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1.
Proc Natl Acad Sci U S A ; 119(23): e2204433119, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35648832

RESUMO

SignificanceMajor depressive, anxiety, and stress-related disorders are highly comorbid and may affect similar neurocircuitry and cognitive processes. However, the neurocircuitry underlying shared dimensions of cognitive impairment is unclear and holds the promise of reimagining psychiatric nosology. Here we leverage population imaging data (n = 27,132) to show that while major depressive and anxiety disorders share functional and structural neural signatures, stress-related disorders are distinct from these two conditions. We report that better cognitive function is associated with lower connectivity of specific nodes of the default mode and frontoparietal networks. These findings provide population benchmarks for brain-cognition associations in healthy participants and those with lifetime major depressive and anxiety disorders, advancing our understanding of intrinsic brain networks underlying cognitive dysfunction.


Assuntos
Transtornos de Ansiedade , Encéfalo , Transtorno Depressivo Maior , Vias Neurais , Estresse Psicológico , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Humanos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/fisiopatologia
2.
Nat Commun ; 13(1): 870, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35169166

RESUMO

Network theory of mental illness posits that causal interactions between symptoms give rise to mental health disorders. Increasing evidence suggests that depression network connectivity may be a risk factor for transitioning and sustaining a depressive state. Here we analysed social media (Twitter) data from 946 participants who retrospectively self-reported the dates of any depressive episodes in the past 12 months and current depressive symptom severity. We construct personalised, within-subject, networks based on depression-related linguistic features. We show an association existed between current depression severity and 8 out of 9 text features examined. Individuals with greater depression severity had higher overall network connectivity between depression-relevant linguistic features than those with lesser severity. We observed within-subject changes in overall network connectivity associated with the dates of a self-reported depressive episode. The connectivity within personalized networks of depression-associated linguistic features may change dynamically with changes in current depression symptoms.


Assuntos
Depressão/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Linguística/estatística & dados numéricos , Mídias Sociais/estatística & dados numéricos , Adulto , Feminino , Humanos , Idioma , Masculino , Autorrelato/estatística & dados numéricos , Índice de Gravidade de Doença
3.
J Psychopharmacol ; 36(2): 151-158, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35166158

RESUMO

BACKGROUND: Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes. AIMS: This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin. METHODS: This randomized, waiting-list controlled study enrolled 27 patients aged 21-75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose. RESULTS: All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression. CONCLUSIONS: These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.


Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo Maior/terapia , Alucinógenos/farmacologia , Psilocibina/farmacologia , Adulto , Idoso , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Terapia Combinada , Transtorno Depressivo Maior/fisiopatologia , Feminino , Seguimentos , Alucinógenos/administração & dosagem , Alucinógenos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psilocibina/administração & dosagem , Psilocibina/efeitos adversos , Escalas de Graduação Psiquiátrica , Psicoterapia/métodos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
4.
Biomed Pharmacother ; 147: 112668, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35104696

RESUMO

Depression is the most prevalent and debilitating mental disorder that affects a substantial number of people globally, hindering all aspects of their lives and leading to a high number of suicides each year. Despite the availability of an array of antidepressant medications, taking these medications does not relieve depressive symptoms in a considerable number of patients, implying that an incomplete understanding of the pathomechanisms involved in the development of depression. Besides that, a subset of those non-responsive patients exhibits an increased systemic and central inflammatory response, which has collectively led to the evolvement of the inflammatory theory of depression. Indeed, peripherally generated inflammatory mediators, as well as insults within the brain, can activate the brain's resident immune cells, resulting in a neuroinflammatory response that interferes with the multitude of neurobiological domains implicated in the pathogenesis of depression. Polyphenols, a group of plant-derived bioactive molecules, have been shown to exert neuroprotective functions on the brain by influencing an array of neuropathological mechanisms, including neuroinflammation. From these perspectives, this review mechanistically provides an overview of the neuropathological roles of sustained neuroinflammatory response in the development of depression and elucidates the therapeutic potential of flavonoid and nonflavonoid polyphenols in modulating inflammatory mediators and signaling cascades as well as promoting other neurophysiological and neuroprotective functions underlying inflammation-associated depressive symptoms. Therefore, given their significant anti-neuroinflammatory effects, polyphenols could be a promising and effective adjunctive therapy for the treatment of neuropsychiatric symptoms associated with inflammation-related depression.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/fisiopatologia , /fisiopatologia , Polifenóis/farmacologia , Animais , Citocinas/metabolismo , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Neurogênese/fisiologia , Plasticidade Neuronal/fisiologia , Ratos , Fatores de Transcrição
5.
J Psychopharmacol ; 36(1): 57-65, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34983261

