Mindfulness in Facilitating Pelvic Floor Botulinum Toxin Injection in Women with Chronic Pelvic Pain.

Botulinum toxin (BoNT) injection can safely be done as an office-based procedure, but can be painful itself, especially when injecting pelvic floor muscles to treat chronic pelvic pain (CPP). Mindfulness interventions may reduce procedure-associated acute anxiety and pain. We applied mindfulness techniques to increase the tolerability of office-based pelvic floor BoNT injections in women with CPP. Women enrolled in a clinical trial of BoNT for endometriosis-associated CPP were offered a brief, guided mindfulness session before and/or after transvaginal injection. Anxiety, pain, and dysphoria were rated on a 0-10 numerical rating scale (NRS) before and after each mindfulness session. Eight women underwent mindfulness sessions. Five participants had a session before and two after the transvaginal injection. One participant had two sessions: one before and one after separate injections. All six women completing a session prior to injection had at least moderate anxiety, which lessened after the mindfulness session (median NRS change: -3.3/10). All three women reporting injection-associated pain experienced less intense pain following the post-injection session (median NRS change: -3/10). Three women experiencing dysphoria improved after the session (median NRS change: -3/10). A brief, guided mindfulness session may lessen acute pain, anxiety, and dysphoria associated with office-based transvaginal BoNT injection.

Psilocybin-assisted group therapy in patients with cancer diagnosed with a major depressive disorder.

BACKGROUND: Depression is common in patients with cancer and is associated with lower treatment adherence and reduced quality of life. Antidepressants and psychotherapy have limited success in improving depression among patients with cancer. This study explored the safety, feasibility, and efficacy of psilocybin-assisted therapy in patients with cancer and major depressive disorder. METHODS: This phase 2, open-label trial enrolled patients with curable and noncurable cancer and major depressive disorder at a single community oncology practice site. A single 25-mg dose of psilocybin was administered simultaneously to cohorts of three to four participants with individual (4.25 hours in 1:1 therapist-to-patient ratio) and group therapeutic support (3.75 hours) before, during, and after psilocybin administration. Outcomes included depression severity, anxiety, pain, demoralization, and disability. RESULTS: Thirty participants completed the study. No psilocybin-related serious adverse events occurred; treatment-related adverse events (e.g., nausea, headache) were generally mild and expected. There were no laboratory or electrocardiogram abnormalities. No suicidality was reported. Efficacy was suggested with a robust reduction in depression severity scores from baseline to posttreatment of 19.1 points (95% CI, 22.3 to -16.0; p < .0001) by week 8. Eighty percent of participants demonstrated a sustained response to psilocybin treatment; 50% showed full remission of depressive symptoms at week 1, which was sustained for 8 weeks. CONCLUSIONS: Psilocybin-assisted therapy in group cohort administration was safe and feasible in patients with cancer and depression. Efficacy was suggested based on clinically meaningful reductions in depressive symptoms. The novel, group-oriented format, compact delivery time, community cancer center setting, and one-to-one therapist-to-patient ratio could also add to therapeutic gains and efficiency of administration. TRIAL REGISTRATION: NCT04593563. PLAIN LANGUAGE SUMMARY: Depression is common in patients with cancer and associated with lower treatment adherence, reduced quality of life, and limited response to antidepressants and psychotherapy. We conducted a phase 2 trial to study a single dose of psilocybin administered in a group therapy setting with one-to-one therapist-to-participant psychological support to patients with curable and noncurable cancer and major depressive disorder. Findings of the study showed safety (no treatment-related serious adverse events or suicidality) with psilocybin and suggested efficacy, with a significant reduction in depression severity scores from baseline to posttreatment. Further investigation is warranted.

Psychosocial-spiritual well-being is related to resilience and mindfulness in patients with severe and/or life-limiting medical illness.

