Sleep disturbances in the context of neurohormonal dysregulation in patients with bipolar disorder.

BACKGROUND: Sleep dysfunction is a core symptom in bipolar disorder (BD), especially during major mood episodes. This study investigated the possible link between subjective and objective sleep disturbances in inter-episode BD, changes in melatonin and cortisol levels, and circadian melatonin alignment. The study included 21 euthymic BD patients and 24 healthy controls. Participants had to wear an actigraphy device, keep a weekly sleep diary and take salivary samples: five samples on the last evening to determine the dim light melatonin onset (DLMO) and one the following morning to measure rising cortisol. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and Regensburg Insomnia Scale (RIS), and circadian alignment by the phase angle difference (PAD). RESULTS: In comparison to healthy controls, BD patients had: (1) higher PSQI (5.52 ± 3.14 vs. 3.63 ± 2.18; p = 0.022) (significant after controlling for age and gender), and higher RIS scores (8.91 ± 5.43 vs. 5.83 ± 3.76; p = 0.031); (2) subjective a longer mean TST (p = 0.024) and TIB (p = 0.002) (both significant after controlling for age and gender), longer WASO (p = 0.019), and worse SE (p = 0.036) (significant after controlling for gender); (3) actigraphically validated earlier sleep onset (p = 0.002), less variation in sleep onset time (p = 0.005) and no longer TST (p = 0.176); (4) no differing melatonin levels (4.06 ± 2.77 vs. 3.35 ± 2.23 p = 0.352), an 1.65 h earlier DLMO (20.17 ± 1.63 vs. 21.82 ± 1.50; p = 0. 001) (significant after controlling for gender), and a phase advance of melatonin (6.35 ± 1.40 vs. 7.48 ± 1.53; p = 0.017) (significant after controlling for gender); and (5) no differing cortisol awakening response (16.97 ± 10.22 vs 17.06 ± 5.37 p = 0.969). CONCLUSIONS: Patients with BD, even in euthymic phase, have a significantly worse perception of their sleep. Advanced sleep phases in BD might be worth further investigation and could help to explain the therapeutic effects of mood stabilizers such as lithium and valproate.

A Systematic Review of Mechanisms of Change in Body-Oriented Yoga in Major Depressive Disorders.

INTRODUCTION: Despite empirical evidence for the efficacy of body-oriented yoga as add-on treatment for major depressive disorder (MDD), the specific mechanisms by which yoga leads to therapeutic changes remain unclear. By means of a systematic review, we evaluate how the field is progressing in its empirical investigation of mechanisms of change in yoga for MDD. METHODS: To identify relevant studies, a systematic search was conducted. RESULTS: The search produced 441 articles, of which 5 were included, that empirically examined 2 psychological mechanisms (mindfulness, rumination) and 3 biological mechanisms (vagal control, heart rate variability [HRV], brain-derived neurotrophic factor [BDNF], cortisol). 2 studies found that decreased rumination and 1 study that increased mindfulness was associated with the effect of yoga on treatment outcome. In addition, preliminary studies suggest that alterations in cortisol, BDNF, and HRV may play a role in how yoga exerts its clinical effect. DISCUSSION: The results suggest that body-oriented yoga could work through some of the theoretically predicted mechanisms. However, there is a need for more rigorous designs that can assess greater levels of causal specificity.

Evidence for an agitated-aggressive syndrome in early-onset psychosis correlated with antisocial personality disorder, forensic history, and substance use disorder.

OBJECTIVE: Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied. METHOD: This study assessed the association between age at onset, an agitated-aggressive syndrome, and its potential correlates in a prospective sample of 52 FEP patients with early-onset and adult-onset followed up for 12months. RESULTS: Twenty-six patients conformed to the criteria of early-onset psychosis. Early age at onset was associated with antisocial personality disorder (p=0.004; φc=0.39), a history of legal involvement (p=0.005; φc=0.39), and higher rates of lifetime substance use disorder (SUD; p=0.002; φc=0.42). Early-onset patients had significantly higher PANSS-EC scores over the course of observation (F(1,44.4)=5.39; p=0.025; d=0.656), but no significant group differences emerged for the remaining PANSS subscores. PANSS-EC scores were correlated positively with antisocial personality disorder and forensic history at 6weeks, 3months, 6months, and 12months, and with lifetime substance use disorder at 3months and 6months. CONCLUSIONS: Patients with early onset psychosis may have increased levels of agitation/aggressiveness, and, more likely, antisocial personality disorder, forensic history, and lifetime substance use disorder. These variables were linked to suicidality, aggressiveness, and involuntary treatment.