RESUMO

BACKGROUND: Depression is a major mental health issue worldwide, with high rates of chronicity and non-recovery associated with the condition. Existing treatments such as antidepressant medication and psychological treatments have modest effectiveness, suggesting the need for alternative interventions. AIM: The aim of this study was to examine the relationships between MDMA (3,4-methylenedioxymethamphetamine)/ecstasy and psilocybin use and major depressive episodes (MDEs). METHODS: This observational study used data from a large (N = 213,437) nationally representative sample of US adults to test the association of lifetime use of MDMA/ecstasy, psilocybin and other classic psychedelics (lysergic acid diethylamide (LSD), peyote, mescaline), other illegal substances (e.g. cocaine, phencyclidine (PCP)), and legal/medicinal substances of misuse (e.g. pain relievers, tranquilizers) with lifetime, past year, and past year severe MDEs. RESULTS: Results revealed that lifetime MDMA/ecstasy use was associated with significantly lowered odds of a lifetime MDE (adjusted odds ratio (aOR) = 0.84; p < 0.001), past year MDE (aOR = 0.84; p < 0.001), and past year severe MDE (aOR = 0.82; p < 0.001). Psilocybin was associated with significantly lowered odds of a past year MDE (aOR = 0.90; p < 0.05) and past year severe MDE (aOR = 0.87; p < 0.05). All other substances either shared no relationship with a MDE or conferred increased odds of an MDE. CONCLUSIONS: These results suggest that MDMA/ecstasy and psilocybin use is associated with lower risk of depression. Experimental studies are needed to test whether there is a causal association between use of these compounds and the alleviation of depressive symptoms.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Alucinógenos/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Psilocibina/farmacologia , Adolescente , Adulto , Idoso , Transtorno Depressivo Maior/fisiopatologia , Feminino , Alucinógenos/administração & dosagem , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Gravidade do Paciente , Psilocibina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estados Unidos , Adulto Jovem
6.
Cell Rep ; 38(2): 110232, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35021088

RESUMO

Cortical processing depends on finely tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered inhibition associated with treatment-resistant major depressive disorder (depression), which is implicated in cognitive deficits and rumination, but the link remains to be better established mechanistically in humans. Here we test the effect of reduced somatostatin interneuron-mediated inhibition on cortical processing in human neuronal microcircuits using a data-driven computational approach. We integrate human cellular, circuit, and gene expression data to generate detailed models of human cortical microcircuits in health and depression. We simulate microcircuit baseline and response activity and find a reduced signal-to-noise ratio and increased false/failed detection of stimuli due to a higher baseline activity in depression. We thus apply models of human cortical microcircuits to demonstrate mechanistically how reduced inhibition impairs cortical processing in depression, providing quantitative links between altered inhibition and cognitive deficits.


Assuntos
Depressão/fisiopatologia , Interneurônios/metabolismo , Somatostatina/metabolismo , Disfunção Cognitiva/metabolismo , Biologia Computacional/métodos , Bases de Dados Factuais , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/metabolismo , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Feminino , Humanos , Masculino , Modelos Teóricos , Rede Nervosa/fisiologia , Inibição Neural , Neurônios/fisiologia , Somatostatina/genética
7.
J Extracell Vesicles ; 11(1): e12185, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35029057

