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1.
Transl Psychiatry ; 11(1): 147, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654078

RESUMO

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.


Assuntos
Disfunção Cognitiva , Demência , Idade de Início , Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Depressão , Humanos , Estudos Longitudinais , Testes Neuropsicológicos , Estudos Prospectivos
2.
J Psychiatr Res ; 114: 67-74, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31039482

RESUMO

INTRODUCTION: All atypical antipsychotics are associated with some degree of weight gain. We applied a novel statistical approach to identify moderators of aripiprazole-induced fat gain using clinical and genetic data from a randomized clinical trial (RCT) of treatment resistant depression in older adults. MATERIALS AND METHODS: Adults aged ≥60 years with non-response to a prospective trial of venlafaxine were randomized to 12 weeks of aripiprazole augmentation (n = 91) or placebo (n = 90). Dual energy x-ray absorptiometry (DEXA) measured adiposity at baseline and 12 weeks. Independent moderators of total body fat gain were used to generate two combined multiple moderators, one including clinical data alone and one including both clinical and genetic data to characterize individuals who gained fat during aripiprazole augmentation. RESULTS: The value of the combined genetic + clinical multiple moderator (Mcg) was 0.57 [95% CI 0.46, 0.68] (effect size: 0.57), compared to the combined clinical moderator (Mc) value of 0.49 [0.34, 0.63] (effect size: 0.49). Individuals who gained adiposity in this study were more likely to be female and younger in age, have lower weight, fasting glucose and lipids at baseline and positive for the HTR2C polymorphism. DISCUSSION: These results demonstrate a combined multiple moderator approach, including both clinical and genetic moderators, can be applied to existing clinical trial data to understand adverse treatment effects. This method allowed for more specific characterization of individuals at risk for the outcome of interest. Further work is needed to identify additional genetic moderators and to validate the approach.


Assuntos
Adiposidade/efeitos dos fármacos , Antidepressivos/efeitos adversos , Aripiprazol/efeitos adversos , Aumento de Peso/efeitos dos fármacos , Absorciometria de Fóton , Adiposidade/genética , Idoso , Antidepressivos/uso terapêutico , Aripiprazol/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Cloridrato de Venlafaxina/uso terapêutico , Aumento de Peso/genética
3.
J Psychiatr Res ; 95: 129-134, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28843842

RESUMO

Late-life depression (LLD) is associated with cognitive impairments and reduced gray matter volume (GMV); however the mechanisms underlying this association are not well understood. The goal of this study was to characterize changes in depression severity, cognitive function, and brain structure associated with pharmacologic antidepressant treatment for LLD. We administered a detailed neurocognitive battery and conducted structural magnetic resonance imaging (MRI) on 26 individuals with LLD, pre-/post-a 12-week treatment trial with venlafaxine. After calculating changes in cognitive performance, GMV, and depression severity, we calculated Pearson's correlations, performed permutation testing, and false discovery rate correction. We found that loss of GMV over 12 weeks in the superior orbital frontal gyrus was associated with less improvement in depression severity and that increased GMV in the same was associated with greater improvement in depression severity. We detected no associations between changes in cognitive performance and improvements in either depressive symptoms or changes in GMV.


Assuntos
Antidepressivos de Segunda Geração/farmacologia , Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/fisiopatologia , Substância Cinzenta/patologia , Avaliação de Resultados em Cuidados de Saúde , Córtex Pré-Frontal/patologia , Cloridrato de Venlafaxina/farmacologia , Idoso , Antidepressivos de Segunda Geração/administração & dosagem , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/complicações , Feminino , Seguimentos , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/diagnóstico por imagem , Índice de Gravidade de Doença , Cloridrato de Venlafaxina/administração & dosagem
4.
Psychol Med ; 47(4): 608-615, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27821201

