[Light - darkness and bipolar disorder]. / Lumière ­ obscurité et trouble bipolaire.

Circadian rhythmicity generated by the biological clock structures the functioning of human beings over a period of almost 24 hours. This clock is entrained daily by internal and external cues among which light is the most powerful. Several disturbances, whether clinical or biological, observed in bipolar disorders are suggestive of a disruption of the circadian rhythm. Thus, treatments that modulate the biological clock have been developed. So far, the results of light therapy are not unanimous and invite us to better specify the treatment modalities. Dark therapy is a promising intervention that is still not much studied nowadays and therefore opens up great prospects for research in the future.

Le rythme circadien généré par l'horloge biologique structure le fonctionnement de l'être humain sur une période de presque 24 heures. Cette horloge est quotidiennement «â€…mise à l'heure ¼ par des synchronisateurs internes et externes parmi lesquels la lumière est la plus puissante. Plusieurs perturbations tant cliniques que biologiques observées chez les personnes souffrant d'un trouble bipolaire sont évocatrices d'un dérèglement du rythme circadien. Ainsi, des traitements permettant de moduler l'horloge biologique ont été développés. Actuellement, les résultats de la luminothérapie ne sont pas unanimes et cela nous invite à mieux préciser les modalités du traitement. La thérapie par l'obscurité est une intervention prometteuse, peu étudiée et ouvre donc de belles perspectives de recherche.

Linking alpha oscillations, attention and inhibitory control in adult ADHD with EEG neurofeedback.

Abnormal patterns of electrical oscillatory activity have been repeatedly described in adult ADHD. In particular, the alpha rhythm (8-12 Hz), known to be modulated during attention, has previously been considered as candidate biomarker for ADHD. In the present study, we asked adult ADHD patients to self-regulate their own alpha rhythm using neurofeedback (NFB), in order to examine the modulation of alpha oscillations on attentional performance and brain plasticity. Twenty-five adult ADHD patients and 22 healthy controls underwent a 64-channel EEG-recording at resting-state and during a Go/NoGo task, before and after a 30 min-NFB session designed to reduce (desynchronize) the power of the alpha rhythm. Alpha power was compared across conditions and groups, and the effects of NFB were statistically assessed by comparing behavioral and EEG measures pre-to-post NFB. Firstly, we found that relative alpha power was attenuated in our ADHD cohort compared to control subjects at baseline and across experimental conditions, suggesting a signature of cortical hyper-activation. Both groups demonstrated a significant and targeted reduction of alpha power during NFB. Interestingly, we observed a post-NFB increase in resting-state alpha (i.e. rebound) in the ADHD group, which restored alpha power towards levels of the normal population. Importantly, the degree of post-NFB alpha normalization during the Go/NoGo task correlated with individual improvements in motor inhibition (i.e. reduced commission errors) only in the ADHD group. Overall, our findings offer novel supporting evidence implicating alpha oscillations in inhibitory control, as well as their potential role in the homeostatic regulation of cortical excitatory/inhibitory balance.

Self-Reported Long-Term Benefits of Mindfulness-Based Cognitive Therapy in Patients with Bipolar Disorder.

OBJECTIVES: This study focused on patients with bipolar disorder (BD), several years after their participation in mindfulness-based cognitive therapy (MBCT). It aimed at documenting sustained mindfulness practice, perceived long-term benefit from the program, and changes regarded as direct consequences of the intervention. DESIGN: This cross-sectional survey took place at least 2 years after MBCT for 70.4% of participants. LOCATION: It was conducted in two specialized outpatient units for BDs that are part of the Geneva University Hospitals (Switzerland) and the Sainte-Anne Hospital in Paris (France). SUBJECTS: Eligibility criteria were a diagnosis of BD according to DSM-IV and participation in at least four MBCT sessions. Response rate was 66.4%. The final sample included 71 outpatients (71.8% bipolar I, 28.2% bipolar II). OUTCOME MEASURES: A questionnaire retrospectively assessed patient-perceived change, benefit from MBCT, and current mindfulness practice. RESULTS: Proportions of respondents who practiced mindfulness at least once a week were 54.9% for formal practice (body scan, sitting meditation, mindful walking, or movements) and 57.7% for informal practice (mindful daily activities). Perceived benefit for the prevention of relapse was moderate, but patients acknowledged long-lasting effects and persistent changes in their way of life. Formal mindfulness practice at least once a week tended to be associated with increased long-lasting effects (p = 0.052), whereas regular informal practice and mindful breathing were significantly associated with persistent changes in daily life (p = 0.038) and better prevention of depressive relapse (p = 0.035), respectively. The most frequently reported positive change was increased awareness of being able to improve one's health. CONCLUSIONS: Despite methodological limitations, this survey allowed documenting mindfulness practice and perceived sustained benefit from MBCT in patients with BD. Participants particularly valued increased awareness that they can influence their own health. Both informal and formal practices, when sustained in the long term, might promote long-lasting changes.

