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1.
Medicine (Baltimore) ; 98(47): e17962, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764799

RESUMO

To explore the characteristics of local brain activity in patients with bipolar depression and its correlation with clinical features.In accord with the diagnostic and statistical manual of mental disorders-IV of bipolar disorder, 21 patients were enrolled while 21 healthy controls were matched with similar gender, age, level of educations. A 3.0T GE magnetic resonance scanner was used to collect the imaging data, and a 2-sample t test was performed. Regional homogeneity (ReHo) method was used to estimate regional activation patterns through indices of localized concordance. ReHo values were compared between groups. Seed-based correlation analysis was used to analyze functional connections.In the patients' group, ReHo (regional homogeneity) values of resting state functional magnetic resonance imaging data on the right cerebellum 4 and 5 area, cerebellar vermis 6 area, left insula were positively correlated with Hamilton depression scale (HAMD) scores. ReHo values on the left of the triangle of inferior frontal gyrus, right inferior frontal gyrus of orbital region showed negative correlation with HAMD scores. The value of ReHo in the patients' group was positively correlated with the patients' Hamilton anxiety scale score in the right fusiform gyrus, and negative correlation was found in the left insula. The ReHo value of the patients' group was negatively correlated with the patients' Montgomery Asberg depression rating scale score in regions of the midbrain. The value of ReHo in patients' group was significantly reduced in the right central front.The depression and anxiety severity of bipolar depression patients may be associated with the consistency activity of left insula, right cerebellum, and cerebellar vermis related area, fusiform gyrus. In addition, the ReHo of the midbrain neurons activity may be associated with depression level of patients with bipolar II disorder.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Adulto , Transtorno Bipolar/classificação , Feminino , Humanos , Masculino , Descanso
2.
Psychiatr Danub ; 31(Suppl 3): 591-594, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488796

RESUMO

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare monogenic disorder caused by mutations in the NOTCH3 gene. The clinical features are primarily neurological, which include recurrent transient ischaemic attacks, strokes, and migraines. However, psychiatric manifestations which mainly include mood disturbances have also been reported in CADASIL. Manic symptoms and bipolar disorders are rarely documented in CADASIL and existing reports generally lack detailed descriptions of the psychiatric evaluation. We discuss a case of Bipolar Affective Disorder (BD) in a British woman with a family history of CADASIL. This case provides insight into the diagnosis and management of BD as well as the possible underlying aetiologies that should be considered. The similarities between BD and CADASIL in terms of imaging, genetic, and therapeutic aspects raise the possibility of common dysfunctional pathways. BD in CADASIL may warrant greater consideration by both psychiatrists as well as non-psychiatric specialists and further studies are required to understand the pathological significance.


Assuntos
Transtorno Bipolar/complicações , CADASIL/complicações , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , CADASIL/genética , CADASIL/fisiopatologia , CADASIL/psicologia , Feminino , Humanos , Transtornos de Enxaqueca/complicações , Transtornos do Humor/complicações , Mutação , Receptor Notch3/genética , Reino Unido
3.
BMJ Case Rep ; 12(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434663

RESUMO

A 53-year-old woman was admitted with thyroid storm and severe behavioural problems. She had longstanding bipolar affective disorder. She was psychotic and obstructed in-patient medical management for thyroid storm. She required one-to-one psychiatric nursing and was placed under section 3 of the Mental Health Act meaning she could be detained in hospital for psychiatric treatment for up to 6 months. She underwent a total thyroidectomy. Due to her paranoid mental state, she refused treatment and the administration of thyroid hormone replacement was difficult. Postoperatively, intramuscular levothyroxine was used effectively to stabilise her thyroid function. There are no consensus guidelines on the use of parenteral levothyroxine and intramuscular levothyroxine is rarely used. This case uniquely illustrates its utility with bi-weekly blood tests showing a fast and stable response to intramuscular hormone replacement.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtornos Mentais/fisiopatologia , Crise Tireóidea/cirurgia , Tireoidectomia , Tiroxina/administração & dosagem , Feminino , Terapia de Reposição Hormonal , Humanos , Injeções Intramusculares , Serviços de Saúde Mental , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Crise Tireóidea/fisiopatologia , Resultado do Tratamento
4.
Expert Opin Drug Saf ; 18(10): 893-913, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31364895

