Drug metabolic enzyme genotype-phenotype discrepancy: High phenoconversion rate in patients treated with antidepressants.

Cytochromes from the P450 family (CYP) play a central role in the primary metabolism of frequently prescribed antidepressants, potentially affecting their efficacy and tolerance. There are however important differences in the drug metabolic capacities of each individual resulting from a combination of intrinsic and environmental factors. This variability can present an important risk for patients and increases the difficulty of drug prescription in clinical practice. Pharmacogenetic studies have uncovered a number of alleles defining the intrinsic metabolizer status, however, additional factors affecting cytochrome activity can modify this activity and result in a phenoconversion. The present study investigates the discrepancy between the genetically predicted and actually measured activities for the six most important liver cytochromes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in a cohort of patients under antidepressant treatment, previously shown to have a high proportion of patients with low metabolizing activities. We now performed the genetic characterization of this cohort to determine the extent of the genetic versus environmental contribution in these decreased activities. For all enzyme tested, we observed an important rate of phenoconversion, affecting between 33 % and 65 % of the patients, as well as a significant (p < 1E-06) global reduction in the effective but not predicted activities of CYP2D6, CYP2C9 and CYP2C19 compared to the general population. Our results highlight the advantages of phenotyping versus genotyping as well as the increased risk of treatment failure or adverse effect occurrence in a polymedicated population.

A simple novel approach for detecting blood-brain barrier permeability using GPCR internalization.

AIMS: Impairment of blood-brain barrier (BBB) is involved in numerous neurological diseases from developmental to aging stages. Reliable imaging of increased BBB permeability is therefore crucial for basic research and preclinical studies. Today, the analysis of extravasation of exogenous dyes is the principal method to study BBB leakage. However, these procedures are challenging to apply in pups and embryos and may appear difficult to interpret. Here we introduce a novel approach based on agonist-induced internalization of a neuronal G protein-coupled receptor widely distributed in the mammalian brain, the somatostatin receptor type 2 (SST2). METHODS: The clinically approved SST2 agonist octreotide (1 kDa), when injected intraperitoneally does not cross an intact BBB. At sites of BBB permeability, however, OCT extravasates and induces SST2 internalization from the neuronal membrane into perinuclear compartments. This allows an unambiguous localization of increased BBB permeability by classical immunohistochemical procedures using specific antibodies against the receptor. RESULTS: We first validated our approach in sensory circumventricular organs which display permissive vascular permeability. Through SST2 internalization, we next monitored BBB opening induced by magnetic resonance imaging-guided focused ultrasound in murine cerebral cortex. Finally, we proved that after intraperitoneal agonist injection in pregnant mice, SST2 receptor internalization permits analysis of BBB integrity in embryos during brain development. CONCLUSIONS: This approach provides an alternative and simple manner to assess BBB dysfunction and development in different physiological and pathological conditions.

An incoherent HIFU transducer for treatment of the medial branch nerve: Numerical study and in vivo validation.

BACKGROUND: Chronic back pain due to facet related degenerative changes affects 4-6 million patients a year in the United States. Patients refractory to conservative therapy may warrant targeted injections of steroids into the joint or percutaneous medial branch nerve denervation with radiofrequency ablation. We numerically tested a novel noninvasive high intensity focused ultrasound transducer to optimize nerve ablation near a bone-soft tissue interface. METHODS: A transducer with 4 elements operating in an incoherent mode was modeled numerically and tested pre-clinically under fluoroscopic guidance. After 6 lumbar medial branch nerve ablations were performed in 2 pigs, they were followed clinically for 1 week and then sacrificed for pathological evaluation. RESULTS: Simulations show that the acoustic spot size in water at 6 dB was 14mm axial x 1.6mm lateral and 52mm axial x 1.6mm lateral for coherent and incoherent modes, respectively. We measured the size of N = 6 lesions induced in vivo in a pig model and compared them to the size of the simulated thermal dose. The best match between the simulated and measured lesion size was found with a maximum absorption coefficient in the cortical bone adjusted to 30 dB/cm/MHz. This absorption was used to simulate clinical scenarios in humans to generate lesions with no potential side effects at 1000 and 1500 J. CONCLUSION: The elongated spot obtained with the incoherent mode facilitates the targeting during fluoroscopic-guided medial branch nerve ablation.

