Design Cohort study with follow-up between 1973 and 2004.
Participants The entire Swedish population.
Main Outcome Measures Affective, psychotic, neurotic, and personality disorders as well as dementia and delirium.
Results Individuals with rheumatic diseases had a higher risk of psychiatric disorders than the general population. Those with systemic lupus erythematosus and ankylosing spondylitis had a higher risk of subsequent psychiatric disorders than did patients with rheumatoid arthritis. The significant standardized incidence ratios for rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were 1.45, 2.38, and 1.69, respectively, for men, and 1.36, 2.16, and 1.95, respectively, for women. Differences were also found based on subtypes of the rheumatic disease and the psychiatric disorder, sex, and various follow-up intervals. Systemic lupus erythematosus carried an increased risk of dementia and delirium. Only women with rheumatoid arthritis and systemic lupus erythematosus had an increased risk of psychotic disorders and severe depression.
Conclusion Health care providers who encounter patients with rheumatic diseases should be aware that these patients are more likely to develop neuropsychiatric disorders and that some subgroups seem to be more vulnerable than others.
]]>Objective To determine in a large population-based cohort whether there is an association between depression and altered 25(OH)D and PTH levels.
Design Population-based cohort study (Longitudinal Aging Study Amsterdam).
Participants One thousand two hundred eighty-two community residents aged 65 to 95 years.
Setting The Netherlands.
Main Outcome Measure Depression was measured using self-reports (Center for Epidemiologic Studies–Depression scale) and diagnostic interviews (Diagnostic Interview Schedule). Levels of 25(OH)D and PTH were assessed. Potentially confounding factors (ie, age, sex, smoking status, body mass index, number of chronic conditions, and serum creatinine concentration) and explanatory factors (ie, season of data acquisition, level of urbanization, and physical activity) were also measured.
Results Levels of 25(OH)D were 14% lower in 169 persons with minor depression and 14% lower in 26 persons with major depressive disorder compared with levels in 1087 control individuals (P < .001). Levels of PTH were 5% and 33% higher, respectively (P = .003). Depression severity (Center for Epidemiologic Studies Depression Scale) was significantly associated with decreased serum 25(OH)D levels (P = .03) and increased serum PTH levels (P = .008).
Conclusion The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH)D levels and increased serum PTH levels in older individuals.
]]>Objectives To estimate risk factors for first lifetime onset and parameters of chronicity following the first episode, including duration, recovery, and recurrence, and to search for predictors of each parameter.
Design Prospective population-based cohort study with 23 years of follow-up.
Setting East Baltimore, Maryland, an urban setting.
Participants Probability sample of 3481 adult household residents in 1981, including 92 with first lifetime onset of major depressive disorder during the course of the follow-up, and 1739 other participants followed up for at least 13 years.
Outcome Measures Diagnostic Interview Schedule and Life Chart Interview.
Results Female participants showed higher risk of onset of disorder, longer duration of episodes, and a nonsignificant tendency for higher risk of recurrence. Sex was not related to recovery. The median episode length was 12 weeks. About 15% of 92 individuals with first episodes did not have a year free of episodes, even after 23 years. About 50% of first episode participants recovered and had no future episodes. The evolution of the course was relatively stable from first to later episodes. Individuals with 1 or 2 short alleles of the serotonin transporter gene were at higher risk for an initial episode, but experienced episodes of shorter duration. There were few strong predictors of recovery or recurrence.
Conclusions Major depressive disorder is unremitting in 15% of cases and recurrent in 35%. About half of those with a first-onset episode recover and have no furtherepisodes.
]]>Objectives To determine whether catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD.
Design Randomized, double-blind, placebo-controlled, crossover, single-site experimental trial.
Setting Psychiatric outpatient clinic.
Participants Fifteen unmedicated subjects with MDD in full remission (hereinafter referred to as RMDD subjects) and 13 healthy controls.
Intervention Induction of CD by oral administration of -methylparatyrosine. Sham depletion used identical capsules containing hydrous lactose.
Main Outcome Measures Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of CD and sham depletion. Behavioral assessments included the Montgomery-Asberg Depression Rating Scale and the Snaith-Hamilton Pleasure Scale (anhedonia).
Results Depressive and anhedonic symptoms increased during CD to a greater extent in RMDD subjects than in controls. In both groups, CD increased metabolism in the anteroventral striatum and decreased metabolism in the orbital gyri. In a limbic-cortical-striatal-pallidal-thalamic network previously implicated in MDD, composed of the ventromedial frontal polar cortex, midcingulate and subgenual anterior cingulate cortex, temporopolar cortex, ventral striatum, and thalamus, metabolism increased in RMDD subjects but decreased or remained unchanged in controls. Metabolic changes induced by CD in the left ventromedial frontal polar cortex correlated positively with depressive symptoms, whereas changes in the anteroventral striatum were correlated with anhedonic symptoms.
