Entretanto, houve maior prevalência do genótipo heterozigoto AG de GR N363S em pacientes depressivos uni e bipolares quando comparados com controles. Combinando-se os biomarcadores genéticos e hormonais, unipolares apresentaram níveis mais baixos de cortisol e de aldosterona quando carregavam genótipo variante GG de MR -2G/C, enquanto bipolares mostraram tendência a redução de cortisol quando carregavam o alelo variante G de MR MI180V. Quando comparados os genótipos por si só, intragrupo, novamente o polimorfismo MR -2G/C mostra influência sobre o fenótipo unipolar. Em unipolares, presença do alelo variante G de MR -2G/C piora significativamente o quadro depressivo, mas o alelo variante G de MI180V mostrou-se protetor frente a EP. Tanto os unipolares frente aos outros 4 polimorfismos, quanto os bipolares frente a todos os polimorfismos estudados, apresentaram piora significativa de seu quadro depressivo se expostos a EP. Bipolares mostraram uma tendência a ser mais suscetíveis que unipolares a alterações endócrinas (aldosterona) quando expostos a EP global e abuso físico. Conclusão: Tendo em vista os vários achados significativos a cerca dos polimorfismos de MR, tanto para unipolar quanto para bipolar, sua influência sobre os níveis de aldosterona e cortisol basais, reforça-se a importância do papel dos receptores MR dentro da etiologia dos transtornos depressivos unipolares e bipolares, e a forma diferente de funcionamento do MR para a distinção entre TDM e TBThere are still few studies assessing biomarkers for differentiation of major depressive disorder (MDD) and bipolar disorder (TB), mainly related to the etiology of these disorders and its relationship with glucocorticoid receptors (GR) and, manily, with mineralocorticoid receptors (MR). Aim: Finding genetic and / or hormonal biomarkers and observing their association to each other and / or external factors (early-life stress - ELS) for better comprehend their pathophysiology and, then, assisting in differential diagnosis between MDD and TB. Material and Methods: A total of N = 273 subjects composed the study sample, being n = 113 control, n = 78 unipolar, and n = 82 bipolar subjects. The diagnostic screening of all subjects was performed applying MINI PLUS, for history of ELS, CTQ; assessment of depressive symptoms, GRID-HAM-D21; and assessment of other comorbidities, BAI, BHS, and BSI. Researching for genetic biomarker, genotypic and allelic frequencies of 3 GR polymorphisms (N363S, R22 / 23K and BclI) and 2 MR polymorphisms (MI180V and -2G/C) were evaluated after allelic discrimination by quantitative polymerase chain reaction (qPCR). Genetic and endocrine variables (and their combination), and the effect of ELS over these variables were assessed intragrups. Also, polymorphisms, hormonal levels and history to ELS were compared between groups to assess whether there was difference in prevalence, endocrine profile, or whether there was greater susceptibility on the part of unipolar or bipolar for alteration of hormonal levels and / or severity of depressive symptoms considering history of ELS and/or a specific genotype. Results: All unipolar and bipolar subjects showed worsening of their depressive symptoms in the presence of ELS and its subtypes. As hormonal biomarker, comparing unipolar x bipolar x control subjects, or comparing unipolar x bipolar, cortisol and aldosterone levels were higher in unipolar subjects, and lower in bipolar subjects, when these patients presented severe or very severe depressive symptoms. Also, bipolar subjects\' exposed to global ELS, physical and emotional abuse showed lower basal levels of aldosterone than did bipolar who were not exposed to ELS. Concerning global ELS and physical abuse, bipolar tended to be more susceptible than unipolar for aldosterone levels to change. For genetic biomarker, frequency of genotypes or alleles did not distinguished unipolar from bipolar sample. However, there was a higher prevalence of GR N363S heterozygous genotype (AG) in unipolar and bipolar depressive patients when compared to controls. Combining the genetic and hormonal biomarkers, unipolar had lower levels of cortisol and aldosterone when carrying GG variant genotype of MR-2G / C, while bipolar showed tendency to reduce cortisol when carrying the variant G allele of MR MI180V. When comparing the genotypes (intragroup), again, MR-2G/C polymorphism shows influence on the unipolar phenotype. In unipolar, the presence of the variant G allele of MR-2G / C significantly worsens the depressive condition, unlike variant G allele of MI180V has shown to be protective against ELS. Both the unipolar compared to the other 4 polymorphisms, and the bipolar ones against all polymorphisms studied, presented a significant worsening of their depressive condition if exposed to ELS. Bipolar tend to be more susceptible than unipolar to endocrine changes (aldosterone) when exposed to global ELS and physical abuse. Conclusion: Considering the several significant findings regarding MR polymorphisms, for both unipolar and bipolar subjects, and their influence on basal aldosterone and cortisol levels, we highlight importance of the role of MR receptors within the etiology of depressive unipolar and bipolar disorders, and different way of MR functioning in each disorder for assisting the distinction between MDD and T

