Search

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.

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.

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.

Resilience refers to possessing a set of adaptive characteristics that enable an individual to cope with and recover from (or even thrive after) stress or trauma. There are neurobiological factors associated with resilience, including genetic factors, neurochemical systems, and the functioning of specific neural networks. Psychosocial factors also contribute to resilience, and in this chapter, we review the psychosocial factors most strongly associated with resilience in the scientific literature: optimism, cognitive flexibility, active coping skills, social support networks, physical activity, and a personal moral compass. This chapter focuses on the cognitive and behavioral components of these factors and provides strategies for cultivating these factors to promote resilience.

Background While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a need to further optimise tDCS for medication resistant patients. In this clinical pilot study we examined the feasibility, safety, and clinical efficacy of combining tDCS with a psychological intervention which targets dysfunctional circuitry related to emotion regulation in depression, Cognitive Emotional Training (CET). Methods tDCS was administered during CET three times a week for a total of 18 sessions over 6 weeks. Mood, cognition and emotion processing outcomes were examined at baseline and after 3 and 6 weeks of treatment. Results Twenty patients with medication resistant depression participated, of whom 17 were study completers. tDCS combined with CET was found to be feasible, safe, and associated with significant antidepressant efficacy at 6 weeks, with 41% of study completers showing treatment response (≥ 50% improvement in depression score). There were no significant cognitive enhancing effects with the exception of improved emotion recognition. Responders demonstrated superior recognition for the emotions fear and surprise at pre-treatment compared to non-responders, suggesting that better pre-treatment emotion recognition may be associated with antidepressant efficacy. Limitations This was an open label study. Conclusions tDCS combined with CET has potential as a novel method for optimising the antidepressant efficacy of tDCS in medication resistant patients. Future controlled studies are required to determine whether tDCS combined with CET has greater antidepressant efficacy compared to either intervention alone.

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)., Significance StatementAnxiety and trauma-related disorders are among the most prevalent medical conditions in the United States. Posttraumatic stress disorder (PTSD) in particular is a debilitating disorder that develops in a subset of individuals exposed to extreme stress. Drug discovery for PTSD and anxiety disorders has been largely stagnant, contributing to a substantial disease burden and continued patient suffering. A large body of evidence implicates neuropeptide Y (NPY) in the regulation of stress-related behaviors, and preclinical data suggest that enhancing NPY signaling may reduce anxiety and symptoms of PTSD. Herein, we conducted phase Ib double-blind, randomized, placebo-controlled, dose-ranging study of intranasal administration of NPY in subjects with PTSD. We found that NPY was well tolerated at all tested doses and that high, but not low, doses of NPY were associated with reduced anxiety on some measures. The NPY system may represent a promising target for treatment development for anxiety and trauma-related disorders.

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.

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 the 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 aquired 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 desynchronization and theta event-related synchronisation), or event-related potentials (P3 component). There was weak evidence for an increase in P2 amplitude, suggesting an improvement to attentional processes, but this result did not survive correction for multiple comparisons. 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.

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, 51 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 = 0.46). 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).

Mood and anxiety disorders are characterized by abnormally persistent affective states. Neuroimaging studies have implicated the functioning of specific brain regions in the aberrant affective processing observed in mood and anxiety disorders: enhanced engagement of subcortical regions responsible for affect generation (amygdala, hippocampus) is coupled with reduced inhibitory cognitive control of affective processing from dorsolateral and ventrolateral prefrontal cortices. Emerging but compelling evidence suggests that neuroplastic mechanisms can be harnessed to remediate these abnormalities, thus offering the prospect of new therapeutic interventions. Cognitive-affective training is a particularly promising strategy for enhancing cognitive control over affective processes via modulation of these abnormally functioning neural networks. This paper presents a review of the current literature and a justification for developing cognitive-affective training, and proposes initial evidence for the efficacy of cognitive-affective training interventions. Cognitive-affective training interventions could represent a novel method for targeting perseverative thinking and negative affective biases in mood and anxiety disorders.

Depressive disorders are among the most disabling medical illnesses worldwide and limited efficacy of currently available medication and psychotherapy treatments adds to this large public health burden. In the current chapter, we consider findings from several large-scale health surveys to estimate the burden of illness, and review the current data available regarding prognosis, psychiatric and medical comorbidities, and socio-demographic factors influencing the prevalence and course of depression. We also consider emerging alternative methods of conceptualizing depression and other mental disorders that emphasize a dimensional rather than categorical approach. Increasing attention to such approaches in the design of psychiatric research related to depression may lead to an improved understanding of depression and more effective treatments.

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 256 mg (SD: 71 mg). 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.

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.

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.

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.