EMOTEO: A Smartphone Application for Monitoring and Reducing Aversive Tension in Borderline Personality Disorder Patients, a Pilot Study.

PURPOSE: We developed a smartphone application (App; EMOTEO: emotion-meteo [weather forecast]) to help borderline personality disorder (BPD) patients to monitor and regulate their inner tension. The App proposes targeted mindfulness-based exercises. DESIGN AND METHODS: We assessed the usability and efficiency of this App for monitoring and reduction of aversive tension in 16 BPD participants over a 6-month period. FINDINGS: We recorded a mean of 318.1 sessions (SD = 166.7) per participants, with a high level of satisfaction. There was a significant decrease in aversive tension (p < .05) and the App was mainly used around 10 a.m. and 9 p.m. PRACTICE IMPLICATIONS: EMOTEO was user-friendly and efficient in reducing aversive tension in BPD patients.

Salivary cortisol profiles in patients remitted from recurrent depression: one-year follow-up of a mindfulness-based cognitive therapy trial.

Few studies have examined changes of diurnal cortisol profiles prospectively, in relation to non-pharmacological interventions such as mindfulness-based cognitive therapy (MBCT). Fifty-six patients remitted from recurrent depression (≥3 episodes) were included in an 8-week randomized controlled trial comparing MBCT plus treatment as usual (TAU) with TAU for depression relapse prophylaxis. Saliva samples (0, 15, 30, 45, 60 min post-awakening, 3 PM, 8 PM) were collected on six occasions (pre- and post-intervention, 3-, 6-, 9-, 12-month follow-up). Cortisol awakening response (CAR), average day exposure (AUCday) and diurnal slope were analyzed with mixed effects models (248 profiles, 1-6 per patient). MBCT (n = 28) and TAU groups (n = 28) did not significantly differ with respect to baseline variables. Intra-individual variability exceeded inter-individual variability for the CAR (62.2% vs. 32.5%), AUC(day) (30.9% vs. 23.6%) and diurnal slope (51.0% vs. 34.2%). No time, group and time by group effect was observed for the CAR and diurnal slope. A significant time effect (p = 0.003) was detected for AUCday, which was explained by seasonal variations (p = 0.012). Later wake-up was associated with lower CAR (-11.7% per 1-hour later awakening, p < 0.001) and lower AUCday (-4.5%, p = 0.014). Longer depression history was associated with dampened CAR (-15.2% per 10-year longer illness, p = 0.003) and lower AUCday (-8.8%, p = 0.011). Unchanged cortisol secretion patterns following participation in MBCT should be interpreted with regard to large unexplained variability, similar relapse rates in both groups and study limitations. Further research is needed to address the scar hypothesis of diminished HPA activity with a longer, chronic course of depression.

Depression relapse prophylaxis with Mindfulness-Based Cognitive Therapy: replication and extension in the Swiss health care system.

BACKGROUND: Mindfulness-Based Cognitive Therapy (MBCT) is a group intervention that integrates elements of Cognitive Behavioural Therapy (CBT) with components of mindfulness training to prevent depressive relapse. The efficacy of MBCT compared to Treatment As Usual (TAU), shown in two randomized controlled trials indicates a significant decrease in 1-year relapse rates for patients with at least three past depressive episodes. The present study is the first independent replication trial comparing MBCT+TAU to TAU alone across both language and culture (Swiss health care system). METHODS: Sixty unmedicated patients in remission from recurrent depression (>or=3 episodes) were randomly assigned to MBCT+TAU or TAU. Relapse rate and time to relapse were measured over a 60 week observation period. The frequency of mindfulness practices during the study was also evaluated. RESULTS: Over a 14-month prospective follow-up period, time to relapse was significantly longer with MBCT+TAU than TAU alone (median 204 and 69 days, respectively), although both groups relapsed at similar rates. Analyses of homework adherence revealed that following treatment termination, the frequency of brief and informal mindfulness practice remained unchanged over 14 months, whereas the use of longer formal meditation decreased over time. LIMITATIONS: Relapse monitoring was 14months in duration and prospective reporting of mindfulness practice would have yielded more precise frequency estimates compared to the retrospective methods we utilized. CONCLUSIONS: Further studies are required to determine which patient characteristics, beyond the number of past depressive episodes, may predict differential benefits from this therapeutic approach.