BACKGROUND: Improvement of psychosocial-spiritual well-being in patients with life-threatening or life-limiting illness is desirable. Resilience and mindfulness are considered to be helpful for enhancing psychosocial-spiritual well-being. Mindfulness-based interventions have been shown to promote resilience to stress and enhance well-being. However, in medical patients, evidence for the associations between mindfulness and resilience is lacking. We hypothesize patients with higher levels of psychosocial-spiritual well-being demonstrate greater resilience and mindfulness. METHODS: 200 patients (mean age = 50.2, SD = 15.5) with serious and or life-limiting illnesses were recruited from the NIH Clinical Center. Patients completed a demographic questionnaire, the NIH-HEALS measure of psychosocial-spiritual well-being, the Connor-Davidson Resilience Scale (CD-RISC-10), and the Mindful Attention Awareness Scale (MAAS). The demographic questionnaire also included a question on current stress level. RESULTS: The NIH-HEALS was positively correlated to CD-RISC-10 (rs=0.44, p < 0.001) and MAAS (rs=0.32, p < 0.001). These findings were consistent across all three NIH-HEALS factors. Additionally, CD-RISC-10 and MAAS demonstrated a meaningful relationship to each other (rs=0.46, p < 0.001). All three constructs were inversely related to current stress level. CONCLUSIONS: Findings suggest that there is a meaningful relationship between psychosocial-spiritual well-being, mindfulness, and resilience. Mindfulness and resilience are positively correlated in a medical population. Clinical interventions aimed at enhancing psychosocial-spiritual well-being through mindfulness and resilience can be highly promising for patients with severe and or life limiting illness.

Psilocybin-assisted therapy improves psycho-social-spiritual well-being in cancer patients.

BACKGROUND: While psychedelics have been shown to improve psycho-spiritual well-being, the underlying elements of this change are not well-characterized. The NIH-HEALS posits that psycho-social-spiritual change occurs through the factors of Connection, Reflection & Introspection, and Trust & Acceptance. This study aimed to evaluate the changes in NIH-HEALS scores in a cancer population with major depressive disorder undergoing psilocybin-assisted therapy. METHODS: In this Phase II, single-center, open label trial, 30 cancer patients with major depressive disorder received a fixed dose of 25 mg of psilocybin. Participants underwent group preparation sessions, simultaneous psilocybin treatment administered in adjacent rooms, and group integration sessions, along with individual care. The NIH-HEALS, a self-administered, 35-item measure of psycho-social spiritual healing was completed at baseline and post-treatment at day 1, week 1, week 3, and week 8 following psilocybin therapy. RESULTS: NIH-HEALS scores, representing psycho-social-spiritual wellbeing, improved in response to psilocybin treatment (p < 0.001). All three factors of the NIH-HEALS (Connection, Reflection & Introspection, and Trust & Acceptance) demonstrated positive change by 12.7 %, 7.7 %, and 22.4 %, respectively. These effects were apparent at all study time points and were sustained up to the last study interval at 8 weeks (p < 0.001). LIMITATIONS: The study lacks a control group, relies on a self-report measure, and uses a relatively small sample size with limited diversity that restricts generalizability. CONCLUSIONS: Findings suggest that psilocybin-assisted therapy facilitates psycho-social-spiritual growth as measured by the NIH-HEALS and its three factors. This supports the factors of Connection, Reflection & Introspection, and Trust & Acceptance as underlying elements for psycho-social-spiritual healing in cancer patients, and validates the use of the NIH-HEALS within psychedelic research.

The FACIT-Sp spiritual wellbeing scale: a factor analysis in patients with severe and/or life-limiting medical illnesses.

BACKGROUND: The Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp) is a widely used measure of spiritual wellbeing. However, consensus on the best factor structure for this measure has not been reached. Both a 2-factor (Meaning/Peace, Faith) and a 3-factor (Meaning, Peace, Faith) structure are reported in the literature. In this study, we examined the factorial structure of the FACIT-Sp in a population of patients with severe and/or life-limiting medical illnesses. METHODS: The present study is a part of a larger study that validated the National Institute of Health-Healing Experiences of All Life Stressors (NIH-HEALS), a measure of psycho-social-spiritual healing developed by the Pain and Palliative Care Service at the National Institutes of Health Clinical Center (NIH-CC). The sample included 200 subjects who were recruited from the NIH Clinical Center inpatient units and outpatient clinics with severe and/or life limiting illnesses (cancer, non-genetic conditions, genetic conditions, blood dyscrasias). FACIT-Sp is a 12-item questionnaire scored on a 5-point Likert scale (0 = not at all; 4 = very much). Exploratory factor analysis (EFA) and principal component analysis (PCA) were used to analyze results and to identify the number of latent constructs and underlying factor structure. RESULTS: The results supported the 3-factor (Meaning, Peace, and Faith) model of the FACIT-Sp and accounted for the most variability (74.20%), followed by the 2-factor solution (64.95%). The identified factors related to Faith, Peace, and Meaning and were consistent with previously reported 3-factor model. CONCLUSIONS: This study confirmed the 3-factor structure of FACIT-Sp. This information can inform interventions aimed at improving quality of life and spiritual wellbeing in clinical and palliative care settings.