Noninvasive vascular occlusion with HIFU for venous insufficiency treatment: preclinical feasibility experience in rabbits.

Venous insufficiency is a common disease arising when veins of the lower limb become incompetent. A conventional surgical strategy consists in stripping the incompetent veins. However, this treatment option is invasive and carries complication risks. In the present study, we propose noninvasive high-intensity focused ultrasound (HIFU) to treat lower limbs venous insufficiency, in particular incompetent perforating veins (mean diameter between 2-6 mm). Sonication parameters were designed by numerical simulations using the k-Wave toolbox to ensure continuous coagulation of a vein with a diameter superior or equal to 2 mm. The selected ultrasound exposures were 4 s pulses in continuous wave mode. Two types of sonication were studied: (1) fixed pulses and (2) moving pulses at constant speed (0.75 mm s-1) across the vein. The potential of these exposures to thermally occlude veins were investigated in vivo on rabbit saphenous veins. The impact of vein compression during ultrasonic exposure was also investigated. Fifteen rabbits were used in these trials. A total of 27 saphenous veins (mean diameter 2.0 ± 0.6 mm) were sonicated with a transducer operated at 3 MHz. After a mean 15 d follow-up, rabbits were euthanized and venous samples were extracted and sent for histologic assessment. Only samples with the vein within the HIFU lesion were considered for analysis. Simulated thermal damage distribution demonstrated that fixed pulses and moving pulses respectively placed every 1.5 and 0.5 mm along the vein and delivered at an acoustic power of 85 W and for 4 s were able to induce continuous thermal damages along the vein segments. Experimentally, both treatment parameters (1) and (2) have proven effective to occlude veins with a success rate of 82%. Occlusion was always observed when compression was applied. Our results demonstrate that HIFU can durably and non-invasively occlude veins of diameters comparable to human veins.

Ex vivo optimisation of a heterogeneous speed of sound model of the human skull for non-invasive transcranial focused ultrasound at 1 MHz.

Transcranial brain therapy has recently emerged as a non-invasive strategy for the treatment of various neurological diseases, such as essential tremor or neurogenic pain. However, treatments require millimetre-scale accuracy. The use of high frequencies (typically ≥1 MHz) decreases the ultrasonic wavelength to the millimetre scale, thereby increasing the clinical accuracy and lowering the probability of cavitation, which improves the safety of the technique compared with the use of low-frequency devices that operate at 220 kHz. Nevertheless, the skull produces greater distortions of high-frequency waves relative to low-frequency waves. High-frequency waves require high-performance adaptive focusing techniques, based on modelling the wave propagation through the skull. This study sought to optimise the acoustical modelling of the skull based on computed tomography (CT) for a 1 MHz clinical brain therapy system. The best model tested in this article corresponded to a maximum speed of sound of 4000 m.s-1 in the skull bone, and it restored 86% of the optimal pressure amplitude on average in a collection of six human skulls. Compared with uncorrected focusing, the optimised non-invasive correction led to an average increase of 99% in the maximum pressure amplitude around the target and an average decrease of 48% in the distance between the peak pressure and the selected target. The attenuation through the skulls was also assessed within the bandwidth of the transducers, and it was found to vary in the range of 10 ± 3 dB at 800 kHz and 16 ± 3 dB at 1.3 MHz.

Equivalence of cell survival data for radiation dose and thermal dose in ablative treatments: analysis applied to essential tremor thalamotomy by focused ultrasound and gamma knife.

Thermal dose and absorbed radiation dose have historically been difficult to compare because different biological mechanisms are at work. Thermal dose denatures proteins and the radiation dose causes DNA damage in order to achieve ablation. The purpose of this paper is to use the proportion of cell survival as a potential common unit by which to measure the biological effect of each procedure. Survival curves for both thermal and radiation doses have been extracted from previously published data for three different cell types. Fits of these curves were used to convert both thermal and radiation dose into the same quantified biological effect: fraction of surviving cells. They have also been used to generate and compare survival profiles from the only indication for which clinical data are available for both focused ultrasound (FUS) thermal ablation and radiation ablation: essential tremor thalamotomy. All cell types could be fitted with coefficients of determination greater than 0.992. As an illustration, survival profiles of clinical thalamotomies performed by radiosurgery and FUS are plotted on a same graph for the same metric: fraction of surviving cells. FUS and Gamma Knife have the potential to be used in combination to deliver a more effective treatment (for example, FUS may be used to debulk the main tumour mass, and radiation to treat the surrounding tumour bed). In this case, a model which compares thermal and radiation treatments is valuable in order to adjust the dose between the two.

Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients.

BACKGROUND: Previous functional magnetic resonance imaging studies in bipolar disorder (BD) have evidenced changes in functional connectivity (FC) in brain areas associated with emotion processing, but how these changes vary with mood state and specific clinical symptoms is not fully understood. METHODS: We investigated resting-state FC between a priori regions of interest (ROIs) from the default-mode network and key structures for emotion processing and regulation in 27 BD patients and 27 matched healthy controls. We further compared connectivity patterns in subgroups of 15 euthymic and 12 non-euthymic patients and tested for correlations of the connectivity strength with measures of mood, anxiety, and rumination tendency. No correction for multiple comparisons was applied given the small population sample and pre-defined target ROIs. RESULTS: Overall, regardless of mood state, BD patients exhibited increased FC of the left amygdala with left sgACC and PCC, relative to controls. In addition, non-euthymic BD patients showed distinctive decrease in FC between right amygdala and sgACC, whereas euthymic patients showed lower FC between PCC and sgACC. Euthymic patients also displayed increased FC between sgACC and right VLPFC. The sgACC-PCC and sgACC-left amygdala connections were modulated by rumination tendency in non-euthymic patients, whereas the sgACC-VLPFC connection was modulated by both the current mood and tendency to ruminate. CONCLUSION: Our results suggest that sgACC-amygdala coupling is critically affected during mood episodes, and that FC of sgACC play a pivotal role in mood normalization through its interactions with the VLPFC and PCC. However, these preliminary findings require replication with larger samples of patients.

Using admixture analysis to examine birth-cohort effects on age at onset of bipolar disorder.

OBJECTIVE: It is suggested that age at onset (AAO) of bipolar I disorder (BP-I) is decreasing. We tested for a birth-cohort effect on AAO using admixture analysis. METHOD: A clinical sample of 3896 BP-I cases was analysed using two approaches: (i) in a subsample with untruncated AAO × birth year distribution (n = 1865), we compared the best-fitting model for the observed AAO in patients born ≤1960 and >1960, (ii) to control for potential confounders, two separate subsamples born ≤1960 and >1960 were matched for age at interview (n = 250), and a further admixture analysis was undertaken. RESULTS: The two approaches indicated that the proportion of cases in the early AAO category was significantly greater in cases born >1960; manic onsets were also more frequent in the early onset BP-I cases born >1960. CONCLUSION: The decrease in AAO of BP-I in recent birth-cohorts appears to be associated with an increase in the proportion of cases in the early onset subgroup; not with a decrease in the mean AAO in each putative subgroup. This could indicate temporal changes in exposure to risk factors for mania.

Borderline personality disorder and childhood maltreatment: a genome-wide methylation analysis.

Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole-genome methylation scan of BPD subjects. Using the Illumina Infinium® HumanMethylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124-3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124-3 that was significantly associated with BPD and severity of childhood maltreatment. miR124-3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome-wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.

[Detection of the IS2404 insertion sequence and ketoreductase produced by Mycobacterium ulcerans in the aquatic Heteroptera in the health districts of Dabou and Tiassalé in Côte d'Ivoire]. / Mise en évidence de la séquence d'insertion IS2404 et de la kétoréductase (Kr) produite par Mycobacterium ulcerans chez les Hétéroptères aquatiques dans les districts sanitaires de Dabou et Tiassalé en Côte d'Ivoire.

Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans, is a major public health problem in Côte d'Ivoire. Until now, the mode of BU transmission was unknown, but recent studies implicate aquatic Heteroptera in the chain of transmission. This study was launched in Côte d'Ivoire to search for specific genetic markers for M. ulcerans in these bugs, including the insertion sequence IS2404 and ketoreductase (Kr), both involved in the synthesis of mycolactone, a toxin produced by these mycobacteria. Samples of aquatic Heteroptera were collected monthly with deep nets from ponds near villages in the health districts of Dabou and Tiassalé. After identification and enumeration of the bugs, batches of the same taxon underwent real-time PCR to search for the IS2404 target and Kr. Saliva of 69 specimens of Diplonychus sp randomly selected in the samples was also analyzed by PCR. In all, 283 single-taxon batches were created. Thus, PCR identified 26 batches belonging to the families of Belostomatidae, Naucoridae, Corixidae, Ranatridae, and Nepidae as positive for both targets. The IS2404 insertion sequence and Kr were present in 6 of the 69 samples analyzed in the saliva of Diplonychus sp. These aquatic Heteroptera suspected of infection by M. ulcerans might release it into the environment because of their ability to fly. They might thus be the source of human contamination.

[Focused ultrasound therapy: current status and potential applications in neurosurgery]. / La thérapie par ultrasons focalisés : état actuel et applications potentielles en neurochirurgie.

High Intensity Focused Ultrasound (HIFU) therapy is an innovative approach for tissue ablation, based on high intensity focused ultrasound beams. At the focus, HIFU induces a temperature elevation and the tissue can be thermally destroyed. In fact, this approach has been tested in a number of clinical studies for the treatment of several tumors, primarily the prostate, uterine, breast, bone, liver, kidney and pancreas. For transcranial brain therapy, the skull bone is a major limitation, however, new adaptive techniques of phase correction for focusing ultrasound through the skull have recently been implemented by research systems, paving the way for HIFU therapy to become an interesting alternative to brain surgery and radiotherapy.

Screening for bipolar disorder among outpatients with substance use disorders.

BACKGROUND: Comorbidity of bipolar disorder and alcohol or substance abuse/dependence is frequent and has marked negative consequences on the course of the illness and treatment compliance. The objective of this study was to compare the validity of two short instruments aimed at screening bipolar disorders among patients treated for substance use disorders. METHODS: The Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32) were tested with reference to the mood section of the Structured Clinical Interview for DSM-IV axis I disorders (SCID) in 152 patients, recruited in two outpatient clinics providing specialized treatment for alcohol and opiate dependence. RESULTS: According to the SCID, 33 patients (21.7%) had a diagnosis within the bipolar spectrum (two bipolar I, 21 bipolar II and 10 bipolar not otherwise specified). The HCL-32 was more sensitive (90.9% vs. 66.7%) and the MDQ more specific (38.7% vs. 77.3%) for the whole sample. The MDQ displayed higher sensitivity and specificity in patients treated for alcohol than for opiate dependence, whereas the HCL-32 was highly sensitive but poorly specific in both samples. Both instruments had a positive predictive value under 50%. CONCLUSIONS: Caution is needed when using the MDQ and HCL-32 in patients treated for substance use disorders.

[Hyperthymic and cyclothymic temperaments: attenuated forms of bipolar disorder?]. / Tempéraments hyperthymique et cyclothymique: expressions atténuées du trouble bipolaire?

A temperament is described as a temporally stable dimension, biologically determined. Several temperaments have been described (hyperthymic, depressive, cyclothymic, irritable and anxious) and could represent premorbid characteristics of an affective disorder. Some temperaments could thus correspond to chronic sub-affective states expressed as attenuated forms of mood disorder. Several studies suggest that a large proportion of bipolar patients have a hyperthymic or cyclothymic temperament. Moreover, temperaments seem to influence the clinical caracteristics of bipolar disorders. Future investigations will evaluate whether temperaments represent a predisposing factor, an attenuated form of bipolar disorders or a distinct entity.

MR-guided adaptive focusing of therapeutic ultrasound beams in the human head.