Objective To explore the psychosocial characteristics of living liver and kidney donors to identify common traits including personality traits, purpose in life, resilience, and postdonation 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.

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.

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. 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. 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). 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). 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.

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.

BackgroundTobacco 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. ObjectiveOur 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. MethodsWe 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. ResultsA 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. ConclusionsIn 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 RegistrationClinicaltrials.gov NCT02656745; https://clinicaltrials.gov/ct2/show/NCT02656745 (Archived by WebCite at http://www.webcitation.org/6peTT4x60)

Major depressive disorder (MDD) is a disabling medical condition associated with significant morbidity, mortality and public health costs. However, neurocircuitry abnormalities underlying depression remain incompletely understood and consequently current treatment options are unfortunately limited in efficacy. Recent research has begun to focus specifically on cognitive aspects of depression and potential neurobiological correlates. Two fundamental types of cognitive dysfunction observed in MDD are cognitive biases, which include distorted information processing or attentional allocation toward negative stimuli, and cognitive deficits, which include impairments in attention, short-term memory and executive functioning. In this article, we present a selective review of current research findings in these domains and examine neuroimaging research that is beginning to characterize the neurocircuitry underlying these biases and deficits. We propose that deficient cognitive functioning, attention biases and the sustained negative affect characteristic of MDD can be understood as arising in part from dysfunctional prefrontal-subcortical circuitry and related disturbances in the cognitive control of emotion. Finally, we highlight potential new pharmacological and non-pharmacological therapeutic strategies for MDD based on an evolving mechanistic understanding of the disorder.

Objectives: Research has found that bipolar spectrum disorders are associated with Behavioral Approach System (BAS) hypersensitivity and both unipolar and bipolar depression are associated with high Behavioral Inhibition System (BIS) sensitivity, but prospective studies of these relationships are lacking. We tested whether BAS and BIS sensitivities prospectively predicted the time to new onsets of major depressive and hypomanic and manic episodes in bipolar spectrum individuals. Methods: We followed 136 bipolar II or cyclothymic and 157 demographically matched normal control individuals prospectively for an average of 33 months. Participants completed the BIS/BAS scales and symptom measures at Time 1 and semi-structured diagnostic interviews every four months of follow-up. Results: The bipolar spectrum group exhibited higher Time 1 BAS, but not BIS, scores than the normal controls, controlling for Time 1 symptoms. Among bipolar spectrum participants, high BAS sensitivity prospectively predicted a shorter time to onset of hypomanic and manic episodes, whereas high BIS sensitivity predicted less survival time to major depressive episodes, controlling for initial symptoms. Conclusions: Consistent with the BAS hypersensitivity model of bipolar disorder, a highly responsive BAS provides vulnerability to onsets of (hypo)manic episodes. In addition, a highly sensitive BIS increases risk for major depressive episodes.

The association between personality disturbance and depression has been noted consistently. Prospective tests of personality's impact on the course of depression, however, are lacking. In a sample of 159 undergraduates who experienced at least one prospective depressive episode, dimensional scores for clusters B and C personality disturbance were examined as prospective predictors of four indicators of the course of depression: severity, episode duration, symptomatic chronicity and number of episodes. Cluster C personality disturbance, characterized by anxious and fearful features, predicted depression chronicity. Cluster B, characterized by dramatic, emotional and/or erratic features, predicted severity and duration of depression. The findings are discussed in terms of the possible mechanisms underlying the effects of clusters B and C, as well as implications for future research.

Background.Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.Method.We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery–Asberg Depression Rating Scale – Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.Results.The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.Conclusions.The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.

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.

In this article, we tested the vulnerability hypoth- esis of the behavioral approach system (BAS) hypersensitiv- ity model of bipolar disorders. We examined whether self- reported BAS sensitivity predicts lifetime bipolar spectrum diagnoses as well as symptoms and personality character- istics associated with bipolar disorder using a retrospective and concurrent behavioral high-risk design. Participants with high (HBAS; n = 28) or moderate (MBAS; n = 24) BAS sen- sitivity were selected and given a lifetime psychiatric diag- nostic interview and self-report measures of proneness to bipolar symptoms, current symptoms, and personality char- acteristics relevant to bipolarity. HBAS participants were significantly and substantially more likely to have a life- time bipolar spectrum disorder diagnosis than were MBAS participants, but did not differ from MBAS participants in their likelihood of a unipolar depression diagnosis. Also, the HBAS group exhibited higher impulsivity and prone- ness to hypomanic symptoms than the MBAS group, and BAS-reward responsiveness predicted hypomanic personal- ity characteristics. Finally, high behavioral inhibition system (BIS) sensitivity was associated with proneness to and cur- rent depressive symptoms.

