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Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.
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Trastorno Depresivo Mayor , Transcriptoma , Humanos , Trastorno Depresivo Mayor/genética , Trastorno Depresivo Mayor/fisiopatología , Femenino , Masculino , Adulto , Corteza Cerebral/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Persona de Mediana Edad , Imagen por Resonancia Magnética , Perfilación de la Expresión GénicaRESUMEN
Vortioxetine is a novel multimodal antidepressant, but its precise efficacy and dose-response relationship for treating different symptoms in major depressive disorder (MDD) is still unclear. This umbrella review aims to assess the effectiveness, tolerability, and dose-response relationship of vortioxetine across a comprehensive range of clinical features in adults with MDD, including cognition, depression, anxiety, quality of life, and side effects. We meticulously searched eight electronic databases and included systematic reviews (SRs) and meta-analyses (MAs) of vortioxetine. The methodological quality of each included SR was independently assessed using the AMSTAR2 tool. To evaluate the credibility of the evidence, we utilized the GRADE framework and the Ioannidis criteria. In total, 35 SRs with 278 MAs met the inclusion criteria and based on these studies we performed 56 MAs of interest. While vortioxetine has been consistently shown to have positive effects on various domains, the evidence regarding cognitive performance and depression symptoms is notably robust compared to placebo, despite of relatively overall low quality of evidence. Finally, a dose-response relationship was observed across all categories within the treatment range of 5-20 mg/d and a dosage of vortioxetine 20 mg/d is recommended for adult MDD patients to achieve full functional recovery.
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Background: Major depressive disorder (MDD) causes significant functional impairments that impact on all aspects of patients' daily lives, including their ability to work, work productivity, and social life. Purpose: To assess the real-world effectiveness of the multimodal antidepressant vortioxetine in working patients with MDD in China. Patients and methods: RELIEVE China was an observational, prospective cohort study. Patients (aged ≥18 years) with MDD initiating treatment with vortioxetine in routine clinical practice settings were followed for 24 weeks. In this subgroup analysis, functioning was assessed using the Sheehan Disability Scale (SDS) in patients in full- or part-time work or education at baseline who remained on treatment at all follow-up visits (n=424). Depressive, cognitive, and anxiety symptoms were also assessed. For all endpoints, mean change from baseline at weeks 8 and 24 was analyzed using mixed models for repeated measures. Results: Clinically relevant and sustained improvements in patient functioning and measures of work productivity were observed over the 24 weeks of vortioxetine treatment. The adjusted mean (standard error) reduction in SDS total score from baseline was 5.4 (0.3) points at week 8 and 8.7 (0.3) points at week 24 (both P<0.001 vs baseline). Significant improvements were observed across all SDS domains and in levels of absenteeism and presenteeism (P<0.001 vs baseline for all endpoints at both time points). Significant improvements in depressive, cognitive, and anxiety symptoms were also observed over the study period (all P<0.001 vs baseline). The proportion of patients in remission (ie, 17-item Hamilton Depression Rating Scale score ≤7) after 24 weeks of vortioxetine treatment was 65.4%. Vortioxetine was well tolerated; nausea was the most common adverse event, reported by 18.6% of patients. Conclusion: These findings support the effectiveness and tolerability of vortioxetine in working patients with MDD receiving treatment in routine clinical practice settings in China.
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BACKGROUND: As a central hub in cognitive and emotional brain circuits, the striatum is considered likely to be integrally involved in the psychopathology of bipolar disorder (BD). However, it remains unclear how alterations in striatal function contribute to distinct symptomatology of BD during different mood states. METHODS: Behavioral assessment (i.e., emotional symptoms and cognitive performance) and neuroimaging data were collected from 125 participants comprising 31 (hypo)manic, 31 depressive, and 31 euthymic patients with BD, and 32 healthy control participants. We compared the functional connectivity (FC) of striatal subregions across BD mood states with healthy control participants and then used a multivariate data-driven approach to explore dimensional associations between striatal connectivity and behavioral performance. Finally, we compared the FC and behavioral composite scores, which reflect the individual weighted representation of the associations, among different mood states. RESULTS: Patients in all mood states exhibited increased FC between the bilateral ventral rostral putamen and ventrolateral thalamus. Bipolar (hypo)mania uniquely exhibited increased ventral rostral putamen connectivity and superior ventral striatum connectivity. One latent component was identified, whereby increased FCs of striatal subregions were associated with distinct psychopathological symptomatology (more manic symptoms, elevated positive mood, less depressive symptoms, and worse cognitive performance). Patients with bipolar (hypo)mania had the highest FC and behavioral composite scores while bipolar patients with depression had the lowest scores. CONCLUSIONS: Our data demonstrated both trait features of BD and state features specific to bipolar (hypo)mania. The findings underscored the fundamental role of the striatum in the pathophysiological processes underlying specific symptomatology across all mood states.
