Prospective longitudinal course of aggression among adults with bipolar disorder.

OBJECTIVES: Bipolar disorder (BP) has been associated with increased aggressive behaviors. However, all existing studies are cross-sectional and include forensic or inpatient populations and many do not take into account the effects of comorbid conditions. The goal of this study was to evaluate the longitudinal course of aggression among adult outpatients with BP compared with non-BP patients and healthy controls. METHODS: Subjects with bipolar I disorder (BP-I)/bipolar II disorder (BP-II) (n = 255), those with non-BP psychopathology (n = 85), and healthy controls (n = 84) (average 38.9 years, 78.7% female, and 84.9% Caucasian) were evaluated at intake and after two and four years of follow-up. Aggression was self-rated using the Aggression Questionnaire (AQ). Comparisons were adjusted for any significant demographic and clinical differences and for multiple comparisons. For subjects with BP, associations of AQ with subtype of BP, current versus past mood episodes, polarity and severity of the current episode, psychosis, and current pharmacological treatment were evaluated. RESULTS: In comparison with subjects with non-BP psychiatric disorders and healthy controls, subjects with BP showed persistently higher total and subscale AQ scores (raw and T-scores) during the four-year follow-up. There were no effects of BP subtype, severity or polarity of the current episode, psychosis, and current pharmacological treatments. Subjects in an acute mood episode showed significantly higher AQ scores than euthymic subjects. CONCLUSIONS: BP, particularly during acute episodes, is associated with increased self-reported verbal and physical aggression, anger, and hostility. These results provide further evidence of the need for treatments to prevent mood recurrences and prompt treatment of acute mood episodes in subjects with BP.

Design considerations of a randomized clinical trial on a cognitive behavioural intervention using communication and information technologies for managing chronic low back pain.

BACKGROUND: Psychological treatments have been successful in treating chronic low back pain (CLBP). However, the effect sizes are still modest and there is room for improvement. A way to progress is by enhancing treatment adherence and self-management using information and communication technologies (ICTs). Therefore, the objective of this study was to design a trial investigating the short- and long-term efficacy of cognitive behavioural treatment (CBT) for CLBP using or not ICTs. A secondary objective of this trial will be to evaluate the influence of relevant variables on treatment response. Possible barriers in the implementation of CBT with and without ICT will also be investigated. METHODS: A randomised controlled trial with 180 CLBP patients recruited from specialised care will be conducted. Participants will be randomly assigned to three conditions: Control group (CG), CBT, and CBT supported by ICTs (CBT + ICT). Participants belonging to the three conditions will receive a conventional rehabilitation program (back school). The CBT group program will last six sessions. The CBT + ICT group will use the internet and SMS to practice the therapeutic strategies between sessions and in the follow-ups at their homes. Primary outcome variables will be self-reported disability and pain intensity. Assessment will be carried out by blinded assessors in five moments: pre-treatment, post-treatment and 3-, 6-, and 12-month follow-ups. The influence of catastrophizing, fear-avoidance beliefs, anxiety and depression in response to treatment in the primary outcomes will also be analysed. DISCUSSION: This study will show data of the possible benefits of using ICTs in the improvement of CBT for treating CLBP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01802671.

Is bipolar disorder specifically associated with aggression?

OBJECTIVE: Several studies have suggested that bipolar disorder (BP) in adults is associated with aggressive behaviors. However, most studies have included only inpatients and have not taken into consideration possible confounding factors. The goal of the present study was to compare the prevalence of aggression in subjects with BP compared to subjects with other, non-BP psychopathology and healthy controls. METHODS: Subjects with bipolar I disorder (BP-I) and bipolar II disorder (BP-II) (n = 255), non-BP psychopathology (n = 85), and healthy controls (n = 84) were recruited. Aggression was measured using the Aggression Questionnaire (AQ). Group comparisons were adjusted for demographic and clinical differences (e.g., comorbid disorders) and multiple comparisons. The effects of the subtype of BP, current versus past episode, polarity of current episode, psychosis, the presence of irritable mania/hypomania only, and pharmacological treatment were examined. RESULTS: Subjects with BP showed significantly higher total and subscale AQ scores (raw and T-scores) when compared to subjects with non-BP psychopathology and healthy controls. Exclusion of subjects with current mood episodes and those with common comorbid disorders yielded similar results. There were no effects of BP subtype, polarity of the current episode, irritable manic/hypomanic episodes only, or current use of pharmacological treatments. Independent of the severity of BP and polarity of the episode, those in a current mood episode showed significantly higher AQ scores than those not in a current mood episode. Subjects with current psychosis showed significantly higher total AQ score, hostility, and anger than those without current psychosis. CONCLUSIONS: Subjects with BP display greater rates of anger and aggressive behaviors, especially during acute and psychotic episodes. Early identification and management of these behaviors is warranted.

