High Levels of Psychological Resilience Associated With Less Disease Activity, Better Quality of Life, and Fewer Surgeries in Inflammatory Bowel Disease.

BACKGROUND: Stress and depression are risk factors for inflammatory bowel disease (IBD) exacerbations. It is unknown if resilience, or one's ability to recover from adversity, impacts disease course. The aim of this study was to examine the association between resilience and IBD disease activity, quality of life (QoL), and IBD-related surgeries. METHODS: We performed a cross-sectional study of IBD patients at an academic center. Patients completed the Connor-Davidson Resilience Scale questionnaire, which measures resilience (high resilience score ≥ 35). The primary outcome was IBD disease activity, measured by Mayo score and Harvey-Bradshaw Index (HBI). The QoL and IBD-related surgeries were also assessed. Multivariate linear regression was conducted to assess the association of high resilience with disease activity and QoL. RESULTS: Our patient sample comprised 92 patients with ulcerative colitis (UC) and 137 patients with Crohn disease (CD). High resilience was noted in 27% of patients with UC and 21.5% of patients with CD. Among patients with UC, those with high resilience had a mean Mayo score of 1.54, and those with low resilience had a mean Mayo score of 4.31, P < 0.001. Among patients with CD, those with high resilience had a mean HBI of 2.31, and those with low resilience had a mean HBI of 3.95, P = 0.035. In multivariable analysis, high resilience was independently associated with lower disease activity in both UC (P < 0.001) and CD (P = 0.037) and with higher QoL (P = 0.016). High resilience was also associated with fewer surgeries (P = 0.001) among patients with CD. CONCLUSIONS: High resilience was independently associated with lower disease activity and better QoL in patients with IBD and fewer IBD surgeries in patients with CD. These findings suggest that resilience may be a modifiable factor that can risk-stratify patients with IBD prone to poor outcomes.

Live Donor Assessment Tool (LDAT): A Turkish validity and reliability study.

BACKGROUND/AIMS: Psychosocial and psychiatric evaluations are crucial components of the assessment of a live donor candidate. The Live Donor Assessment Tool (LDAT) was developed for this purpose. This study aims to evaluate the validity and reliability of the Turkish version of LDAT. MATERIALS AND METHODS: 132 live kidney or liver donor were referred to assess their psychosocial/psychiatric appropriateness for donation and were randomized for clinical evaluation as usual or with LDAT. The internal consistency of LDAT was measured by Chronbach's alpha coefficient. Inter-rater reliability was measured by using Spearman's correlation coefficient. The potential validity of LDAT was assessed by comparing LDAT scores to clinical decisions. The Mann-Whitney U test was used to compare LDAT scores across two clinically classified groups (acceptable/declined). Logistic regression was performed using LDAT scores to predict the clinical decision. RESULTS: The Turkish version of LDAT items demonstrate good internal consistency (α=0.773). Inter-rater reliability of LDAT demonstrated strong correlation (ICC=0.72). LDAT scores differentiated the accepted/declined groups, and strongly predicted the clinical decision. With a cut-off score of 60.5, LDAT was found to have high sensitivity and specificity. CONCLUSION: The Turkish version of LDAT was found to be a valid and reliable tool. LDAT could be an appropriate tool to assess live donor candidates.

Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive-emotional training for treatment-resistant depression.

Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive-emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment-resistant depression took part in this open-label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting-state and task-related EEG during a 3-back working memory task were acquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting-state power spectral density (frontal theta and alpha asymmetry), time-frequency power (alpha event-related desynchronisation and theta event-related synchronisation) or event-related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near-transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham-controlled group may be necessary to identify the neurophysiological effects of the intervention.

Initial Evidence for Brain Plasticity Following a Digital Therapeutic Intervention for Depression.

BACKGROUND: Digital therapeutics such as cognitive-emotional training have begun to show promise for the treatment of major depressive disorder. Available clinical trial data suggest that monotherapy with cognitive-emotional training using the Emotional Faces Memory Task is beneficial in reducing depressive symptoms in patients with major depressive disorder. The aim of this study was to investigate whether Emotional Faces Memory Task training for major depressive disorder is associated with changes in brain connectivity and whether changes in connectivity parameters are related to symptomatic improvement. METHODS: Fourteen major depressive disorder patients received Emotional Faces Memory Task training as monotherapy over a six-week period. Patients were scanned at baseline and posttreatment to identify changes in resting-state functional connectivity and effective connectivity during emotional working memory processing. RESULTS: Compared to baseline, patients showed posttreatment reduced connectivity within resting-state networks involved in self-referential and salience processing and greater integration across the functional connectome at rest. Moreover, we observed a posttreatment increase in the Emotional Faces Memory Task-induced modulation of connectivity between cortical control and limbic brain regions, which was associated with clinical improvement. DISCUSSION: These findings provide initial evidence that cognitive-emotional training may be associated with changes in short-term plasticity of brain networks implicated in major depressive disorder. CONCLUSION: Our findings pave the way for the principled design of large clinical and neuroimaging studies.

