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1.
Zhonghua Yi Xue Za Zhi ; 100(3): 197-201, 2020 Jan 21.
Artigo em Chinês | MEDLINE | ID: mdl-32008286

RESUMO

Objective: To explore the efficacy, adverse reactions, feasibility, and acceptability of transcranial alternating current stimulation (tACS) treating drug-naive adult patients with major depressive disorder (MDD), and provide basis for further study with a large sample. Methods: The study was performed in the Neuromodulation laboratory, Department of Neurology of Xuanwu Hospital, Capital Medical University (Beijing, China) from July, 2017 to June, 2018. Thirty Eligible first-episode MDD outpatients were randomized 1∶1 to receive active tACS or sham intervention. The tACS was administered in a 40 minute, 77.5 Hz frequency, 15 mA session with one forehead (Fp1, Fpz, and Fp2, in the 10/20 international placement system, 4.45 cm×9.53 cm) and two mastoid (3.18 cm×3.81 cm) stimulation for 20 times in 4 consecutive weeks at fixed day time frame once daily from Monday through Friday, with weekends off (week 4), followed by 4 weeks with no tACS treatment (week 8). By utilizing the Hamilton rating scale for depression-17 item (HRSD-17) to assess the depressive severity of MDD patients, adverse events were administered by the treatment-emergent adverse events, the Young mania rating scale, and the self-made common questionnaire on cranial electrical stimulation. The primary efficacy outcome was the remission rate defined as HRSD-17 score ≤7 at week 8. Secondary outcomes included the rates of remission at week 4 and response at weeks 4 and 8. Safety was assessed by evaluation of adverse events. Also the proportions of participants accepting the intervention and this study procedure were evaluated at weeks 4 and 8. Results: Thirty MDD patients completed the study, and both groups had no statistical differences on their demographic characteristics (P>0.05). At week 8, the active group had a remission rate of 10/15, which was higher than 3/15 in the sham group (P<0.05). Also, the remission rate (14/15) in the active group was higher than 5/15 of the sham group at week 4 (P<0.05). For the response rates, significant differences were found between groups at week 8. For safety, both groups showed no severe adverse events and no mania/hypomania. One participant per group had 2 times of tinnitus cerebri during the intervention days. All patients accepted the intervention and the study procedure. Conclusions: The pilot study indicated that tACS with 77.5 Hz and 15 mA may have a therapeutic effect on depressive symptoms. It is well-tolerated and safe, as well as feasible and acceptable for adults with MDD.


Assuntos
Transtorno Depressivo Maior , Estimulação Transcraniana por Corrente Contínua , Adulto , China , Transtorno Depressivo Maior/terapia , Método Duplo-Cego , Humanos , Projetos Piloto , Resultado do Tratamento
2.
Adv Exp Med Biol ; 1191: 219-235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002932

RESUMO

Although anxiety and depression have been considered as two distinct entities according to the diagnostic criteria, anxious depression (comorbid anxiety and depression) is relatively a common syndrome. According to the DSM-5 criteria, it uses "with anxious distress specifier" to define anxious depression in its MDD section. Anxious depression is known to have different neurobiological profiles compared to non-anxious depression. Several studies have revealed significant differences between anxious depression and non-anxious depression regarding the hypothalamic-pituitary-adrenal (HPA) axis function, structural and functional brain imaging findings, inflammation markers, etc. Patients with anxious depression were significantly more likely to be found in primary care setting and more likely to be associated with female gender, non-single, unemployed, less educated, and more severe depression. Previous reports also showed that patients with anxious depression had more frequent episodes of major depression and a higher risk of suicidal ideation and previous suicide attempts than those with non-anxious depression. Although anxious depression is known to be associated with poor treatment outcomes in several studies, recent researches have sought to find better treatment strategy to improve patients with anxious depression.