PURPOSE: This study aims to demonstrate, using human cadavers the feasibility of energy-based adaptive focusing of ultrasonic waves using magnetic resonance acoustic radiation force imaging (MR-ARFI) in the framework of non-invasive transcranial high intensity focused ultrasound (HIFU) therapy. METHODS: Energy-based adaptive focusing techniques were recently proposed in order to achieve aberration correction. The authors evaluate this method on a clinical brain HIFU system composed of 512 ultrasonic elements positioned inside a full body 1.5 T clinical magnetic resonance (MR) imaging system. Cadaver heads were mounted onto a clinical Leksell stereotactic frame. The ultrasonic wave intensity at the chosen location was indirectly estimated by the MR system measuring the local tissue displacement induced by the acoustic radiation force of the ultrasound (US) beams. For aberration correction, a set of spatially encoded ultrasonic waves was transmitted from the ultrasonic array and the resulting local displacements were estimated with the MR-ARFI sequence for each emitted beam. A noniterative inversion process was then performed in order to estimate the spatial phase aberrations induced by the cadaver skull. The procedure was first evaluated and optimized in a calf brain using a numerical aberrator mimicking human skull aberrations. The full method was then demonstrated using a fresh human cadaver head. RESULTS: The corrected beam resulting from the direct inversion process was found to focus at the targeted location with an acoustic intensity 2.2 times higher than the conventional non corrected beam. In addition, this corrected beam was found to give an acoustic intensity 1.5 times higher than the focusing pattern obtained with an aberration correction using transcranial acoustic simulation-based on X-ray computed tomography (CT) scans. CONCLUSIONS: The proposed technique achieved near optimal focusing in an intact human head for the first time. These findings confirm the strong potential of energy-based adaptive focusing of transcranial ultrasonic beams for clinical applications.

In vivo bubble nucleation probability in sheep brain tissue.

Gas nuclei exist naturally in living bodies. Their activation initiates cavitation activity, and is possible using short ultrasonic excitations of high amplitude. However, little is known about the nuclei population in vivo, and therefore about the rarefaction pressure required to form bubbles in tissue. A novel method dedicated to in vivo investigations was used here that combines passive and active cavitation detection with a multi-element linear ultrasound probe (4-7 MHz). Experiments were performed in vivo on the brain of trepanated sheep. Bubble nucleation was induced using a focused single-element transducer (central frequency 660 kHz, f-number = 1) driven by a high power (up to 5 kW) electric burst of two cycles. Successive passive recording and ultrafast active imaging were shown to allow detection of a single nucleation event in brain tissue in vivo. Experiments carried out on eight sheep allowed statistical studies of the bubble nucleation process. The nucleation probability was evaluated as a function of the peak negative pressure. No nucleation event could be detected with a peak negative pressure weaker than -12.7 MPa, i.e. one order of magnitude higher than the recommendations based on the mechanical index. Below this threshold, bubble nucleation in vivo in brain tissues is a random phenomenon.

Optimal transcostal high-intensity focused ultrasound with combined real-time 3D movement tracking and correction.

Recent studies have demonstrated the feasibility of transcostal high intensity focused ultrasound (HIFU) treatment in liver. However, two factors limit thermal necrosis of the liver through the ribs: the energy deposition at focus is decreased by the respiratory movement of the liver and the energy deposition on the skin is increased by the presence of highly absorbing bone structures. Ex vivo ablations were conducted to validate the feasibility of a transcostal real-time 3D movement tracking and correction mode. Experiments were conducted through a chest phantom made of three human ribs immersed in water and were placed in front of a 300 element array working at 1 MHz. A binarized apodization law introduced recently in order to spare the rib cage during treatment has been extended here with real-time electronic steering of the beam. Thermal simulations have been conducted to determine the steering limits. In vivo 3D-movement detection was performed on pigs using an ultrasonic sequence. The maximum error on the transcostal motion detection was measured to be 0.09 ± 0.097 mm on the anterior-posterior axis. Finally, a complete sequence was developed combining real-time 3D transcostal movement correction and spiral trajectory of the HIFU beam, allowing the system to treat larger areas with optimized efficiency. Lesions as large as 1 cm in diameter have been produced at focus in excised liver, whereas no necroses could be obtained with the same emitted power without correcting the movement of the tissue sample.

Adaptive projection method applied to three-dimensional ultrasonic focusing and steering through the ribs.

