Association Between Affective-Cognitive Symptoms of Depression and Exacerbation of Crohn's Disease.

OBJECTIVES: The prevalence of depression is high in patients with Crohn's disease (CD). We examined the influence of affective-cognitive symptoms of depression on the risk of exacerbation of CD. METHODS: We studied 2,144 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD status, and an affective-cognitive index of depression. Linear and logistic regression analyses were used to determine whether CD status at 12 months was associated with the baseline measure of depression. Analyses were adjusted for confounders including age, gender, race, baseline disease activity, disease duration, prior hospitalization and surgery, corticosteroid and anti-TNF use, medication adherence, body mass index, current smoking, education, and sleep quality. RESULTS: Depression was significantly associated with subsequent increases in SCDAI score in both unadjusted (P<0.001) and adjusted (P<0.001) analyses. This association was non-linear, with a shallower slope for lower levels of depression. A 10-point increase in depression t-scores from 55 to 65 was associated with a 18.6-point increase in SCDAI (95% CI 11.5-25.6) and an odds ratio of 1.27 for SCDAI>150 at follow-up (CI: 1.01-1.60). We also found a significant association between depressive symptoms and hospitalization. CONCLUSIONS: Cognitive-affective depressive symptoms were significantly associated with a risk of exacerbation of CD and hospitalization.

Validation of the NetSCID: an automated web-based adaptive version of the SCID.

The present study developed and validated a configurable, adaptive, web-based version of the Structured Clinical Interview for DSM, the NetSCID. The validation included 24 clinicians who administered the SCID and 230 participants who completed the paper SCID and/or the NetSCID. Data-entry errors, branching errors, and clinician satisfaction were quantified. Relative to the paper SCID, the NetSCID resulted in far fewer data-entry and branching errors. Clinicians 'preferred' using the NetSCID and found that the NetSCID was easier to administer.

Cognitive dysfunction in postural tachycardia syndrome.

Mental clouding is an almost universal complaint among patients with postural tachycardia syndrome (POTS) but remains poorly understood. Thus, we have determined whether POTS patients exhibit deficits during neuropsychological testing relative to healthy subjects. A comprehensive battery of validated neuropsychological tests was administered to 28 female POTS patients and 24 healthy subjects in a semi-recumbent position. Healthy subjects were matched to POTS patients on age and gender. Selective attention, a primary outcome measure, and cognitive processing speed were reduced in POTS patients compared with healthy subjects (Ruff 2&7 Speed t-score: 40±9 compared with 49±8; P=0.009; Symbol Digit Modalities Test t-score: 45±12 compared with 51±8; P=0.011). Measures of executive function were also lower in POTS patients (Trails B t-score: 46±8 compared with 52±8; P=0.007; Stroop Word Color t-score: 45±10 compared with 56±8; P=0.001), suggesting difficulties in tracking and mental flexibility. Measures of sustained attention, psychomotor speed, memory function or verbal fluency were not significantly different between groups. The present study provides evidence for deficits in selective attention and cognitive processing in patients with POTS, in the seated position when orthostatic stress is minimized. In contrast, other measures of cognitive function, including memory assessments, were not impaired in these patients, suggesting selectivity in these deficits. These findings provide new insight into the profile of cognitive dysfunction in POTS and provide the basis for further studies to identify clinical strategies to better manage the mental clouding associated with this condition.

Enhancement of human immunodeficiency virus (HIV)-specific CD8+ T cells in cerebrospinal fluid compared to those in blood among antiretroviral therapy-naive HIV-positive subjects.

During untreated human immunodeficiency virus type 1 (HIV-1) infection, virus-specific CD8(+) T cells partially control HIV replication in peripheral lymphoid tissues, but host mechanisms of HIV control in the central nervous system (CNS) are incompletely understood. We characterized HIV-specific CD8(+) T cells in cerebrospinal fluid (CSF) and peripheral blood among seven HIV-positive antiretroviral therapy-naïve subjects. All had grossly normal brain magnetic resonance imaging and spectroscopy and normal neuropsychometric testing. Frequencies of epitope-specific CD8(+) T cells by direct tetramer staining were on average 2.4-fold higher in CSF than in blood (P = 0.0004), while HIV RNA concentrations were lower. Cells from CSF were readily expanded ex vivo and responded to a broader range of HIV-specific human leukocyte antigen class I restricted optimal peptides than did expanded cells from blood. HIV-specific CD8(+) T cells, in contrast to total CD8(+) T cells, in CSF and blood were at comparable maturation states, as assessed by CD45RO and CCR7 staining. The strong relationship between higher T-cell frequencies and lower levels of viral antigen in CSF could be the result of increased migration to and/or preferential expansion of HIV-specific T cells within the CNS. This suggests an important role for HIV-specific CD8(+) T cells in control of intrathecal viral replication.