A nature-based health intervention at a military healthcare center: a randomized, controlled, cross-over study.

We describe a mixed qualitative and quantitative research study in a military facility regarding the role of nature in well-being. Study intervention included two 20-minute walks. One walk was in an intentionally designed woodland environment (Green Road) and the other was on a busy campus road in a medical treatment facility (Urban Road). Twelve volunteers from a military facility participated in both walks in a cross-over experimental design. The two walking sessions were randomly ordered and preceded by pre-walk instructions appropriate to each road's characteristics and incorporated focused attention and present moment orientation. A semi-structured post-walk interview, the primary outcome, was conducted after the conclusion of each walk. Qualitative data analyses consisted of sentiments and themes by using NVivo 12 software. The Green Road was unanimously rated as positive (100%). Responses to Urban Road were evenly distributed among positive (33.3%), negative (33.3%), and neutral/mixed (33.3%) sentiments. The Green Road yielded predominantly positive themes such as enjoyment of nature, relaxation, and feelings of privacy and safety. Urban Road produced significantly more negative themes such as concerns for safety, dislike of noise and other noxious experiences. Quantitative assessment of distress and mindfulness with Distress Thermometer (DT) and Mindful Attention Awareness Scale-state version (MAAS) demonstrated that a walk on the Green Road significantly decreased distress and increased mindfulness compared to a walk on the Urban Road. We also observed that pre-walk instructions could direct attention to both obvious and subtle elements of experience and enhance awareness. Results support the notion that an intentional nature-based environment may produce significantly more positive experiences and result in health-promoting benefits in a military health-care setting compared to an urban environment. Future studies with clinical populations could advance our understanding of the healing value of nature-based interventions. The impact of intentional green environments may be enhanced by well-designed instructions for both recreational and therapeutic use.

Effect of a Brief Mindfulness-Based Program on Stress in Health Care Professionals at a US Biomedical Research Hospital: A Randomized Clinical Trial.

Importance: Stress among health care professionals is well documented. The use of mindfulness-based interventions to reduce stress has shown promising results; however, the time commitment of typical programs can be a barrier to successful implementation in health care settings. Objective: To determine the efficacy and feasibility of a brief mindfulness-based program to reduce stress during work hours among health care professionals. Design, Setting, and Participants: This intent-to-treat randomized clinical trial was conducted among full-time health care professionals at the Clinical Center at the National Institutes of Health in Bethesda, Maryland, between September 2017 and May 2018. Participants were randomized to receive mindfulness-based self-care (MBSC) training or life-as-usual control. Data were analyzed from June 2018 to January 2020. Interventions: The MBSC intervention included 5 weekly, 1.5-hour in-class mindfulness practice sessions. Main Outcomes and Measures: Stress level was the primary outcome, assessed with the Perceived Stress Scale 10-Item version. Secondary outcomes included anxiety, burnout, positive and negative affect, mindfulness (trait and state), and self-care. Assessments were taken at baseline and at the end of the intervention (week 5) in the intervention and control groups, and at follow-up (week 13) in the intervention group to test for a maintenance effect. A postprogram evaluation was also obtained. Results: Of 82 randomized participants, 78 who completed the study at week 5 were included in the modified intent-to-treat analysis (median [interquartile range] age, 32 [23-48] years; 65 [83%] women), including 43 participants in the MBSC group and 35 participants in the control group. At the end of the intervention, compared with the control group, the MBSC group had reduced levels of stress (mean [SD] score, 17.29 [5.84] vs 18.54 [6.30]; P = .02) and anxiety (mean [SD] score, 2.58 [1.52] vs 4.23 [1.73]; P < .001), and improved positive affect (mean [SD] score, 35.69 [7.12] vs 31.42 [7.27]; P < .001), state mindfulness (mean [SD] score, 3.74 [1.18] vs 2.78 [1.16]; P < .001), and mindful self-care (mean [SD] score, 7.29 [2.44] vs 5.54 [2.77]; P < .001). Burnout, negative affect, and trait mindfulness levels did not differ between groups. Changes within the MBSC group through follow-up included sustained reductions in stress (change, -6.14; 95% CI, -7.84 to -4.44; P < .001), anxiety (change, -1.46; 95% CI, -1.97 to -0.94; P < .001), trait mindfulness (change, 0.63; 95% CI, 0.36 to 0.90; P < .001), and state mindfulness (change, 1.89; 95% CI, 1.39 to 2.39; P < .001). Conclusions and Relevance: This randomized clinical trial found that this brief mindfulness-based intervention was an effective and feasible means to reduce stress in health care professionals. Larger studies are needed to assess the effects on clinical care and patient outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03781336.