RESUMO

BACKGROUND: Persistent complex bereavement disorder (PCBD) is a protracted form of grief included in DSM Section 3 indicating a need for more research. Two other criteria sets [prolonged grief disorder (PGD) and complicated grief (CG) disorder] are also currently in use by researchers. This study evaluates rates of diagnosis of each proposed criteria set in a clinical sample of bereaved individuals participating in clinical research. METHOD: Two groups in which persistent grief was judged to be present or absent completed an assessment instrument that included items needed to diagnose PCBD as well as PGD and CG. One group included grief treatment-seeking participants in our multicenter National Institute of Mental Health (NIMH)-sponsored study who scored ⩾30 on the Inventory of Complicated Grief (ICG) and the other comprised bereaved adults enrolled in clinical research studies who scored <20 on the ICG. Rates of diagnosis were determined for proposed PCBD, PGD and CG criteria. RESULTS: PCBD criteria diagnosed 70 [95% confidence interval (CI) 64.2-75.8] % of the grief treatment-seeking group, PGD criteria identified 59.6 (95% CI 53.4-65.8) % of these individuals and CG criteria identified 99.6 (95% CI 98.8-100.0) %. None of the three proposed criteria identified any cases in the bereaved comparison group. CONCLUSIONS: Both proposed DSM-5 criteria for PCBD and criteria for PGD appear to be too restrictive as they failed to identify substantial numbers of treatment-seeking individuals with clinically significant levels of grief-related distress and impairment. Use of CG criteria or a similar algorithm appears to be warranted.


Assuntos
Luto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Guias de Prática Clínica como Assunto/normas , Escalas de Graduação Psiquiátrica , Trauma Psicológico/diagnóstico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Síndrome
5.
Psychol Med ; 46(2): 381-91, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26446615

RESUMO

BACKGROUND: Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters' inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior. METHOD: A total of 48 participants aged 46-90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls. RESULTS: More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses. CONCLUSIONS: Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.


Assuntos
Desvalorização pelo Atraso , Transtorno Depressivo Maior/fisiopatologia , Giro do Cíngulo/fisiopatologia , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Tentativa de Suicídio/psicologia , Idoso , Idoso de 80 Anos ou mais , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Comportamento de Escolha , Transtorno Depressivo Maior/psicologia , Feminino , Neuroimagem Funcional , Humanos , Comportamento Impulsivo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recompensa
6.
Mol Psychiatry ; 20(5): 594-601, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25092249

RESUMO

Cognitive impairment is highly prevalent among individuals with late-life depression (LLD) and tends to persist even after successful treatment. The biological mechanisms underlying cognitive impairment in LLD are complex and likely involve abnormalities in multiple pathways, or 'cascades,' reflected in specific biomarkers. Our aim was to evaluate peripheral (blood-based) evidence for biological pathways associated with cognitive impairment in older adults with LLD. To this end, we used a data-driven comprehensive proteomic analysis (multiplex immunoassay including 242 proteins), along with measures of structural brain abnormalities (gray matter atrophy and white matter hyperintensity volume via magnetic resonance imaging), and brain amyloid-ß (Aß) deposition (PiB-positron emission tomography). We analyzed data from 80 older adults with remitted major depression (36 with mild cognitive impairment (LLD+MCI) and 44 with normal cognitive (LLD+NC)) function. LLD+MCI was associated with differential expression of 24 proteins (P<0.05 and q-value <0.30) related mainly to the regulation of immune-inflammatory activity, intracellular signaling, cell survival and protein and lipid homeostasis. Individuals with LLD+MCI also showed greater white matter hyperintensity burden compared with LLD+NC (P=0.015). We observed no differences in gray matter volume or brain Aß deposition between groups. Machine learning analysis showed that a group of three proteins (Apo AI, IL-12 and stem cell factor) yielded accuracy of 81.3%, sensitivity of 75% and specificity of 86.4% in discriminating participants with MCI from those with NC function (with an averaged cross-validation accuracy of 76.3%, sensitivity of 69.4% and specificity of 81.8% with nested cross-validation considering the model selection bias). Cognitive impairment in LLD seems to be related to greater cerebrovascular disease along with abnormalities in immune-inflammatory control, cell survival, intracellular signaling, protein and lipid homeostasis, and clotting processes. These results suggest that individuals with LLD and cognitive impairment may be more vulnerable to accelerated brain aging and shed light on possible mediators of their elevated risk for progression to dementia.


Assuntos
Biomarcadores/sangue , Encéfalo/patologia , Transtornos Cognitivos/etiologia , Depressão , Proteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Benzotiazóis/farmacocinética , Encéfalo/diagnóstico por imagem , Depressão/sangue , Depressão/complicações , Depressão/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Proteômica/métodos , Escalas de Graduação Psiquiátrica , Tiazóis
7.
Psychol Med ; 45(7): 1413-24, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25319564

RESUMO

BACKGROUND: Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions. METHOD: Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning). RESULTS: Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure. CONCLUSIONS: Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.


Assuntos
Córtex Cerebral/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Função Executiva/fisiologia , Neostriado/fisiopatologia , Reforço Psicológico , Recompensa , Tálamo/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
8.
J Psychiatr Res ; 47(5): 599-603, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23414701

RESUMO

Subsyndromal depression in later life is common in primary care. Comorbid anxiety disorders could exacerbate the negative effect of subsyndromal depression on functioning, health-related quality of life, comorbidity and/or cognition. We examined anxiety disorders co-existing with subsyndromal depression in participants ≥ age 50 in an NIH trial of Problem Solving Therapy for Primary Care for indicated prevention of major depression. There were 247 participants, with Centers for Epidemiologic Studies - Depression scores ≥ 11. Participants could have multiple psychiatric diagnoses: 22% of the sample had no DSM IV diagnosis; 39% of the sample had only 1 DSM IV diagnosis; 28% had 2 diagnoses; 6% had 3 DSM IV diagnoses; 4% had 4 DSM IV diagnoses; and 1% had 5 diagnoses. Furthermore, 34% of participants had a current comorbid DSM IV diagnosis of a syndromal anxiety disorder. We hypothesized that those with subsyndromal depression, alone relative to those with co-existing anxiety disorders, would report better health-related quality of life, less disability, less medical comorbidity and less cognitive impairment. However, there were no differences in quality of life based on the SF 12 nor in disability based on Late Life Function and Disability Instrument scores. There were no differences in medical comorbidity based on the Cumulative Illness Scale-Geriatrics scale scores nor in cognitive function based on the Executive Interview (EXIT), Hopkins Verbal Learning Test-Revised and Mini-Mental Status Exam. Our findings suggest that about one third of participants 50 years and older with subsyndromal depression have comorbid anxiety disorders; however, this does not appear to be associated with worse quality of life, functioning, disability, cognitive function or medical comorbidity.


Assuntos
Ansiedade , Transtornos Cognitivos/epidemiologia , Depressão , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos Cognitivos/diagnóstico , Comorbidade , Depressão/diagnóstico , Depressão/epidemiologia , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida , Autorrelato , Método Simples-Cego , Estatística como Assunto
9.
Osteoporos Int ; 24(5): 1741-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23358607