Assuntos
Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/terapia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/terapia , Ansiedade/complicações , Ansiedade/diagnóstico , Ansiedade/terapia , Transtornos de Ansiedade/diagnóstico , Comorbidade , Depressão/complicações , Depressão/diagnóstico , Depressão/terapia , Transtorno Depressivo Maior/diagnóstico , Humanos
3.
Praxis (Bern 1994) ; 109(1): 9-12, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31910766

RESUMO

PsyCoLaus: A Prospective Study of the Links between Mental Health and Cardiovascular Diseases Abstract. PsyCoLaus, which includes an investigation of mental disorders and cognitive functioning, aims to determine the prevalence and the course of mental disorders in the general population and to study the mechanisms underlying the association between these disorders and cardiovascular diseases. This investigation revealed a very high lifetime prevalence rate of 43.6 % for major depressive disorder in Lausanne. We have also observed that the association between major depression and cardio-metabolic risk factors is essentially attributable to the atypical subtype, characterized by an increased appetite, heaviness in limbs, hypersomnia and conserved affective reactivity. Patients who suffer from this type of depression have an increased risk to develop overweight, diabetes and the metabolic syndrome and deserve particular clinical attention on the metabolic level.


Assuntos
Transtorno Depressivo Maior , Síndrome Metabólica , Comorbidade , Depressão , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Humanos , Síndrome Metabólica/complicações , Estudos Prospectivos
4.
Gene ; 726: 144147, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31629822

RESUMO

BACKGROUND: Suicidal ideation (SI) is the most serious symptom of major depressive disorder (MDD) and considered an extreme state. The serotonin transporter gene (SLC6A4) plays a significant role in MDD and suicide pathophysiology. Previous studies have revealed an association between common variants of SLC6A4 with the risk of MDD and suicide. However, very few studies have so far focused on the degree to which rare variants of SLC6A4 are responsible for the depression observed in adolescent and young adult suicide patients. The aim of this study was to examine the impact of common and rare variants of SLC6A4 on the risk of Han Chinese adolescents and young adults suffering MDD with SI. METHODS: Targeted sequencing of the SLC6A4 gene was conducted using FastTarget technology in Han Chinese adolescents and young adults, of which 74 were MDD patients with SI and 150 were healthy controls. Gene-based association analyses of rare variants were performed using enrichment analysis and a cumulative allele test. An allele association study was performed against common variants. RESULTS: After sequencing and bioinformatics analysis, a total of 15 single nucleotide variants (SNVs) were detected in the targeted regions from all participants, including 9 common and 6 rare variants. Among these, 5 rare variants were identified within the study group. Enrichment analysis of rare variants demonstrated a statistical difference (p = 0.042) between the study and control groups. Using cumulative allele analysis, alternative alleles in the SLC6A4 gene exhibited an association with MDD patients with SI (cumulative allele: OR = 10.18, 95% CI = 1.18-87.32, p = 0.017). No significant association was found between the 9 common SLC6A4 variants and MDD patients with SI. CONCLUSIONS: Our results suggest that rare variants of SLC6A4 may contribute to a genetic risk of adolescents and young adults suffering MDD with SI.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Adulto , Alelos , Feminino , Testes Genéticos/métodos , Humanos , Masculino , Fatores de Risco , Ideação Suicida , Suicídio , Adulto Jovem
5.
World Neurosurg ; 133: 278-282, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31606510

RESUMO

BACKGROUND: Depression following resection of diffuse low-grade glioma has rarely been described. Location of the tumor and surgical route are potential causes. Lesion network mapping (LNM), leveraging high-quality resting-state functional magnetic resonance imaging data from large samples of healthy adults, has been used to explore the broader network connectivity for given lesions. However, LNM has not been applied to large intra-axial masses or surgical lesions. We used LNM to examine a potential cause of postoperative depression in a patient with a cingulate diffuse low-grade glioma (zones I-III). CASE DESCRIPTION: A 34-year-old woman underwent surgery for medically refractory seizures attributable to diffuse low-grade glioma. Near-total resection was attained via a single-stage, transcortical route through the medial prefrontal cortex. Despite freedom from seizure and lack of tumor growth at 42 months of follow-up, she developed symptoms of major depressive disorder soon after surgery that persisted. To identify functional networks potentially engaged by the surgical corridor and tumor resection cavity, both were segmented separately and used as seeds for normative resting-state functional magnetic resonance imaging connectivity mapping. To study depression specifically, networks associated with the tumor and surgical approach were compared with networks associated with subgenual cingulate deep brain stimulation. LNM results suggested that the surgical corridor, rather than the tumor, had greater overlap with deep brain stimulation-based depression networks (32% vs. 8%). CONCLUSIONS: Early postoperative development of major depressive disorder following resection of a cingulate region tumor, although likely multifactorial, should be considered and patients appropriately counseled preoperatively. Further validation of LNM as a viable methodology for correlating symptoms to lesions could make it a valuable tool in selection of surgical approach and patient counseling.