Gender Differences in Psycho-Social-Spiritual Healing.

Background: Many individuals exhibit significant distress in response to serious and/or life-limiting illness. However, there are others who make life-transforming changes, which involve healing experiences in the psychological, social, and spiritual domains of life regardless of illness outcome. The aim of the present study is to determine if there are any differences in psycho-social-spiritual healing between genders. Materials and Methods: The NIH Healing Experiences in All Life Stressors (NIH-HEALS), a 35-item measure of psycho-social-spiritual healing, is composed of three factors: Connection, Reflection & Introspection, and Trust & Acceptance. NIH-HEALS and a demographic questionnaire were administered to 193 patients with serious and/or life-limiting illness at the National Institutes of Health Clinical Center. Results: In response to NIH-HEALS, men and women significantly differed on the Reflection & Introspection factor. Women reported increased enjoyment of mind-body practices (p < 0.001), compassion (p = 0.005), gratitude (p = 0.014), and a desire to be more positive (p = 0.044) compared to men. Men rated their pain levels (p = 0.035) and severity of illness (p = 0.016) higher and their overall level of health (p = 0.010) poorer compared to women. Women's responses to items regarding compassion (rs = 0.37, p < 0.001) and gratitude (rs = 0.24, p = 0.015) correlated positively with better overall health ratings. Conclusion: Men and women show some differences in their self-reported psycho-social-spiritual healing, which may have implications when designing interventions aimed at promoting a healing experience in the context of serious and life-limiting illness.

Periaqueductal Gray Sheds Light on Dark Areas of Psychopathology.

Neurons in the periaqueductal gray (PAG) integrate negative emotions with the autonomic, neuroendocrine, and immune systems to facilitate responses to threat. Modern functional track tracing in animals and optogenetic and chemogenetic techniques show that the PAG is a rich substrate for the integration of active and passive responses to threat. In humans, the same regions of the PAG that give rise to adaptive anger/fight, fear/panic, depression/shutdown, pain, and predatory behaviors in response to challenging situations or overwhelming threats can become activated pathologically, resulting in symptoms that resemble those of psychiatric disorders. This review coalesces human and animal studies to link PAG neuropathways to specific elements of psychiatric diagnoses. The insights gained from this overview may eventually lead to new therapeutic interventions.

The National Institutes of Health measure of Healing Experience of All Life Stressors (NIH-HEALS): Factor analysis and validation.

Two hundred patients with severe and/or life-threatening disease were recruited form the NIH Clinical Center and participated in the validation of the NIH-HEALS, which included exploratory factor analysis, principal component analysis, reliability, convergent validity, and divergent validity analyses. Item-reducing principal components analysis and internal consistency and split-half reliability demonstrated excellent internal consistency and split-half reliability (Cronbach's alpha = 0.89, split-half reliability = 0.95). Exploratory factor analysis revealed a three-factor structure, namely Connection (including religious, spiritual, and interpersonal), Reflection & Introspection, and Trust & Acceptance. Seven items were not retained. Convergent and divergent validity of 35-item NIH-HEALS against other validated measures of healing and spirituality provided strong evidence for its validity. As predicted, the Healed factor of the Self-Integration Scale (SIS), and Meaning, Peace, and Faith factors of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being-12 Scale (FACIT-SP12) were all positively and significantly correlated with the NIH-HEALS and its three factors. Divergent validity was also confirmed by the significant negative correlation between the NIH-HEALS and the Codependent factor on the SIS. Confirmatory Factor Analyses revealed good model fit by GFI (0.96), adjusted GFI (0.95), SRMR (0.077), and RMSEA (0.065), supporting the use of the NIH-HEALS with 35 items.

