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1.
Gen Hosp Psychiatry ; 90: 6-11, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38878593

RESUMO

OBJECTIVES: To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. METHODS: OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). RESULTS: After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. CONCLUSIONS: This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women.

2.
Int J Geriatr Psychiatry ; 39(3): e6057, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38511929

RESUMO

OBJECTIVES: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset. DESIGN/METHODS: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601). RESULTS: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning. CONCLUSIONS: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning.


Assuntos
Transtorno Bipolar , Sintomas Inexplicáveis , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Envelhecimento , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/diagnóstico , Bases de Dados Factuais , Mania , Adulto
3.
Int J Geriatr Psychiatry ; 39(2): e6073, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38393311

RESUMO

OBJECTS: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups. METHODS: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies. RESULTS: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59). CONCLUSIONS: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD.


Assuntos
Transtorno Bipolar , Idoso , Humanos , Transtorno Bipolar/diagnóstico , Estudos Transversais , Envelhecimento , Bases de Dados Factuais , Análise por Conglomerados
4.
Front Digit Health ; 4: 920706, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082232

RESUMO

Digital surveys, such as mobile phone ecological momentary assessment (EMA), bear the potential to assess and target individual wellbeing in a personalized, real-time approach and allow for interaction in situations when in-person contact is not possible, such as during the coronavirus pandemic. While the use of digital technology might especially benefit research in older adults who find themselves in circumstances of reduced mobility, little is known about their barriers to adherence. We investigated baseline and structural factors that predict study withdrawal and adherence from daily smartphone EMA self-report surveys in the StayWELL Study. The StayWELL study is a longitudinal, observational study on the relationship between social restrictions during the coronavirus pandemic and mental well-being in 95 community-dwelling older aged adults (67-87 years) who were participants in a randomized clinical trial using EMA. Withdrawal was associated with less research staff changes and less likely in participants that reached the study mid-point. No baseline characteristics predicted withdrawal. Main reasons for withdrawal were communication issues, i.e. staff not being able to contact participants. We found an adherence rate of 82% and no fatigue effects. Adherence was predicted by education status, study participation duration, reaching the study midpoint and time between study start and enrollment. COVID infections or supporting people in the household was not related to adherence. To conclude, it is feasible to conduct an EMA study in older people without impacting engagement during a pandemic. Furthermore, personal characteristics and smartphone operating system (Android vs. iOS) used did not relate to engagement, allowing for a broad distribution of digital health technologies. Our study adds information on single predictive variables relevant for adherence and withdrawal from EMA smartphone surveys in older people that can inform the design of future digital EMA research to maximize engagement and reliability of study results.

5.
Front Psychiatry ; 13: 966439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032250

RESUMO

Brain structural abnormalities have been demonstrated in schizophrenia (SZ); these resemble those seen in typical aging, but are seen at younger ages. Furthermore, SZ is associated with accelerated global brain aging, as measured by brain structure-based brain predicted age difference (Brain-PAD). High heterogeneity exists in the degree of brain abnormalities in SZ, and individual differences may be related to levels of peripheral inflammation and may relate to cognitive deficits and negative symptoms. The goal of our study was to investigate the relationship between brain aging, peripheral inflammation, and symptoms of SZ. We hypothesized older brain-PAD in SZ vs. healthy comparison (HC) participants, as well as positive relationships of brain-PAD with peripheral inflammation markers and symptoms in SZ. We analyzed data from two cross-sectional studies in SZ (n = 26; M/F: 21/5) and HC (n = 28; 20/8) (22-64 years). Brain-PAD was calculated using a previously validated Gaussian process regression model applied to raw T1-weighted MRI data. Plasma levels of inflammatory biomarkers (CRP, Eotaxin, Fractalkine, IP10, IL6, IL10, ICAM1, IFNγ, MCP1, MIP1ß, SAA, TNFα, VEGF, VCAM1) and cognitive and negative symptoms were assessed. We observed a higher brain-PAD in SZ vs. HC, and advanced brain age relative to chronological age was related to higher peripheral levels of TNFα in the overall group and in the SZ group; other inflammatory markers were not related to brain-PAD. Within the SZ group, we observed no association between cognitive or negative symptoms and brain-PAD. These results support our hypothesis of advanced brain aging in SZ. Furthermore, our findings on the relationship of the pro-inflammatory cytokine TNFα with higher brain-PAD of SZ are relevant to explain heterogeneity of brain ages in SZ, but we did not find strong evidence for cognitive or negative symptom relationships with brain-PAD.