RESUMO

Introduction: The use of antidepressants (AD) in the treatment of bipolar depression is one of the most controversial issues in psychopharmacology. For some, AD are useful, but, for others, they should never be used in bipolar depression. Areas covered: This review examines published clinical studies on the use of ADs in bipolar depression, addressing their clinical efficacy and the occurrence of side effects, manic switches, cycle acceleration, and suicidal behavior. Meta-analyzes and review articles on the subject are also discussed. Expert opinion: Approved therapeutic options for bipolar depression are associated with not very high response rates and a high incidence of adverse effects. Patients with bipolar depression present very heterogeneous responses to the use of ADs. Some improve significantly, while others, especially those with concomitant manic symptoms, have had previous episodes of treatment-emergent mania or are rapid cyclers, exhibit manic switches or cycle acceleration. The authors conclude that the real question is not whether ADs should or should not be used in bipolar depression, but which patients benefit from these drugs and which ones are impaired. The concept of bipolar spectrum and a dimensional approach on bipolar/unipolar distinction may be useful for understanding the heterogeneity of responses to ADs.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Seleção de Pacientes , Antidepressivos/efeitos adversos , Transtorno Bipolar/fisiopatologia , Humanos , Resultado do Tratamento
5.
Acta Neuropsychiatr ; 31(4): 193-201, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31159897

RESUMO

OBJECTIVE: Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients. The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD. RESULTS: We highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches. CONCLUSION: The probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Canabinoides/uso terapêutico , Cannabis , Endocanabinoides/fisiologia , Endocanabinoides/uso terapêutico , Afeto/efeitos dos fármacos , Afeto/fisiologia , Encéfalo/efeitos dos fármacos , Humanos , Extratos Vegetais/uso terapêutico , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/fisiologia , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/fisiologia
6.
PLoS Comput Biol ; 15(6): e1006903, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31185008

RESUMO

Popular computational models of decision-making make specific assumptions about learning processes that may cause them to underfit observed behaviours. Here we suggest an alternative method using recurrent neural networks (RNNs) to generate a flexible family of models that have sufficient capacity to represent the complex learning and decision- making strategies used by humans. In this approach, an RNN is trained to predict the next action that a subject will take in a decision-making task and, in this way, learns to imitate the processes underlying subjects' choices and their learning abilities. We demonstrate the benefits of this approach using a new dataset drawn from patients with either unipolar (n = 34) or bipolar (n = 33) depression and matched healthy controls (n = 34) making decisions on a two-armed bandit task. The results indicate that this new approach is better than baseline reinforcement-learning methods in terms of overall performance and its capacity to predict subjects' choices. We show that the model can be interpreted using off-policy simulations and thereby provides a novel clustering of subjects' learning processes-something that often eludes traditional approaches to modelling and behavioural analysis.


Assuntos
Simulação por Computador , Tomada de Decisões/fisiologia , Aprendizagem/fisiologia , Modelos Psicológicos , Adulto , Transtorno Bipolar/fisiopatologia , Biologia Computacional , Transtorno Depressivo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
BMC Neurosci ; 20(1): 30, 2019 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208340

RESUMO

BACKGROUND: Distinctive patterns of functional connectivity (FC) abnormalities in neural circuitry has been reported in patients with bipolar depression (BD) and unipolar depression (UD). However, it is unclear that whether this distinct functional connectivity patterns are diagnosis specific between BD and UD. This study aimed to compare patterns of functional connectivity among BD, UD and healthy controls (HC) and determine the distinct functional connectivity patterns which can differentiate BD from UD. METHOD: Totally 23 BD, 22 UD, and 24 HC were recruited to undergo resting-state fMRI scanning. FC between each pair of brain regions was calculated and compared among the three groups, the associations of FC with depressive symptom were also analyzed. RESULTS: Both patient groups showed significantly decreased cerebral-limbic FC located between the default mode network [posterior cingulated gyrus (PCG) and precuneus] and limbic regions (hippocampus, amygdala and thalamus) than HC. Moreover, the BD group exhibited more decreased FC mainly in the cortical regions (middle temporal gyrus, PCG, medial superior frontal gyrus, inferior occipital gyrus and superior temporal gyrus), but the UD group is more associated with limbic alterations. These decreased FCs were negatively correlated with HAMD scores in both BD and UD patients. CONCLUSIONS: BD and UD patients demonstrate different patterns of abnormal cerebral-limbic FC, reflected by decreased FC within cerebral cortex and limbic regions in BD and UD, respectively. The distinct FC abnormal pattern of the cerebral-limbic circuit might be applied as biomarkers to differentiate these two depressive patient groups.