RESUMO

UNLABELLED: Antidepressants are associated with bone loss and fractures in older adults. We treated depressed older adults with an antidepressant and examined its effects on bone turnover by comparing blood samples before and after treatment. Bone resorption increased after antidepressant treatment, which may increase fracture risk. INTRODUCTION: Antidepressants have been associated with increased bone loss and fractures in older adults in observational studies, but the mechanism is unclear. We examined the effects of a serotonin-norepinephrine reuptake inhibitor, venlafaxine, on biomarkers of bone turnover in a prospective treatment study of late-life depression. METHODS: Seventy-six individuals aged 60 years and older with current major depressive disorder received a 12-week course of venlafaxine XR 150-300 mg daily. We measured serum C-terminal cross-linking telopeptide of type I collagen (ß-CTX) and N-terminal propeptide of type I procollagen (P1NP), measures of bone resorption and formation, respectively, before and after treatment. We then analyzed the change in ß-CTX and P1NP within each participant. Venlafaxine levels were measured at the end of the study. We assessed depression severity at baseline and remission status after treatment. RESULTS: After 12 weeks of venlafaxine, ß-CTX increased significantly, whereas P1NP did not significantly change. The increase in ß-CTX was significant only in participants whose depression did not remit (increase by 10 % in non-remitters vs. 4 % in remitters). Change in ß-CTX was not correlated with serum levels of venlafaxine or norvenlafaxine. CONCLUSION: Our findings suggest that the primary effect of serotonergic antidepressants is to increase bone resorption. However, such an increase in bone resorption seemed to depend on whether or not participants' depression remitted. Our results are in agreement with prior observational studies reporting increased bone loss in older adults taking serotonergic antidepressants. These negative effects on bone homeostasis could potentially contribute to increased fracture risk in older adults.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Reabsorção Óssea/induzido quimicamente , Cicloexanóis/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Idoso , Antidepressivos de Segunda Geração/administração & dosagem , Antidepressivos de Segunda Geração/uso terapêutico , Biomarcadores/sangue , Reabsorção Óssea/sangue , Colágeno Tipo I/sangue , Cicloexanóis/administração & dosagem , Cicloexanóis/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Cloridrato de Venlafaxina
10.
Psychol Med ; 43(4): 801-11, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22846332

RESUMO

BACKGROUND: While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD. Method We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects ('controls') were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs. RESULTS: The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years. CONCLUSIONS: Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.


Assuntos
Atividades Cotidianas , Transtorno Bipolar/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Progressão da Doença , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Cognição , Transtornos Cognitivos/etiologia , Feminino , Humanos , Entrevista Psicológica , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Estatísticas não Paramétricas
11.
Int J Geriatr Psychiatry ; 27(11): 1106-11, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23044651

RESUMO

OBJECTIVES: This study examined the rates of syndromal and subthreshold post-traumatic stress disorder (PTSD) and PTSD symptom scores in participants with symptoms of emotional distress, subsyndromal depression, and a history of traumatic exposure. Participants had been referred to a study of an indicated depression prevention intervention using problem-solving therapy in primary care. We hypothesized that higher severity of PTSD symptom scores would predict poorer problem-solving skills. In addition, some reports have suggested that there are higher rates of PTSD in minority populations relative to Caucasians; thus we hypothesized that race would also predict problem-solving skills in these individuals. METHODS: We examined the rates of traumatic exposure, syndromal, and subthreshold PTSD. In those exposed to trauma, we performed a multiple linear regression to examine the effects of PTSD symptoms, depression symptoms, race, age, and gender on social problem-solving skills. RESULTS: Of the 244 participants, 64 (26.2%) reported a traumatic event; 6/234 (2.6%) had syndromal PTSD, and 14/234 (6.0%) had subthreshold PTSD. By way of regression analysis, higher PTSD symptom scores predicted poorer problem-solving skills. In addition, racial status (Caucasian vs. African American) predicted problem-solving skills; Caucasians exhibited lower levels of problem-solving skills. CONCLUSIONS: Individuals presenting with subsyndromal depressive symptoms may also have a history of traumatic exposure, subthreshold and syndromal PTSD. Thus, screening these individuals for PTSD symptoms is important and may inform clinical management decisions because problem-solving skills are lower in those with more severe PTSD symptoms (even after adjusting for race, age, gender, and depressive symptoms).


