Affect Modulated Startle Response in Anorexia Nervosa, Restricting Type: Implications for Theory and Practice.

OBJECTIVE: Individuals with anorexia nervosa (AN), restricting type demonstrate unique emotional responses to hedonically positive stimuli beyond eating disorder (ED)-related stimuli. The goal of this study was to evaluate differences in responses to five types of emotionally positive stimuli among acutely ill anorexia nervosa (IAN), restricting type patients, weight-recovered anorexia patients (WRAN), and healthy controls (HCs) using affect modulated startle response (AMSR) as an objective measure. METHOD: A total of 28 participants were recruited (n=28). Fourteen participants were recruited as IAN using the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria, seven were WRAN, and seven were HC females. All participants were female and aged between 8 and 18 years. The participants viewed images depicting negative, neutral, standardized, and non-eating disorder (ED)-related positive stimuli. Additionally, four categories of ED-related stimuli (high-calorie food, body image, success, and parent-child relationships) were presented to all participants during a standard AMSR paradigm. RESULTS:  No significant between-group differences were found for any of the four ED stimulus categories; all groups showed an inhibited startle response to the four ED-related categories. In contrast, IAN and WRAN showed reduced hedonic responses to standardized positive stimuli relative to HC-replicating previous results. Reduced hedonic response to the standardized (non-ED) positive stimuli was highly correlated with self-reported social anxiety, low self-esteem, body dissatisfaction, asceticism, interpersonal problems, and ineffectiveness. CONCLUSION: AN patients had a reduced hedonic response to some non-ED-related positive stimuli, which correlated with several anxiety-related traits. In contrast, their early automatic responses to high-calorie food, normal weight models, images of success, and positive parent-child relationships did not differ from HC, suggesting these stimuli are either being evaluated as highly interesting or hedonically positive.

Reregulation of cortisol levels and sleep in patients with prescription opioid use disorder during long-term residential treatment.

OBJECTIVE: Research has demonstrated that hypothalamic-pituitary-adrenal (HPA) axis function and sleep patterns are dysregulated in patients diagnosed with opioid use disorder (OUD). It is unclear whether and/or when cortisol and sleep might re-regulate over time, and, whether re-regulation is associated with abstinence following discharge from residential treatment. The current study evaluated changes in sleep and basal cortisol levels in prescription OUD patients in residential treatment, and the association between these measures and treatment outcome following discharge. METHOD: As part of a larger study, 55 participants with prescription OUD provided two days of salivary cortisol samples and 12 consecutive nights of sleep actigraphy between days 19-30 of residential treatment (Time Point 1; TP1). Thirteen of the original 55 participants remained in residence and repeated the measures between days 60-72 (Time Point 2; TP2). Thirty-seven healthy controls (HC) provided baseline measures (TP1) of salivary cortisol and sleep. Treatment outcome data, abstinence vs relapse, were established at 120 days following discharge. RESULTS: Prescription OUD patients had higher cortisol levels and lower total sleep time (TST) than HC at TP1. At TP2, TST and cortisol levels no longer differed from HCs in the subgroup of patients who remained abstinent following discharge after TP2. Individuals whose cortisol and TST did not change from TP1 to TP2 were more likely to relapse following discharge from residential treatment. CONCLUSION: Re-regulation of TST and cortisol levels while in residential treatment was associated with better treatment outcome following discharge for prescription OUD patients.

Daily sleep quality affects drug craving, partially through indirect associations with positive affect, in patients in treatment for nonmedical use of prescription drugs.

OBJECTIVE: Sleep disturbance has been identified as a risk factor for relapse in addiction to a range of substances. The relationship between sleep quality and treatment outcome has received relatively little attention in research on nonmedical use of prescription drugs (NMUPD). This study examined the within-person association between sleep quality and craving in medically detoxified patients in residence for the treatment of NMUPD. METHOD: Participants (n=68) provided daily reports of their sleep quality, negative affect (NA), positive affect (PA), and craving for an average of 9.36 (SD=2.99) days. Within-person associations of sleep quality and craving were examined using multilevel modeling. Within-person mediation analyses were used to evaluate the mediating roles of NA and PA in the relationship between sleep quality and craving. RESULTS: Greater cravings were observed on days of lower than usual sleep quality (γ10=-0.10, p=0.003). Thirty-one percent of the overall association between sleep quality and craving was explained by PA, such that poorer sleep quality was associated with lower PA and, in turn, lower PA was associated with greater craving. No evidence emerged for an indirect association between sleep quality and craving through NA. CONCLUSIONS: Daily fluctuations in sleep quality were associated with fluctuations in craving, an association partially explained by the association between sleep quality and daily PA. These data encourage further research on the relationship between sleep, affect, and craving in NMUPD patients, as well as in patients with other substance use disorders.

Degree of anxiety in food allergic children in a tertiary care center.

