Fiber tract-specific white matter lesion severity Findings in late-life depression and by AGTR1 A1166C genotype.

Past work demonstrated that late-life depression is associated with greater severity of ischemic cerebral hyperintense white matter lesions, particularly frontal lesions. However, these lesions are also associated with other neuropsychiatric deficits, so these clinical relationships may depend on which fiber tracts are damaged. We examined the ratio of lesion to nonlesioned white matter tissue within multiple fiber tracts between depressed and nondepressed elders. We also sought to determine if the AGTR1 A1166C and BDNF Val66Met polymorphisms contributed to vulnerability to lesion development in discrete tracts. The 3T structural MR images and blood samples for genetic analyses were acquired on 54 depressed and 37 nondepressed elders. Lesion maps were created through an automated tissue segmentation process and applied to a probabilistic white matter fiber tract atlas allowing for identification of the fraction of the tract occupied by lesion. The depressed cohort exhibited a significantly greater lesion ratio only in the left upper cingulum near the cingulate gyrus (F((1,86)) = 4.62, P = 0.0344), supporting past work implicating cingulate dysfunction in the pathogenesis of depression. In the 62 Caucasian subjects with genetic data, AGTR1 C1166 carriers exhibited greater lesion ratios across multiple tracts including the anterior thalamic radiation and inferior fronto-occipital fasciculus. In contrast, BDNF Met allele carriers exhibited greater lesion ratios only in the frontal corpus callosum. Although these findings did not survive correction for multiple comparisons, this study supports our hypothesis and provides preliminary evidence that genetic differences related to vascular disease may increase lesion vulnerability differentially across fiber tracts.

Association of depression and survival in patients with chronic heart failure over 12 Years.

OBJECTIVE: To examine the relationship between depression and survival in patients with chronic heart failure (HF) over a 12-year follow-up period. BACKGROUND: The survival associated with depression has been demonstrated in HF patients for up to 7 years. Longer-term impact of depression on survival of these patients remains unknown. METHODS: Prospectively conducted observational study examining adults with HF who were admitted to a cardiology service at Duke University Medical Center between March 1997 and June 2003 and completed the Beck depression inventory (BDI) scale. The national death index was queried for vital status. Cox proportional hazards modeling was used to determine the association of survival and depression. RESULTS: During a mean follow-up of 1792.33 ± 1372.82 days (median 1600; range 0-4683), 733 of 985 participants with HF died of all causes, representing 80% of those with depression (BDI > 10) and 73% of those without (P = 0.01). Depression was significantly and persistently associated with decreased survival over follow-up (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.15-1.57), and was independent of conventional risk factors (HR 1.40, 95% CI 1.16-1.68). Furthermore, survival was inversely associated with depression severity (BDI (continuous) HR 1.02, 95% CI 1.006-1.025, P = 0.001). CONCLUSIONS: The impact of co-morbid depression during the index hospitalization on significantly increased mortality of HF patients is strong and persists over 12 years. These findings suggest that more investigation is needed to understand the trajectory of depression and the mechanisms underlying the impact of depression as well as to identify effective management strategies for depression of patients with HF.

AGTR1 gene variation: association with depression and frontotemporal morphology.

The renin-angiotensin system (RAS) is implicated in the response to physiological and psychosocial stressors, but its role in stress-related psychiatric disorders is poorly understood. We examined if variation in AGTR1, the gene coding for the type 1 angiotensin II receptor (AT(1)R), is associated with a diagnosis of depression and differences in white matter hyperintensities and frontotemporal brain volumes. Participants comprised 257 depressed and 116 nondepressed elderly Caucasian subjects who completed clinical assessments and provided blood samples for genotyping. We used a haplotype-tagging single nucleotide polymorphism (htSNP) analysis to test for variation in AGTR1. For measurement of hyperintense lesions, 1.5 Tesla magnetic resonance imaging (MRI) data were available on 33 subjects. For measurements of the hippocampus and dorsolateral prefrontal cortex (dlPFC), 3 Tesla MRI data were available on 70 subjects. Two htSNPs exhibited statistically significant frequency differences between diagnostic cohorts: rs10935724 and rs12721331. Although hyperintense lesion volume did not significantly differ by any htSNP, dlPFC and hippocampus volume differed significantly for several htSNPs. Intriguingly, for those htSNPs differing significantly for both dlPFC and hippocampus volume, the variant associated with smaller dlPFC volume was associated with larger hippocampal volume. This supports the idea that genetic variation in AGTR1 is associated with depression and differences in frontotemporal morphology.

Genomics-based identification of a potential causal role for acylcarnitine metabolism in depression.