ETHICAL CONSIDERATIONS FOR COGNITIVE-BEHAVIORAL THERAPISTS IN PSYCHOTHERAPY RESEARCH TRIALS.

Psychotherapy research studies can place particular demands on clinicians, patients, and research staff due to the need to balance the pursuit of knowledge with the offer of treatment. However, the literature with regard to ethical considerations in psychotherapy trials is minimal. The current paper aims to depict CBT community standards of practice in the context of two NIMH-funded treatment trials of major depression, both involving CBT and medication. We describe issues that arose; discuss the ethical considerations involved; and describe our course of action, along with our rationale.

Psychologic distress and head and neck cancer: part 1--review of the literature.

Patients with head and neck cancer (HNC) experience a variety of psychiatric symptoms and disorders, possibly at rates greater than those seen in patients with other types of cancer. This paper reviews the literature on psychologic distress in HNC patients and will also focus on symptoms and diagnoses of depression, anxiety, and substance abuse--conditions requiring the involvement of healthcare professionals. An awareness of the type of issues experienced by HNC patients is vital for accurate assessment and effective intervention.

Can integrating the Memory Support Intervention into cognitive therapy improve depression outcome? Study protocol for a randomized controlled trial.

BACKGROUND: The Memory Support Intervention was developed in response to evidence showing that: (1) patient memory for treatment is poor, (2) poor memory for treatment is associated with poorer adherence and poorer outcome, (3) the impact of memory impairment can be minimized by the use of memory support strategies and (4) improved memory for treatment improves outcome. The aim of this study protocol is to conduct a confirmatory efficacy trial to test whether the Memory Support Intervention improves illness course and functional outcomes. As a "platform" for the next step in investigating this approach, we focus on major depressive disorder (MDD) and cognitive therapy (CT). METHOD/DESIGN: Adults with MDD (n = 178, including 20% for potential attrition) will be randomly allocated to CT + Memory Support or CT-as-usual and will be assessed at baseline, post treatment and at 6 and 12 months' follow-up (6FU and 12FU). We will compare the effects of CT + Memory Support vs. CT-as-usual to determine if the new intervention improves the course of illness and reduces functional impairment (aim 1). We will determine if patient memory for treatment mediates the relationship between treatment condition and outcome (aim 2). We will evaluate if previously reported poor treatment response subgroups moderate target engagement (aim 3). DISCUSSION: The Memory Support Intervention has been developed to be "transdiagnostic" (relevant to a broad range of mental disorders) and "pantreatment" (relevant to a broad range of types of treatment). This study protocol describes a "next step" in the treatment development process by testing the Memory Support Intervention for major depressive disorder (MDD) and cognitive therapy (CT). If the results are promising, future directions will test the applicability to other kinds of interventions and disorders and in other settings. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01790919 . Registered on 6 October 2016.

Prevention of relapse following cognitive therapy vs medications in moderate to severe depression.

BACKGROUND: Antidepressant medication prevents the return of depressive symptoms, but only as long as treatment is continued. OBJECTIVES: To determine whether cognitive therapy (CT) has an enduring effect and to compare this effect against the effect produced by continued antidepressant medication. DESIGN: Patients who responded to CT in a randomized controlled trial were withdrawn from treatment and compared during a 12-month period with medication responders who had been randomly assigned to either continuation medication or placebo withdrawal. Patients who survived the continuation phase without relapse were withdrawn from all treatment and observed across a subsequent 12-month naturalistic follow-up. SETTING: Outpatient clinics at the University of Pennsylvania and Vanderbilt University. PATIENTS: A total of 104 patients responded to treatment (57.8% of those initially assigned) and were enrolled in the subsequent continuation phase; patients were initially selected to represent those with moderate to severe depression. INTERVENTIONS: Patients withdrawn from CT were allowed no more than 3 booster sessions during continuation; patients assigned to continuation medication were kept at full dosage levels. MAIN OUTCOME MEASURES: Relapse was defined as a return, for at least 2 weeks, of symptoms sufficient to meet the criteria for major depression or Hamilton Depression Rating Scale scores of 14 or higher during the continuation phase. Recurrence was defined in a comparable fashion during the subsequent naturalistic follow-up. RESULTS: Patients withdrawn from CT were significantly less likely to relapse during continuation than patients withdrawn from medications (30.8% vs 76.2%; P = .004), and no more likely to relapse than patients who kept taking continuation medication (30.8% vs 47.2%; P = .20). There were also indications that the effect of CT extends to the prevention of recurrence. CONCLUSIONS: Cognitive therapy has an enduring effect that extends beyond the end of treatment. It seems to be as effective as keeping patients on medication.