BACKGROUND: The link between internalizing psychiatric disorders, such as anxiety and depression, and allergic diseases has attracted a high level of interest from psychiatrists and immunologists. Recent studies have found increased anxiety in children with asthma, but findings in children with food allergy (FA) have been inconsistent. OBJECTIVE: It was hypothesized that children with FA would score significantly higher on a standardized anxiety screen than general pediatric (GP) patients but not as high as patients with diagnosed anxiety disorders. METHODS: A total of 114 patients aged 8 to 16 years (37 with confirmed anxiety disorder from a pediatric psychiatry clinic, 40 with confirmed FA from a pediatric allergy clinic, and 43 well-care patients from a GP clinic) and their mothers completed the Screen for Child Anxiety Related Emotional Disorders (SCARED). RESULTS: Children and mothers in the allergy group did not report increased levels of anxiety in children on total SCARED scores or subscales compared with children and mothers from the GP group. There was a trend toward increased panic disorder symptoms reported in children by mothers of children in the allergy group, but this finding did not reach statistical significance. CONCLUSION: Children with FA did not have increased anxiety; however, there was a trend for mothers of children with allergies to report more symptoms of panic disorder in their children. It remains important to screen families for anxiety-related symptoms and refer them to mental health services when indicated.

Direct comparison of the psychometric properties of multiple interview and patient-rated assessments of suicidal ideation and behavior in an adult psychiatric inpatient sample.

OBJECTIVE: Compare the accuracy, agreement, internal consistency, and interrater reliability of 3 interviews to assess suicidal ideation and behavior in accordance with US Food and Drug Administration guidance about reporting categories. METHOD: Adults admitted to a psychiatric inpatient unit (N = 199) completed 3 assessments of past month and lifetime suicidal ideation and behavior-the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Tracking Scale (STS), and the Sheehan Suicidality Tracking Scale (S-STS)-in randomized, counterbalanced order. "Missing gold standard" latent class analyses defined categories for ideation and behavior. Analyses also evaluated the S-STS mapping to C-SSRS categories. Three trained judges re-rated 89 randomly selected interview videotapes. Cohen κ, the primary outcome measure, quantified agreement above chance. Data were collected between November 2011 and June 2013. RESULTS: All 3 assessments showed excellent accuracy for suicidal ideation (κ = 0.72 to 1.00) and attempts (κ = 0.82 to 0.95) calibrated against latent classes. Interrater agreement ranged from κ = 0.52 to 1.00. Interrater agreement about more granular C-SSRS categories varied more widely (κ = 0.48 to 1.00), and the C-SSRS and S-STS assigned significantly different numbers of cases to many categories. Cronbach α was < 0.55 for the C-SSRS ideation and between 0.78 and 0.92 for the other scales. CONCLUSIONS: All 3 assessments showed good accuracy for broad categories of suicidal ideation and behavior. More granular, specific categories usually were rated reliably, but the C-SSRS and S-STS differed significantly in regard to which patients were assigned to these subcategories. Using any of these interviews would improve reliability over unstructured assessment in evaluating suicidal ideation and behavior. Clinical predictive validity of these interviews, and particularly the more granular categories, remains to be shown.

Effects of injectable extended-release naltrexone (XR-NTX) for opioid dependence on residential rehabilitation outcomes and early follow-up.

BACKGROUND AND OBJECTIVES: Little is known about the use of extended-release naltrexone (XR-NTX) during residential rehabilitation, and its effects on early outcomes and rates of follow-up treatment. This study examined patient characteristics and rates of treatment completion and engagement in post-residential care of opioid dependent patients who received XR-NTX during residential rehabilitation, compared with patients who did not receive this medication. METHODS: Electronic records for opioid dependent patients from three Pennsylvania residential detoxification and treatment facilities (N = 7,687) were retrospectively analyzed. We determined the proportion of patients who received XR-NTX (INJ), and compared rates of treatment completion and engagement in follow-up care relative to a naturalistic control group of patients recommended for, but not administered, XR-NTX (Non-INJ). Data on whether the patient initiated follow-up care were available from one site (N = 3,724). RESULTS: Overall, 598 (7.8%) patients were recommended for XR-NTX and of these, 168 (28.1%) received injections. Compared to non-INJ patients, INJ patients were less likely to leave against medical advice (4.8% vs. 30.2%, p < .001) and more likely to initiate follow-up care (37.7% vs. 19.7%, p < .001). These differences remained significant after controlling for demographic covariates using regression analysis. CONCLUSIONS: XR-NTX was associated with higher rates of residential and early post-residential care engagement in patients with opioid dependence. SCIENTIFIC SIGNIFICANCE: XR-NTX may be an effective adjunct in the residential treatment and aftercare of patients with opioid dependence.

Possible evidence for re-regulation of HPA axis and brain reward systems over time in treatment in prescription opioid-dependent patients.