BACKGROUND: Altered metabolism of acylcarnitines - transporting fatty acids to mitochondria - may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization. METHODS: Summary statistics were obtained from large GWAS: the Fenland Study (N = 9363), and the Psychiatric Genomics Consortium (246,363 depression cases and 561,190 controls). Two-sample Mendelian randomization analyses tested the potential causal link of 15 endogenous acylcarnitines with depression. RESULTS: In univariable analyses, genetically-predicted lower levels of short-chain acylcarnitines C2 (odds ratio [OR] 0.97, 95% confidence intervals [CIs] 0.95-1.00) and C3 (OR 0.97, 95%CIs 0.96-0.99) and higher levels of medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.01-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06) were associated with increased depression risk. No reverse potential causal role of depression genetic liability on acylcarnitines levels was found. Multivariable analyses showed that the association with depression was driven by the medium-chain acylcarnitines C8 (OR 1.04, 95%CIs 1.02-1.06) and C10 (OR 1.04, 95%CIs 1.02-1.06), suggesting a potential causal role in the risk of depression. Causal estimates for C8 (OR = 1.05, 95%CIs = 1.02-1.07) and C10 (OR = 1.05, 95%CIs = 1.02-1.08) were confirmed in follow-up analyses using genetic instruments derived from a GWAS meta-analysis including up to 16,841 samples. DISCUSSION: Accumulation of medium-chain acylcarnitines is a signature of inborn errors of fatty acid metabolism and age-related metabolic conditions. Our findings point to a link between altered mitochondrial energy production and depression pathogenesis. Acylcarnitine metabolism represents a promising access point for the development of novel therapeutic approaches for depression.

One-year change in anterior cingulate cortex white matter microstructure: relationship with late-life depression outcomes.

OBJECTIVE: differences in white matter structure measured with diffusion tensor imaging (DTI) are associated with late-life depression, but results examining how these differences relate to antidepressant remission are mixed. To better describe these relationships, the authors examined how 1-year change in DTI measures are related to 1-year course of depression. DESIGN: one-year cross-sectional follow-up to a 12-week clinical trial of sertraline. SETTING: outpatients at an academic medical center. PARTICIPANTS: twenty-nine depressed and 20 never-depressed elderly subjects. Over the 1-year period, 16 depressed subjects achieved and maintained remission, whereas 13 did not. MEASUREMENTS: one-year change in fractional anisotropy (FA) and diffusivity in frontal white matter, as measured by DTI. RESULTS: contrary to our hypotheses, depressed subjects who did not remit over the study interval exhibited significantly less change in anterior cingulate cortex (ACC) white matter FA than did never-depressed or depressed-remitted subjects. There were no group differences in other frontal or central white matter regions. Moreover, there was a significant positive relationship between change in Montgomery-Asberg Depression Rating Scale (MADRS) and change in ACC FA, wherein greater interval decline in FA was associated with greater interval decline in MADRS. CONCLUSION: older depressed individuals who remit exhibit white matter changes comparable with what is observed in never-depressed individuals, whereas nonremitters exhibit significantly less change in ACC FA. Such a finding may be related to either antidepressant effects on brain structure or the effects of chronic stress on brain structure. Further work is needed to better understand this relationship.

Amygdala volume in late-life depression: relationship with age of onset.

OBJECTIVES: Depression is common in the elderly population. Although numerous neuroimaging studies have examined depressed elders, there is limited research examining how amygdala volume may be related to depression. DESIGN: A cross-sectional examination of amygdala volume comparing elders with and without a diagnosis of major depressive disorder, and between depressed subjects with early and later initial depression onset. SETTING: An academic medical center. PARTICIPANTS: Ninety-one elderly patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for major depression (54 early-onset depressed and 37 late-onset depressed) and 31 elderly subjects without any psychiatric diagnoses. MEASUREMENTS: Amygdala and cerebral volumes were measured using reliable manual tracing methods. RESULTS: In models controlling for age, sex, and cerebral volume, there was a significant difference between diagnostic cohorts in amygdala volume bilaterally (left: F[2, 116] = 16.28, p < 0.0001; right: F[2, 116] = 16.28, p < 0.0001). Using least squares mean group analyses, both early- and late-onset depressed subjects exhibited smaller bilateral amygdala volumes than did the nondepressed cohort (all comparisons p < 0.0001), but the two depressed cohorts did not exhibit a statistically significant difference. LIMITATIONS: Limitations include missing antidepressant treatment data, recall bias, inability to establish a causal relationship between amygdala size and depression given the cross-sectional nature of the design. CONCLUSIONS: Depression in later life is associated with smaller amygdala volumes, regardless of age of initial onset of depression.

Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia.

BACKGROUND: TOR1A encodes a chaperone-like AAA-ATPase whose Delta GAG (Delta E) mutation is responsible for an early onset, generalised dystonia syndrome. Because of the established role of the TOR1A gene in heritable generalised dystonia (DYT1), a potential genetic contribution of TOR1A to the more prevalent and diverse presentations of late onset, focal dystonia has been suggested. RESULTS: A novel TOR1A missense mutation (c.613T-->A, p.F205I) in a patient with late onset, focal dystonia is reported. The mutation occurs in a highly evolutionarily conserved region encoding the AAA-ATPase domain. Expression assays revealed that expression of F205I or Delta E, but not wildtype TOR1A, produced frequent intracellular inclusions. CONCLUSIONS: A novel, rare TOR1A variant has been identified in an individual with late onset, focal dystonia and evidence provided that the mutation impairs TOR1A function. Together these findings raise the possibility that this novel TOR1A variant may contribute to the expression of dystonia. In light of these findings, a more comprehensive genetic effort is warranted to identify the role of this and other rare TOR1A variants in the expression of late onset, focal dystonia.

Comprehensive model of how reality distortion and symptoms occur in schizophrenia: could impairment in learning-dependent predictive perception account for the manifestations of schizophrenia?

Conventional wisdom has not laid out a clear and uniform profile of schizophrenia as a unitary entity. One of the key first steps in elucidating the neurobiology of this entity would be to characterize the essential and common elements in the group of entities called schizophrenia. Kraepelin in his introduction notes 'the conviction seems to be more and more gaining ground that dementia praecox on the whole represents, a well characterized form of disease, and that we are justified in regarding the majority of the clinical pictures which are brought together here as the expression of a single morbid process, though outwardly they often diverge very far from one another'. But what is that single morbid process? We suggest that just as the uniform defect in all types of cancer is impaired regulation of cell proliferation, the primary defect in the group of entities called schizophrenia is persistent defective hierarchical temporal processing. This manifests in the form of chronic memory-prediction errors or deficits in learning-dependent predictive perception. These deficits account for the symptoms that present as reality distortion (delusions, thought disorder and hallucinations). This constellation of symptoms corresponds with the profile of most patients currently diagnosed as suffering from schizophrenia. In this paper we describe how these deficits can lead to the various symptoms of schizophrenia.

Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas). The relation between indoxyl sulfate and psychic anxiety was mediated only through the metabolite's effect on the SCC-FC with the premotor area. Baseline indole abundances were unrelated to post-treatment outcome measures, and changes in symptoms were not correlated with changes in indole concentrations. These results suggest that CBT and antidepressant medications relieve anxiety via mechanisms unrelated to modulation of indoles derived from gut microbiota; it remains possible that treatment-related improvement stems from their impact on other aspects of the gut microbiome. A peripheral gut microbiome-derived metabolite was associated with altered neural processing and with psychiatric symptom (anxiety) in humans, which provides further evidence that gut microbiome disruption can contribute to neuropsychiatric disorders that may require different therapeutic approaches. Given the exploratory nature of this study, findings should be replicated in confirmatory studies.Clinical trial NCT00360399 "Predictors of Antidepressant Treatment Response: The Emory CIDAR" https://clinicaltrials.gov/ct2/show/NCT00360399 .

Reductions in neuronal density in elderly depressed are region specific.

OBJECTIVE: Frontal regions, including the orbitofrontal cortex (ORB) and dorsolateral prefrontal cortex (dlPFC) have been implicated in the neuropathology of geriatric depression. Prominent reductions in pyramidal neuron density have been recently reported in the ORB of older depressed subjects. However, the cellular pathology of the dlPFC has not yet been examined in these subjects. METHODS: Postmortem tissue from the dlPFC (Brodmann's area 9, BA9) was collected from 10 older (>60 years old) subjects diagnosed with major depression and 10 age-matched non-psychiatric controls (CTRL). The majority of the subjects were the same as those used for our previous study on neuronal reductions in the ORB in older depressed. Overall (all six layers combined), and laminar density of pyramidal (presumably glutamatergic), and non-pyramidal (GABAergic) neurons as well as cortical and laminar width were measured using linear optical disector of Stereoinvestigator software. RESULTS: Neither the overall nor laminar density of pyramidal or non-pyramidal neurons was significantly different between groups. The cortical and laminar widths were also not affected. CONCLUSIONS: These results suggest that neuronal prefrontal pathology in elderly depressed is region specific. No significant changes were detected in the density of any type of neurons in the dlPFC of elderly depressed subjects (present study) whereas, prominent reductions in the density of pyramidal glutamatergic neurons were observed previously in the ORB.