6.
Psychopharmacol Bull ; 52(2): 8-33, 2022 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-35721813

RESUMO

Objectives: Antipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS. Experimental Design: The observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models. Principal Observations: 46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012). Conclusions: APS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships.


Assuntos
Antipsicóticos , Transtorno Bipolar , Adulto , Idoso , Envelhecimento/psicologia , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Estudos Transversais , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
7.
J Psychiatr Res ; 141: 385-389, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34329990

RESUMO

BACKGROUND: Wrist-worn actigraphy can objectively measure sleep, and has advantages over self-report, particularly for people with Bipolar Disorder (BD) for whom self-reports might be influenced by affect. Clinically useful data reduction approaches are needed to explore these complex data. METHODS: We created a composite score of sleep metrics in BD based on 51 BD and 80 healthy comparison (HC) participants. Subjects wore an actigraph for up to 14 consecutive 24-h periods, and we assessed total sleep time (TST), wake after sleep onset (WASO), percent sleep (PS), and number of awakenings (NA). We focused on participants who had at least 5 nights of actigraphy data. We computed z-scores for within-person means of sleep measures for BD subjects versus HCs, which were averaged to create a composite measure. We correlated this composite with participant characteristics, and used LASSO regression to identify sleep measures best explaining variability in identified correlates. RESULTS: Sleep measures and the composite did not differ between BDs and HCs; however, there was considerable variability in z-scores among those with BD. In BDs, the composite score was higher in women (t(49) = 2.28, p = 0.027) and those who were employed (t(34) = 2.34, p = 0.025), and positively correlated with medication load (r = 0.41, p = 0.003) while negatively correlated with Young Mania Rating Scale (YMRS; r = -0.35, p = 0.030). In LASSO regression, TST and NA best explained medication load while PS best explained employment and YMRS. CONCLUSION: While a composite score of sleep metrics may provide useful information about sleep quality globally, our findings suggest that selection of theory-driven sleep measures may be more clinically meaningful.


Assuntos
Transtorno Bipolar , Transtornos do Sono-Vigília , Actigrafia , Feminino , Humanos , Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/etiologia , Punho
8.
Psychiatry Res Neuroimaging ; 275: 1-4, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29572076

RESUMO

Insomnia is prevalent in bipolar disorder (BD) even during periods of euthymic mood. We compared resting state brain activity and cognitive function between euthymic BD with and without insomnia, and secondarily to healthy individuals. BD patients with insomnia symptoms showed a significantly lower functional connectivity within the task-positive network, compared to those without insomnia. They also showed significantly slower cognitive processing speed. These two features of BD with insomnia appeared relatively independent of each other. Preliminary findings suggest that exploration of the mechanisms of sleep disturbance in BD could lead to improved understanding and treatment of inattention in BD.


Assuntos
Transtorno Bipolar/fisiopatologia , Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Conectoma/métodos , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adulto , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Distúrbios do Início e da Manutenção do Sono/etiologia
9.
Am J Geriatr Psychiatry ; 25(7): 744-752, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28342644

RESUMO

OBJECTIVES: Bipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). Few studies, however, have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy counterpart (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cognitive aging. DESIGN: Cross-sectional study. SETTING: University of California San Diego and the Veterans Administration San Diego Healthcare System. PARTICIPANTS: 33 euthymic BD and 38 HC participants. MEASUREMENTS: Diffusion tensor imaging was acquired as a measure of WM integrity, and tract-specific fractional anisotropy (FA) was extracted utilizing the Johns Hopkins University probability atlas. PS was assessed with the Number and Letter Sequencing conditions of the Delis-Kaplan Executive Function System Trail Making Test. RESULTS: BD participants demonstrated slower PS compared with the HC group, but no group differences were found in FA across tracts. Multiple linear regressions revealed a significant group-by-age interaction for the right uncinate fasciculus, the left hippocampal portion of the cingulum, and for PS, such that older age was associated with lower FA values and slower PS in the BD group only. The relationship between age and PS did not significantly change after accounting for uncinate FA, suggesting that the observed age associations occur independently. CONCLUSIONS: Results provide support for future study of the accelerated aging hypothesis by identifying markers of brain health that demonstrate a differential age association in BD.


Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Transtorno Bipolar/patologia , Transtorno Bipolar/fisiopatologia , Cognição/fisiologia , Substância Branca/patologia , Adulto , Idoso , Anisotropia , Encéfalo/patologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Teste de Sequência Alfanumérica
10.
J Int Neuropsychol Soc ; 21(5): 330-41, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26037664

RESUMO

Evidence for abnormal brain function as measured with diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) and cognitive dysfunction have been observed in inter-episode bipolar disorder (BD) patients. We aimed to create a joint statistical model of white matter integrity and functional response measures in explaining differences in working memory and processing speed among BD patients. Medicated inter-episode BD (n=26; age=45.2±10.1 years) and healthy comparison (HC; n=36; age=46.3±11.5 years) participants completed 51-direction DTI and fMRI while performing a working memory task. Participants also completed a processing speed test. Tract-based spatial statistics identified common white matter tracts where fractional anisotropy was calculated from atlas-defined regions of interest. Brain responses within regions of interest activation clusters were also calculated. Least angle regression was used to fuse fMRI and DTI data to select the best joint neuroimaging predictors of cognitive performance for each group. While there was overlap between groups in which regions were most related to cognitive performance, some relationships differed between groups. For working memory accuracy, BD-specific predictors included bilateral dorsolateral prefrontal cortex from fMRI, splenium of the corpus callosum, left uncinate fasciculus, and bilateral superior longitudinal fasciculi from DTI. For processing speed, the genu and splenium of the corpus callosum and right superior longitudinal fasciculus from DTI were significant predictors of cognitive performance selectively for BD patients. BD patients demonstrated unique brain-cognition relationships compared to HC. These findings are a first step in discovering how interactions of structural and functional brain abnormalities contribute to cognitive impairments in BD.


Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/patologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Adulto , Idoso , Anisotropia , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Oxigênio/sangue , Tempo de Reação/fisiologia , Análise de Regressão
11.
J Int Neuropsychol Soc ; 21(2): 105-15, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25771682

RESUMO

Impairment on inhibitory tasks has been well documented in bipolar disorder (BD). Differences in cerebral blood flow (CBF) between BD patients and healthy comparison (HC) participants have also been reported. Few studies have examined the relationship between cognitive performance and regional CBF in this patient population. We hypothesized that group differences on an inhibitory task (the Delis-Kaplan Executive Function Scale's Color-Word Inhibition task) would be associated with differential CBF in bilateral anterior cingulate cortex (ACC), inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) regions. Whole brain resting CBF was measured using Multiphase Pseudocontinuous Arterial Spin Labeling MR imaging for 28 euthymic BD and 36 HC participants. Total gray matter (GM) CBF was measured, and regional CBF values were extracted for each region of interest (ROI) using Freesurfer-based individual parcellations. Group, CBF, and group-by-CBF interaction were examined as predictors of inhibition performance. Groups did not differ in age, gender or education. BD patients performed significantly worse on Color-Word inhibition. There were no significant group differences in CBF in either total GM or in any ROI. There was a group by CBF interaction in the bilateral ACC, right IPL and right DLPFC such that better inhibitory performance was generally associated with higher resting state CBF in BD subjects, but not HC participants. Although CBF was not abnormal in this euthymic BD sample, results confirm previous reports of inter-episode inhibitory deficits and indicate that the perfusion-cognition relationship is different in BD compared to HC individuals.


Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/patologia , Circulação Cerebrovascular/fisiologia , Inibição Psicológica , Deficiências da Aprendizagem/etiologia , Adulto , Idoso , Feminino , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Marcadores de Spin
12.
Bipolar Disord ; 16(3): 289-99, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24119150

RESUMO

OBJECTIVES: Individuals with bipolar disorder (BD) have trait-like deficits in attention and working memory (WM). A fundamental dissociation for most verbal WM theories involves the separation of sensory-perceptual encoding, reliant upon attention, from the maintenance of this information in WM proper. The present study examined if patients with BD demonstrate differential neural changes in encoding and maintenance WM processes that underlie cognitive impairment. METHODS: Event-related functional magnetic resonance imaging during a delayed match-to-sample WM paradigm was employed in 23 inter-episode medicated patients with BD and 23 demographically similar healthy comparison participants. We examined brain regions during encoding and maintenance task intervals to identify regions that demonstrated differential effects between groups. Medication effects and functional connectivity between prefrontal cortex and basal ganglia/thalamus were examined during the encoding interval due to the importance of these regions and the connection among them for encoding into WM. RESULTS: Patients with BD exhibited deficits in task accuracy and attenuated brain response during the encoding interval in areas of the prefrontal cortex, caudate, thalamus, and posterior visual regions. In contrast, patients with BD exhibited hyperactivation in posterior sensory regions during the maintenance interval. Among the BD group, those with greater medication load exhibited the greatest brain response within the prefrontal cortex. CONCLUSIONS: Reduction in activation during the encoding interval suggests that attentional deficits underlie WM deficits in patients with BD. These deficits appear to be trait-like in so far as they were observed during periods of euthymia in patients with BD. Medication effects remain to be further explored as there was evidence of prefrontal changes dependent on medication load.


Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/patologia , Encéfalo/patologia , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Aprendizagem Verbal/fisiologia , Adulto , Idoso , Análise de Variância , Transtorno Bipolar/tratamento farmacológico , Encéfalo/irrigação sanguínea , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio
13.
Biol Psychol ; 74(3): 389-95, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17118517

RESUMO

Intense abrupt stimuli can elicit a startle reflex; a weak "prepulse" 30-300 ms earlier can reduce both startle and perceived stimulus intensity. Prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, is used to understand brain disorders characterized by gating deficits. Compared to startle, PPI of perceived stimulus intensity (PPIPSI) may provide information that is distinct, and easier to acquire and analyze. To develop this experimental measure, we examined PPIPSI under different stimulus conditions. Both PPI and PPIPSI exhibited a non-linear relationship to prepulse intensity, with prepulses 15 dB(A) above background causing maximal inhibition of both measures. A 50 ms broadband noise prepulse produced maximal PPI and PPIPSI, whereas 5 and 20 ms pure tone prepulses produced maximal PPIPSI and PPI, respectively. PPIPSI is a robust, parametrically sensitive and "low tech" measure of sensory gating that may become a valuable tool for understanding the biology of certain mental disorders.


Assuntos
Percepção Auditiva , Inibição Psicológica , Percepção Sonora , Percepção da Altura Sonora , Psicoacústica , Reflexo de Sobressalto , Estimulação Acústica , Adolescente , Adulto , Atenção , Sinais (Psicologia) , Eletromiografia , Feminino , Habituação Psicofisiológica , Humanos , Masculino , Medição da Dor , Espectrografia do Som
14.
Adv Neurol ; 99: 69-88, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16536353

RESUMO

Preclinical models, if used appropriately, can greatly accelerate the understanding of neuropsychiatric disorders. A number of animal models have predictive validity for antidopaminergic compounds that have traditionally been used to suppress motor and vocal tics in TS. Other models have been proposed that may have construct validity for specific hypotheses of infectious/immune and neural circuit etiologies of TS. A more comprehensive set of models is described, based on the hypothesis that primary symptoms of TS, including sensory tics and premonitory urges, result from dysfunction in brain mechanisms that regulate sensorimotor gating. These models utilize operational measures of central gating mechanisms, including PPI of the startle reflex, to achieve predictive validity across a number of different chemical classes of drugs, and to achieve construct validity across broad domains of neurodevelopmental, immune and genetic etiologies of TS. PPI-based animal models offer a number of strong advantages for predictive and mechanistic studies of TS. Ultimately, the utility of these "deficient gating" models will be judged by their ability to bring us closer to identifying the causes and effective treatments of this disorder.


Assuntos
Modelos Animais de Doenças , Síndrome de Tourette/fisiopatologia , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Síndrome de Tourette/tratamento farmacológico , Síndrome de Tourette/patologia
15.
Psychiatry Res ; 146(3): 213-22, 2006 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-16545553

RESUMO

This study used functional magnetic resonance imaging (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: 1) depressed responders' baseline ventral anterior cingulate (AC) perfusion will be greater than that of nonresponders and controls; 2) following partial sleep deprivation (PSD), ventral AC perfusion will significantly decrease in responders only. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Talairach-transformed gray matter masks were merged with Talairach Daemon-based region of interest (ROI) templates. Baseline left ventral AC (LVAC) perfusion was greater in responders than nonresponders. There was no difference involving the medial frontal cortex. Responders' LVAC perfusion dropped from baseline to PSD scans compared with nonresponders and controls, as did perfusion in the right dorsal AC. In the patient group as a whole, decrease in LVAC perfusion from baseline to PSD scans correlated directly with the decrease in the modified 17-item Hamilton Depression Rating Scale (HDRS17) between baseline and PSD conditions. These data--the first using fMRI--show greater anatomic specificity than previous findings of SD and depression in linking decreased brain activity in this area with clinical improvement.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Lobo Frontal/anatomia & histologia , Lobo Frontal/efeitos dos fármacos , Imageamento por Ressonância Magnética , Privação do Sono/fisiopatologia , Adolescente , Adulto , Feminino , Lobo Frontal/metabolismo , Lateralidade Funcional/fisiologia , Gadolínio/farmacocinética , Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Índice de Gravidade de Doença , Privação do Sono/diagnóstico , Inquéritos e Questionários
16.
Neuropsychopharmacology ; 31(9): 2011-21, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16482083