Efect of long‑term treatment with classical neuroleptics on NPQ/ spexin, kisspeptin and POMC mRNA expression in the male rat amygdala

Neuroleptics modulate the expression level of some regulatory neuropeptides in the brain. However, if these therapeutics infuence the peptidergic circuits in the amygdala remains unclear. This study specifes the impact profle of the classical antipsychotic drugs on mRNA expression of the spexin/NPQ, kisspeptin-1 and POMC in the rat amygdala. Animals were treated with haloperidol and chlorpromazine for 28 days prior to transcript quantifcation via qPCR. Haloperidol and chlorpromazine induced a change in the expression of all neuropeptides analyzed. Both drugs led to the decrease of Kiss-1 expression, whereas in POMC and spexin/NPQ their up-regulation in the amygdala was detected. These modulating efects on may represent alternative, so far unknown mechanisms, of classical antipsychotic drugs triggering pharmacological response

The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173 receptor expressions in the female rat hypothalamic-pituitary-gonadal (HPG) axis

The recently discovered peptide phoenixin (PNX) and its receptor GPR173 are novel factors that exhibit a large spectrum of regulatory activity, especially when considered as a central modulator of GnRH-related hormonal control of reproductive processes. It has been already proven that GnRH agonists and antagonists can modulate peptidergic signaling in the HPG axis. Despite these findings, there is so far no information regarding the influence of treatment with GnRH analogues on SMIM20/phoenixin signaling in the hypothalamic-pituitary-gonadal axis. In the current study we measured SMIM20/phoenixin and GPR173 mRNA levels in the hypothalamus, pituitary and ovaries of female rats in the diestrus phase following treatment with GnRH-R agonist (buserelin) and antagonist (cetrorelix) using quantitative Real-Time PCR. The serum PNX concentrations were also estimated with ELISA technique. Results: The hypothalamic, hypophyseal and especially ovarian levels of SMIM20 mRNA were increased after both buserelin and cetrorelix administration. The GPR173 expressions were in turn decreased in the hypothalamus and pituitary. Treatment with the GnRH analogues led to the modulation of SMIM20/phoenixin and GPR173 mRNA expression in the female rat hypothalamic-pituitary-gonadal axis. By identifying buserelin and cetrorelix as novel modulators of phoenixin signalling in the animal HPG axis, these results cast new light on the GnRH analogues mode of action and contribute to a better understanding of the mechanisms responsible for the hormonal control of reproduction

Sexual behavior and dendritic spine density of posterodorsal medial amygdala neurons in oxytocin knockout female mice