RESUMO

Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and severely limits psychosocial function and quality of life, but no effective medication is currently available. Circular RNAs (circRNAs) have been revealed to participate in the MDD pathological process. Targeted delivery of circRNAs without blood-brain barrier (BBB) restriction for remission of MDD represents a promising approach for antidepressant therapy. In this study, RVG-circDYM-extracellular vesicles (RVG-circDYM-EVs) were engineered to target and preferentially transfer circDYM to the brain, and the effect on the pathological process in a chronic unpredictable stress (CUS) mouse model of depression was investigated. The results showed that RVG-circDYM-EVs were successfully purified by ultracentrifugation from overexpressed circDYM HEK 293T cells, and the characterization of RVG-circDYM-EVs was successfully demonstrated in terms of size, morphology and specific markers. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that systemic administration of RVG-circDYM-EVs efficiently delivered circDYM to the brain, and alleviated CUS-induced depressive-like behaviours, and we discovered that RVG-circDYM-EVs notably inhibited microglial activation, BBB leakiness and peripheral immune cells infiltration, and attenuated astrocyte disfunction induced by CUS. CircDYM can bind mechanistically to the transcription factor TAF1 (TATA-box binding protein associated factor 1), resulting in the decreased expression of its downstream target genes with consequently suppressed neuroinflammation. Taken together, our findings suggest that extracellular vesicle-mediated delivery of circDYM is effective for MDD treatment and promising for clinical applications.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Vesículas Extracelulares/metabolismo , RNA Circular/administração & dosagem , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Modelos Animais de Doenças , Glicoproteínas/administração & dosagem , Glicoproteínas/genética , Glicoproteínas/metabolismo , Células HEK293 , Histona Acetiltransferases/genética , Humanos , Inflamação , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Proteínas Virais/administração & dosagem , Proteínas Virais/genética , Proteínas Virais/metabolismo
8.
Hum Brain Mapp ; 43(4): 1449-1462, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34888973

RESUMO

Aberrant affective neural processing and negative emotional bias are trait-marks of major depression disorders (MDDs). However, most research on biased emotional perception in depression has only focused on unimodal experimental stimuli, the neural basis of potentially biased emotional processing of multimodal inputs remains unclear. Here, we addressed this issue by implementing an audiovisual emotional task during functional MRI scanning sessions with 37 patients with MDD and 37 gender-, age- and education-matched healthy controls. Participants were asked to distinguish laughing and crying sounds while being exposed to faces with different emotional valences as background. We combined general linear model and psychophysiological interaction analyses to identify abnormal local functional activity and integrative processes during audiovisual emotional processing in MDD patients. At the local neural level, MDD patients showed increased bias activity in the ventromedial prefrontal cortex (vmPFC) while listening to negative auditory stimuli and concurrently processing visual facial expressions, along with decreased dorsolateral prefrontal cortex (dlPFC) activity in both the positive and negative visual facial conditions. At the network level, MDD exhibited significantly decreased connectivity in areas involved in automatic emotional processes and voluntary control systems during perception of negative stimuli, including the vmPFC, dlPFC, insula, as well as the subcortical regions of posterior cingulate cortex and striatum. These findings support a multimodal emotion dysregulation hypothesis for MDD by demonstrating that negative bias effects may be facilitated by the excessive ventral bottom-up negative emotional influences along with incapability in dorsal prefrontal top-down control system.


Assuntos
Percepção Auditiva/fisiologia , Mapeamento Encefálico , Cérebro/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Percepção Social , Adulto , Cérebro/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
9.
Schizophr Bull ; 48(1): 37-46, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34499169

RESUMO

BACKGROUND: Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. METHODS: We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. RESULTS: Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen's d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). CONCLUSIONS: These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.


Assuntos
Transtornos Psicóticos Afetivos/sangue , Fator Ativador de Células B/sangue , Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Esquizofrenia/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Adulto , Transtornos Psicóticos Afetivos/fisiopatologia , Transtorno Bipolar/fisiopatologia , Estudos Transversais , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/fisiopatologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-34389436

RESUMO

BACKGROUND: The latest studies have considered the time-dependent structures in dynamic brain networks. However, the effect of periphery structures on the temporal flow of information remains unexplored in patients with major depressive disorder (MDD). In this work, we aimed to explore the pattern of interactions between brain regions in MDD across space and time. METHODS: We concentrated on the temporal reachability of nodes in temporal brain networks derived from the resting-state functional magnetic resonance imaging (rs-fMRI) of 55 MDD patients and 62 sex-, age-matched healthy controls. Specifically, temporal connectedness and temporal efficiency (TEF) were estimated based on the length of temporal paths between node pairs. Subsequently, the temporal clustering coefficient (TCC) and temporal distance were jointly employed to explore the patterns in which a node's periphery structure affects its reachability. RESULTS: Significantly higher TEF and lower TCC were found in temporal brain networks in MDD. Besides, significant between-group differences of nodal TCC were detected in regions of sensory perception systems. Considering the temporal paths that begin or end at these regions, MDD patients showed several altered temporal distances. CONCLUSION: Our results showed that the temporal reachability of specific brain regions in MDD could be affected as their periphery structures evolve, which may explain the dysfunction of sensory perception systems in the spatiotemporal domain.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Rede Nervosa/fisiopatologia , Percepção , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Fatores de Tempo
11.
Sci Rep ; 11(1): 22007, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759276