Assuntos
Transtorno Depressivo Maior/prevenção & controle , Resolução de Problemas , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Estresse Psicológico/psicologia , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores Sexuais , Transtornos de Estresse Pós-Traumáticos/psicologia
12.
Psychol Med ; 42(6): 1203-15, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21999930

RESUMO

BACKGROUND: Converging evidence implicates basal ganglia alterations in impulsivity and suicidal behavior. For example, D2/D3 agonists and subthalamic nucleus stimulation in Parkinson's disease (PD) trigger impulse control disorders and possibly suicidal behavior. Furthermore, suicidal behavior has been associated with structural basal ganglia abnormalities. Finally, low-lethality, unplanned suicide attempts are associated with increased discounting of delayed rewards, a behavior dependent upon the striatum. Thus, we tested whether, in late-life depression, changes in the basal ganglia were associated with suicide attempts and with increased delay discounting. METHOD: Fifty-two persons aged ≥ 60 years underwent extensive clinical and cognitive characterization: 33 with major depression [13 suicide attempters (SA), 20 non-suicidal depressed elderly] and 19 non-depressed controls. Participants had high-resolution T1-weighted magnetization prepared rapid acquisition gradient-echo (MPRAGE) magnetic resonance imaging (MRI) scans. Basal ganglia gray matter voxel counts were estimated using atlas-based segmentation, with a highly deformable automated algorithm. Discounting of delayed rewards was assessed using the Monetary Choice Questionnaire (MCQ) and delay aversion with the Cambridge Gamble Task (CGT). RESULTS: SA had lower putamen but not caudate or pallidum gray matter voxel counts, compared to the control groups. This difference persisted after accounting for substance use disorders and possible brain injury from suicide attempts. SA with lower putamen gray matter voxel counts displayed higher delay discounting but not delay aversion. Secondary analyses revealed that SA had lower voxel counts in associative and ventral but not sensorimotor striatum. CONCLUSIONS: Our findings, although limited by small sample size and the case-control design, suggest that striatal lesions could contribute to suicidal behavior by increasing impulsivity.


Assuntos
Gânglios da Base/patologia , Transtorno Depressivo Maior/patologia , Comportamento Impulsivo/patologia , Imageamento por Ressonância Magnética/métodos , Recompensa , Tentativa de Suicídio/psicologia , Idoso , Análise de Variância , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Tomada de Decisões/fisiologia , Transtorno Depressivo Maior/psicologia , Humanos , Interpretação de Imagem Assistida por Computador , Comportamento Impulsivo/psicologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Putamen/patologia , Índice de Gravidade de Doença
13.
Aging Ment Health ; 7(1): 53-60, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12554315

RESUMO

This study evaluated a novel intervention for older osteoarthritis (OA) patients and their spousal caregivers that consisted of standard patient education supplemented by information related to effectively managing arthritis as a couple. Twenty-four female OA patients and their husbands were randomly assigned to either an educational intervention that was targeted at both patient and spouse or to a patient education intervention that was targeted at only the patient. Findings revealed that both interventions were evaluated favorably but the couple intervention was better attended than the patient intervention. In addition, patients in the couple intervention experienced greater increased efficacy in managing arthritis pain and other symptoms. The findings of this pilot study point to the utility of a dyadic intervention approach to management of OA in late life.


Assuntos
Cuidadores , Osteoartrite/terapia , Apoio Social , Cônjuges , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Depressão/diagnóstico , Depressão/psicologia , Avaliação da Deficiência , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Osteoartrite/complicações , Dor/diagnóstico , Dor/etiologia , Medição da Dor , Satisfação Pessoal , Projetos Piloto , Autoeficácia , Índice de Gravidade de Doença , Cônjuges/psicologia
14.
Ethics Behav ; 12(1): 43-62, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12171082

RESUMO

Employing the National Institute of Mental Health-funded Prevention of Suicide in Primary Care Elderly Collaborative Trial as a case study, we discuss 2 sets of ethical issues: obtaining informed consent for a clinic-based intervention study and using treatment as usual (TAU) as the control condition. We then address these ethical issues in the context of the debate about the quality improvement efforts of health care organizations. Our analysis reveals the tension between ethics and scientific integrity involved with using TAU as a control condition and the difficulty in designing high-quality research in a community-based setting.