A pilot study of minocycline for the treatment of bipolar depression: Effects on cortical glutathione and oxidative stress in vivo.

BACKGROUND: The antibiotic minocycline appears to promote neuroprotection through antioxidant and other mechanisms that may be relevant to the pathophysiology of bipolar disorder. The present study assessed the efficacy of minocycline in bipolar depression and examined the association between minocycline treatment and brain glutathione (GSH), an essential regulator of oxidative stress. METHOD: Twenty patients with bipolar disorder experiencing acute depressive symptoms enrolled in an 8-week, open-label trial of adjuvant minocycline. Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and proton magnetic resonance spectroscopy (1H MRS) measures of cortical GSH within a voxel prescribed in the precuneus and aspects of the occipital cortex were obtained from a subset of patients (n=12) before and after treatment. RESULTS: The daily dose of minocycline at study end was 256mg (SD: 71mg). Treatment was associated with improvements in depression severity [MADRS score change: -14.6 (95% CI: -7.8 to -21.3)]. Ten patients (50%) were classified as responders based on a ≥50% reduction in MADRS score and 8 patients (40%) were classified as remitters (MADRS score ≤ 9). Higher baseline GSH levels were associated with greater improvement in MADRS score following treatment (ρ=0.51, p=0.05). Increases in GSH levels at study end were higher in non-responders than in responders (p=0.04). LIMITATIONS: Small sample size, lack of a placebo group. CONCLUSION: Minocycline may be an effective adjuvant treatment for bipolar depression, particularly in patients with high baseline GSH levels. Further research is needed to evaluate the potential of minocycline in this population.

A randomized, controlled pilot trial of the Emotional Faces Memory Task: a digital therapeutic for depression.

There is an urgent need for more effective treatments for major depressive disorder (MDD). Digital therapeutics, such as computerized cognitive-emotional training interventions, represent a promising new strategy for treating MDD. Here we report a replication of efficacy of a digital cognitive-emotional training intervention designed to enhance cognitive control for emotional information-processing. In a randomized, double-blind, controlled study design, fifty-one participants with MDD in a current major depressive episode were randomly assigned to participate in a digital cognitive-emotional training regimen (Emotional Faces Memory Task (EFMT); n= 28) involving 18 sessions over 6 weeks, or an active control condition (CT; n= 23) involving computerized working memory training. MDD symptoms were assessed weekly using a clinician-rated measure (Hamilton Depression Rating Scale; Ham-D); and neurocognition (working memory), at baseline and study outcome. Mixed-effects model for repeated measures (MMRM) analysis of all participants randomized revealed a significantly greater reduction in MDD symptom severity (Ham-D) from baseline to outcome in the EFMT group (8.65 points) compared to the CT group (4.77 points) (F(6,205)= 3.23, p= .005, d= .46). Ten of 28 EFMT participants achieved clinical response (≥ 50% reduction in symptoms) compared to 4 of 23 in CT. Both groups exhibited similar, small improvements in working memory. This replicated the preliminary efficacy of a digital cognitive-emotional training approach for the treatment of MDD. EFMT may be a feasible and effective intervention strategy for MDD, but future studies to elucidate its mechanism of action are warranted. This study is registered with Clinicaltrials.gov (NCT: 01934491).

A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.

Background: Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Methods: Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Results: Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Conclusions: Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519).

A Prospective Study of the Reliability and Validity of the Live Donor Assessment Tool.

