Archives of general psychiatry最新文献

Context: Apathy in community-dwelling elderly individuals has been associated with a history of stroke and other cardiovascular disease.

Objective: To assess the relationship between symptoms of apathy and cardiovascular risk factors or disease (stroke or other) in a large sample of elderly people aged 70 to 78 years without depression or dementia.

Design: Cross-sectional data analysis within an ongoing cluster-randomized, open, multicenter trial.

Setting: The Netherlands, general community.

Participants: We studied 3534 elderly individuals without dementia who were included in the Prevention of Dementia by Intensive Vascular Care trial.

Main outcome measures: Symptoms of apathy, assessed with 3 items from the 15-item Geriatric Depression Scale, in participants with few or no depressive symptoms.

Results: The median age of participants was 74.3 years. Principal components analysis of the Geriatric Depression Scale confirmed a separate factor for the apathy items (Geriatric Depression Scale-3A). Two or more symptoms of apathy were present in 699 participants (19.9%), of whom 372 (53.2%) were without depressive symptoms (Geriatric Depression Scale-12D score <2). Ordinal regression analysis showed that increasing apathy in the absence of depressive symptoms was associated with a history of stroke (odds ratio, 1.79; 95% CI, 1.38-2.31) and cardiovascular disease other than stroke (1.28; 1.09-1.52). Exploratory analysis among 1889 participants free from stroke and other cardiovascular disease revealed an association between apathy score and the following cardiovascular risk factors: systolic blood pressure (P = .03), body mass index (P = .002), type 2 diabetes mellitus (P = .07), and C-reactive protein (P < .001).

Conclusions: Symptoms indicative of apathy are common in community-dwelling nondemented older people who are free from depression. The independent association of stroke, other cardiovascular disease, and cardiovascular risk factors with symptoms of apathy suggests a causal role of vascular factors.

Context: Child emotional maltreatment can result in lasting immune dysregulation that may be heightened in the context of more recent life stress. Basal cell carcinoma (BCC) is the most common skin cancer, and the immune system plays a prominent role in tumor appearance and progression.

Objective: To address associations among recent severe life events, childhood parental emotional maltreatment, depression, and messenger RNA (mRNA) coding for immune markers associated with BCC tumor progression and regression.

Design: We collected information about early parent-child experiences, severe life events in the past year as assessed by the Life Events and Difficulties Schedule, depression, and mRNA for immune markers associated with BCC tumor progression and regression from patients with BCC tumors.

Setting: University medical center.

Participants: Ninety-one patients with BCC (ages, 23-92 years) who had a previous BCC tumor.

Main outcome measures: The expression of 4 BCC tumor mRNA markers (CD25, CD3ε, intercellular adhesion molecule 1, and CD68) that have been linked to BCC tumor progression and regression were assessed in BCC tumor biopsy specimens.

Results: Both maternal and paternal emotional maltreatment interacted with the occurrence of severe life events to predict the local immune response to the tumor (adjusted P = .009 and P = .03, respectively). Among BCC patients who had experienced a severe life event within the past year, those who were emotionally maltreated by their mothers (P = .007) or fathers (P = .02) as children had a poorer immune response to the BCC tumor. Emotional maltreatment was unrelated to BCC immune responses among those who did not experience a severe life event. Depressive symptoms were not associated with the local tumor immune response.

Conclusions: Troubled early parent-child relationships, in combination with a severe life event in the past year, predicted immune responses to a BCC tumor. The immunoreactivity observed in BCCs and the surrounding stroma reflects an anti-tumor-specific immune response that can be altered by stress.

Context: GAD67 regulation involves a network of genes implicated in schizophrenia and bipolar disorder. We have studied the copy number intensities of these genes in specific hippocampal subregions to clarify whether abnormalities of genomic integrity covary with gene expression in a circuitry-based manner.

Objective: To compare the copy number intensities of genes associated with GAD67 regulation in the stratum oriens of sectors CA3/2 and CA1 in patients with schizophrenia, patients with bipolar disorder, and healthy controls.

Design: Samples of sectors CA3/2 and CA1 were obtained from patients with schizophrenia, patients with bipolar disorder, and healthy controls. Genomic integrity was analyzed using microarrays, and the copy number intensities identified were correlated with the gene expression profile from a subset of these cases previously reported.

Setting: Harvard Brain Tissue Resource Center at McLean Hospital, Belmont, Massachusetts.

Patients: A total of 15 patients with schizophrenia, 15 patients with bipolar disorder, and 15 healthy controls.