Assuntos
Idoso , Serviços de Saúde Comunitária , Grupos Controle , Transtorno Depressivo/terapia , Serviços de Saúde para Idosos , Consentimento Livre e Esclarecido , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Prevenção do Suicídio , Revelação , Humanos , Serviços de Saúde Mental , Atenção Primária à Saúde , Risco
15.
Int J Geriatr Psychiatry ; 17(7): 664-9, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12112165

RESUMO

OBJECTIVE: This study examined whether MRI evidence of cerebrovascular disease in the form of white matter hyperintensities (WMH) was associated with decreased implicit sequence learning performance in a high-functioning group of normal elderly volunteers. METHOD: One hundred and eight community-dwelling elderly individuals received an MRI and performed an implicit sequence learning task, the serial reaction time (SRT) task. RESULTS: Hyperintensities present in the white matter were associated with a decreased learning effect. This association was found with both deep white matter and periventricular changes. Other factors affecting SRT performance (i.e., baseline reaction time and switch-cost) were not significantly related to the presence of WMH. CONCLUSIONS: The results indicate that in addition to previously identified generalized cognitive deficits, WMH are also associated with a specific decrease in the implicit learning of sequences.


Assuntos
Encéfalo/patologia , Transtornos Cerebrovasculares/fisiopatologia , Aprendizagem , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Transtornos Cerebrovasculares/patologia , Humanos , Imageamento por Ressonância Magnética , Tempo de Reação
16.
CNS Spectr ; 7(11): 805-10, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12947243

RESUMO

Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.

17.
CNS Spectr ; 7(11): 816-21, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12947244

RESUMO

BACKGROUND: Studies of postmortem brain tissue are advancing the understanding of the pathophysiology of major depressive disorder (MDD). The nature and quality of subject samples, however, limit their applicability to late-life MDD. OBJECTIVE: To examine the feasibility of establishing a brain bank for late-life MDD, and identify clinical, demographic, and procedural factors that might facilitate subject enrollment. METHODS: Elderly subjects participating in clinical trials associated with the Mental Health Intervention Research Center for Late-Life Mood Disorders (MHIRC/LLMD) at the University of Pittsburgh were approached by clinical research staff for consent to future brain-only autopsy. Subjects who consented to participation were compared with those who refused participation on demographic and clinical variables. MHIRC/LLMD clinical research staff were interviewed to determine factors that may have facilitated or hindered the consent process and reasons for subject consent or refusal. RESULTS: Eighty out of 242 subjects (33%) subjects approached for participation in the brain bank provided consent. Consent to participate was associated with higher level of education and with lower Mini-Mental State Examination score. Several factors facilitating and hindering the consent process were identified. CONCLUSION: We provide preliminary evidence for the feasibility of establishing a brain bank for the study of late-life MDD. Future efforts may be guided by the factors identified as facilitating the consent process, especially the inclusion of family in the consent process.

18.
Am J Psychiatry ; 158(12): 2074-6, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11729031

RESUMO

OBJECTIVE: Depression has been associated with increased platelet activation. Variations in the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism may influence the degree of activation. The authors examined the association among depression, platelet activation, and 5-HTTLPR genotype. METHOD: Elderly subjects with (N=61) and without (N=12) major depression were assessed for cognitive impairment, cardiovascular disease, and two indices of platelet activation. The depressed subjects were genotyped for the 5-HTTLPR polymorphism. RESULTS: The depressed subjects were older, were more cognitively impaired, and had higher platelet factor 4 and beta-thromboglobulin levels; cardiovascular disease was minimal in both groups. In the depressed group, subjects with the 5-HTTLPR l/l genotype had significantly higher platelet factor 4 and beta-thromboglobulin levels. CONCLUSIONS: Platelet activation is increased in elderly depressed patients, especially those with the 5-HTTLPR l/l genotype. This finding suggests how genetic differences may influence cardiovascular mortality in depressed patients with ischemic heart disease.