Biochemical abnormalities of the medial temporal lobe and medial prefrontal cortex in late-life depression.

We utilized single-voxel (1)H magnetic resonance spectroscopy (MRS) to investigate biochemical abnormalities related to late-life depression in the medial prefrontal cortex and medial temporal lobe. Fourteen elderly subjects whose depression responded to treatment and 12 nondepressed subjects were enrolled. Subjects were scanned using a GE 3.0 Tesla whole body MR scanner. Metabolite concentrations were quantified using the LC Model software and adjusted for CSF and ratio of gray to white matter. ANCOVA models tested for group differences while controlling for age and sex. Older previously depressed individuals showed significantly reduced concentrations of total N-acetyl aspartate (NAA), choline, and creatine in the prefrontal cortex and significantly elevated left medial temporal lobe concentrations of NAA and myo-inositol. There were no significant group differences in right temporal metabolite concentrations. The prefrontal cortex observations suggest that reduced neuronal, phospolipid, and energy metabolism is present even in clinically improved depression. In contrast, elevated NAA and myo-inositol concentrations in the left medial temporal lobe could be associated with neuronal and glial cell changes in the amygdala.

Pilot Study of Metabolomic Clusters as State Markers of Major Depression and Outcomes to CBT Treatment.

Major depressive disorder (MDD) is a common and disabling syndrome with multiple etiologies that is defined by clinically elicited signs and symptoms. In hopes of developing a list of candidate biological measures that reflect and relate closely to the severity of depressive symptoms, so-called "state-dependent" biomarkers of depression, this pilot study explored the biochemical underpinnings of treatment response to cognitive behavior therapy (CBT) in medication-free MDD outpatients. Plasma samples were collected at baseline and week 12 from a subset of MDD patients (N = 26) who completed a course of CBT treatment as part of the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study. Targeted metabolomic profiling using the AbsoluteIDQ® p180 Kit and LC-MS identified eight "co-expressed" metabolomic modules. Of these eight, three were significantly associated with change in depressive symptoms over the course of the 12-weeks. Metabolites found to be most strongly correlated with change in depressive symptoms were branched chain amino acids, acylcarnitines, methionine sulfoxide, and α-aminoadipic acid (negative correlations with symptom change) as well as several lipids, particularly the phosphatidlylcholines (positive correlation). These results implicate disturbed bioenergetics as an important state marker in the pathobiology of MDD. Exploratory analyses contrasting remitters to CBT versus those who failed the treatment further suggest these metabolites may serve as mediators of recovery during CBT treatment. Larger studies examining metabolomic change patterns in patients treated with pharmacotherapy or psychotherapy will be necessary to elucidate the biological underpinnings of MDD and the -specific biologies of treatment response.

Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.

Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline. Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17 scores. In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure. In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine-homogentisic acid and methionine-tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.

Hippocampal volumes and depression subtypes.

Studies of depression and hippocampal volume have yielded inconsistent results. This inconsistency could stem from the heterogeneity of depressive disorders. We conducted cross-sectional and longitudinal analyses of hippocampal volumes in atypical depressive, melancholic depressive, and control subjects. We found no effect of depression subtype on hippocampal volume or memory performance.

Prefrontal mechanisms for executive control over emotional distraction are altered in major depression.

A dysfunction in the interaction between executive function and mood regulation has been proposed as the pathophysiology of depression. However, few studies have investigated the alteration in brain systems related to executive control over emotional distraction in depression. To address this issue, 19 patients with major depressive disorder (MDD) and 20 healthy controls were scanned using functional magnetic resonance imaging. Participants performed an emotional oddball task in which infrequently presented circle targets required detection while sad and neutral pictures were irrelevant novel distractors. Hemodynamic responses were compared for targets, sad distractors, and for targets that followed sad or neutral distractors (Target-after-Sad and Target-after-Neutral). Patients with MDD revealed attenuated activation overall to targets in executive brain regions. Behaviorally, MDD patients were slower in response to Target-after-Sad than Target-after-Neutra stimuli. Patients also revealed a reversed activation pattern from controls in response to this contrast in the left anterior cingulate, insula, right inferior frontal gyrus (IFG), and bilateral middle frontal gyrus. Those patients who engaged the right IFG more during Target-after-Neutral stimuli responded faster to targets, confirming a role of this region in coping with emotional distraction. The results provide direct evidence of an alteration in the neural systems that interplay cognition with mood in MDD.

Decision-making and risk aversion among depressive adults.

Depression is associated with behavioral avoidance of potentially rewarding environmental contexts. The present study examined the performance of depressive individuals and controls on a neuropsychological measure of decision-making that favors risk avoidance. Depressive (n=41) and control (n=44) participants were administered the Iowa Gambling Task, which measures the ability of participants to maximize earnings by choosing low-risk, low-reward responses over high-risk, high-reward responses. Results provided partial support for the hypothesis that depressive participants would learn to avoid risky responses faster than control participants. Depressive participants demonstrated better performance than controls, scoring higher than controls overall and showing a trend toward earning more money overall. However, the lack of an interaction between depressive status and time does not support the specific hypothesis of more rapid learning. Findings suggested enhanced feedback-based decision-making and risk aversion among depressive individuals.

Relationship between depressive symptoms and long-term mortality in patients with heart failure.

BACKGROUND: Depression is prevalent in patients with heart failure (HF) and is associated with short-term poor prognosis. However, the long-term effect of depression and the use of self-administered depression evaluation on HF prognosis remained unknown. The study sought to assess the association of depressive symptoms and long-term mortality of patients with HF and to explore the prognostic predictability of the Beck Depression Inventory (BDI) scale for patients with HF. METHODS: Hospitalized patients with HF between March 1997 and June 2003 were recruited. All participants were given the self-administered BDI scale for depression assessment during the index admission. They were then followed for 6 months for the collection of vital status, and annually thereafter. RESULTS: Total study population comprises 1006 patients. The mean BDI score was 8.3 +/- 7.1. The average days of follow-up were 971 +/- 730 and the vital status was obtained from all participants. During this period, 42.6% of the participants died. Depression (defined by BDI score > or = 10) was significantly and independently associated with reduced survival (adjusted hazard ratio 1.36, 95% CI 1.09-1.70, P < .001). Patients whose BDI scores were 5 to 9, 10 to 18, and > or = 19 were 21%, 53%, and 83% more likely to die, respectively, than patients whose BDI score was < 5 (P < .001). CONCLUSIONS: Self-rated depression by BDI is independently linked with higher long-term mortality in patients with HF. Significant dose effect of depressive symptoms on higher mortality is noted.

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

Differences in brain volumes among males and female hormone-therapy users and nonusers.

Numerous studies have shown gender differences in the brain volumes of elderly adults. Some evidence shows that higher estrogen levels may be neuroprotective, suggesting that hormone therapy (HT) may in part be responsible for these gender differences; however, few studies have examined the relation between HT and brain volumes. Brain volumes of caudate, putamen, hippocampus, gray matter, white matter, white-matter lesions, and cerebrospinal fluid were measured on magnetic resonance imaging scans. A comprehensive neuropsychological battery was administered. Women were separated into two groups based on HT use, and we used multiple regression analyses to compare these groups with one another and with men. Results of brain-volume measurements showed that HT users had significantly less gray matter and more cerebrospinal fluid than nonusers. Results of the neuropsychological testing showed that HT users performed better on the Shipley Vocabulary Test than males did.

Prognostic value of anxiety and depression in patients with chronic heart failure.

BACKGROUND: Anxiety is often present with depression and may be one of its manifestations. Although the adverse effects of depression in patients with chronic heart failure (CHF) have been well studied, the relation between anxiety and CHF prognosis has not been addressed. In a secondary analysis of data collected for a published study of depression and prognosis in patients with CHF, we examined the relations among anxiety, depression, and prognosis. METHODS AND RESULTS: We measured symptoms of anxiety with the Spielberger State-Trait Anxiety Inventory (STAI) scale and symptoms of depression with the Beck Depression Inventory (BDI) scale in 291 patients with CHF hospitalized as a result of cardiac events. We followed up these patients for all-cause mortality over 1 year. The mean scores for state anxiety (State-A) and trait anxiety (Trait-A) were identical at 33.5; the mean BDI score was 8.7+/-7.6. State-A and Trait-A scores correlated highly with each other (r=0.85; P<0.01) and with BDI score (State-A, r=0.52; Trait-A, r=0.59; P<0.01). Cox proportional-hazards model with and without confounding variables showed no relation between State-A or Trait-A and 1-year mortality. BDI scores, however, significantly predicted increased mortality during 1-year follow-up (hazard ratio, 1.04 for each 1-unit increase; P<0.01). CONCLUSIONS: Although anxiety and depression are highly correlated in CHF patients, depression alone predicts a significantly worse prognosis for these patients.