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Afecto , Trastorno Bipolar , Cuerpo Estriado , Imagen por Resonancia Magnética , Humanos , Trastorno Bipolar/fisiopatología , Trastorno Bipolar/diagnóstico por imagen , Masculino , Femenino , Adulto , Afecto/fisiología , Cuerpo Estriado/fisiopatología , Cuerpo Estriado/diagnóstico por imagen , Persona de Mediana Edad , Manía/fisiopatología , Estriado Ventral/fisiopatología , Estriado Ventral/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Adulto JovenRESUMEN
Trace amine-associated receptor 1 (TAAR1) is an intracellular expressed G-protein-coupled receptor that is widely expressed in major dopaminergic areas and plays a crucial role in modulation of central dopaminergic neurotransmission and function. Pharmacological studies have clarified the roles of dopamine D1 receptor (D1R) in the medial prefrontal cortex (mPFC) in cognitive function and social behaviors, and chronic stress can inhibit D1R expression due to its susceptibility. Recently, we identified TAAR1 in the mPFC as a potential target for treating chronic stress-induced cognitive and social dysfunction, but whether D1R is involved in mediating the effects of TAAR1 agonist remains unclear. Combined genomics and transcriptomic studies revealed downregulation of D1R in the mPFC of TAAR1-/- mice. Molecular dynamics simulation showed that hydrogen bond, salt bridge, and Pi-Pi stacking interactions were formed between TAAR1 and D1R indicating a stable TAAR1-D1R complex structure. Using pharmacological interventions, we found that D1R antagonist disrupted therapeutic effect of TAAR1 partial agonist RO5263397 on stress-related cognitive and social dysfunction. Knockout TAAR1 in D1-type dopamine receptor-expressing neurons reproduced adverse effects of chronic stress, and TAAR1 conditional knockout in the mPFC led to similar deficits, along with downregulation of D1R expression, all of these effects were ameliorated by viral overexpression of D1R in the mPFC, suggesting the functional interaction between TAAR1 and D1R. Collectively, our data elucidate the possible molecular mechanism that D1R in the mPFC mediates the effects of TAAR1 activation on chronic stress-induced cognitive and social deficits.
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Ratones Endogámicos C57BL , Ratones Noqueados , Corteza Prefrontal , Receptores de Dopamina D1 , Receptores Acoplados a Proteínas G , Estrés Psicológico , Animales , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/agonistas , Estrés Psicológico/metabolismo , Masculino , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/genética , Ratones , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/etiología , Conducta SocialRESUMEN
Multiple lines of evidence suggest that the trace amine-associated receptor 1 (TAAR1) holds promise as a potential target for stress-related disorders, such as treating major depressive disorder (MDD). The role of TAAR1 in the regulation of adult neurogenesis is recently supported by transcriptomic data. However, it remains unknown whether TAAR1 in dentate gyrus (DG) mediate chronic stress-induced negative effects on hippocampal plasticity and related behavior in mice. The present study consisted of a series of experiments using RNAscope, genetic approaches, behavioral tests, immunohistochemical staining, Golgi-Cox technique to unravel the effects of TAAR1 on alterations of dentate neuronal plasticity and cognitive function in the chronic social defeat stress model. The mice subjected to chronic defeat stress exhibited a noteworthy decrease in the mRNA level of TAAR1 in DG. Additionally, they exhibited compromised social memory and spatial object recognition memory, as well as impaired proliferation and maturation of adult-born dentate granule cells. Moreover, the selective knockout TAAR1 in DG mostly mimicked the cognitive function deficits and neurogenesis impairment induced by chronic stress. Importantly, the administration of the selective TAAR1 partial agonist RO5263397 during stress exposure attenuated the adverse effects of chronic stress on cognitive function, adult neurogenesis, dendritic arborization, and the synapse number of dentate neurons in DG. In summary, our findings suggest that TAAR1 plays a crucial role in mediating the detrimental effects of chronic stress on hippocampal plasticity and cognition. TAAR1 agonists exhibit therapeutic potential for individuals suffering from cognitive impairments associated with MDD.