Assuntos
Proteínas de Transporte/genética , Transtorno Depressivo Maior/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Ativação Plaquetária/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Trombose Coronária/sangue , Trombose Coronária/genética , Transtorno Depressivo Maior/sangue , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Fator Plaquetário 4/metabolismo , Fatores de Risco , Proteínas da Membrana Plasmática de Transporte de Serotonina , beta-Tromboglobulina/metabolismo
19.
J Fam Pract ; 50(12): 1068, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11742610

RESUMO

OBJECTIVES: The purpose of our study was to determine if factors other than the patient' clinical presentation were associated with the likelihood of depression being recognized during a physician office visit. STUDY DESIGN: We used a cross-sectional design. POPULATION: Data from the 1997 and 1998 National Ambulatory Medical Care Surveys were examined. OUTCOMES MEASURED: We assessed the association of factors such as age, sex, race, physician specialty, type of insurance, and visit duration with a recorded depression diagnosis during office visits to primary care physicians. RESULTS: After controlling for symptom presentation, primary care physicians were 56% less likely to record a diagnosis of depression during visits made by elderly patients, 37% less likely to do so during visits by African Americans, and 35% less likely to do so during visits by Medicaid patients. Visits with a depression diagnosis were, on average, 2.9 minutes longer in duration (16.4 vs 19.3) than visits without a depression diagnosis. Family practice and general practice physicians were 65% more likely to record a diagnosis of depression than internists. CONCLUSIONS: Many factors were associated with making and recording a depression diagnosis beyond the patient' reported symptoms. If rates of diagnosis are to improve, interventions that go beyond getting physicians to recognize the symptoms of depression are needed.


Assuntos
Competência Clínica/estatística & dados numéricos , Depressão/diagnóstico , Medicina de Família e Comunidade/métodos , Visita a Consultório Médico/estatística & dados numéricos , Relações Médico-Paciente , Atenção Primária à Saúde/métodos , Adulto , Distribuição por Idade , Idoso , Estudos Transversais , Coleta de Dados , Depressão/epidemiologia , Medicina de Família e Comunidade/normas , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/normas , Medição de Risco , Sensibilidade e Especificidade , Distribuição por Sexo , Estados Unidos/epidemiologia
20.
Int J Geriatr Psychiatry ; 16(12): 1149-55, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11748774

RESUMO

BACKGROUND: Prior research suggests that elderly patients are less likely to respond to antidepressant treatment if they have low self-rated health. However, successful treatment for depression has been associated with improvement in self-rated health and other health measures. OBJECTIVES: To examine measures of self-rated health, physical disability, and social function as predictors of treatment response in late-life depression, and to assess these same health measures as treatment outcomes. We hypothesized that greater impairment in these measures would predict poorer treatment response, and that these measures would show significant improvements with recovery from depression. METHOD: Subjects were enrolled in a depression intervention study for people aged 60 and older with recurrent unipolar major depression; they were assessed with measures of self-rated health, physical disability, and social functioning at baseline and at the end of treatment. Baseline measures were compared between the 88 remitters, 11 non-remitters, and seven dropouts. Additionally, changes in the measures were examined in subjects who recovered from the index depressive episode. RESULTS: Subjects with poorer self-rated health at baseline were more likely both to drop out of treatment and to not respond to adequate treatment. This relationship was independent of demographic measures, severity of depression, physical and social functioning, medical illness, personality, hopelessness, overall medication use, and side effects or non-compliance with treatment. CONCLUSION: Although this finding is preliminary because of the small number of dropouts and non-remitters, it suggests that lower self-rated health may independently predict premature discontinuation of treatment for depression. Additionally, subjects who recovered from depression showed significant improvements in self-rated health, physical disability, and social functioning.


Assuntos
Atitude Frente a Saúde , Transtorno Depressivo Maior/terapia , Avaliação Geriátrica , Nortriptilina/uso terapêutico , Psicoterapia , Atividades Cotidianas/psicologia , Idoso , Terapia Combinada , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Autoavaliação (Psicologia) , Resultado do Tratamento
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