Gray matter differences in patients with functional movement disorders.

OBJECTIVE: To explore alterations in gray matter volume in patients with functional movement disorders. METHODS: We obtained T1-weighted MRI on 48 patients with clinically definite functional movement disorders, a subset of functional neurologic symptom disorder characterized by abnormal involuntary movements, and on 55 age- and sex-matched healthy controls. We compared between-group differences in gray matter volume using voxel-based morphometry across the whole brain. All participants in addition underwent a thorough neuropsychological battery, including the Hamilton Anxiety and Depression Scales and the Childhood Trauma Questionnaire. To determine whether confounding factors such as comorbid depression, anxiety, or childhood trauma exposure contributed to the observed structural changes, nonparametric correlation analysis was performed. RESULTS: Patients with functional movement disorders exhibited increased volume of the left amygdala, left striatum, left cerebellum, left fusiform gyrus, and bilateral thalamus, and decreased volume of the left sensorimotor cortex (whole-brain corrected p ≤ 0.05). Volumetric differences did not correlate with measures of disease duration or patient-rated disease severity. CONCLUSION: This study demonstrates that patients with functional movement disorders exhibit structural gray matter abnormalities in critical components of the limbic and sensorimotor circuitry. These abnormalities may represent a premorbid trait rendering patients more susceptible to disease, the disease itself, or a compensatory response to disease.

Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials.

BACKGROUND: Identifying clinical correlates associated with reduced suicidal ideation may highlight new avenues for the treatment of suicidal thoughts. Anhedonia occurs across psychiatric diagnoses and has been associated with specific neural circuits in response to rapid-acting treatments, such as ketamine. This analysis sought to evaluate whether reductions in suicidal ideation after ketamine administration were related to reduced levels of anhedonia, independent of depressive symptoms. METHODS: This post-hoc analysis included treatment-resistant patients with either major depressive disorder (MDD) or bipolar disorder (BD) from several clinical trials of ketamine. Anhedonia was assessed using a subscale of the Beck Depression Inventory (BDI) and the Snaith-Hamilton Pleasure Scale (SHAPS). The outcome of interest was suicidal ideation, as measured by a subscale of the Scale for Suicide Ideation (SSI5), one day post-ketamine administration. RESULTS: Anhedonia, as measured by the SHAPS, was associated with suicidal thoughts independent of depressive symptoms both before and after ketamine administration. One day post-ketamine administration, improvements on the SHAPS accounted for an additional 13% of the variance in suicidal thought reduction, beyond the influence of depressive symptoms. The BDI anhedonia subscale was not significantly associated with suicidal thoughts after adjusting for depressive symptoms. LIMITATIONS: Data were limited to patients experiencing a major depressive episode and may not be generalizable to patients experiencing an active suicidal crisis. CONCLUSIONS: Suicidal thoughts may be related to symptoms of anhedonia independent of other depressive symptoms. These results have implications for the potential mechanisms of action of ketamine on suicidal thoughts.

Impaired self-agency in functional movement disorders: A resting-state fMRI study.

OBJECTIVE: To investigate the neural mechanisms underlying impaired self-agency in patients with functional movement disorders using resting-state functional MRI (fMRI). METHODS: We obtained resting-state fMRI on 35 patients with clinically definite functional movement disorders and 35 age- and sex-matched healthy controls. Between-group differences in functional connectivity from the right temporo-parietal junction (TPJ), a region previously demonstrated to play a critical role in self-agency by comparing internal predictions of movement with actual external events, were assessed using t tests. All participants were screened for psychiatric diagnoses using a structured clinical interview and completed the Beck Depression Inventory and Childhood Trauma Questionnaire. RESULTS: Compared to the healthy controls, patients with functional movement disorders showed decreased functional connectivity between the right TPJ and the right sensorimotor cortex, cerebellar vermis, bilateral supplementary motor area, and right insula. These findings were independent of depression, anxiety, and childhood trauma scores included in our assessment as covariates. CONCLUSIONS: The decreased functional connectivity between the right TPJ and bilateral sensorimotor regions observed in patients with functional movement disorders supports a model whereby impaired motor feed-forward together with altered sensory feedback from sensorimotor regions and areas of sensorimotor integration to the right TPJ contributes to patients' impaired sense of self-agency.