An adaptive projection method for ultrasonic focusing through the rib cage, with minimal energy deposition on the ribs, was evaluated experimentally in 3D geometry. Adaptive projection is based on decomposition of the time-reversal operator (DORT method) and projection on the "noise" subspace. It is shown that 3D implementation of this method is straightforward, and not more time-consuming than 2D. Comparisons are made between adaptive projection, spherical focusing, and a previously proposed time-reversal focusing method, by measuring pressure fields in the focal plane and rib region using the three methods. The ratio of the specific absorption rate at the focus over the one at the ribs was found to be increased by a factor of up to eight, versus spherical emission. Beam steering out of geometric focus was also investigated. For all configurations projecting steered emissions were found to deposit less energy on the ribs than steering time-reversed emissions: thus the non-invasive method presented here is more efficient than state-of-the-art invasive techniques. In fact, this method could be used for real-time treatment, because a single acquisition of back-scattered echoes from the ribs is enough to treat a large volume around the focus, thanks to real time projection of the steered beams.

[Bipolar disorder and attention deficit/hyperactivity disorder in adults: differential diagnosis or comorbidity]. / Trouble déficit d'attention-hyperactivité et trouble bipolaire chez l'adulte: diagnostic différentiel ou comorbidité?

Attention deficit/hyperactivity disorder (ADHD) can sometimes coexist with bipolar disorder (BD). Despite controversies about the coexistence of the two disorders, recent clinical as well as biological studies support the concept of comorbid adult ADHD and BD. Although there is some overlapping symptomatology between both disorders, ADHD can be diagnosed in patients suffering from with BD after a detailed clinical evaluation. Clinicians should be particularly attentive to specific symptoms in order to treat adequately both disorders since untreated ADHD comorbidity with BD is associated with poor clinical and socio-professional outcome.

[Micronecta sp (Corixidae) and Diplonychus sp (Belostomatidae), two aquatic Hemiptera hosts and/or potential vectors of Mycobacterium ulcerans (pathogenic agent of Buruli ulcer) in Cote d'Ivoire]. / Micronecta sp (Corixidae) et Diplonychus sp (Belostomatidae), deux hémiptères aquatiques hôtes et/ou vecteurs potentiels de Mycobacterium ulcerans agent pathogène de l'ulcère de Buruli en Côte d'Lvoire.

Buruli ulcer is currently a major public health problem in Côte d'Ivoire. It is a neglected tropical disease closely associated with aquatic environments. Aquatic insects of the Hemiptera order have been implicated in human transmission of Mycobacterium ulcerans, the pathogenic agent of Buruli ulcer. The purpose of this preliminary study using the polymerase chain reaction (PCR) method was to evaluate aquatic insects in Sokrogbo, a village in the Tiassalé sanitary district where Buruli ulcer is endemic. Findings identified two water bugs hosting Mycobacterium ulcerans, i.e., one of the Micronecta genus in the Corixidae family and another of the Diplonychus genus in the Belostomatidae family. The PCR technique used revealed the molecular signatures of M. ulcerans in tissue from these two insects. Based on these findings, these two water bugs can be considered as potential hosts and/or vectors of M. ulcerans in the study zone. Unlike Diplonychus sp., this is the first report to describe Micronecta sp as a host of M. ulcerans. Further investigation will be needed to assess the role of these two water bugs in human transmission of M. ulcerans in Côte d'Ivoire.

Mindfulness-based cognitive therapy for bipolar disorder: a feasibility trial.

BACKGROUND: The present open study investigates the feasibility of Mindfulness-based cognitive therapy (MBCT) in groups solely composed of bipolar patients of various subtypes. MBCT has been mostly evaluated with remitted unipolar depressed patients and little is known about this treatment in bipolar disorder. METHODS: Bipolar outpatients (type I, II and NOS) were included and evaluated for depressive and hypomanic symptoms, as well as mindfulness skills before and after MBCT. Patients' expectations before the program, perceived benefit after completion and frequency of mindfulness practice were also recorded. RESULTS: Of 23 included patients, 15 attended at least four MBCT sessions. Most participants reported having durably, moderately to very much benefited from the program, although mindfulness practice decreased over time. Whereas no significant increase of mindfulness skills was detected during the trial, change of mindfulness skills was significantly associated with change of depressive symptoms between pre- and post-MBCT assessments. CONCLUSIONS: MBCT is feasible and well perceived among bipolar patients. Larger and randomized controlled studies are required to further evaluate its efficacy, in particular regarding depressive and (hypo)manic relapse prevention. The mediating role of mindfulness on clinical outcome needs further examination and efforts should be provided to enhance the persistence of meditation practice with time.