Assuntos
Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Transtorno Depressivo/fisiopatologia , Sistema Límbico/fisiopatologia , Adulto , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/fisiopatologia , Índice de Gravidade de Doença , Adulto Jovem
8.
Dev Psychopathol ; 31(3): 1037-1052, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064610

RESUMO

Aberrant face emotion processing has been demonstrated in youth with and at a familial risk for bipolar and major depressive disorders. However, the neurobiological factors related to emotion processing that underlie resilience from youth-onset mood disorders are not well understood. Functional magnetic resonance imaging data during an implicit emotion processing task were collected at baseline from a sample of 50 youth, ages 8-17, who were healthy but also familially at high risk for either bipolar disorder or major depressive disorder, and 24 healthy controls with no family history of psychopathology (HCL). Participants were reevaluated 3 years later and classified into three groups for analysis: high-risk youth who converted to a psychiatric diagnosis (CVT; N = 23), high-risk youth who were resilient from developing any psychopathology (RES; N = 27), and HCL youth (N = 24) who remained healthy at follow-up. For happy > calm faces, the CVT and RES groups had significantly lower activation in the left inferior parietal lobe (IPL), while the RES group had lower activation in the right supramarginal gyrus. For fear > calm faces, the RES group had lower activation in the right precuneus and inferior frontal gyrus (IFG) compared to the CVT group. Connectivity analyses revealed the RES group exhibited higher left IPL connectivity with visual cortical regions for happy > calm faces, and higher IFG connectivity with frontal, temporal, and limbic regions for fear > calm faces. These connectivities were correlated with improvements in prosocial behaviors and global functioning. Our findings suggest that differential activation and connectivity in the IPL, IFG, and precuneus in response to emotional stimuli may represent distinct resilience and risk markers for youth-onset mood disorders.


Assuntos
Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Emoções/fisiologia , Expressão Facial , Resiliência Psicológica , Adolescente , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Encéfalo/fisiopatologia , Criança , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Feminino , Predisposição Genética para Doença , Humanos , Imagem por Ressonância Magnética/métodos , Masculino
9.
Brain Behav ; 9(6): e01257, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31066228

RESUMO

INTRODUCTION: Previous studies have established graph theoretical analysis of functional network connectivity (FNC) as a potential tool to detect neurobiological underpinnings of psychiatric disorders. Despite the promising outcomes in studies that examined FNC aberrancies in bipolar disorder (BD) and major depressive disorder (MDD), there is still a lack of research comparing both mood disorders, especially in a nondepressed state. In this study, we used graph theoretical network analysis to compare brain network properties of euthymic BD, euthymic MDD and healthy controls (HC) to evaluate whether these groups showed distinct features in FNC. METHODS: We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 BD patients, 15 patients with recurrent MDD as well as 30 age- and gender-matched HC. Graph theoretical analyses were then applied to investigate functional brain networks on a global and regional network level. RESULTS: Global network analysis revealed a significantly higher mean global clustering coefficient in BD compared to HC. We further detected frontal, temporal and subcortical nodes in emotion regulation areas such as the limbic system and associated regions exhibiting significant differences in network integration and segregation in BD compared to MDD patients and HC. Participants with MDD and HC only differed in frontal and insular network centrality. CONCLUSION: In conclusion, our findings indicate that a significantly altered brain network topology in the limbic system might be a trait marker specific to BD. Brain network analysis in these regions may therefore be used to differentiate euthymic BD not only from HC but also from patients with MDD.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Imagem por Ressonância Magnética/métodos , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/fisiopatologia , Masculino
10.
Int J Psychiatry Clin Pract ; 23(2): 128-133, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31081413

RESUMO

Objectives: Agmatine is a cationic amine resulting from the decarboxylation of l-arginine. Agmatine has neuroprotective, anti-inflammatory, anti-stress, and anti-depressant properties. In this study, plasma agmatine, arginine decarboxylase, and agmatinase levels were measured during manic episode and remission period in patients with bipolar disorder. Methods: Thirty healthy volunteers and 30 patients who meet Bipolar Disorder Manic Episode diagnostic criteria were included in the study. Additionally, the changes in the patient group between manic episode and remission period were examined. We evaluated the relationship between levels of l-arginine and arginine decarboxylase in the agmatine synthesis pathway, and level of agmatinase that degrades agmatine. Results: Levels of agmatine and l-arginine were significantly increased than control group during manic episode (p < .01). All parameters were increased during manic episode compared to remission period (p < .05). Agmatinase was significantly decreased both during manic episode (p < .01) and remission period (p < .05) in comparison to the control group. Arginine decarboxylase levels did not show a significant difference between the groups (p > .05). Conclusions: This study indicate that there may be a relationship between bipolar disorder and agmatine and its metabolic pathway. Nonetheless, we believe more comprehensive studies are needed in order to reveal the role of agmatine in etiology of bipolar disorder. Key points Agmantine, agmatinase, l-arginine and arginine decarboxylase levels in BD have not been explored before. Various neuro-chemical mechanisms act to increase agmatine in BD; however, agmatine could have elevated to compensate agmatine deficit prior to the manifestation of the disease as in schizophrenia. Elevated agmatine degradation resulting from excess expression of agmatinase which is suggested to be effective in pathogenesis of mood disorders was compensated by this way. Elevated agmatine may be one of the causes which play a role in mania development. Elevated agmatine levels are also suggested to trigger psychosis and be related with the etiology of manic episode and lead to BD.


Assuntos
Agmatina/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/fisiopatologia , Carboxiliases/sangue , Redes e Vias Metabólicas , Ureo-Hidrolases/sangue , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão
11.
Psychiatry Res ; 276: 151-159, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31085419

RESUMO

OBJECTIVE: To assess the reversibility of weight gain associated with psychotropic medications in children. METHODS: A retrospective cohort study was conducted using an ambulatory electronic medical records database. Individuals under 18 years of age were identified if they were initiating a new course of second generation/atypical antipsychotics (SGA) or mood stabilizers (MS) following a bipolar disorder diagnosis and subsequently discontinued treatment within 24 months of treatment initiation. RESULTS: Of the 297 children who had experienced positive BMI percentile increase (mean±SD: 8.71±11.94) during the treatment of SGA and/or MS, treatment discontinuation led to an average of 1.88 (±13.41) unit decrease in BMI percentile during a 12-month period since the treatment discontinuation. Repeated measure mixed model analysis showed that the reduction of BMI percentile after treatment discontinuation was neither associated with the treatment regimens patients previously received, nor associated with time since the treatment discontinuation. The three statistically significant predictors were baseline BMI percentile, BMI percentile gained during the treatment, and comorbid substance abuse disorder. CONCLUSION: Children with bipolar disorder were able to lose a fraction of weight gained during pharmacotherapy after the treatment discontinuation, however, their BMI percentile may not return to the prior treatment level within a year post-medication discontinuation.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Psicotrópicos/efeitos adversos , Ganho de Peso/efeitos dos fármacos , Adolescente , Transtorno Bipolar/fisiopatologia , Índice de Massa Corporal , Peso Corporal , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Suspensão de Tratamento
12.
Neurobiol Learn Mem ; 161: 158-168, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31004802

RESUMO

Episodic memories, when reactivated, can be modified or updated by new learning. Since such dynamic memory processes remain largely unexplored in psychiatric disorders, we examined the impact of depression on episodic memory updating. Unipolar and bipolar depression patients, and age/education matched controls, first learned a set of objects (List-1). Two days later, participants in all three groups were either reminded of the first learning session or not followed by the learning of a new set of objects (List-2). Forty-eight hours later, List-1 recall was impaired in unipolar and bipolar patients compared to control participants. Further, as expected, control participants who received a reminder spontaneously recalled items from List-2 during recall of List-1, indicative of an updated List-1 memory. Such spontaneous intrusions were also seen in the unipolar and bipolar patients that received the reminder, suggesting that memory updating was unaffected in these two patient groups despite impaired recall of List 1. Unexpectedly, we observed a trend towards higher intrusions, albeit statistically insignificant, not only in the reminder but also in the no-reminder subgroups of bipolar patients. We probed this further in a second cohort by testing recall of List-2, which was also impaired in both depression groups. Again bipolar patients showed intrusions, but this time in the reverse order from List-1 into List-2, independent of a reminder. Taken together, despite impaired recall, updating of episodic memories was intact and unidirectional in unipolar depression. In contrast, indiscriminate updating, as evidenced by bidirectional interference between episodic memories, was seen in bipolar depression. These findings reveal a novel distinction between unipolar versus bipolar depression using a reactivation-dependent memory updating paradigm.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Depressivo/fisiopatologia , Transtornos da Memória/fisiopatologia , Memória Episódica , Rememoração Mental/fisiologia , Adolescente , Adulto , Transtorno Bipolar/complicações , Estudos de Coortes , Transtorno Depressivo/complicações , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Adulto Jovem
13.
Intern Med ; 58(15): 2195-2199, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30996193

RESUMO

We herein report two cases of patients with thyroid storm with a delayed diagnosis due to psychosis. The patients were a 63-year-old woman with bipolar II disorder and a 37-year-old man with major depressive disorder. The psychoses in both patients were well controlled with medication. Although they both showed symptoms of thyrotoxicosis, the symptoms were ignored, presumably because the psychological manifestations of worsening of psychosis and thyroid storm are similar. When the mental or physical state of patients with psychosis changes, thyroid hormone levels should be measured for early treatment.


Assuntos
Transtorno Bipolar/diagnóstico , Diagnóstico Tardio , Transtorno Depressivo Maior/diagnóstico , Adulto , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos , Crise Tireóidea/diagnóstico , Crise Tireóidea/fisiopatologia , Hormônios Tireóideos , Tireotoxicose/diagnóstico , Tireotoxicose/fisiopatologia
14.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atenção/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia
15.
PLoS One ; 14(3): e0213657, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30870472

RESUMO

The main aim of the present study was to explore the value of several measures of handwriting in the study of motor abnormalities in patients with bipolar or psychotic disorders. 54 adult participants with a schizophrenia spectrum disorder or bipolar disorder and 44 matched healthy controls, participated in the study. Participants were asked to copy a handwriting pattern consisting of four loops, with an inking pen on a digitizing tablet. We collected a number of classical, non-linear and geometrical measures of handwriting. The handwriting of patients was characterized by a significant decrease in velocity and acceleration and an increase in the length, disfluency and pressure with respect to controls. Concerning non-linear measures, we found significant differences between patients and controls in the Sample Entropy of velocity and pressure, Lempel-Ziv of velocity and pressure, and Higuchi Fractal Dimension of pressure. Finally, Lacunarity, a measure of geometrical heterogeneity, was significantly greater in handwriting patterns from patients than from controls. We did not find differences in any handwriting measure on function of the specific diagnosis or the antipsychotic dose. Results indicate that participants with a schizophrenia spectrum disorder or bipolar disorder exhibit significant motor impairments and that these impairments can be readily quantified using measures of handwriting movements. Besides, they suggest that motor abnormalities are a core feature of several mental disorders and they seem to be unrelated to the pharmacological treatment.


Assuntos
Transtorno Bipolar/diagnóstico , Escrita Manual , Esquizofrenia/diagnóstico , Adulto , Idoso , Algoritmos , Antipsicóticos/uso terapêutico , Fenômenos Biomecânicos , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/fisiopatologia , Estudos de Casos e Controles , Entropia , Feminino , Fractais , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/efeitos dos fármacos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Adulto Jovem
16.
Psychiatry Res ; 275: 39-45, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30878855

RESUMO

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) share numerous clinical features, which can make the differential diagnosis challenging. Studies conducted in adults suggest that patients with BD and ADHD have different sleep patterns. However, in pediatric populations, data on these potential differences are scant. The present preliminary study was conducted to identify potential differences in sleep alterations among youths diagnosed with BD or ADHD compared to healthy controls (HC). A total of 26 patients diagnosed with BD (n = 13) or ADHD (n = 13) were compared to 26 sex- and age-matched HC ([HCBD], n = 13, and [HCADHD], n = 13). All participants underwent polysomnography. The mean duration of stage N2 sleep was shorter in the BD group than in controls (HCBD). The BD group also had higher (non-significant) REM density (REMd) scores than controls while mean REMd scores were lower in the ADHD group versus controls. Compared to the ADHD group, the BD group presented a shorter N2 stage, a longer first REM sleep duration (R1), and greater REMd. According to our findings, these three variables-N2 stage, REMd, and R1-appear to differentiate patients with BD from those with ADHD and from HC.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Polissonografia/tendências , Fases do Sono/fisiologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Bipolar/psicologia , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Sono/fisiologia , Sono REM/fisiologia
17.
Braz J Psychiatry ; 41(4): 289-296, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30892378