Insights into Chronic Functional Movement Disorders: The Value of Qualitative Psychiatric Interviews.

BACKGROUND: Patients with functional movement disorders (FMDs) are commonly seen by neurologists and psychosomatic medicine psychiatrists. Research literature provides scant information about the subjective experiences of individuals with this often chronic problem. OBJECTIVE: To enhance our understanding of psychologic aspects of FMDs by conducting qualitative interviews of research subjects. METHODS: In total, 36 patients with FMDs were recruited from the Human Motor Control clinic at the National Institutes of Health. Each subject participated in a qualitative psychiatric interview and a structured diagnostic psychiatric interview. RESULTS: Of our 36 subjects, 28 had current or lifetime psychiatric disorders in addition to conversion disorder and 22 had current disorders. Qualitative interviews provided rich information on patients' understanding of their illnesses and impaired cognitive processing of emotions. CONCLUSION: Our study supports the addition of open-ended qualitative interviews to delineate emotional dynamics and conceptual frameworks among such patients. Exploratory interviews generate enhanced understanding of such complex patients, above and beyond that gained by assessing DSM diagnostic comorbidities.

Impaired resting vagal tone in patients with functional movement disorders.

INTRODUCTION: The autonomic nervous system plays an integral role in the maintenance of homeostasis during times of stress. The functioning of the autonomic nervous system in patients with functional movement disorders (FMD) is of particular interest given the hypothesis that converted psychological stress plays a critical role in FMD disease pathogenesis. We sought to investigate autonomic nervous system activity in FMD patients by examining heart rate variability (HRV), a quantitative marker of autonomic function. METHODS: 35 clinically definite FMD patients and 38 age- and sex-matched healthy controls were hospitalized overnight for continuous electrocardiogram recording. Standard time and frequency domain measures of HRV were calculated in the awake and asleep stages. All participants underwent a thorough neuropsychological battery, including the Hamilton Anxiety and Depression scales and the Beck Depression Inventory. RESULTS: Compared to controls, patients with FMD exhibited decreased root mean square of successive differences between adjacent NN intervals (RMSSD) (p = 0.02), a marker of parasympathetic activity, as well as increased mean heart rate (p = 0.03). These measures did not correlate with the depression and anxiety scores included in our assessment as potential covariates. CONCLUSION: In this exploratory study, patients with FMD showed evidence of impaired resting state vagal tone, as demonstrated by reduced RMSSD. This decreased vagal tone may reflect increased stress vulnerability in patients with FMD.

Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant.

Rapid reduction of suicidal thoughts is critical for treating suicidal patients. Clinical trials evaluating these treatments require appropriate measurement. Key methodological issues include: 1) the use of single or multi-item assessments, and 2) evaluating whether suicidal ideation measures can track rapid change over time. The current study presents data from two randomized, placebo-controlled, crossover clinical trials evaluating ketamine in individuals with treatment-resistant depression (n = 60). Participants were assessed for suicidal thoughts using the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Scale for Suicidal Ideation (SSI) at eight time points over three days. Assessments were compared using correlational analyses and effect sizes at 230 min and three days after ketamine infusion. Linear mixed models evaluated change in ideation across all time points. The HAM-D and MADRS suicide items demonstrated correlations of r > .80 with the first five items of the SSI (SSI5). On linear mixed models, an effect for ketamine was found for the HAM-D, MADRS, BDI items, and SSI5 (p < .001), but not for the full SSI (p = .88), which suggests a limited ability to assess change over time in patients with low levels of suicidal thoughts. Taken together, the results suggest that repeated suicidal assessments over minutes to days appear to detect improvement in suicidal thoughts after ketamine infusion compared to placebo. The MADRS suicide item, BDI suicide item, and SSI5 may be particularly sensitive to rapid changes in suicidal thoughts.

A biological measure of stress levels in patients with functional movement disorders.