BACKGROUND: The psychosocial evaluation is an important part of the live organ donor evaluation process, yet this is not standardized across institutions. OBJECTIVE: This study was designed to prospectively test the reliability and validity of a semistructured psychosocial evaluation tool that was recently developed and reported in the literature (the Live Donor Assessment Tool [LDAT]). METHODS: A total of 248 live donor candidates who presented for evaluation were invited to participate in a study that involved the LDAT being scored as part of the standard psychosocial evaluation process; 222 provided informed consent. Evaluations were conducted by staff experienced with psychosocial evaluation of living donors and trained in the use of the LDAT. Furthermore, 123 donor candidates were evaluated twice, as per routine standard of care, and had 2 LDATs administered. Reliability of the LDAT was assessed by calculating the internal consistency of the LDAT items and inter-rater reliability. Validity was assessed by comparing LDAT scores across the risk-group categories (the traditional outcome designation of the psychosocial evaluation) and in 86 eventual donors, associations between LDAT scores, and indicators of psychosocial outcomes post-donation. RESULTS: The LDAT was found to have good internal consistency, strong inter-rater reliability, and showed signs of validity: LDAT scores differentiated the traditional risk-group categories, and a significant association between LDAT score and treatment adherence post-donation was revealed. CONCLUSIONS: The LDAT demonstrated good reliability and validity, but future research on the LDAT and the ability to implement the LDAT across institutions is warranted.

Religion, spirituality, and mental health of U.S. military veterans: Results from the National Health and Resilience in Veterans Study.

BACKGROUND: In the last three decades, there has been increased interest in studying the association between religion/spirituality (R/S), and mental health and functional outcomes. METHODS: Using data from a contemporary, nationally representative sample of 3151 U.S. military veterans maintained by GfK Knowledge Networks, Inc., we evaluated the relation between R/S and a broad range of mental health, and psychosocial variables. Veterans were grouped into three groups based on scores on the Duke University Religion Index: High R/S (weighted 11.6%), Moderate R/S (79.7%) and Low R/S (8.7%). RESULTS: A "dose-response" protective association between R/S groups and several mental health outcomes was revealed, even after adjustment for sociodemographic and military variables. High R/S was associated with decreased risk for lifetime posttraumatic stress disorder (odds ratio [OR]=0.46), major depressive disorder (MDD; OR=0.50), and alcohol use disorder (OR=0.66), while Moderate R/S was associated with decreased risk for lifetime MDD (OR=0.66), current suicidal ideation (OR=0.63), and alcohol use disorder (OR=0.76). Higher levels of R/S were also strongly linked with increased dispositional gratitude, purpose in life, and posttraumatic growth. LIMITATIONS: In this cross-sectional study, no conclusions regarding causality can be made. The study provides a current snapshot of the link between R/S and mental health. The study also cannot determine whether religious coping styles (negative vs positive coping) contributed to observed differences. CONCLUSIONS: Although the present study does not have treatment implications, our results suggest that higher levels of R/S may help buffer risk for certain mental disorders and promote protective psychosocial characteristics in U.S. military veterans.

Clickotine, A Personalized Smartphone App for Smoking Cessation: Initial Evaluation.

BACKGROUND: Tobacco smoking is the leading cause of preventable death in the United States, and the annual economic burden attributable to smoking exceeds US $300 billion. Obstacles to smoking cessation include limited access and adherence to effective cessation interventions. Technology can help overcome these obstacles; many smartphone apps have been developed to aid smoking cessation, but few that conform to the US clinical practice guideline (USCPG) have been rigorously tested and reported in the literature. Clickotine is a novel smartphone app for smoking cessation, designed to deliver the essential features of the USCPG and engineered to engage smokers by personalizing intervention components. OBJECTIVE: Our objective was to assess the engagement, efficacy, and safety of Clickotine in an initial, single-arm study. Outcomes measured were indicators of engagement with the smartphone app (number of app opens, number of interactions with the Clickotine program, and weeks active with Clickotine), cessation outcomes of 7- and 30-day self-reported abstinence from smoking, and negative health events. METHODS: We recruited US residents between 18 and 65 years of age who owned an iPhone and smoked 5 or more cigarettes daily for the study via online advertising. Respondents were prescreened for eligibility by telephone and, if appropriate, directed to a Web portal to provide informed consent, confirm eligibility, and download the Clickotine app. Participants completed study assessments via the online portal at baseline and after 8 weeks. Data were collected in Amazon S3 with no manual data entry, and access to all data was maximally restrictive, logged, and auditable. RESULTS: A total of 416 participants downloaded the app and constituted the intention-to-treat (ITT) sample. On average, participants opened the Clickotine app 100.6 times during the 8-week study (median 69), logged 214.4 interactions with the Clickotine program (median 178), and remained engaged with Clickotine for 5.3 weeks (median 5). Among the ITT sample, 45.2% (188/416) reported 7-day abstinence and 26.2% (109/416) reported 30-day abstinence from smoking after 8 weeks. Completer analysis focused on 365 (87.7%) of the 416 enrolled participants who completed the 8-week questionnaire revealed that 51.5% (188/365) of completers reported 7-day abstinence and 29.9% (109/365) reported 30-day abstinence. Few adverse events, mostly consistent with nicotine withdrawal symptoms, were reported and overall no safety signal was detected. CONCLUSIONS: In this initial single-arm trial, Clickotine users appeared to demonstrate encouraging indicators of engagement in terms of the number of app opens, number of program interactions, and continued engagement over time. Clickotine users reported encouraging quit rates while reporting few adverse events. Future research is warranted to assess Clickotine's efficacy in a randomized controlled trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT02656745; https://clinicaltrials.gov/ct2/show/NCT02656745 (Archived by WebCite at http://www.webcitation.org/6peTT4x60).

Risk factors for the development of psychopathology following trauma.

Traumatic experiences can lead to a range of mental health problems with posttraumatic stress disorder (PTSD) leading as the most documented disorder following trauma. Epidemiological research has found the rate of exposure to trauma to far outweigh the prevalence of PTSD. Indicating that most people do not develop PTSD following a traumatic event, this phenomenon has led to an interest in evaluating risk factors to determine who develops PTSD. Risk factors for the development of psychopathology following trauma exposure fall into three categories: pre-trauma, peri-trauma and post-trauma factors. Pre-trauma factors can include age, gender, race/ethnicity, education, prior psychopathology, and neurobiological factors. Peri-trauma factors can include the duration/severity of trauma experience and the perception that the trauma has ended. Post-trauma factors can include access to needed resources, social support, specific cognitive patterns, and physical activity. To date, several important risk factors have been found to impact the risk of developing PTSD including gender, age, education, IQ, race and ethnicity, sexual orientation, pre-trauma psychopathology, prior trauma exposure, familial psychiatric history, and neurobiological factors. This article outlines the state of research findings on pretraumatic, peritraumatic, and posttraumatic risk factors for the development of PTSD and associated psychopathology following trauma.

The live donor assessment tool: a psychosocial assessment tool for live organ donors.

BACKGROUND: Psychosocial evaluation is an important part of the live organ donor evaluation process, yet it is not standardized across institutions, and although tools exist for the psychosocial evaluation of organ recipients, none exist to assess donors. OBJECTIVE: We set out to develop a semistructured psychosocial evaluation tool (the Live Donor Assessment Tool, LDAT) to assess potential live organ donors and to conduct preliminary analyses of the tool's reliability and validity. METHODS: Review of the literature on the psychosocial variables associated with treatment adherence, quality of life, live organ donation outcome, and resilience, as well as review of the procedures for psychosocial evaluation at our center and other centers around the country, identified 9 domains to address; these domains were distilled into several items each, in collaboration with colleagues at transplant centers across the country, for a total of 29 items. Four raters were trained to use the LDAT, and they retrospectively scored 99 psychosocial evaluations conducted on live organ donor candidates. Reliability of the LDAT was assessed by calculating the internal consistency of the items in the scale and interrater reliability between raters; validity was estimated by comparing LDAT scores between those with a "positive" evaluation outcome and "negative" outcome. RESULTS: The LDAT was found to have good internal consistency, inter-rater reliability, and showed signs of validity: LDAT scores differentiated the positive vs. negative outcome groups. CONCLUSIONS: The LDAT demonstrated good reliability and validity, but future research on the LDAT and the ability to implement the LDAT prospectively is warranted.

Psychosocial facets of resilience: implications for preventing posttrauma psychopathology, treating trauma survivors, and enhancing community resilience.

BACKGROUND: There is a range of potential responses to stress and trauma. Whereas, on one extreme, some respond to stress and trauma by developing psychiatric disorders (e.g., posttraumatic stress disorder, PTSD), on the other extreme are the ones who exhibit resilience. Resilience is broadly defined as adaptive characteristics of an individual to cope with and recover from adversity. OBJECTIVE: Understanding of the factors that promote resilience is warranted and can be obtained by interviewing and learning from particularly resilient individuals as well as empirical research. In this paper, we discuss a constellation of factors comprising cognitive, behavioral, and existential elements that have been identified as contributing to resilience in response to stress or trauma. RESULTS: The psychosocial factors associated with resilience include optimism, cognitive flexibility, active coping skills, maintaining a supportive social network, attending to one's physical well-being, and embracing a personal moral compass. CONCLUSIONS: These factors can be cultivated even before exposure to traumatic events, or they can be targeted in interventions for individuals recovering from trauma exposure. Currently available interventions for PTSD could be expanded to further address these psychosocial factors in an effort to promote resilience. The cognitive, behavioral, and existential components of psychosocial factors that promote individual resilience can also inform efforts to promote resilience to disaster at the community level.

Cognitive-emotional training as an intervention for major depressive disorder.

BACKGROUND: There is an urgent need for more effective treatments for major depressive disorder (MDD). As understanding of the cognitive and affective neuroscience underlying psychiatric disorders expands, so do opportunities to develop interventions that capitalize on the capacity for brain plasticity. Cognitive training is one such strategy. In this article, we report a proof-of-concept study of a novel cognitive-emotional training exercise designed to enhance cognitive control for emotional information processing and targeting components of the neural networks that have been implicated in MDD. METHODS: Twenty-one participants with MDD in a current episode were randomly assigned to one of the two treatment conditions: 11 participating in a cognitive-emotional training paradigm (emotional faces memory task (EFMT)) involving eight sessions over 4 weeks, and 10 participating in an active control condition (control training, CT). Assessments of MDD symptoms, negative affective bias in cognitive processing, and neurocognition (attention and working memory) were administered at baseline and after 4 weeks. RESULTS: Participants in the EFMT group exhibited a greater reduction in MDD symptoms compared to the CT group, and 6 of the 11 EFMT participants achieved clinical response (≥ 50% reduction in symptoms). EFMT participants also exhibited changes in negative affective bias in the hypothesized direction whereas the CT participants did not. Both groups exhibited similar, small improvements in attention and working memory. CONCLUSIONS: Cognitive-emotional training may represent a feasible and effective intervention strategy for MDD. This proof-of-concept study highlights the need for future studies to fully understand the effectiveness, and mechanisms of effect, of these training strategies.

Attention bias variability and symptoms of posttraumatic stress disorder.

Cognitive theories implicate information-processing biases in the etiology of anxiety disorders. Results of attention-bias studies in posttraumatic stress disorder (PTSD) have been inconsistent, suggesting biases towards and away from threat. Within-subject variability of attention biases in posttraumatic patients may be a useful marker for attentional control impairment and the development of posttrauma symptoms. This study reports 2 experiments investigating threat-related attention biases, mood and anxiety symptoms, and attention-bias variability following trauma. Experiment 1 included 3 groups in a cross-sectional design: (a) PTSD, (b) trauma-exposed without PTSD, and (c) healthy controls with no trauma or Axis I diagnoses. Greater attention-bias variability was found in the PTSD group compared to the other 2 groups (η(p)2=.23); attention-bias variability was significantly and positively correlated (r = .37) with PTSD symptoms. Experiment 2 evaluated combat-exposed and nonexposed soldiers before and during deployment. Attention-bias variability did not differentiate groups before deployment, but did differentiate groups during deployment (ηp2=.16); increased variability was observed in groups with acute posttraumatic stress symptoms and acute depression symptoms only. Attention-bias variability could be a useful marker for attentional impairment related to threat cues associated with mood and anxiety symptoms after trauma exposure.

Resilience and personality traits among living liver and kidney donors.

OBJECTIVE: To explore the psychosocial characteristics of living liver and kidney donors to identify common traits including personality traits, purpose in life, resilience, and post donation growth. METHODS: Questionnaires were mailed to 835 living donors. Included were a survey of demographic characteristics and donation experiences, the NEO Five-Factor Inventory, the Purpose in Life Scale, the Posttraumatic Growth Inventory, and the Connor-Davidson Resilience Scale. Analyses compared the donor groups with the scale norms (where available) and compared differences between donor groups. RESULTS: Eighteen percent of donors (n=151) responded anonymously. The sample was as resilient as the general population and significantly more resilient than the population of primary care patients. Kidney donors were significantly more resilient than liver donors. Live donors demonstrated scores on the NEO Five-Factor Inventory in the "high" range for agreeableness and conscientiousness and "low" for neuroticism. Kidney donors scored significantly lower on the neuroticism scale than liver donors scored. Purpose in Life scores and Post Donation Growth scores were skewed and were overwhelmingly high in this sample. Additional differences in psychosocial variables are also described. CONCLUSION: Live donors are resilient and show adaptive personality traits. It is difficult to conclude whether these traits were inspired by the act of donation or if they make one more apt to choose donation. Moreover, the study methods introduce the possibility of selection bias: those with certain characteristics may have been more likely to respond. Prospective studies before and after donation are warranted.

Neurocognitive effects of ketamine in treatment-resistant major depression: association with antidepressant response.

RATIONALE: The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD). Despite the promise of a novel and urgently needed treatment for refractory depression, concerns regarding potential adverse neurocognitive effects of ketamine remain. OBJECTIVES: Although extensive research has been conducted in healthy volunteers, there is a paucity of studies examining the neurocognitive effects of ketamine in depressed patients. Therefore, the aims of the current study were to characterize the relationship between baseline neurocognition and antidepressant response to ketamine, measure the acute impact of ketamine on neurocognition, and investigate the relationship between acute neurocognitive effects of ketamine and antidepressant response. METHODS: Neurocognitive functioning was assessed in 25 patients with TRD using a comprehensive battery: estimated premorbid intelligence quotient (IQ), current IQ, and tests from the MATRICS Consensus Cognitive Battery (MCCB). A subset of the MCCB was repeated immediately following a 40-min intravenous infusion of ketamine (0.5 mg/kg). RESULTS: Patients who responded to ketamine 24 h following treatment had poorer baseline neurocognitive performance relative to nonresponders and, in particular, slower processing speed (F = 8.42; df = 23; p = 0.008). Ketamine was associated with selective impairments in memory recall, and the degree of cognitive change carried negative prognostic significance (e.g., negative cognitive effects immediately after ketamine predicted lower response rate at 24 h; Fisher's exact test two-sided p = 0.027). CONCLUSIONS: Taken together, our findings suggest a potential baseline neurocognitive predictor of ketamine response and an inverse relationship between the cognitive effects of ketamine and antidepressant efficacy.

Patterns of symptom onset and remission in episodes of hopelessness depression.

BACKGROUND: Hopelessness depression (HD) is a subtype of depression postulated by the Hopelessness Theory of Depression to present as a constellation of symptoms occurring when an individual with a specific cognitive vulnerability (negative inferential style) experiences negative life events. In the current study, the course of HD episodes was evaluated prospectively and analyzed to explore patterns of symptom onset and remission. METHODS: In 169 HD episodes reported by 65 participants, survival analyses were conducted on the time to onset or remission for 29 individual symptoms. Survival analyses yielded probability density graphs for risk of onset and risk of offset that indicated whether the symptom tended to appear or remit early, late, or unpredictably during the episode. RESULTS: The symptom of hopelessness often appeared earliest in HD episodes, followed by self-blame, brooding/worry, decreased self-esteem, dependency, and decreased appetite. Hopelessness, decreased self-esteem, self-blame, brooding/worry, dependency, and increased appetite were typically the latest symptoms to remit. CONCLUSIONS: The current study provided evidence for patterns of symptom onset and remission in HD episodes. Hopelessness and other symptoms predicted to appear according to the Hopelessness Theory were generally the earliest to appear, latest to remit, and appeared to form the core syndrome of these HD episodes. Identifying patterns of symptom onset and remission may provide a tool for subtyping depression episodes. Clinically, these results point to the utility of attending to patterns of symptom onset and remission in patients presenting with HD episodes, particularly for treatment planning and monitoring.

Functional outcomes, functional capacity, and cognitive impairment in schizotypal personality disorder.

BACKGROUND: Individuals with schizotypal personality disorder (SPD) exhibit impaired cognitive functioning in a pattern similar to that found in schizophrenia; less clear is the extent to which these individuals also share schizophrenia patients' impairments in functional capacity and real-world functioning. METHOD: We evaluated 46 SPD patients, as well as 38 individuals with avoidant personality disorder (AvPD) and 55 healthy controls (HC) on: cognitive functioning, real-world functioning (employment and residential status), and functional capacity (indexed by the UPSA, a performance-based skills assessment). RESULTS: We found that individuals with SPD exhibited worse performance on both the cognitive battery and the UPSA than the other groups; they were also less likely to be employed and to be living independently. Additionally, cognitive and UPSA performance in the SPD group was intercorrelated to a degree comparable to what has been found in schizophrenia, and this relationship was not present in the AvPD group. Finally, real-world functioning was related to UPSA performance for both patient groups. CONCLUSIONS: SPD patients exhibit impaired real-world functioning suggesting that these deficits extend across the schizophrenia spectrum. In addition, there is supportive evidence for the validity and importance of performance-based measures such as the UPSA to predict everyday outcomes across the schizophrenia spectrum.