Cost-effectiveness of 12-month therapeutic assertive community treatment as part of integrated care versus standard care in patients with schizophrenia treated with quetiapine immediate release (ACCESS trial).

OBJECTIVE: To compare the 1-year cost-effectiveness of therapeutic assertive community treatment (ACT) with standard care in schizophrenia. ACT was specifically developed for patients with schizophrenia, delivered by psychosis experts highly trained in respective psychotherapies, and embedded into an integrated care system. METHOD: Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT (n = 64) or standard care (n = 56) to 120 first- and multiple-episode patients with schizophrenia spectrum disorders (DSM-IV), the latter with a history of relapse due to medication nonadherence. Primary outcome was the incremental cost-effectiveness ratio (ICER) based on mental health care costs from a payer perspective and quality-adjusted life-years (QALYs) as a measure of health effects during the 12-month follow-up period (2006-2007). RESULTS: ACT was associated with significantly lower inpatient but higher outpatient costs than standard care, resulting in nonsignificantly lower total costs (P = .27). Incremental QALYs in the ACT group were 0.1 (P < .001). Thus, the point estimate for the ICER showed dominance of ACT. The probability of an ICER below €50,000 per QALY gained was 99.5%. CONCLUSIONS: The implementation of a psychotherapeutically oriented schizophrenia-specific and -experienced ACT team led to an improved patient outcome with reduced need of inpatient care. Despite the introduction of such a rather "costly" ACT team, treatment in ACT was cost-effective with regard to improved quality of life at comparable yearly costs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01081418.

Assertive community treatment as part of integrated care versus standard care: a 12-month trial in patients with first- and multiple-episode schizophrenia spectrum disorders treated with quetiapine immediate release (ACCESS trial).

OBJECTIVE: The ACCESS trial examined the 12-month effectiveness of continuous therapeutic assertive community treatment (ACT) as part of integrated care compared to standard care in a catchment area comparison design in patients with schizophrenia spectrum disorders treated with quetiapine immediate release. METHOD: Two catchment areas in Hamburg, Germany, with similar population size and health care structures were assigned to offer 12-month ACT as part of integrated care (n = 64) or standard care (n = 56) to 120 patients with first- or multiple-episode schizophrenia spectrum disorders (Structured Clinical Interview for DSM-IV Axis I Disorders criteria); multiple-episode patients were restricted to those with a history of relapse due to medication nonadherence. The primary outcome was time to service disengagement. Secondary outcomes comprised medication nonadherence, improvements of symptoms, functioning, quality of life, satisfaction with care from patients' and relatives' perspectives, and service use data. The study was conducted from April 2005 to December 2008. RESULTS: 17 of 120 patients (14.2%) disengaged with service, 4 patients (6.3%) in the ACT and 13 patients (23.2%) in the standard care group. The mean Kaplan-Meier estimated time in service was 50.7 weeks in the ACT group (95% CI, 49.1-52.0) and 44.1 weeks in the standard care group (95% CI, 40.1-48.1). This difference was statistically significant (P = .0035). Mixed models repeated measures indicated larger improvements for ACT compared to standard care regarding symptoms (P < . 01), illness severity (P < . 001), global functioning (P < . 05), quality of life (P < . 05), and client satisfaction as perceived by patients and family (both P < . 05). Logistic regression analyses revealed that ACT was associated with a higher likelihood of being employed/occupied (P = .001), of living independently (P = .007), and of being adherent with medication (P < . 001) and a lower likelihood of persistent substance misuse (P = .027). CONCLUSIONS: Compared to standard care, intensive therapeutic ACT as part of integrated care could improve 1-year outcome. Future studies need to address in which settings these improvements can be sustained. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01081418.