Assuntos
Neoplasias Encefálicas/cirurgia , Craniotomia/efeitos adversos , Transtorno Depressivo Maior/etiologia , Glioma/cirurgia , Giro do Cíngulo/cirurgia , Convulsões/cirurgia , Adulto , Neoplasias Encefálicas/complicações , Feminino , Glioma/complicações , Humanos , Complicações Pós-Operatórias/etiologia , Convulsões/etiologia
6.
Orv Hetil ; 161(1): 3-10, 2020 Jan.
Artigo em Húngaro | MEDLINE | ID: mdl-31884813

RESUMO

The rapidly evolving field of repetitive transcranial magnetic stimulation as a neuromodulational technique may mean a safe, alternative approach to the management of several mental disorders, especially treatment-resistant major depressive disorder. Our aim is to describe the current role of transcranial magnetic stimulation in research and routine clinical practice, based on the literature and clinical protocols. Since the discovery, that an outer magnetic source can depolarize neurons, both neurology and psychiatry seek the method's possible clinical utility. To date, in the field of psychiatry, the method is only approved in the treatment of major depressive disorder and obsessive-compulsive disorder, but research continues to find application in other mental disorders (schizophrenia, bipolar disorder), too. The next step in the evolution of repetitive transcranial magnetic stimulation is based on magnetic resonance guided, real-time navigation with the help of positioning algorithms. The so-called neuronavigational systems make precise aiming of neuronal circuits responsible for the development of depression, thus increasing the excitability of the left dorsolateral prefrontal cortex and decreasing it on the right hemisphere. The method has few contraindications, and the occurrence of side effects can be minimized by carefully selected patient population. For today, transcranial magnetic stimulation became an evidence-based, effective treatment for some mental disorders, especially treatment-resistant major depressive disorder. It is to be assumed that in the future neuronavigational neuromodulation techniques, including repetitive transcranial magnetic stimulation, will be widely used in the field of psychiatry and neurology. Magnetic stimulation is currently available in a number of centres in Hungary, but the financial approval and the implementation of this neuromodulation method for treating mental disorders in the everyday clinical practice are still in progress. Orv Hetil. 2020; 161(1): 3-10.


Assuntos
Transtorno Depressivo Maior/terapia , Estimulação Magnética Transcraniana/métodos , Transtorno Depressivo Maior/psicologia , Humanos , Hungria , Córtex Pré-Frontal , Estimulação Magnética Transcraniana/efeitos adversos , Resultado do Tratamento
7.
Lancet Psychiatry ; 7(1): 29-40, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860455

RESUMO

BACKGROUND: Stimulation adjustment is required to optimise outcomes of deep brain stimulation (DBS) for treatment-resistant depression, but controlled data for ideal stimulation parameters are poor or insufficient. We aimed to establish the efficacy and safety of short pulse width (SPW) and long pulse width (LPW) subcallosal cingulate DBS in depression. METHODS: We did a double-blind, randomised, crossover trial in an academic hospital in Calgary, AB, Canada. Patients had DSM IV-defined major depressive disorder and bipolar depression (20-70 years old, both sexes) and did not respond to treatment for more than 1 year, with a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS) at recruitment. Patients underwent bilateral DBS implantation into the subcallosal cingulate white matter using diffusion tensor imaging tractography. Patients were randomly assigned 1:1 without stratification using a computerised list generator to receive either SPW (90 µs) or LPW (210-450 µs) stimulation for 6 months. Patients and the clinician assessing outcomes were masked to the stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using the HDRS. Patients who did not respond to treatment (<50% reduction in HDRS from baseline) at 6 months crossed over to the opposite stimulation for another 6 months. All patients received individualised cognitive behavioural therapy (CBT) for 12 weeks. The primary outcome was change in HDRS at 6 months and 12 months using intention-to-treat analysis. This study is registered with ClinicalTrials.gov, NCT01983904. FINDINGS: Between Dec 5, 2013, and Sept 30, 2016, of 225 patients screened for eligibility, 23 patients were selected for DBS surgery. After one patient withdrew, 22 (mean age 46·4 years, SEM 3·1; 10 [45%] female, 12 [55%] male) were randomly assigned, ten (45%) to LPW stimulation and 12 (55%) to SPW stimulation. Patients were followed up at 6 months and 12 months. There was a significant reduction in HDRS scores (p<0·0001) with no difference between SPW and LPW groups (p=0·54) in the randomisation phase at 6 months. Crossover groups did not show a significant decrease in HDRS within groups (p=0·15) and between groups (p=0·21) from 6-12 months. Adverse events were equal between groups. Worsening anxiety and depression were the most common psychological adverse events. One patient in the SPW group died by suicide. INTERPRETATION: Both LPW and SPW stimulation of subcallosal cingulate white matter tracts carried similar risks and were equally effective in reducing depressive symptoms, suggesting a role for both pulse width and amplitude titration in optimising clinical outcomes in patients with treatment-resistant depression. FUNDING: Alberta Innovates Health Solutions.