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Giro Dentado , Trastorno Depresivo Mayor , Receptores Acoplados a Proteínas G , Animales , Ratones , Giro Dentado/fisiología , Hipocampo/fisiología , Cognición/fisiología , Plasticidad Neuronal/fisiología , NeurogénesisRESUMEN
Trace amine-associated receptor 1 (TAAR1) is a classical type of G-protein-coupled receptor, which is widely distributed in the brain of mammals, especially in the limbic system and the region rich in monoaminergic neurons, and it is a highly conserved TAAR subtype in all species. TAAR1 can specifically respond to endogenous trace amines in the central nervous system and peripheral tissues, and plays an important role in the pathophysiological mechanisms involving the dysregulation of monoamine system and glutamate system leading to mental disorders. In addition, TAAR1 modulator can act on inwardly rectifying potassium channels and regulate synaptic transmission and neuronal activity. According to the latest research findings, TAAR1 exerts a series of functions by regulating signal pathways and substrate phosphorylation, which is related to emotion, cognition, fear and addiction. Therefore, we conducted a detailed review of relevant studies on the TAAR1 signaling pathways, aiming at revealing the great potential of TAAR1 as a new target for drug treatment of neuropsychiatric disorders.
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Receptores Acoplados a Proteínas G , Transmisión Sináptica , Animales , Humanos , Encéfalo , Aminas , MamíferosRESUMEN
Witnessing violent or traumatic events is common during childhood and adolescence and could cause detrimental effects such as increased risks of psychiatric disorders. This stressor could be modeled in adolescent laboratory animals using the chronic witnessing social defeat (CWSD) paradigm, but the behavioral consequences of CWSD in adolescent animals remain to be validated for cognitive, anxiety-like, and depression-like behaviors and, more importantly, the underlying neural mechanisms remain to be uncovered. In this study, we first established the CWSD model in adolescent male mice and found that CWSD impaired cognitive function and increased anxiety levels and that these behavioral deficits persisted into adulthood. Based on the dorsal-ventral functional division in hippocampus, we employed immediate early gene c-fos immunostaining after behavioral tasks and found that CWSD-induced cognition deficits were associated with dorsal CA3 overactivation and anxiety-like behaviors were associated with ventral CA3 activity reduction. Indeed, chemogenetic activation and inhibition of dorsal CA3 neurons mimicked and reversed CWSD-induced recognition memory deficits (not anxiety-like behaviors), respectively, whereas both inhibition and activation of ventral CA3 neurons increased anxiety-like behaviors in adolescent mice. Finally, chronic administration of vortioxetine (a novel multimodal antidepressant) successfully restored the overactivation of dorsal CA3 neurons and the cognitive deficits in CWSD mice. Together, our findings suggest that dorsal CA3 overactivation mediates CWSD-induced recognition memory deficits in adolescent male mice, shedding light on the pathophysiology of adolescent CWSD-induced adverse effects and providing preclinical evidence for early treatment of stress-induced cognitive deficits.
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Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. In this naturalistic prospective study (NCT03294525), we aimed to investigate relationships among subcortical functional connectivity (FC), mood symptom profiles and treatment outcome in MDD using multivariate methods. Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) correlation analysis to explore the association between subcortical FC and mood symptom profiles. FC score, reflecting the weighted representation of each individual in this association, was computed. Replication analysis was undertaken in an independent sample (n = 74). We also investigated the relationship between FC score and treatment outcome in the main sample. A distinctive subcortical connectivity pattern was found to be associated with negative affect. In general, higher FC between the caudate, putamen and thalamus was associated with greater negative affect. This association was partly replicated in the independent sample (similarity between the two samples: r = 0.66 for subcortical connectivity, r = 0.75 for mood symptom profile). Lower FC score predicted both remission and response to treatment after 8 weeks of antidepressant monotherapy. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical FC with negative affect. However, while the FC score significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.
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Trastorno Depresivo Mayor , Humanos , Afecto , Antidepresivos/uso terapéutico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD. METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients. RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide. CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/psicología , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Intento de Suicidio , Prevalencia , Errores DiagnósticosRESUMEN
The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.