RESUMO

Default mode network (DMN) is a set of functional brain structures coherently activated when individuals are in resting-state. In this study, we constructed multi-frequency band resting-state EEG-based DMN functional network models for major psychiatric disorders to easily compare their pathophysiological characteristics. Phase-locking values (PLVs) were evaluated to quantify functional connectivity; global and nodal clustering coefficients (CCs) were evaluated to quantify global and local connectivity patterns of DMN nodes, respectively. DMNs of patients with post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), panic disorder, major depressive disorder (MDD), bipolar disorder, schizophrenia (SZ), mild cognitive impairment (MCI), and Alzheimer's disease (AD) were constructed relative to their demographically-matched healthy control groups. Overall DMN patterns were then visualized and compared with each other. In global CCs, SZ and AD showed hyper-clustering in the theta band; OCD, MCI, and AD showed hypo-clustering in the low-alpha band; OCD and MDD showed hypo-clustering and hyper-clustering in low-beta, and high-beta bands, respectively. In local CCs, disease-specific patterns were observed. In the PLVs, lowered theta-band functional connectivity between the left lingual gyrus and the left hippocampus was frequently observed. Our comprehensive comparisons suggest EEG-based DMN as a useful vehicle for understanding altered brain networks of major psychiatric disorders.


Assuntos
Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Rede Nervosa/fisiopatologia , Doença de Alzheimer/fisiopatologia , Transtorno Bipolar/fisiopatologia , Mapeamento Encefálico , Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Humanos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno de Pânico/fisiopatologia , Esquizofrenia/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
12.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769155

RESUMO

Depression is characterized by impairments in adult neurogenesis. Reduced hippocampal function, which is suggestive of neurogenesis impairments, is associated with depression-related phenotypes. As adult neurogenesis operates in an activity-dependent manner, disruption of hippocampal neurogenesis in depression may be a consequence of neural circuitry impairments. In particular, the entorhinal cortex is known to have a regulatory effect on the neural circuitry related to hippocampal function and adult neurogenesis. However, a comprehensive understanding of how disruption of the neural circuitry can lead to neurogenesis impairments in depression remains unclear with respect to the regulatory role of the entorhinal cortex. This review highlights recent findings suggesting neural circuitry-regulated neurogenesis, with a focus on the potential role of the entorhinal cortex in hippocampal neurogenesis in depression-related cognitive and emotional phenotypes. Taken together, these findings may provide a better understanding of the entorhinal cortex-regulated hippocampal neurogenesis model of depression.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Córtex Entorrinal/fisiopatologia , Hipocampo/fisiopatologia , Neurogênese , Adulto , Animais , Cognição , Transtorno Depressivo Maior/patologia , Emoções , Córtex Entorrinal/patologia , Hipocampo/patologia , Humanos
13.
J Biochem Mol Toxicol ; 35(12): e22930, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34676637

RESUMO

Uncontrolled stress can lead to vascular injury, hypertension, arrhythmia, compromised immune system alteration in microbiota activity, and neurobehavioral changes, including depression. The gut microbiota has been recently developed, not only for major depressive disorders but also cardiovascular problems, as a therapeutic concern. Since then, >100 studies have studied the link between depression and cardiovascular disease (CVD), and have shown that depression is common (≈20%-35%) in patients with CVD, and seems to be indicative of negative heart effects in patients. Depressive symptoms patients have demonstrated an elevated platelet reactivity, reduced cardiac variability, and enhanced proinflammatory signals, which are all cardiovascular-related risk factors. The pathophysiology of depression-related CVD is nevertheless a challenge because of the heterogeneous depressive syndromes and the etiologies. The cardiovascular effects of tetrahydrocannabinol (THC) (the key psychotropic credential of cannabis) and endocannabinoids (THC endogenous equivalents which cause type 1 [CB1] and 2 [CB2] cannabinoids) have been extensively examined based on well-documented effects of marijuana smoke on blood pressure (BP) and heart rate (HR). Therefore, the aim of the review article is to establish the relationship of abnormal cannabidiols system-mediated cardiovascular protection in disrupted gut/brain axis associated depression to determine the translational potential of targeting abnormal cannabidiols receptors in clinical studies.