RESUMO

OBJECTIVE: To evaluate whether exposing rats to individual or combined environmental stressors triggers endophenotypes related to mood and anxiety disorders, and whether this effect depends on the nature of the behavior (i.e., innate or learned). METHODS: We conducted a three-phase experimental protocol. In phase I (baseline), animals subjected to mixed schedule of reinforcement were trained to press a lever with a fixed interval of 1 minute and a limited hold of 3 seconds. On the last day of phase I, an open-field test was performed and the animals were divided into four experimental groups (n=8/group). In phase II (repeated stress), each group was exposed to either hot air blast (HAB), paradoxical sleep deprivation (PSD) or both (HAB+PSD group) on alternate days over a 10-day period. Control group animals were not exposed to stressors. In phase III (post-stress evaluation), behavior was analyzed on the first (short-term effects), third (mid-term effects), and fifth (long-term effects) days after repeated stress. RESULTS: The PSD group presented operant hyperactivity, the HAB group presented spontaneous hypoactivity and anxiety, and the HAB+PSD group presented spontaneous hyperactivity, operant hypoactivity, impulsivity, loss of interest, and cognitive impairment. CONCLUSION: A combination of environmental stressors (HAB and PSD) may induce endophenotypes related to bipolar disorder.


Assuntos
Comportamento Animal , Transtorno Bipolar/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Ansiedade , Cognição , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Privação do Sono
18.
Bipolar Disord ; 21(5): 449-457, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30848539

RESUMO

OBJECTIVES: While widespread cortical and subcortical brain functional abnormalities have been found in bipolar disorder, the changes that take place between illness phases and recovery are less clearly documented. Only a small number of longitudinal studies of manic patients, in particular, have been carried out. METHODS: Twenty-six bipolar patients underwent fMRI during performance of the n-back working memory task when manic and again after recovery. Twenty-six matched healthy controls were also scanned on two occasions. Task-related activations and de-activations were examined. RESULTS: When manic, the patients showed clusters of significantly reduced activation in the left dorsolateral prefrontal cortex (DLPFC)/precentral cortex and the parietal cortex/superior precuneus bilaterally. They also showed failure of de-activation in the ventromedial frontal cortex (vmPFC). After recovery, activation in the left DLPFC/precentral cortex and in the bilateral parietal cortex/superior precuneus clusters increased significantly. However, failure of de-activation remained present in the vmPFC. CONCLUSIONS: Recovery from mania is associated with normalization of DLPFC and parietal hypoactivation, but not with vmPFC failure of de-activation, which accordingly appears to represent a trait abnormality in the disorder.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Feminino , Lobo Frontal/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia
19.
Braz J Psychiatry ; 41(5): 419-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30843957

RESUMO

OBJECTIVE: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. METHODS: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1ß, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. RESULTS: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. CONCLUSION: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.


Assuntos
Anti-Inflamatórios/farmacologia , Transtorno Bipolar/imunologia , Modelos Animais de Doenças , Dimesilato de Lisdexanfetamina , Lítio/farmacologia , Fatores de Crescimento Neural/efeitos dos fármacos , Animais , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Lipopolissacarídeos/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase Tipo II/sangue , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
20.
Curr Psychiatry Rep ; 21(3): 14, 2019 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30826893

RESUMO

PURPOSE OF REVIEW: Disruptions in circadian rhythms are believed to underlie the illness course of bipolar disorder (BD). This review evaluates recent studies on the treatment of circadian dysfunction in BD. RECENT FINDINGS: Targeted social rhythm therapy may be useful for bipolar depression though some studies suggest that a non-targeted psychosocial or pharmacological intervention may be just as efficacious. Lithium holds potential for addressing circadian dysfunction in BD. Blue-blocking therapy may be useful for mania and midday bright light therapy may relieve depression. CONCLUSIONS: Psychosocial, pharmacological, and light-based approaches are promising avenues for treating circadian dysfunction in BD.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/terapia , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/efeitos da radiação , Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Depressão/complicações , Depressão/fisiopatologia , Depressão/terapia , Transtorno Depressivo/complicações , Transtorno Depressivo/fisiopatologia , Transtorno Depressivo/terapia , Humanos , Compostos de Lítio/uso terapêutico , Fototerapia
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