Risk for opioid misuse in chronic pain patients is associated with endogenous opioid system dysregulation.

µ-Opioid receptors (MOR) are a major target of endogenous and exogenous opioids, including opioid pain medications. The µ-opioid neurotransmitter system is heavily implicated in the pathophysiology of chronic pain and opioid use disorder and, as such, central measures of µ-opioid system functioning are increasingly being considered as putative biomarkers for risk to misuse opioids. To explore the relationship between MOR system function and risk for opioid misuse, 28 subjects with chronic nonspecific back pain completed a clinically validated measure of opioid misuse risk, the Pain Medication Questionnaire (PMQ), and were subsequently separated into high (PMQ > 21) and low (PMQ ≤ 21) opioid misuse risk groups. Chronic pain patients along with 15 control participants underwent two separate [11C]-carfentanil positron emission tomography scans to explore MOR functional measures: one at baseline and one during a sustained pain-stress challenge, with the difference between the two providing an indirect measure of stress-induced endogenous opioid release. We found that chronic pain participants at high risk for opioid misuse displayed higher baseline MOR availability within the right amygdala relative to those at low risk. By contrast, patients at low risk for opioid misuse showed less pain-induced activation of MOR-mediated, endogenous opioid neurotransmission in the nucleus accumbens. This study links human in vivo MOR system functional measures to the development of addictive disorders and provides novel evidence that MORs and µ-opioid system responsivity may underlie risk to misuse opioids among chronic pain patients.

Pharmacological treatments for methamphetamine addiction: current status and future directions.

INTRODUCTION: Methamphetamine (MA) abuse remains a global health challenge despite intense research interest in the development of pharmacological treatments. This review provides a summary of clinical trials and human studies on the pharmacotherapy of methamphetamine use disorder (MUD). Areas covered: We summarize published clinical trials that tested candidate medications for MUD and also conducted PubMed and Google Scholar searches to identify recently completed clinical trials using the keywords 'methamphetamine' 'addiction' 'pharmacotherapy' and 'clinical trial.' To determine the status of ongoing clinical trials targeting MUD, we also searched the ClinicalTrials.gov online database. We conclude this review with a discussion of current research gaps and future directions. Expert commentary: Clinical trials examining the potential for pharmacotherapies of MUD have largely been negative. Future studies need to address several limitations to reduce the possibility of Type II errors: small sample sizes, high dropout rates or multiple comorbidities. Additionally, new treatment targets, such as MA-induced disruptions in cognition and in the neuroimmune system, merit trials with agents that selectively modulate these processes.

Disruptive mood dysregulation disorder and chronic irritability in youth at familial risk for bipolar disorder.

OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in the DSM-5. Youth with a family history of bipolar disorder (BD) are at increased risk for BD and non-bipolar psychopathology. No studies to date have examined rates of DMDD among offspring of parents with BD. This study examines the risk for DMDD in offspring of parents with BD compared to community controls and considers rates of chronic irritability (independent of a DMDD diagnosis) across diagnoses in youth with parents with BD. METHOD: Modified DMDD criteria were applied post hoc to 375 offspring of parents with BD and 241 offspring, aged 6 to 17 years, of community control parents. We calculated odds ratios using generalized linear mixed models. In addition, we explored associations with a severe chronic irritability phenotype and various diagnoses in the high-risk cohort. RESULTS: Offspring of parents with BD were more likely to meet criteria for DMDD than were the offspring of community control parents (Odds ratio [OR] = 8.3, 6.7% vs. 0.8%), even when controlling for demographic variables and comorbid parental diagnoses (OR = 5.4). They also had higher rates of chronic irritability compared to community controls (12.5% vs. 2.5%, χ(2) = 18.8, p < .005). Within the offspring of parents with BD, the chronic irritability phenotype was frequently present in offspring with diagnoses of BD, depression, attention-deficit/hyperactivity disorder, and disruptive behavior disorders. CONCLUSIONS: Like other non-BD diagnoses, family history of BD increases the risk for DMDD. Severe chronic irritability and temper tantrums are the core features of DMDD, and are associated with mood and behavioral disorders in youth at risk for BD.