Assuntos
Encéfalo/efeitos dos fármacos , Canabidiol/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Transtorno Depressivo Maior/fisiopatologia , Intestinos/efeitos dos fármacos , Encéfalo/fisiologia , Humanos , Intestinos/fisiologia
14.
Biomarkers ; 26(8): 752-759, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34664533

RESUMO

Despite research advances, recently identified biological markers for depression are either non-specific or impractical in daily clinical practice. Hence, we aim to identify a novel biomarker: δEPCD, the electrophysiologic coefficient of depressiveness. δEPCD must be sensitive and specific to the vulnerability towards depression. It should also detect the presence of a depressive clinical state and be able to quantify its severity. Moreover, it should be easily accessible and cost-effective. Accordingly, combining high-frequency heart rate variability (HF-HRV), which reflects a reduction in vagal tone, and tryptophan metabolism, which influences serotonin synthesis pathway, may have a good diagnostic and prognostic accuracy in depression. δEPCD is the multiplication of the intrinsic difference between state 0 (rest) and state 1 (exposure to stress) of HF-HRV and the plasma concentration ratio between quinolinic acid and kynurenine. δEPCD theoretically fluctuates between -1000 and 0 where being closer to 0 signifies no vulnerability to depression. Individuals with a score between -16.7 and -167 have a high vulnerability to depression. Finally, individuals with a δEPCD closer to -1000 have the most severe forms of depression. δEPCD is theoretically conceived to be easy to assess and monitor which makes it a candidate for further evaluation of reliability and validity.CLINICAL SIGNIFICANCEDepression is currently diagnosed based on emotional and behavioural symptoms; however there is currently a rising interest in the field of neurobiological markers that could improve diagnostic accuracy.Many current biological approaches are primarily based on single neurobiological markers that are either non-specific or impractical in daily clinical practice.Among other neurological effects, depression may modify the parasympathetic nervous system tone and disturb the tryptophan metabolism.The electrophysiological coefficient of depressiveness δEPCD combines heart rate variability (HRV) and tryptophan metabolism to reflect the intrinsic individual vulnerability towards depression and the inherent severity of an index depressive disorder.δEPCD is the intrinsic difference between state 0 (without stress) and state 1 (exposed to a stressful task) of the high-frequency heart rate variability multiplied by the intrinsic difference between both states, e.g. state 0 and 1, of the plasma concentration ratio of quinolinic acid over kynurenine.


Assuntos
Transtorno Depressivo Maior/sangue , Frequência Cardíaca/fisiologia , Cinurenina/sangue , Ácido Quinolínico/sangue , Triptofano/sangue , Biomarcadores/sangue , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse Fisiológico/fisiologia
15.
Clin Neurophysiol ; 132(11): 2739-2750, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34571367

RESUMO

OBJECTIVES: The study investigated the role of top-down versus bottom-up connectivity, during the processing of predictive information, in three different psychiatric disorders. METHODS: Electroencephalography (EEG) was recorded during the performance of a task, which evaluates the ability to use predictive information in order to facilitate predictable versus random target detection. We evaluated EEG event-related directed connectivity, in patients with schizophrenia (SZ), major depressive disorder (MDD), and autism spectrum disorder (ASD), compared with healthy age-matched controls. Directed connectivity was evaluated using phase transfer entropy. RESULTS: We showed that top-down frontal-parietal connectivity was weaker in SZ (theta and beta bands) and ASD (alpha band) compared to control subjects, during the processing of stimuli consisting of the predictive sequence. In SZ patients, top-down connectivity was also attenuated, during the processing of predictive targets in the beta frequency band. In contrast, compared with controls, MDD patients displayed an increased top-down flow of information, during the processing of predicted targets (alpha band). CONCLUSIONS: The findings suggest that top-down frontal-parietal connectivity is altered differentially across three major psychiatric disorders, specifically during the processing of predictive stimuli. SIGNIFICANCE: Altered top-down connectivity may contribute to the specific prediction deficits observed in each of the patient populations.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Rede Nervosa/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Transtorno do Espectro Autista/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Eletroencefalografia/métodos , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa/métodos , Desempenho Psicomotor/fisiologia , Esquizofrenia/diagnóstico , Adulto Jovem
16.
J Psychiatry Neurosci ; 46(5): E518-E527, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34548386

RESUMO

BACKGROUND: Rumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging because of the need to distinguish self effects from the emotional content of task stimuli. This study employed an emotionally neutral self-related paradigm to investigate possible altered self-processing in depression and its link to rumination. METHODS: People with major depressive disorder (n = 25) and controls (n = 25) underwent task-based electro-encephalogram recording. We studied late event-related potentials, along with low-frequency oscillatory power. We compared electroencephalogram metrics between groups and correlated them with depressive symptoms and reported rumination. RESULTS: Participants with major depressive disorder displayed a difference in late positive potentials across frontocentral electrodes between self-related and non-self-related conditions. We found no such difference in controls. The magnitude of this difference was positively correlated with depressive symptoms and reported rumination. Participants with major depressive disorder also had elevated theta oscillation power at central electrodes in self-related conditions, a finding that we did not see in controls. LIMITATIONS: Patients with major depressive disorder were medicated at the time of the study. The group studied was primarily female, so the observed effects may have been sex-specific. CONCLUSION: Rumination appears to be linked to altered self-related processing in depression, independent of stimuli-related emotional confounds. This connection between self-related processing and depression may point to a self disorder as a core component of depression.


Assuntos
Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Ruminação Cognitiva , Adulto , Encéfalo/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Emoções , Feminino , Humanos , Masculino
17.
Hum Brain Mapp ; 42(16): 5458-5476, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34431584

RESUMO

Working memory (WM) impairments are common features of psychiatric disorders. A systematic meta-analysis was performed to determine common and disorder-specific brain fMRI response during performance of WM tasks in patients with SZ and patients with MDD relative to healthy controls (HC). Thirty-four published fMRI studies of WM in patients with SZ and 18 published fMRI studies of WM in patients with MDD, including relevant HC, were included in the meta-analysis. In both SZ and MDD there was common stronger fMRI response in right medial prefrontal cortex (MPFC) and bilateral anterior cingulate cortex (ACC), which are part of the default mode network (DMN). The effects were of greater magnitude in SZ than MDD, especially in prefrontal-temporal-cingulate-striatal-cerebellar regions. In addition, a disorder-specific weaker fMRI response was observed in right middle frontal gyrus (MFG) in MDD, relative to HC. For both SZ and MDD a significant correlation was observed between the severity of clinical symptoms and lateralized fMRI response relative to HC. These findings indicate that there may be common and distinct anomalies in brain function underlying deficits in WM in SZ and MDD, which may serve as a potential functional neuroimaging-based diagnostic biomarker with value in supporting clinical diagnosis, measuring illness severity and assessing the efficacy of treatments for SZ and MDD at the brain level.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Imageamento por Ressonância Magnética , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiopatologia , Esquizofrenia/fisiopatologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Rede Nervosa/diagnóstico por imagem , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem
18.
Clin Neurophysiol ; 132(10): 2654-2665, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34456164

RESUMO

OBJECTIVE: Deficits of mismatch negativity (MMN), a general index of echoic memory function, have been documented in patients with schizophrenia. However, it remains controversial whether patients with major depressive disorder (MDD) demonstrate MMN defects compared with healthy controls (HC). METHODS: After screening 41 potential studies identified in PubMed and Medline, 13 studies consisting of 343 HC and 339 patients with MDD were included in the present meta-analysis. The effect sizes (Hedges's g) with a random-effect and inverse-variance weighted model were estimated for the MMN amplitudes and latencies. The effects of different deviant types (i.e., frequency and duration) and of different illness stages (i.e., acute and chronic) on MMN were also examined. RESULTS: We found that 1) MMN amplitudes (g = 1.273, p < 0.001) and latencies (g = 0.303, p = 0.027) to duration, but not frequency deviants, were significantly impaired in patients with MDD compared to HC; 2), acute patients exhibited lower MMN amplitudes (g = 1.735, p < 0.001) and prolonged MMN latencies (g = 0.461, p = 0.007) for the duration deviants compared to HC. Only the attenuated duration MMN amplitudes were detected in patients with chronic MDD (g = 0.822, p = 0.027); and 3) depressive symptoms did not significantly correlate with MMN responses. CONCLUSIONS: Patients with MDD demonstrated abnormal MMN responses to duration deviants compared to HC. SIGNIFICANCE: Duration MMN may constitute an electrophysiological indicator to differentiate HC from patients with MDD, particularly those in the acute stage.