Main outcome measures: The copy number intensities for 28 target genes were individually examined using single-nucleotide polymorphism microarrays and correlated with homologous messenger RNA (mRNA) fold changes.

Results: The copy number intensities examined using both microarrays and quantitative real-time polymerase chain reaction for the GAD67 gene were significantly decreased in sector CA3/2 of patients with schizophrenia and patients with bipolar disorder. Other genes associated with GAD67 regulation also showed changes in copy number intensities, and these changes were similar in magnitude and direction to those previously reported for mRNA fold changes in sector CA3/2 but not sector CA1. Moreover, the copy number intensities and mRNA fold changes were significantly correlated for both patients with schizophrenia (r=0.649; P=.0003) and patients with bipolar disorder (r=0.772; P=.0002) in sector CA3/2 but not in sector CA1.

Conclusion: Insertions and deletions of genomic DNA in γ-aminobutyric acid cells at a key locus of the hippocampal circuit are reflected in transcriptional changes in GAD67 regulation that are circuitry-based and diagnosis-specific.

Context: Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression.

Objective: To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations.

Data sources: Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride.

Study selection: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine.

Data extraction: Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine.

Data synthesis: Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction.

Conclusions: To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.

Context: Smoking is a possible risk factor for dementia, although its impact may have been underestimated in elderly populations because of the shorter life span of smokers.

Objective: To examine the association between smoking history and cognitive decline in the transition from midlife to old age.

Design: Cohort study.

Setting: The Whitehall II study. The first cognitive assessment was in 1997 to 1999, repeated over 2002 to 2004 and 2007 to 2009.

Participants: Data are from 5099 men and 2137 women in the Whitehall II study, mean age 56 years (range, 44-69 years) at the first cognitive assessment.

Main outcome measures: The cognitive test battery was composed of tests of memory, vocabulary, executive function (composed of 1 reasoning and 2 fluency tests), and a global cognitive score summarizing performance across all 5 tests. Smoking status was assessed over the entire study period. Linear mixed models were used to assess the association between smoking history and 10-year cognitive decline, expressed as z scores.

Results: In men, 10-year cognitive decline in all tests except vocabulary among never smokers ranged from a quarter to a third of the baseline standard deviation. Faster cognitive decline was observed among current smokers compared with never smokers in men (mean difference in 10-year decline in global cognition=-0.09 [95% CI, -0.15 to -0.03] and executive function=-0.11 [95% CI, -0.17 to -0.05]). Recent ex-smokers had greater decline in executive function (-0.08 [95% CI, -0.14 to -0.02]), while the decline in long-term ex-smokers was similar to that among never smokers. In analyses that additionally took dropout and death into account, these differences were 1.2 to 1.5 times larger. In women, cognitive decline did not vary as a function of smoking status.

Conclusions: Compared with never smokers, middle-aged male smokers experienced faster cognitive decline in global cognition and executive function. In ex-smokers with at least a 10-year cessation, there were no adverse effects on cognitive decline.

Context: Decreased brain serotonin (5-hydroxytryptamine) levels are considered to mediate depressive relapse induced by the tryptophan depletion paradigm. However, in patients who recently achieved remission from a major depressive episode with antidepressant treatment, only about half become depressed following tryptophan depletion. We hypothesized that downregulation of brain serotonin(2) receptors might be a compensatory mechanism that prevents some patients from becoming depressed with tryptophan depletion.

Objective: To assess, with use of positron emission tomography, whether brain serotonin(2) receptor downregulation occurs in patients with recently remitted depression who do not have depressive relapse, but not in those who become depressed, following tryptophan depletion.

Design: Each patient underwent 2 fluorine 18-labeled- setoperone positron emission tomography scans, one following a tryptophan depletion session and another following a control session. The order of scanning was counterbalanced.

Setting: Academic university hospital with imaging facilities.

Participants: Seventeen patients in recent remission from a DSM-IV major depressive episode following treatment with selective serotonin reuptake inhibitors.

Main outcome measures: Changes in brain serotonin(2) receptor binding.

Results: Of the 17 patients, 8 (47%) became depressed during the tryptophan depletion session, and none developed depression during the control session. The depletion session was associated with a significant reduction in brain serotonin(2) receptor binding compared with the control session for all participants. A subgroup analysis revealed that the reduction in serotonin(2) receptor binding was significant only for the nondepressed group.

Conclusion: Reduction in brain serotonin(2) receptors might be a potential compensatory mechanism to prevent tryptophan depletion-induced depressive relapse.