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Experiencias Adversas de la Infancia , Fluoxetina , Humanos , Femenino , Ratones , Masculino , Animales , Fluoxetina/farmacología , Vortioxetina , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológicoRESUMEN
BACKGROUND: The utilization of once-monthly paliperidone palmitate (PP1M) in schizophrenia treatment has increased due to its enhanced adherence and convenience. However, there is limited evidence on patient characteristics that may influence treatment outcomes when switching from oral antipsychotics (OAPs) to PP1M therapy. This systematic review aims to identify such patient characteristics and explore potential beneficial factors to aid healthcare professionals in clinical practice. METHODS: A systematic literature search was conducted in the PubMed, Embase, and Cochrane Library databases up to July 19, 2022. Studies related to patients with schizophrenia who had been previously treated with OAPs and switched to PP1M were identified and included. Outcomes included the Positive and Negative Syndrome Scale (PANSS) total score, the clinical Global Impressions - Severity (CGI-S) score, the Personal and Social Performance (PSP) total score, and hospitalisation rate. Data were independently extracted and analysed. The results were presented through a narrative synthesis. RESULTS: Eleven studies with a total of 4150 patients were included, identifying nine potential characteristics. The most commonly reported characteristics was patient's prior treatment with OAPs, followed by the stage of disease, duration of illness (DI), ethnicity, reason for switching to PP1M, history of hospitalisation, time of start injection of PP1M, the PANSS and PSP total score at baseline. Patients in the acute stage, with a shorter DI, a less than 1-week time interval to PP1M injection, and a lower PANSS total score at baseline may have a trend on providing better improvements on PANSS total score. Acute stage and shorter DI also showed potential trends in reducing CGI-S score. Early initiation of PP1M, switching for reasons other than lack of efficacy, and a higher PSP score at baseline exhibited potential trends towards better PSP total score improvements. CONCLUSION: Our findings may suggest that patients in acute stage, with a shorter duration of illness, with early initiation of PP1M injection, and lower PANSS or PSP scores may trend towards better clinical results when transitioning to PP1M from OAPs. Further research is necessary to validate these potential associations and identify any unexplored characteristics. Such investigations are crucial for providing comprehensive clinical recommendations and informing treatment strategies in this context.
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Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Palmitato de Paliperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Administración Oral , Resultado del TratamientoRESUMEN
Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression. Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder. However, the pathophysiology underlying mood instability, mood switching and the development of extreme mood states is less well understood. This review presents a comprehensive overview of current evidence from functional MRI studies from the perspective of mood states. We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder, irrespective of the mood state. We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects. Finally, we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research. A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.
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BACKGROUND: Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis. RESULTS: A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients. CONCLUSIONS: Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.
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Trastorno Bipolar , Humanos , Manía , Mapeo Encefálico/métodos , Vías Nerviosas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , EncéfaloRESUMEN
The functional connectome of the human brain represents the fundamental network architecture of functional interdependence in brain activity, but its normative growth trajectory across the life course remains unknown. Here, we aggregate the largest, quality-controlled multimodal neuroimaging dataset from 119 global sites, including 33,809 task-free fMRI and structural MRI scans from 32,328 individuals ranging in age from 32 postmenstrual weeks to 80 years. Lifespan growth charts of the connectome are quantified at the whole cortex, system, and regional levels using generalized additive models for location, scale, and shape. We report critical inflection points in the non-linear growth trajectories of the whole-brain functional connectome, particularly peaking in the fourth decade of life. Having established the first fine-grained, lifespan-spanning suite of system-level brain atlases, we generate person-specific parcellation maps and further show distinct maturation timelines for functional segregation within different subsystems. We identify a spatiotemporal gradient axis that governs the life-course growth of regional connectivity, transitioning from primary sensory cortices to higher-order association regions. Using the connectome-based normative model, we demonstrate substantial individual heterogeneities at the network level in patients with autism spectrum disorder and patients with major depressive disorder. Our findings shed light on the life-course evolution of the functional connectome and serve as a normative reference for quantifying individual variation in patients with neurological and psychiatric disorders.
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BACKGROUND: The social signal transduction theory of depression proposes that life stress can be transformed into inflammatory signals, and ultimately lead to the development of major depressive disorder (MDD). The hypotheses of this study were: (1) The pro-inflammatory effect of life stress was only seen in patients with MDD, but not in healthy controls (HCs); (2) Inflammation can mediate the relationship between life stress and depressive symptoms. METHODS: This study included 170 MDD patients and 196 HCs, and 13 immune-inflammatory biomarkers closely related to MDD were measured, principal component analysis (PCA) was adopted to extract the inflammatory index. Life stress was assessed by Life Event Scale (LES), a total score of >32 points on the LES was considered as adulthood adversity (AA). Path analyses were used to explore the relationship among adulthood stress, inflammatory index, and severity of depression. RESULTS: Among MDD patients, α2M, CXCL-1, IL-1ß, and TLR-1 levels were higher in patients with AA than non-AA group (all FDR-adjusted P values <0.05), meanwhile, the levels of CCL-2 and IL-18 were lower. Path analyses suggested that pro- and anti-inflammatory index could mediate the association between AA and severity of depression in MDD patients. CONCLUSION: This study found that inflammatory signals can mediate the relationship between adulthood adversity and depression, however, the causal relationship need to be further confirmed. These findings shed light on further understanding the theory of social signal transduction in MDD and provide clues for stress management and controlling inflammation strategies in depression. CLINICAL TRIALS: NCT02023567.