RESUMO

Development of new antipsychotics and their novel applications may be facilitated through the use of physiological markers in clinically normal individuals. Both genetic and neurochemical evidence suggests that reduced prepulse inhibition of startle (PPI) may be a physiological marker for individuals at-risk for schizophrenia, and the ability of antipsychotics to normalize PPI may reflect properties linked to their clinical efficacy. We assessed the effects of the atypical antipsychotic quetiapine (12.5 mg p.o.) on PPI in 20 normal men with a 'low PPI' trait, based on PPI levels in the lowest 25% of a normal PPI distribution. The effects of quetiapine (7.5 mg/kg s.c.) on PPI were then assessed in rats with phenotypes of high PPI (Sprague Dawley (SD)) and low PPI (Brown Norway (BN)); effects of clozapine (7.5 mg/kg i.p.) and haloperidol (0.1 mg/kg s.c.) on PPI were also tested in SD rats. At a time of maximal psychoactivity, quetiapine significantly enhanced PPI to short prepulse intervals (20-30 ms) in 'low gating' human subjects. Quetiapine increased PPI in low gating BN rats for prepulse intervals <120 ms; this effect of quetiapine was limited to 20 ms prepulse intervals in SD rats, who also exhibited this pattern in response to clozapine but not haloperidol. In both humans and rats, normal 'low gating' appears to be an atypical antipsychotic-sensitive phenotype. PPI at short intervals may be most sensitive to pro-gating effects of these drugs.


Assuntos
Antipsicóticos/farmacologia , Reflexo de Sobressalto/efeitos dos fármacos , Estimulação Acústica , Adolescente , Adulto , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Estudos Cross-Over , Dibenzotiazepinas/farmacologia , Humanos , Masculino , Fenótipo , Fumarato de Quetiapina , Ratos , Ratos Sprague-Dawley , Fases do Sono/efeitos dos fármacos
17.
Psychiatry Res ; 146(1): 43-51, 2006 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16380239

RESUMO

This study used functional MRI (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: (1) baseline perfusion in right and left amygdalae will be greater in responders than in nonresponders; (2) following partial sleep deprivation (PSD), perfusion in responders' right and left amygdalae would decrease. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD. Baseline bilateral amygdalar perfusion was greater in responders than nonresponders. Clusters involving both amygdalae decreased from baseline to PSD specifically in responders. Right amygdalar perfusion diverged with PSD, increasing in nonresponders and decreasing in responders. These novel amygdalar findings are consistent with the overarousal hypothesis of SD as well as other functional imaging studies showing increased baseline amygdalar activity in depression and decreased amygdalar activity with remission or antidepressant medications.


Assuntos
Tonsila do Cerebelo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Privação do Sono/diagnóstico , Adolescente , Adulto , Tonsila do Cerebelo/irrigação sanguínea , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiopatologia , Nível de Alerta/fisiologia , Circulação Cerebrovascular/efeitos dos fármacos , Transtorno Depressivo Maior/diagnóstico , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
18.
Pharmacol Ther ; 108(3): 281-93, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15970330

RESUMO

The science of Tourette Syndrome (TS) is advancing at multiple levels of analysis and will be enhanced through the use of animal models. Particular challenges in the development of TS animal models reflect complex features of this disorder, including its waxing and waning course and its "invisible" sensory and psychic symptoms. Animal models can achieve face, predictive, or construct validity based on their particular features. Predictive validity, of most direct relevance to drug development for TS, is achieved to some degree by a several animal models, although the reliance of most of these models on measures of motor suppression may ultimately limit their utility. Other models achieve construct validity with proposed pathophysiological mechanisms related to the immune and neural circuit etiologies of TS. One model-deficient sensorimotor gating of the startle reflex-is discussed in terms of its present and future applications towards advancing our understanding of the pathophysiology and treatment of TS. In addition to models that will advance the pharmacotherapy of TS, other animal models may enhance the utility of nonpharmacologic TS treatments, ranging from behavior therapy to deep brain stimulation (DBS).


Assuntos
Modelos Animais de Doenças , Síndrome de Tourette , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Síndrome de Tourette/tratamento farmacológico , Síndrome de Tourette/terapia
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