Central oxytocin (OT) and arginine-vasopressin (AVP) have been shown to play an important role in sexual behavior and neuroendocrine secretion in rodents. The results of exogenous OT administration on sexual behaviors in male and female mice are controversial. This study aimed to analyze the role of OT in sexual behavior, the number of oocytes and the density of dendritic spines in the posterodorsal medial amygdala (MePD) of female mice with selective deletion of the OT gene (OTKO). Female C57BL/6 mice were genotyped and divided into control (WT) and OTKO groups (n = 11 each). All experiments were performed in the proestrus phase. Compared to WT data, our results showed that the OTKO group had a significant increase in the latency for the display of lordosis behavior (490.8 ± 113.8 and 841.9 ± 53.9, respectively) and a decrease in both the frequency (6.3 ± 2.4 and 0.5 ± 0.4) and duration (49.3 ± 19.9 and 7.2 ± 7.1) of lordosis and a reduction in the number of oocytes (12.2 ± 0.8 and 9.9 ± 0.6). However, the OTKO group showed a higher density of proximal dendritic spines in the MePD compared to the WT group (2.4 ± 0.1 and 1.9 ± 0.1 spines/dendritic μm, respectively). No significant difference was observed in the plasma levels of AVP between the groups (OTKO: 617.1 ± 96.0 and WT: 583.3 ± 112.0 pg/mL). Our data suggest that OT plays a crucial role in the sexual behavior display, number of released oocytes and density of dendritic spines in the MePD of female mice. The AVP plasma concentration was not affected in the OTKO animals

Differential Diagnosis of Major Depressive Disorder and Bipolar Disorder: Genetic and Hormonal Assessment and the Influence of Early-Life Stress

Few studies have assessed biomarkers for the differentiation of major depressive disorder (MDD) and bipolar disorder (BD). However, some elements of depression such as hormones and receptors of the renin–angiotensin–adrenal system (RAAS), the hypothalamus–pituitary–adrenal (HPA) axis, and history of early-life stress (ELS) could be considered for differential diagnosis. Therefore, this study aimed to assess aldosterone and cortisol levels, MR and GR gene polymorphisms, and ELS as potential biomarkers for differentiating MDD and BD. This study presents a case–control design. Groups comprised samples for genetic, cortisol, and aldosterone analysis: healthy control (HC; n = 113/97/103), MDD (n = 78/69/67) and BD (n = 82/68/65) subjects. Furthermore, all subjects were assessed for diagnostic screening, the severity of depression, and history of ELS by applying MINI-PLUS, GRID-HDRS, and CTQ, respectively. In addition, genotype and allelic frequencies of GR (N363S, R22/23K and BclI) and MR (MI180V and -2G/C) polymorphisms were evaluated via PCR. Our findings demonstrate that basal aldosterone levels may be a biomarker for differentiating BD and MDD. Furthermore, ELS affects the HPA axis in BD, cortisol may be considered a biomarker for distinguishing BD and MDD, but only in the absence of ELS, and, finally, history of ELS and MR-2G/C variant alleles are factors that contribute to the severity of depressive symptoms in MDD and BD

The Association of Biochemical and Genetic Biomarkers in VEGF Pathway with Depression

VEGF is an important neurotrophic and vascular factor involved in mental disorders. The objective of this study was to verify the effect of genetic polymorphisms in the VEGF pathway on the risk for depression, symptom intensity, and suicide attempts. To examine the association between the VEGF pathway and depression, we genotyped polymorphisms and measured the plasma concentrations of VEGF, KDR, and FLT1 proteins. The participants were 160 patients with depression and 114 healthy controls. The questionnaires that assessed the clinical profile of the patients were the MINI-International Neuropsychiatric Interview, GRID-HAMD21, CTQ, BSI, and the number of suicide attempts. Genotyping of participants was performed using the real-time PCR and protein measurements were performed using the enzyme-linked immunosorbent assay (ELISA). VEGF and its inhibitors were reduced in depression. Individuals with depression and displaying the homozygous AA of the rs699947 polymorphism had higher plasma concentrations of VEGF (p-value = 0.006) and were associated with a greater number of suicide attempts (p-value = 0.041). Individuals with depression that were homozygous for the G allele of the FLT1 polymorphism rs7993418 were associated with lower symptom severity (p-value = 0.040). Our results suggest that VEGF pathway polymorphisms are associated with the number of suicide attempts and the severity of depressive symptoms