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Trastorno Depresivo Mayor , Humanos , Adulto , Depresión , Fenotipo , Inflamación , Transducción de SeñalRESUMEN
BACKGROUND: Identifying and managing major depressive disorder (MDD) patients with suicidal ideation or behavior (MDSI) is critical for reducing the disease burden. This scoping review aims to map the existing evidence related to MDSI in the Chinese population. METHOD: A scoping review was conducted to summarize the published evidence regarding epidemiology or disease burden, evaluation, diagnosis, management, and prognosis of MDSI. The search strategy imposed restriction on English or Chinese publications between 1 January 2011 and 28 February 2022. RESULTS: Of the 14,005 identified records, 133 met the eligibility criteria and were included for analysis. The included studies were characterized as high heterogeneity in evaluation of suicidal ideation or behavior. Compared with MDD patients without suicidal ideation or behavior, MDSI patients were more likely to suffer from psychological and somatic symptoms, social function impairment, and lower quality of life. Younger age, female gender, longer disease course, and comorbid psychological or physical symptoms were consistently found to be risk factors of suicidal ideation or behavior. Relevant research gaps remain regarding comprehensive evaluation of standard clinical diagnosis, disease burden, social-cultural risk factors, and effectiveness of interventions targeting MDSI. Studies with large sample size, representative population are warranted to provide high-quality evidence. CONCLUSIONS: MDD patients with suicidal ideation or behavior should be prioritized in treatment and resource allocation. Heterogeneity exists in the definition and evaluation of MDSI in different studies. To better inform clinical practice, it is imperative to establish a unified standard for evaluation and diagnosis of suicidal ideation or behavior among MDD population.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/terapia , Pueblos del Este de Asia , Calidad de Vida , Factores de Riesgo , Ideación SuicidaRESUMEN
BACKGROUND: The neural correlate of cognitive deficits in bipolar disorder (BD) is an issue that warrants further investigation. However, relatively few studies have examined the intrinsic functional connectivity (FC) underlying cognitive deficits involving sustained attention and executive function at both the region and network levels, as well as the different relationships between connectivity patterns and cognitive performance, in BD patients and healthy controls (HCs). METHODS: Patients with BD (n = 59) and HCs (n = 52) underwent structural and resting-state functional magnetic resonance imaging and completed the Wisconsin Card Sorting Test (WCST), the continuous performance test and a clinical assessment. A seed-based approach was used to evaluate the intrinsic FC alterations in three core neurocognitive networks (the default mode network [DMN], the central executive network [CEN] and the salience network [SN]). Finally, we examined the relationship between FC and cognitive performance by using linear regression analyses. RESULTS: Decreased FC was observed within the DMN, in the DMN-SN and DMN-CEN and increased FC was observed in the SN-CEN in BD. The alteration direction of regional FC was consistent with that of FC at the brain network level. Decreased FC between the left posterior cingulate cortex and right anterior cingulate cortex was associated with longer WCST completion time in BD patients (but not in HCs). CONCLUSIONS: These findings emphasize the dominant role of the DMN in the psychopathology of BD and provide evidence that cognitive deficits in BD may be associated with aberrant FC between the anterior and posterior DMN.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/complicaciones , Trastorno Bipolar/diagnóstico por imagen , Función Ejecutiva , Vías Nerviosas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , CogniciónRESUMEN
Sertraline has been shown to be effective in the treatment of depression. However, the relationship between the dosage of sertraline and its efficacy and safety are unclear. We identified RCTs that compared sertraline with placebo for the treatment of depression, conducted conventional meta-analyses on the efficacy and safety of sertraline, and assessed the nonlinear dose-response relationship between sertraline dosage and the changes in HAM-D and CGI-S scores, dropout from care for any reason or due to adverse effects, and the rate of adverse effects, using a 1-stage restricted cubic spline regression model. Twenty-one RCTs involving 4,235 patients were included. The pooled mean differences (MD) in the change in HAM-D total score [MD=-2.34, 95% confidence interval (CI) -2.93, -1.76], CGI-S score and MADRS score, but also the dropout rate for adverse effects, and rate of adverse effects were higher in sertraline group. The therapeutic response of sertraline for treating depression increased with the dosage. Meanwhile, the risk of total adverse reactions slightly decreased between 50 and 150 mg, and increased at doses above 150 mg. The dose-dependence of both efficacy and safety need to be considered when choosing the optimal dosage of sertraline.