Conclusions This study provides direct evidence for catecholaminergic dysfunction as a trait abnormality in MDD. It demonstrates that depressive and anhedonic symptoms as a result of decreased catecholaminergic neurotransmission are related to elevated activity within the limbic-cortical-striatal-pallidal-thalamic circuitry.
]]>Objective To determine if high-arousing stimuli directly modulated activity in attention and arousal–related sensory brain regions in patients with MDD.
Design Between-group comparison (patients with MDD vs healthy control subjects) of neuromagnetic oscillatory activity driven by flickering emotional and neutral pictures (steady-state visual evoked fields [ssVEFs]).
Setting Center of magnetoencephalography at a public university and public ambulatory mental health service.
Participants Fifteen female low-anxious patients with MDD and 15 female controls. The groups were matched with respect to age and handedness.
Intervention Magnetoencephalographic recordings and self-report ratings.
Main Outcome Measures Modulation of current source strengths obtained by frequency domain minimum norm source localization of ssVEFs.
Results Controls and patients with MDD showed enhanced current source strengths at ssVEF frequency in occipital and parietal cortex for high-arousing emotional pictures (P < .05 for permutation statistics). While this arousal modulation in controls was pronounced in the right temporoparietal cortex, weak arousal modulation characterized that brain region in patients with MDD (F 1,28 = 7.2, P < .05 for interaction group by quadraticcontrast).
Conclusions Although emotional pictures engaged the dorsal visual stream to a greater extent than neutral pictures in both study groups, only controls showed strong arousal modulation in the right temporoparietal cortex. Because the right temporoparietal cortex is associated with the arousal dimension of emotion, subjects with depression may have difficulties in activating arousal-related brain areas, whereas basic stimulus processing related to activation of the dorsal visual stream is intact.
]]>Objective To characterize plasma Aβ40:Aβ42 ratio and cognitive function in elderly individuals with and without depression.
Design Cross-sectional study.
Setting Homecare agencies.
Participants A total of 995 homebound elderly individuals of whom 348 were defined as depressed by a Center for Epidemiological Studies Depression score of 16 or greater.
Main Outcome Measures Cognitive domains of memory, language, executive, and visuospatial functions according to levels of plasma Aβ40 and Aβ42 peptides.
Results Subjects with depression had lower plasma Aβ42 levels (median, 14.1 vs 19.2 pg/mL; P = .006) and a higher plasma Aβ40:Aβ42 ratio (median, 8.9 vs 6.4; P < .001) than did those without depression in the absence of cardiovascular disease and antidepressant use. The interaction between depression and plasma Aβ40:Aβ42 ratio was associated with lower memory score (β = –1.9, SE = 0.7, P = .006) after adjusting for potentially confounders. Relative to those without depression, "amyloid-associated depression," defined by presence of depression and a high plasma Aβ40:Aβ42 ratio, was associated with greater impairment in memory, visuospatial ability, and executive function; in contrast, nonamyloid depression was not associated with memory impairment but with other cognitive disabilities.
Conclusion Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.
]]>Objective To determine the efficacy of eszopiclone combined with escitalopram oxalate in treating insomnia comorbid with GAD.
Design Double-blind, randomized, placebo-controlled, parallel-group, add-on therapy 10-week study.
Setting Multicenter outpatient study from July 2005 to April 2006.
Patients Adults aged 18 to 64 years meeting DSM-IV-TR criteria for GAD and insomnia.
Interventions Patients received 10 mg of escitalopram oxolate for 10 weeks and were randomized to also receive either 3 mg of eszopiclone (n = 294) or placebo (n = 301) nightly for 8 weeks. For the last 2 weeks, eszopiclone was replaced with a single-blind placebo.
Main Outcome Measures Sleep, daytime functioning, psychiatric measures, and adverse events.
Results Compared with treatment with placebo and escitalopram, treatment with eszopiclone and escitalopram resulted in significantly improved sleep and daytime functioning (P < .05), with no evidence of tolerance. Patients taking eszopiclone and escitalopram had greater improvements in total Hamilton Anxiety Scale (HAM-A) scores at each week (P < .05) and at weeks 4 through 10 with the insomnia item removed. Clinical Global Impressions (CGI) of Improvement scores were improved with eszopiclone and escitalopram at every point (P < .02), while CGI of Severity of Illness scores were not significantly different after week 1. The HAM-A response (63% vs 49%, respectively, P = .001) and remission (42% vs 36%, respectively, P = .09) rates at week 8 were higher in patients treated with eszopiclone and escitalopram than those treated with placebo and escitalopram, and median time to onset of anxiolytic response was significantly reduced (P ≤ .05). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and while treatment differences in anxiety measures were maintained, differences in sleep outcomes were not. Overall adverse event rates were 77.6% with cotherapy and 67.9% with monotherapy. The most common adverse events with cotherapy were unpleasant taste, headache, dry mouth, and somnolence.