INTRODUCTION: While the presence of co-existing psychological stressors has historically been used as a supportive factor in the diagnosis of functional neurological disorders, many patients with functional neurological disorders deny the presence of these stressors. The stress response circuitry in these patients remains largely unexplored. METHODS: We performed an observational study examining biological stress levels in patients with functional movement disorders as compared with matched healthy controls. Specifically, we compared levels of circulating cortisol, the end-product of the hypothalamic-pituitary-adrenal axis. Salivary cortisol samples were collected from patients with "clinically definite" functional movement disorders (n = 33) and their age- and sex-matched controls (n = 33). Collections were performed at five standardized time points, reflecting participants' diurnal cortisol cycles. To rule out confounders, participants also underwent extensive psychological assessment including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Hamilton Anxiety Rating Scale, and Hamilton Rating Scale for Depression. RESULTS: Patients with functional movement disorders did not differ from matched controls with respect to levels of circulating cortisol. CONCLUSION: We demonstrate that current stress levels are not altered in patients with functional movement disorders. Our results warrant careful review of current management of patients with functional neurological symptoms, and suggest that the insistence on heightened stress levels in these patients is unjustified.

Rating depression over brief time intervals with the Hamilton Depression Rating Scale: standard vs. abbreviated scales.

Although antidepressant trials typically use weekly ratings to examine changes in symptoms over six to 12 weeks, antidepressant treatments may improve symptoms more quickly. Thus, rating scales must be adapted to capture changes over shorter intervals. We examined the use of the 17-item Hamilton Depression Rating Scale (HDRS) to evaluate more rapid changes. Data were examined from 58 patients with major depressive disorder or bipolar disorder enrolled in double-blind, placebo-controlled, crossover studies who received a single infusion of ketamine (0.5 mg/kg) or placebo over 40 min then crossed over to the other condition. HDRS subscales, a single HDRS Depressed mood item, and a visual analogue scale were used at baseline, after a brief interval (230 min), and one week post-infusion. Effect sizes for the ketamine-placebo difference were moderate (d > 0.50), but one and two-item HDRS subscales had the smallest effects. Response rates on active drug were lowest for the complete HDRS (43%); the remaining scales had higher response rates to active drug, but the shortest subscales had higher response rates to placebo. Correlations between the changes from baseline to 230 min post-ketamine across scores were similar for most subscales (r = 0.82-0.97), but correlations using the single items were lower (r < 0.74). Overall, effect sizes for drug-placebo differences and correlations between changes were lower for one- and two-item measures. Response rates were lower with the full HDRS scale. The data suggest that, to best identify rapid antidepressant effects, a scale should have more than two items, but fewer items than a full scale.

Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety.

OBJECTIVE: Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms. METHODS: 133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion. RESULTS: At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004). CONCLUSIONS: Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.

SHAPS-C: the Snaith-Hamilton pleasure scale modified for clinician administration.

Anhedonia, a diminished or lack of ability to experience and anticipate pleasure represents a core psychiatric symptom in depression. Current clinician assessment of anhedonia is generally limited to one or two all-purpose questions and most well-known psychometric scales of anhedonia are relatively long, self-administered, typically not state sensitive, and are unsuitable for use in clinical settings. A user-friendly tool for a more in-depth clinician assessment of hedonic capacity is needed. The present study assessed the validity and reliability of a clinician administered version of the Snaith-Hamilton Pleasure Scale, the SHAPS-C, in 34 depressed subjects. We compared total and specific item scores on the SHAPS-C, SHAPS (self-report version), Montgomery-Åsberg Depression Rating Scale (MADRS), and the Inventory of Depressive Symptomatology-Self Rating version (IDS-SR). We also examined construct, content, concurrent, convergent, and discriminant validity, internal consistency, and split-half reliability of the SHAPS-C. The SHAPS-C was found to be valid and reliable. The SHAPS and the SHAPS-C were positively correlated with one another, with levels of depression severity, as measured by the MADRS, and the IDS-SR total scores, and with specific items of the MADRS and IDS-SR sensitive to measuring hedonic capacity. Our investigation indicates that the SHAPS-C is a user friendly, reliable, and valid tool for clinician assessment of hedonic capacity in depressed bipolar and unipolar patients.