Assuntos
Transtorno Bipolar/terapia , Estimulação Encefálica Profunda , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Resistente a Tratamento/terapia , Imagem de Tensor de Difusão , Córtex Pré-Frontal , Canadá , Terapia Cognitivo-Comportamental , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Psychiatr Hung ; 35(1): 46-57, 2020.
Artigo em Húngaro | MEDLINE | ID: mdl-31854322

RESUMO

The authors summarize the last 10 years of an ongoing collaborative study between the Universities of Szeged and Pittsburgh on early onset major depression. First, the "Risk factors of childhood depression" grant is presented briefly as an initial research study in which the subjects of the current studies were recruited. This is a prominently large clinical sample in the field of child psychiatry even on an international level. In addition to the follow-up of the prognosis of the disorder, recent studies continue to explore the early onset depression in two directions. On the one hand, two studies investigate the role of biobehavioral inflexibility markers in the development of major depression ("Biobehavioral inflexibility and risk for juvenile-onset depression" and "Biobehavioral inflexibility and risk for juvenile-onset depression - renewal grant"). On the other hand, the authors would like to have a better understanding of the possible relationship between the major depression and cardiovascular diseases ("Pediatric depression and subsequent cardiac risk factors: a longitudinal study"). The most significant aims of the three studies will be demonstrated, as well as how the studies were prepared and organized along with the already existing experience concerning research management and involvement of new collaborating partners and experts.


Assuntos
Pesquisa Biomédica/economia , Depressão , Transtorno Depressivo Maior , Organização do Financiamento/tendências , Pesquisa Biomédica/organização & administração , Criança , Depressão/etiologia , Transtorno Depressivo Maior/etiologia , Humanos , Estudos Longitudinais , Fatores de Risco , Universidades/organização & administração
9.
Psychiatr Hung ; 35(1): 58-67, 2020.
Artigo em Húngaro | MEDLINE | ID: mdl-31854323

RESUMO

INTRODUCTION: Several long-term follow-up studies investigate the progression of adolescent onset major depressive disorder but much less explore short and long-term consequences and prognosis into adulthood of childhood- onset depression. The aim of the present study is to follow childhood-onset depression, lifetime comorbid psychiatric disorders and suicidal behavior into adulthood. METHODS: Subjects (N=166) were 25.95+2.42 years old on average, 54.2% were women. Follow-up period lasted for a mean of 14.74+1.31 years. Psychiatric diagnosis was assessed by a DSM-IV based semi-structured interview. Subjects reported on 4 stages of suicidal behavior as one of the symptoms of depressive disorder. RESULTS: The onset of the first depressive episode was at the mean age of 10.17+2.34 years. 40,4% of the sample had only 1 episode while recurrent depressive episode presented in 32.5% above 18 years of age. Lifetime comorbid psychiatric disorders were present in more than 1/3 of the sample. The most frequent lifetime comorbidity was anxiety (42.4%), and specific phobia among anxiety disorders. Lifetime attention deficit-hyperactivity disorder and oppositional/conduct disorder were also frequent (25.9% and 16.9%, respectively). Suicidal behavior was not present life-time in 19.1% of the sample. Thoughts of death and thoughts of suicide were quite frequent (80.8% and 69.5%, respectively), specific plans and suicidal attempt were more frequent in girls (plan:female vs male 53.9% vs 38.4%, attempt: 33.3% vs 9.6%) during follow-up. CONCLUSION: About one-third of childhood-onset depression had recurrence above 18 years of age, which is lower than the recurrence rate for adolescent onset depression. A high rate of lifetime comorbidity was found between depression and anxiety disorders. The assessment of the actual level of suicidal behavior is important in the prevention of selfdestructive behavior.


Assuntos
Depressão/diagnóstico , Depressão/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Suicídio/psicologia , Adolescente , Adulto , Idade de Início , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Criança , Comorbidade , Depressão/complicações , Transtorno Depressivo Maior/complicações , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Fatores de Risco , Adulto Jovem
10.
Nat Genet ; 51(12): 1679-1690, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31784728

RESUMO

NRXN1 undergoes extensive alternative splicing, and non-recurrent heterozygous deletions in NRXN1 are strongly associated with neuropsychiatric disorders. We establish that human induced pluripotent stem cell (hiPSC)-derived neurons well represent the diversity of NRXN1α alternative splicing observed in the human brain, cataloguing 123 high-confidence in-frame human NRXN1α isoforms. Patient-derived NRXN1+/- hiPSC-neurons show a greater than twofold reduction in half of the wild-type NRXN1α isoforms and express dozens of novel isoforms from the mutant allele. Reduced neuronal activity in patient-derived NRXN1+/- hiPSC-neurons is ameliorated by overexpression of individual control isoforms in a genotype-dependent manner, whereas individual mutant isoforms decrease neuronal activity levels in control hiPSC-neurons. In a genotype-dependent manner, the phenotypic impact of patient-specific NRXN1+/- mutations can occur through a reduction in wild-type NRXN1α isoform levels as well as the presence of mutant NRXN1α isoforms.


Assuntos
Processamento Alternativo , Proteínas de Ligação ao Cálcio/genética , Células-Tronco Pluripotentes Induzidas/fisiologia , Moléculas de Adesão de Célula Nervosa/genética , Esquizofrenia/genética , Animais , Transtorno do Espectro Autista/genética , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Expressão Gênica , Heterozigoto , Humanos , Masculino , Camundongos , Isoformas de Proteínas/genética , Deleção de Sequência
11.
Adv Exp Med Biol ; 1180: 1-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784955

RESUMO

Depressive disorder is one of the most widespread forms of mental disorders which lead to a significant public health concern, such as disability, suicide, and so on. Its etiology remains vague but it is believed that depressive disorder is a multifactorial disease which is induced by the interaction of social, psychological, and biological factors. Thus, there is no clear and definite pathological theory could illustrate its mechanism independently until now, involving genetics, neuroimaging, neuroinflammation, neuroendocrine, and others. Comprehensive assessment to patients with depression is the starting point for a right diagnosis. History-taking of physical condition is as important as psychiatric interview and rational usage of scales would be beneficial for screening. There are many kinds of therapeutic measures for depressive patients nowadays, including general intervention, pharmacotherapy, psychotherapy, and physical therapy. For now, anti-depressants used in clinical practice is almost monoamine-based drugs while much more progress have been made in developing new antidepressant medications, like prototypical N-methyl-D-aspartate (NMDA) receptor antagonists, opioid agonists, gamma-aminobutyric acid (GABAA) receptors, and psychedelics. Once these novel drugs are proved to be practicable, it will create a historical evolution in the field of psychiatry. In addition, we advocate that measurement-based care (MBC) should run through the whole duration of treatment and goals of MBC in every stage are different. As brain projects in many countries are conducting in inspiring ways, we believe that our understanding about depressive disorder, of course, and other neuropsychiatric disorders will be better in the future.


Assuntos
Depressão/terapia , Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Humanos , Psicoterapia
12.
Adv Exp Med Biol ; 1180: 19-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784956

RESUMO

Major depressive disorder (MDD) and bipolar disorder (BPD) are both chronic, severe mood disorder with high misdiagnosis rate, leading to substantial health and economic burdens to patients around the world. There is a high misdiagnosis rate of bipolar depression (BD) just based on symptomology in depressed patients whose previous manic or mixed episodes have not been well recognized. Therefore, it is important for psychiatrists to identify these two major psychiatric disorders. Recently, with the accumulation of clinical sample sizes and the advances of methodology and technology, certain progress in the genetics of major depression and bipolar disorder has been made. This article reviews the candidate genes for MDD and BD, genetic variation loci, chromosome structural variation, new technologies, and new methods.


Assuntos
Transtorno Bipolar/genética , Transtorno Depressivo Maior/genética , Humanos
13.
Adv Exp Med Biol ; 1180: 59-83, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784957

RESUMO

Neuroimaging shed light on the understanding of psychopathological mechanisms underlying major depressive disorder, despite its inconsistent findings. Noninvasive neuroimaging studies have indicated that various behavioral deficits in major depressive disorder are implicated with structural and functional abnormalities in specific brain regions. Moreover, disrupted brain morphological and functional properties may map out the underlying pathways from genetic and environmental factors to the prognosis of depression. Molecular neuroimaging studies have also provided novel method to probe transmitters and metabolites in brain regions rather than simply measuring brain morphological changes. Recent advanced neuroimaging approaches (e.g., pattern recognition) provides great opportunity to probe neuroimaging biomarkers that may contributes to improving diagnostic accuracy and predicting treatment outcomes. In this chapter, we conclude neuroimaging studies in the research field of depression from psychopathological, molecular, genetic/environmental, diagnostic, and therapeutic perspectives.


Assuntos
Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Neuroimagem , Biomarcadores , Humanos
14.
Adv Exp Med Biol ; 1180: 85-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784958

RESUMO

Major depressive disorder (MDD) or depression is one of the most highly prevalent, chronic, and recurrent disorders, which is associated with a high burden of disease and substantial impairment in social functions. Both immune molecules and cells have been implicated in the pathophysiology and maintenance of MDD. Findings in animals and MDD patients have suggested that both pro- and anti-inflammatory cytokines are activated in the neuroinflammation which contribute to behavioral symptoms and changes in the course of depression. There is a growing body of evidence to support that neuroinflammation is a mediator for the communication among stress response, neuroendocrine, neurotransmission, neurogenesis, and gut microbiota. These communications have been known as risk factors in the pathogenesis of MDD. In the meantime, accumulating evidence has suggested that some interventions targeting the inflammatory processes may play an important role in the treatment of MDD.


Assuntos
Transtorno Depressivo Maior/imunologia , Animais , Citocinas/imunologia , Microbioma Gastrointestinal , Humanos , Inflamação , Neurogênese , Transmissão Sináptica
15.
Adv Exp Med Biol ; 1180: 99-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784959

RESUMO

Enormous efforts for near half-century have harvested a plenty of understanding on major depressive disorder (MDD), although the underlying mechanisms are still elusive. The available antidepressants are far from satisfaction due to long-delay action (LDA) of antidepressant efficacy and low response rates in MDD patients. Notably, discovery of a single low-dose ketamine-producing rapid-onset and sustained antidepressant efficacy has inspired new research direction. These new studies have revealed ketamine's NMDAR-dependent and NMDAR-independent mechanisms, most of which are well known to be the key bases of synaptic plasticity as well as learning and memory. In fact, animal models of MDD are all based on the principle of learning and memory, i.e., the change of a behavior, for which monoaminergic and glutamatergic systems are the major modulators and executors, respectively. Reconsidering MDD as an aberrant form of emotion-related learning and memory would endow us a clearer research direction for developing new techniques or ways to prevent, diagnose, and treat MDD.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Plasticidade Neuronal , Animais , Antidepressivos/uso terapêutico , Humanos , Ketamina/uso terapêutico
16.
Adv Exp Med Biol ; 1180: 117-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784960

RESUMO

Most processes of human body, such as brain function, are regulated by biological rhythms. Disturbance of biological rhythms impairs mood, behavior, cognition, sleep, and social activity and may lead to mental disorders. Disturbed rhythms are widely observable in patients with major depressive disorders (MDD) and make risk of onset, comorbidity, response of antidepressants, recurrence, cognition, social function, and complications of physical health. Therefore, it is crucial to assess and manage focus on biological rhythms for patients with MDD. There are several validated ways of assessing the biological rhythms, including 24 h fluctuations in cortisol or melatonin, sleep monitoring, actigraphy, and self-report scales. Chronotherapy, such as cognitive-behavioral therapy, interpersonal and social rhythm therapy, sleep deprivation, and bright light therapy was widely reported for treatment in patients with MDD. Monoamine antidepressants and lithium are attributed to regulation of biological rhythm. And some rhythm-regulated agents have been shown efficacy of antidepressant. Considering the crucial clinical significance of disturbed biological rhythms in MDD, we describe the mechanisms, clinical features, measurements, and treatments of the biological rhythms in patients with MDD.


Assuntos
Ritmo Circadiano , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Terapia Cognitivo-Comportamental , Humanos , Hidrocortisona/fisiologia , Melatonina/fisiologia , Sono
17.
Adv Exp Med Biol ; 1180: 179-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784963

RESUMO

Diagnosis for MDD in modern psychiatry has developed for decades based on long traceable historic efforts on conceptualizing the illness. This article reviews the historical background of current diagnostic framework for MDD, diagnostic criteria and two newly added specifiers ("with anxious distress" and "with mixed features" specifiers) of MDD in the DSM-5, the most influential diagnostic instrument in the world, as well as problems and limitations of symptom-based diagnosis for sake of better understanding about the inter-relationship between diagnostic criteria and MDD.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos
18.
Adv Exp Med Biol ; 1180: 193-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784964

RESUMO

The treatment strategies of depressive disorder include pharmacological treatment, psychotherapy, and physical therapy (electroconvulsive therapy [ECT], transcranial magnetic stimulation [TMS], etc.). The updated CANMAT guidelines recommended the most second-generation antidepressants as first-line treatments for patients with a major depressive disorder (MDD) of moderate or greater severity. Before antidepressant treatment, comprehensive assessment and safety monitoring are necessary. The application of measurement-based care in the diagnosis and treatment of depression would better ensure that enough dosage and response of antidepressant is achieved at each key point, and the final outcome of disease is improved. It is recommended that antidepressant is used with monotherapy in patients with depression. Antidepressants of different types and different mechanisms could be combined to improve the efficacy for patients with treatment-resistant depression (TRD). To prevent the relapse and recurrence of disease, the long-term treatment comprised of acute treatment, consolidation treatment, and maintenance treatment must be considered for all patients.


Assuntos
Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Eletroconvulsoterapia , Humanos , Psicoterapia , Estimulação Magnética Transcraniana , Resultado do Tratamento
19.
Adv Exp Med Biol ; 1180: 201-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784965

RESUMO

Despite many advances in pharmacotherapy over the past half centurye, only a fraction of patients with Major Depressive Disorder (MDD) can achieve remission after the first or second trial of pharmacotherapy. Those who failed standard antidepressant treatment are termed as Treatment-Resistant Depression (TRD). Pharmacotherapy for TRD is more viable over past 15 years in part due to advances in clinical trials such as the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and the US Department of Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study. In general, optimizing pharmacotherapy consists of switching to different agents, combination with different antidepressants, or augmentation with different class of psychotropic medications, and the latter is preferred. Augmenting agents with strong evidence include Bupropion, Lithium, Triiodothyronine (T3), Aripiprazole, Brexpiprazole, Quetiapine, and Olanzapine in combination with Fluoxetine. Many works need to be done to further advance this field. These include (1) Establish agreement on a standardized, systematic, and feasible definition of TRD, (2) Establish safety and tolerability beyond acute treatment phase, (3) Establish individual psychosocial and neurobiological marks such as pharmacogenetic variance, and (4) Utilize multi-treatment modules such as combination of psychotherapy and pharmacotherapy in conjunction with brain stimulation therapy such as electroconvulsive therapy, vagus nerve stimulation and transcranial magnetic stimulation; as well as non-traditional therapy such as nutritional supplements, exercise and light therapy.


Assuntos
Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Quimioterapia Combinada , Eletroconvulsoterapia , Humanos , Psicoterapia , Estimulação Magnética Transcraniana , Resultado do Tratamento
20.
Adv Exp Med Biol ; 1180: 277-295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784969

RESUMO

Numerous antidepressants are available for the treatment of the major depressive disorder (MDD). Unfortunately, the disadvantages of these antidepressive medications, including inadequate treatment response, the therapeutic lag between drug administration and the onset of symptoms alleviation, and the safety consideration limit their clinical use and accelerate the exploration of advanced antidepressants with novel action mechanisms/newer targets, with fewer side effects. In this chapter, a series of compounds showing clinical potent in the treatment of MDD has been reviewed based on their reported results from different phase clinical trials. Although the majority of these strategies currently only lead to a systematic approach in the aspects of treatment resistant depression, some of them would be a routine clinical practice which is usable in the treatment of MDD, such as ketamine. Additionally, beyond the mechanism of action for novel therapeutic molecules involving glutamatergic, opiate, cholinergic receptors, and neuroplasticity, some supplemental procedures such as polyunsaturated fatty acids were also included in this chapter due to their solid property against MDD.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/terapia , Ensaios Clínicos como Assunto , Humanos
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