Research in unipolar depression suggests that neuroticism is associated with poor long-term outcome and greater chronicity. The objective of this study was to determine whether baseline neuroticism scores predict response to treatment with fluoxetine in depressed outpatients. Seventy-six depressed outpatients participating in a clinical trial of fluoxetine (fixed/flexible dosing) completed the NEO-FFI (five factor inventory short form) at baseline. Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Depression Rating Scale (HAM-D-17) total score (final visit--baseline). Logistic regression evaluated NEO-FFI factor scores as predictors of treatment outcome within an intent-to-treat model. Scores on the neuroticism scale were not found to significantly predict treatment response as measured by the HAM-D-17. Strengths of this study include a standardized treatment protocol and use of structured interview instruments, while limitations include a modest sample size, lack of continuation data, state/trait effects, and lack of generalizability to other antidepressant treatments.

Background: Tobacco smoking is the leading cause of preventable death in the US, with the economic burden attributable to smoking exceeding $300 billion annually. Although smoking cessation medications are effective in clinical trials, their real-world effectiveness is sub-optimal. Poor adherence to smoking cessation medications is associated with failed quit attempts. Technology has been used to promote medication adherence in other conditions. Clickotine is a science-based mobile application for smoking cessation, designed to assist smokers according to the US Public Health Service Clinical Practice Guidelines. Clickotine has been tested in a single arm trial and shows promise as a smoking cessation aid. One core component of the Clickotine program aims to educate smokers about smoking cessation medications including nicotine replacement therapy, varenicline, and bupropion and to facilitate access and adherence to these medications through targeted Clickotine missions and personalized messages. Clickotine missions direct the user to do something specific related to their quit journey. Missions related to smoking cessation medications included “read here to learn about NRT options and efficacy”; “set a reminder to take your meds”; or “make a plan to order your refill.” Personalized messages provide encouragement and reminders and included information relevant to the user or their quit journey. Objective: To measure use of smoking cessation medications among Clickotine users and measure medication adherence at baseline and 8-weeks in a single-arm trial of Clickotine for smoking cessation. Methods: U.S. residents between 18-65 years of age who owned an iPhone and smoked 5 or more cigarettes daily were recruited via online advertising from May to July 2016. Respondents were pre-screened for eligibility by telephone and directed to a web portal to complete informed consent, confirm eligibility, and download the Clickotine app. Participants completed study assessments via the web portal at baseline and after 8-weeks (primary outcome). The proportion of participants using a smoking cessation medication was measured at baseline and at the 8-week outcome. To assess adherence to smoking cessation medications, the Morisky Medication Adherence Scale- 4 item version (MMAS-4) was compared at baseline and study outcome. MMAS-4 yields scores of 0-4 with greater scores indicating decreased adherence. Results: 416 participants downloaded the app and constituted the intention-to-treat (ITT) sample in the Clickotine trial. Of these, 31 (7.5%) reported using a smoking cessation medication at baseline. At 8 weeks, 68 participants (16.3%) reported using a smoking cessation medication. Increases were observed for all medications (e.g., medications (varenicline or bupropion): 183%; NRT: 93%) and subcategories (e.g., varenicline: 233%; nicotine gum: 200%). MMAS-4 score at baseline (mean = 2.35; SD= 1.43) was significantly greater than the MMAS-4 score observed at study outcome (mean = 1.28; SD= 1.31), t(87)= 3.30, P=.001, and Chi-square analysis of distribution of MMAS-4 scores indicated a shift toward greater adherence from study baseline to outcome (2(4)= 10.56, P=.032). Conclusions: Access and adherence to smoking cessation medications increased during an 8-week, single-arm clinical trial of Clickotine.

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.

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 (ηp2 = .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.

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.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.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.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.

Acute and chronic stress–related mechanisms play an important role in the development of addiction and its chronic, relapsing nature. Multisystem adaptations in brain, body, behavioral, and social function may contribute to a dysregulated physiological state that is maintained beyond the homeostatic range. In addition, chronic abuse of substances leads to an altered set point across multiple systems. Resilience can be defined as the absence of psychopathology despite exposure to high stress and reflects a person’s ability to cope successfully in the face of adversity, demonstrating adaptive psychological and physiological stress responses. The study of resilience can be approached by examining interindividual stress responsibility at multiple phenotypic levels, ranging from psychological differences in the way people cope with stress to differences in neurochemical or neural circuitry function. The ultimate goal of such research is the development of strategies and interventions to enhance resilience and coping in the face of stress and prevent the onset of addiction problems or relapse.

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.

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.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.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.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.