Effects of olanzapine and quetiapine on corticotropin-releasing hormone release in the rat brain.

An altered regulation of the corticotropin-releasing hormone (CRH) system in the CNS is consistently associated with anxiety and depression; several drugs used to treat CNS disorders modulate--usually in a negative manner--CRH turnover in the brain, and it can be postulated that their effectiveness may be at least in part related to their effects on CRH. This study was aimed to investigate the effects of two atypical antipsychotics also employed in the treatment of bipolar disorders, i.e. quetiapine (QTP) and olanzapine (OLZ), on CRH release from isolated rat brain regions. Acute rat hypothalamic and hippocampal explants were exposed for 1 h to plain medium or medium containing the test drugs, either under baseline conditions or after stimulation of CRH release by veratridine or 56 mM KCl. CRH immunoreactivity present in the incubation medium and in the tissues was assessed by radioimmunoassay. QTP 10 microM but not OLZ inhibited baseline CRH secretion from the hypothalamus; neither drug affected basal CRH release from the hippocampus. Both QTP and OLZ, 1 and 10 microM, inhibited veratridine- or K(+)-stimulated CRH release from the hypothalamus, whereas OLZ only, when given at 10 microM, was able to inhibit stimulated CRH release from the hippocampus. In conclusion, two widely used atypical antipsychotics, QTP and OLZ are able to acutely reduce the release of CRH from isolated rat hypothalami and hippocampi.

Lamotrigine inhibits basal and Na+-stimulated, but not Ca2+-stimulated, release of corticotropin-releasing hormone from the rat hypothalamus.

RATIONALE: Corticotropin-releasing hormone (CRH) is a peptide neurotransmitter involved in the pathogenesis of anxiety and depressive disorders; CRH receptor antagonists are currently developed as anxiolytic and antidepressive agents, and several antidepressants negatively modulate CRH in the central nervous system. OBJECTIVES AND METHODS: Originally marketed as an antiepileptic drug, lamotrigine (LTG) was subsequently shown to be effective as a mood stabilizer and an antidepressant. In this study, we used acute rat hypothalamic explants to investigate the effects of LTG on the gene expression and secretion of CRH from the hypothalamus in short-term incubation experiments. RESULTS: We found that LTG reduces basal CRH release in a time- and concentration-dependent manner. LTG also inhibits veratridine-stimulated, but not K+-stimulated, CRH release in 1-h experiments. Moreover, LTG tended to reduce CRH mRNA expression in 1-h experiments, regardless of whether the drug was given alone or in combination with veratridine or high K+ concentrations; such reduction achieved statistical significance after 3 h of incubation. CONCLUSION: In 1-h experiments, LTG reduces CRH release from CRH-containing neurons in the rat hypothalamus by interfering with Na+-driven secretion mechanisms. After 3-h incubations, the reduction in CRH release is also accounted for by LTG-induced decrease in CRH gene expression.

Cortisol responses to combined dexamethasone/CRH test in outpatients with a major depressive episode.

The DEX/CRH test is now a well established method to test the hypothalamic-pituitary-adrenal (HPA) axis for depressed patients in an inpatient setting. The aim of this study was to evaluate this test in an outpatient population suffering from major depression compared to a healthy control group. The main result is a statistically significant difference concerning the delta value for cortisol plasma value on the DEX/CRH test for depressed patients with two or more previous episodes compared to healthy controls. On the contrary, the difference was not statistically significant for patients with only one or no previous episodes. In future studies, it could be interesting to use this test more specifically by dividing ambulatory patients into subgroups according to their past depressive history. It could also be interesting to measure the ACTH level.