Improving outcome for mental disorders by enhancing memory for treatment.

Patients exhibit poor memory for treatment. A novel Memory Support Intervention, derived from basic science in cognitive psychology and education, is tested with the goal of improving patient memory for treatment and treatment outcome. Adults with major depressive disorder (MDD) were randomized to 14 sessions of cognitive therapy (CT)+Memory Support (n = 25) or CT-as-usual (n = 23). Outcomes were assessed at baseline, post-treatment and 6 months later. Memory support was greater in CT+Memory Support compared to the CT-as-usual. Compared to CT-as-usual, small to medium effect sizes were observed for recall of treatment points at post-treatment. There was no difference between the treatment arms on depression severity (primary outcome). However, the odds of meeting criteria for 'response' and 'remission' were higher in CT+Memory Support compared with CT-as-usual. CT+Memory Support also showed an advantage on functional impairment. While some decline was observed, the advantage of CT+Memory Support was evident through 6-month follow-up. Patients with less than 16 years of education experience greater benefits from memory support than those with 16 or more years of education. Memory support can be manipulated, may improve patient memory for treatment and may be associated with an improved outcome.

Objectively measured sedentary time is related to quality of life among cancer survivors.

PURPOSE: While exercise has been shown to be beneficial in improving health-related quality of life (HRQOL) among cancer survivors, evidence is limited on the independent role of sedentary behavior. We examined how objectively measured sedentary time was associated with HRQOL among long-term cancer survivors. METHODS: This cross-sectional study included 54 cancer survivors, on average 3.4 years postdiagnosis, who were enrolled into an exercise trial designed to improve cognitive function. At baseline, we measured sedentary time and moderate-vigorous intensity physical activity with the ActivPal, cardiorespiratory fitness with treadmill testing, and self-reported HRQOL with an established scale (SF-36). In multivariate models, we regressed HRQOL on sedentary time (percent of waking time spent sitting and lying). RESULTS: Survivors with higher sedentary time had significantly poorer physical functioning (ß = -0.50, p = 0.028), general health (ß = -0.75, ptrend = 0.004), and physical summary scores (ß = -0.34, p = 0.003). We did not observe associations between sedentary time and role-physical (p = 0.342), bodily-pain (p = 0.117), vitality (p = 0.095), social functioning (p = 0.407), role-emotional (p = 0.509), mental health (p = 0.494), or mental summary scores (p = 0.527). CONCLUSION: In this cross-sectional study of cancer survivors, we observed deleterious associations between sedentary time and aspects of physical HRQOL. Future prospective studies of sedentary time and HRQOL are needed to establish temporality and to facilitate the design of effective health promotion interventions for cancer survivors.

Functional abdominal pain in childhood and long-term vulnerability to anxiety disorders.

BACKGROUND: Cross-sectional studies link functional abdominal pain (FAP) to anxiety and depression in childhood, but no prospective study has evaluated psychiatric status in adulthood or its relation to pain persistence. METHODS: Pediatric patients with FAP (n = 332) and control subjects (n = 147) were tracked prospectively and evaluated for psychiatric disorders and functional gastrointestinal disorders (FGIDs) at follow-up in adolescence and young adulthood (mean age = 20.01 years). Participants were classified according to presence (FGID-POS) or absence (FGID-NEG) of FGIDs at follow-up. RESULTS: Lifetime and current risk of anxiety disorders was higher in FAP than controls (lifetime: 51% vs 20%; current: 30% vs 12%). Controlling for gender and age, the odds ratio was 4.9 (confidence interval = 2.83-7.43) for lifetime anxiety disorder and 3.57 (confidence interval = 2.00-6.36) for current anxiety disorder at follow-up for FAP versus controls. Lifetime risk of depressive disorder was significantly higher in FAP versus controls (40% vs. 16%); current risk did not differ. In most cases, initial onset of anxiety disorders was before pediatric FAP evaluation; onset of depressive disorders was subsequent to FAP evaluation. Within the FAP group, risk of current anxiety disorders at follow-up was significantly higher for FGID-POS versus FGID-NEG (40% vs 24%), and both were higher than controls (12%); current depressive disorders did not differ across FGID-POS, FGID-NEG, and controls. CONCLUSIONS: Patients with FAP carry long-term vulnerability to anxiety that begins in childhood and persists into late adolescence and early adulthood, even if abdominal pain resolves.

Depression in patients with head and neck cancer and a functional genetic polymorphism of the serotonin transporter gene.

BACKGROUND: Polymorphism of the serotonin transporter gene, 5-HTTLPR (short allele) has been associated with depression. The purpose of this study was to show the evaluated depression in patients with head and neck cancer and a possible association with the 5-HTTLPR. METHODS: The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID for DSM-IV) was administered to 94 patients with head and neck cancer, of which 33 patients were genotyped for 5-HTTLPR. We also evaluated the prevalence of 5-HTTLPR polymorphism in 121 patients with head and neck cancer and 97 controls. RESULTS: Forty-three percent of the patients met the criteria for a depressive diagnosis, 19% of which was new onset. In depressed patients, 85.7% (n = 12 of 14) had at least 1 short allele versus 68.4% (n = 13 of 19) of the patients without depressive diagnosis (p < .04). No difference was noted in the prevalence of the short allele in head and neck cancer cases versus controls (odds ratio = 0.8; p = .490). CONCLUSION: Despite the high rate of depressive diagnosis, patients with head and neck cancer did not demonstrate a higher prevalence of this short allele of the 5-HTTLPR compared with a control population.

A randomized, double-blind, crossover trial of modafinil on mood.

Modafinil, a medication for the excessive sleepiness associated with narcolepsy, has been hypothesized to improve not just alertness but mood as well. The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers. Normal healthy volunteers (n = 12, 10 men and 2 women; 30-44 years) underwent a 3-day, counterbalanced, randomized, crossover, inpatient trial of modafinil (400 mg daily) versus placebo with 4-day washout period between 2 treatments. Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale, which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10. Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales. These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect (anxiety). The findings may have implications for clinical practice, in particular for the adjunctive use of modafinil in treatment-resistant depression.

A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder.

OBJECTIVE: Sertraline may produce dual neurotransmitter effects similar to the serotonin-norepinephrine reuptake inhibitors (SNRIs); however, it has been tested against an SNRI in only 1 previous study, and never at an optimal dose. The objective of the current multisite study was to compare relatively higher doses of sertraline (i.e., 150 mg/day) and venlafaxine extended release (XR) (225 mg/day) in outpatients with major depressive disorder. METHOD: Subjects with DSM-IV major depressive disorder were randomly assigned to 8 weeks of double-blind treatment with sertraline (N = 82) or venlafaxine XR (N = 78). The study ran from January 2002 through January 2003. The primary outcome measure was the Quality of Life Enjoyment and Satisfaction Questionnaire; secondary outcome variables included the 17-item Hamilton Rating Scale for Depression. RESULTS: Both treatments led to significant improvement in depressive symptoms and quality-of-life measures. No significant differences were noted between treatment groups for final scores on the primary or secondary measures. The treatment groups did not differ significantly in the percentage of responders (sertraline = 55%, venlafaxine XR = 65%; intent-to-treat [ITT] sample) or remitters (sertra-line = 38%, venlafaxine XR = 49%; ITT sample), although the proportions are similar to those found in earlier selective serotonin reuptake inhibitor (SSRI) vs. venlafaxine meta-analyses. In patients who achieved the maximum dose of drug and maintained it for 3 weeks, response rates were similar to those found at lower doses (sertraline = 59%, venlafaxine XR = 70%); however, remission rates for this sample were comparable for both drug groups (sertraline = 48%, venlafaxine XR = 50%). CONCLUSIONS: The efficacies of sertraline and venlafaxine XR were comparable. Although response and remission rates did not differ statistically, the rates were analogous to those reported in previous meta-analyses. However, at clinically relevant higher doses, the remission rates were very similar. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00179283.