The present study explored longitudinal evidence for prodromal symptoms of depression episodes. A model based on previous findings of the relations between prodromal and residual symptoms was described and used to generate hypotheses tested in this study. Data were analyzed from 160 participants from the Cognitive Vulnerability to Depression (CVD) project (L. Alloy & L. Abramson, 1999) who experienced an episode of depression during the prospective follow-up period and 60 CVD participants who did not. Congruent with the hypothesis, individuals who subsequently developed an episode of depression experienced significantly greater numbers of depression symptoms in the period of time leading up to the acute episode compared with those who did not develop a depressive episode. Seven depression symptoms were particularly likely to appear before the onset of an acute episode. Furthermore, all 3 predictions from the model were supported: the durations of prodromal and residual phases were correlated, the prodromal and residual symptom profiles were quite similar, and the order of symptom onset was significantly and highly negatively correlated with the order of symptom remission. Additionally, residual symptom profiles were similar to subsequent prodromal symptom profiles in individuals who experienced more than 1 depressive episode. These findings are discussed in terms of the importance of understanding the earliest prodromal symptoms to appear and their relation to the symptomatic course of depression episodes. Implications for early intervention are also discussed.

Prospective tests of the impact of sociotropy and autonomy on the course of depression are lacking. In a sample of 97 cognitive high-risk and 62 cognitive low-risk undergraduates who experienced at least one prospective depressive episode, the interactions of sociotropy and interpersonal life events and autonomy and achievement-related life events were examined as predictors of four indicators of the course of depression. Initial analyses failed to support the hypothesis that global scores for sociotropy and autonomy interact with domain-congruent life events to predict the course indicators. The autonomy-achievement events interaction predicted less severe episodes, contrary to hypothesis. Then, factors hypothesized to underlie Sociotropy (Fear of Criticism and Rejection; Preference for Affiliation) and Autonomy (Independent Goal Attainment; Sensitivity to Others’ Control; Bieling et al., Cognitive Ther Res 24:763–780, 2000) were also analyzed. The puzzling autonomy-achievement life event interaction was explained by the underlying Independent Goal Attainment factor. Interactions between Fear of Criticism and Rejection and achievement events, and between Sensitivity to Others’ Control and interpersonal events, significantly predicted chronicity, number and severity of episodes. The findings are discussed in terms of the event-congruency hypothesis.

Background: Most research to date on the role of maltreatment experiences in depression has focused on physical and sexual maltreatment. However, several researchers have theorized that emotional maltreatment may be more strongly linked to depression. Furthermore, prospective studies in this area are lacking. This study addressed these issues by examining whether experiences of current emotional maltreatment predicted the development of new prospective episodes of major (MD) or minor depression (MiD), and the subtype of hopelessness depression (HD) in young adults. It also assessed whether current emotional maltreatment from peers and from authority figures separately predicted the occurrence of depressive episodes. Method: One hundred and sixty-five participants from the Cognitive Vulnerability to Depression Project were followed prospectively for 2.5 years. Current emotional maltreatment and new depressive episodes were assessed with life event and diagnostic interviews administered every 6 weeks. Results: Greater overall emotional maltreatment predicted shorter time to onset of new MD, MiD, and HD episodes. Peer- and authority-perpetrated emotional maltreatment separately predicted shorter time to development of new HD episodes. Conclusions: Greater emotional maltreatment in young adults prospectively predicts onset of depression, particularly HD. These findings highlight the importance of adult emotional maltreatment experiences in determining targets for prevention and treatment. Depression and Anxiety 26:174–181, 2009. r 2009 Wiley-Liss, Inc.

The social zeitgeber theory emphasizes the importance that social rhythm regularity may play in promoting internal synchronization of circadian rhythms in individuals with or at risk for bipolar spectrum disorders. This study examined the relationship of lifestyle regularity, affective symptomatology, and sleep in 71 individuals exhibiting cyclothymic mood and behavior patterns. Participants were randomly assigned to either an experimental group in which they were encouraged to regulate their daily routines or to a control group. Participants in the experimental group were able to successfully regulate their daily schedules. Although relationships between regularity and severity of depressive symptoms, across-day variances in mood and behavior, and sleep duration were identified during baseline, increased lifestyle regularity did not differentially result in changes in these variables.

The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was assessed before treatment and at the 3rd, 5th, and 9th weeks of treatment. Among patients initially preferring psychotherapy, those receiving psychotherapy experienced increases in their alliance over time, whereas those receiving active medication or placebo experienced decreases. Among patients preferring pharmacotherapy, there were no differences in alliance development whether they received psychotherapy, active medication, or placebo. These relations were observed even when controlling for symptom severity. Thus, the congruence of patients' treatment preference and the treatment that they ultimately received influenced the development of the therapeutic alliance. Because alliance is a robust predictor of outcome, treatment preferences may need to be carefully considered in randomized controlled trial settings.