Assuntos
Estimulação Acústica/métodos , Percepção Auditiva/fisiologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Eletroencefalografia/métodos , Potenciais Evocados Auditivos/fisiologia , Transtorno Depressivo Maior/psicologia , Humanos
19.
Psychophysiology ; 58(12): e13918, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34403515

RESUMO

Aberrant effective connectivity between default mode (DMN) and salience (SAL) networks may support the tendency of depressed individuals to find it difficult to disengage from self-focused, negatively-biased thinking and may contribute to the onset and maintenance of depression. Assessment of effective connectivity, which can statistically characterize the direction of influence between regions within neural circuits, may provide new insights into the nature of DMN-SAL connectivity disruptions in depression. Functional magnetic resonance imaging (fMRI) was collected from 38 individuals with a history of major depression and 50 healthy comparison participants during completion of an emotion-word Stroop task. Activation within DMN and SAL networks and effective connectivity between DMN and SAL, assessed via Granger causality, were examined. Individuals with a history of depression exhibited greater overall network activation, greater directed connectivity from DMN to SAL, and less directed connectivity from SAL to DMN than healthy comparison participants during negative-word trials. Among individuals with a history of depression, greater DMN-to-SAL connectivity was associated with lower overall network activation and worse task performance during positive-word trials; this pattern was not observed among healthy participants. Present findings indicate that greater network activation and, specifically, influence of DMN on SAL, support negativity bias among previously depressed individuals.


Assuntos
Córtex Cerebral/fisiopatologia , Conectoma , Rede de Modo Padrão/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Emoções/fisiologia , Função Executiva/fisiologia , Rede Nervosa/fisiopatologia , Pensamento/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Rede de Modo Padrão/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem
20.
Hum Brain Mapp ; 42(16): 5322-5333, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34390089

RESUMO

Depression symptom heterogeneity limits the identifiability of treatment-response biomarkers. Whether improvement along dimensions of depressive symptoms relates to separable neural networks remains poorly understood. We build on work describing three latent symptom dimensions within the 17-item Hamilton Depression Rating Scale (HDRS) and use data-driven methods to relate multivariate patterns of patient clinical, demographic, and brain structural changes over electroconvulsive therapy (ECT) to dimensional changes in depressive symptoms. We included 110 ECT patients from Global ECT-MRI Research Collaboration (GEMRIC) sites who underwent structural MRI and HDRS assessments before and after treatment. Cross validated random forest regression models predicted change along symptom dimensions. HDRS symptoms clustered into dimensions of somatic disturbances (SoD), core mood and anhedonia (CMA), and insomnia. The coefficient of determination between predicted and actual changes were 22%, 39%, and 39% (all p < .01) for SoD, CMA, and insomnia, respectively. CMA and insomnia change were predicted more accurately than HDRS-6 and HDRS-17 changes (p < .05). Pretreatment symptoms, body-mass index, and age were important predictors. Important imaging predictors included the right transverse temporal gyrus and left frontal pole for the SoD dimension; right transverse temporal gyrus and right rostral middle frontal gyrus for the CMA dimension; and right superior parietal lobule and left accumbens for the insomnia dimension. Our findings support that recovery along depressive symptom dimensions is predicted more accurately than HDRS total scores and are related to unique and overlapping patterns of clinical and demographic data and volumetric changes in brain regions related to depression and near ECT electrodes.


Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Aprendizado de Máquina , Neuroimagem/normas , Avaliação de Resultados em Cuidados de Saúde/normas , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Avaliação de Resultados em Cuidados de Saúde/métodos
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