Conclusions Coadministration of eszopiclone and escitalopram was well tolerated and associated with significantly improved sleep, daytime functioning, anxiety, and mood in patients with insomnia and GAD.
Trial Registration clinicaltrials.gov Identifier:
Objective To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD.
Design Case-control study.
Setting Government clinical research institute.
Participants Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis.
Main Outcome Measures We used functional magnetic resonance imaging to measure blood oxygenation level–dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces.
Results When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects.
Conclusions Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.
]]>Objective To assess whether prolonged and exclusive breastfeeding improves children's cognitive ability at age 6.5 years.
Design Cluster-randomized trial, with enrollment from June 17, 1996, to December 31, 1997, and follow-up from December 21, 2002, to April 27, 2005.
Setting Thirty-one Belarussian maternity hospitals and their affiliated polyclinics.
Participants A total of 17 046 healthy breastfeeding infants were enrolled, of whom 13 889 (81.5%) were followed up at age 6.5 years.
Intervention Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF.
Main Outcome Measures Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence, and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects.
Results The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months (43.3% for the experimental group vs 6.4% for the control group; P < .001) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months. The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures, with cluster-adjusted mean differences (95% confidence intervals) of +7.5 (+0.8 to +14.3) for verbal IQ, +2.9 (–3.3 to +9.1) for performance IQ, and +5.9 (–1.0 to +12.8) for full-scale IQ. Teachers' academic ratings were significantly higher in the experimental group for both reading and writing.
Conclusion These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children's cognitive development.
Trial Registration isrctn.org Identifier:
Objective To determine the neural regions that underlie the reversal learning impairments in children with psychopathic traits plus conduct or oppositional defiant disorder.
Design Case-control study.
Setting Government clinical research institute.
Participants Forty-two adolescents aged 10 to 17 years: 14 with psychopathic traits and oppositional defiant disorder or conduct disorder, 14 with attention-deficit/hyperactivity disorder only, and 14 healthy controls.
Main Outcome Measure Blood oxygenation level–dependent signal as measured via functional magnetic resonance imaging during a probabilistic reversal task.
Results Children with psychopathic traits showed abnormal responses within the ventromedial prefrontal cortex (Brodmann area 10) during punished reversal errors compared with children with attention-deficit/hyperactivity disorder and healthy children (P < .05 corrected for multiple comparisons).
Conclusions To our knowledge, this study provides the first evidence of abnormal ventromedial prefrontal cortex responsiveness in children with psychopathic traits and demonstrates this dysfunction was not attributable to comorbid attention-deficit/hyperactivity disorder. These findings suggest that reversal learning impairments in patients with developmental psychopathic traits relate to abnormal processing of reinforcement information.
]]>Objectives To test the hypotheses that (1) clinically relevant depressive symptoms are an independent risk factor of incident stroke in cardiac and noncardiac patients and (2) more chronic and severe depressive symptoms are associated with incident stroke.
Design A cohort of elderly Dutch people (aged ≥ 55 years) was followed up for 9 years in the Longitudinal Aging Study Amsterdam (baseline measurements were taken in 1992 or 1993, and the study concluded in 2001 or 2002, respectively).
Setting General community.
Participants Randomly selected population-based sample (N = 2965) without a history of stroke.
Main Outcome Measures The study end point was a first stroke (nonfatal or fatal). Depression was measured using the National Institute of Mental Health Diagnostic Interview Schedule and the Center for Epidemiological Studies–Depression Scale. Multivariate Cox proportional hazards regression analyses of stroke incidence were performed. The association of the chronicity and severity of depressive symptoms was studied in extended models with time-dependent variables.
Results The sample's mean (SD) age was 70.5 (8.7) years, 52.1% were women, and the mean (SD) follow-up was 7.7 (3.1) years. Inclusion of an interaction between cardiac disease and clinically relevant depressive symptoms improved the model for stroke (P = .03). In participants with preexistent cardiac disease, but not in participants without cardiac disease, clinically relevant depressive symptoms at baseline (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.17-4.09) and the severity (range, 0-60; HR, 1.08; 95% CI, 1.02-1.13) and chronicity (HR, 3.51; 95% CI, 1.13-10.93) of symptoms during follow-up were associated with stroke.
Conclusions Preexistent cardiac disease moderates the association between depressive symptoms and incident stroke. In cardiac patients, baseline depressive symptoms and both the severity and chronicity of symptoms during follow-up are associated with incident stroke.
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