OBJECTIVES: There is growing evidence for a neuroadaptive model underlying vulnerability to relapse in opioid dependence. The purpose of this study was to evaluate clinical measures hypothesized to mirror elements of allostatic dysregulation in patients dependent on prescription opioids at 2 time points after withdrawal, compared with healthy control participants. METHODS: Recently withdrawn (n = 7) prescription opioid-dependent patients were compared with the patients in supervised residential care for 2 to 3 months (extended care; n = 7) and healthy controls (n = 7) using drug cue reactivity, affect-modulated startle response tasks, salivary cortisol, and 8 days of sleep actigraphy. Prefrontal cortex was monitored with functional near-infrared spectroscopy during the cue reactivity task. RESULTS: Startle response results indicated reduced hedonic response to natural rewards among patients recently withdrawn from opioids relative to extended care patients. The recently withdrawn patients showed increased activation to pill stimuli in right dorsolateral prefrontal cortex relative to extended care patients. Cortisol levels were elevated among recently withdrawn patients and intermediate for extended care relative to healthy controls. Actigraphy indicated disturbed sleep between recently withdrawn patients and extended care patients; extended care patients were similar to controls. Dorsolateral prefrontal cortex activation to drug and natural reward cues, startle responses to natural reward cues, day-time cortisol levels, time in bed, and total time spent sleeping were all correlated with the number of days since last drug use (ie, time in supervised residential treatment). CONCLUSIONS: These results suggest possible re-regulation of dysregulated hypothalamic-pituitary-adrenal axis and brain reward systems in prescription opioid-dependent patients over the drug-free period in residential treatment.

The Alcohol Clinical Trials Initiative (ACTIVE): purpose and goals for assessing important and salient issues for medications development in alcohol use disorders.

Although progress has been made in the treatment of alcohol use disorders, more effective treatments are needed. In the last 15 years, several medications have been approved for use in alcohol dependence but have only limited effectiveness and clinical acceptance. While academics have developed some 'standards' for the performance of clinical trials for alcohol dependence, they vary considerably, in the type of populations to be studied, the length of trials, salient outcome measures, and data analyses to be used (especially in the treatment of missing data). This variability impedes the commercial development of medications to treat alcohol dependence. Using a model similar to that used to develop an expert consensus for medications to improve cognitive aspects of schizophrenia (MATRICS) and in the treatment of pain (IMMPACT), a workgroup has been formed under the auspices of ACNP, known as the ACTIVE (Alcohol Clinical Trials Initiative) group, to evaluate data from completed clinical trials to develop a consensus on key issues in the conduct of clinical trials in alcohol dependence. ACTIVE consists of academic experts, industry representatives, and staff from the Food and Drug Administration, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Drug Abuse. This paper describes the rationale behind the effort, its history and organization, and initial key questions that have been identified as the primary focus of the workgroup. Future papers will focus on knowledge gained from the re-analysis of completed trials and provide consensus opinions regarding the performance of clinical trials that might be undertaken in the future.

Financing academic departments of psychiatry.

OBJECTIVE: The authors describe the many financial challenges facing academic departments of psychiatry and the resulting opportunities that may arise. METHOD: The authors review the history of financial challenges, the current economic situation, and what may lie ahead for academic departments of psychiatry. RESULTS: The current environment has many risks and opportunities for departments of psychiatry. Successful departments will be those that assess their particular strengths and limitations and explore their options for funding. CONCLUSION: Departments of psychiatry should have multiple funding streams and take advantage of opportunities in their local or regional service area.

Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a consensus statement.

OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies of major depression, bipolar disorder, schizophrenia, substance abuse/dependence, and other psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this scholarly article, which has been developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement have been noted. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's effort to promote standard definitions and definable expectations for investigators and industry sponsors by endorsing the terminology in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to build upon its new authority to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk within informative large health care-related databases in the United States and abroad. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the current Agency requirement that all CNS clinical drug trials must include a C-CASA-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed, and they need to be included to enable premarket assessments of the risks and benefits of medications related to suicidal ideation, suicidal behavior, and suicide in such patients.

Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a brief report.

OBJECTIVE: To address issues concerning potential treatment-emergent "suicidality," a consensus conference was convened March 23-24, 2009. PARTICIPANTS: This gathering of participants from academia, government, and industry brought together experts in suicide prevention, clinical trial design, psychometrics, pharmacoepidemiology, and genetics, as well as research psychiatrists involved in studies in studies of psychiatric disorders associated with elevated suicide risk across the life cycle. The process involved reviews of the relevant literature, and a series of 6 breakout sessions focused on specific questions of interest. EVIDENCE: Each of the participants at the meeting received references relevant to the formal presentations (as well as the slides for the presentations) for their review prior to the meeting. In addition, the assessment instruments of suicidal ideation/behavior were reviewed in relationship to standard measures of validity, reliability, and clinical utility, and these findings were discussed at length in relevant breakout groups, in the final plenary session, and in the preparation of the article. Consensus and dissenting views were noted. CONSENSUS PROCESS: Discussion and questions followed each formal presentation during the plenary sessions. Approximately 6 questions per breakout group were prepared in advance by members of the Steering Committee and each breakout group chair. Consensus in the breakout groups was achieved by nominal group process. Consensus recommendations and any dissent were reviewed for each breakout group at the final plenary session. All plenary sessions were recorded and transcribed by a court stenographer. Following the transcript, with input by each of the authors, the final paper went through 14 drafts. The output of the meeting was organized into this brief report and the accompanying full article from which it is distilled. The full article was developed by the authors with feedback from all participants at the meeting and represents a consensus view. Any areas of disagreement at the conference have been noted in the text. CONCLUSIONS: The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed.