[Treatment resistant depression: actuality and perspectives in 2017]. / Dépression résistante au traitement : actualité et perspective en 2017.

Major depressive disorder (MDD) affects 3 to 17 % of adults. 15 to 30 % of patients with MDD suffer from treatment resistant depression (TRD). No international consensus defines TRD. The most common definition is " MDD that is not enough improved after two successive and different classes of antidepressant treatments in appropriate dose and duration ". The appropriate dose corresponds to maximal dose accepted by scientific reports and clinical recommendations, while the appropriate duration is around 6 weeks. TRD is diagnosed after excluding a pseudoresistant depression, that is related to weak compliance or to somatic and psychiatric differential diagnosis. As well as in MDD, molecular, neuro-anatomical and metabolic disturbances are involved in TRD. A decreased cerebral plasticity induced by low level of Brain-Derived Neurotrophic Factor (BDNF) is also reported. Several authors describe that the cerebral atrophy and the dopaminoglutaminergic system disturbances are more severe in TRD than in MDD. In contrast to MDD treatment, TRD treatment is most often physical treatment. Electroconvulsive therapy (ECT) followed by a tricyclic antidepressant and/or lithium is the most effective treatment. Deep brain stimulation and vagal nerve stimulation reach also a high rate of remission but they are both very invasive technique. Repetitive transcranial magnetic stimulation in TRD seems to be effective in TRD but lower than ECT. There are two majors purposes for this review. First it may help the clinician to understand the TRD's complexity and also it details the kind of treatment useful to care it.

3 à 17 % de la population adulte souffre d'un épisode dépressif majeur (EDM). Parmi ceux-ci, 15 à 30 % présenteront une dépression résistante au traitement (DRT). Malgré l'absence de consensus international sur une définition de la DRT, la définition la plus fréquemment utilisée est " l'EDM est caractérisé par l'absence d'effet acceptable après deux traitements médicamenteux antidépresseurs de classes différentes prescrits à dose et durée adéquates ". La dose adéquate est reconnue comme la dose maximale autorisée par les recommandations officielles ; tandis que la durée adéquate, basée sur un ensemble d'études pharmacologiques contrôlées et randomisées, varie souvent autour de 6 semaines. Le diagnostic de DRT peut être posé après avoir exclu toutes causes de pseudorésistance : soit une mauvaise compliance au traitement, soit la présence d'un autre diagnostic différentiel psychiatrique ou somatique. Tout comme dans l'EDM, des perturbations moléculaires, neuro-anatomiques et métaboliques sont également en cause dans la DRT. Une diminution de la plasticité cérébrale provoquée par une diminution du facteur de croissance Brain-Derived Neurotrophic Factor (BDNF) est également rapportée. Plusieurs auteurs décrivent une atrophie cérébrale plus importante et un plus grand dysfonctionnement des systèmes dopamino-glutaminergiques chez les patients souffrant de DRT. Le traitement des DRT est essentiellement basé sur les techniques de neurostimulation. L'électroconvulsivothérapie (ECT) avec relais vers un antidépresseur tricyclique et/ou le lithium reste le plus efficace. La stimulation cérébrale profonde et la stimulation du nerf vague présentent également des taux de rémission élevés mais restent des techniques invasives. La stimulation magnétique trans-crânienne répétitive apporte également de bons résultats en cas de DRT. Toutefois son efficacité reste inférieure à celle de ECT. Le but de cet article est double : aider le clinicien à comprendre la complexité de la DRT, et offrir une revue détaillée des différents traitements, pharmacologiques ou non, pouvant y faire face.

[Impact of aging on sexuality]. / Impact des vieillissements physiologique et pathologique sur la relation sexuelle.

Numerous authors on sexual behaviors have studied the link between the persistence of a sexually active life and progressive aging. The knowledge of sexual health in the elderly has shown that biological sexual aging is extremely diverse and heterogeneous in men as well as in women, and contradicts the stereotype of age that would inevitably alter the sexual biological response in each human. Sexual diseases (lubrication, dyspareunia, erectile dysfunction, inability to achieve orgasm) and diseases of aging that impact sexual function have a growing incidence but don't never touch 100% of individuals. There is a decline in sexual interest correlated with the life-span, but the negative effects of age on desire are related to health problems. Moreover, sexual desire is more correlated with personal attitudes toward sexuality than with biological factors and diseases. Several predictors account for the pursuit of an active sexuality (including the presence of a partner, good health, having good sexual self-esteem, enjoyable past experience, an attitude that values the importance of sex in couple relationship), but the most decisive factor to successfully face the specific markers of aging is the ability to adapt to a more sensory sexuality, less focused on performance and coitus.

[Sexuality of our seniors: happy end or new beginning?]. / Sexualité après 55 ans: fin du ou faim de sexe?

Comparing surveys from successive periods demonstrates that elderly people now enjoy a better and more varied sexual life than previous generations. The proportion of older people who remain sexually active has significantly increased, and the practices of masturbation or oral sex have spread considerably. The generation effect has an incidence upon sexual behaviour: older people's repertoire of sexual practices differs from that of younger people, in the sense that it focuses less on sexual intercourse and oral sex. Women and men, beyond the common trends towards sexuality characterised by a more open repertoire of sexual practices, differ in terms of sexual interest and subjective sexual wellbeing. The cessation of sexual activity by individuals who had previously been sexually active is often the result of a cascade of reactions, such as the occurrence of a sexual dysfunction in one or both partners, anticipation of failure, increased anxiety, lack of adaptation of sexuality and/or avoidance behaviour.

Altered interaction between cardiac vagal influence and delta sleep EEG suggests an altered neuroplasticity in patients suffering from major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD), which is associated with altered neuroplasticity and increased relative cardiac sympathic activity, enhances the risk of cardiovascular pathologies. Interaction between cardiac sympatho-vagal indexes and delta sleep power is probably altered in MDD. METHOD: Sleep characteristics and cardiac sympatho-vagal indexes of 10 depressive patients were compared to 10 control men across the first three non-rapid eye movement (NREM)-REM cycles. Interaction between normalized high frequency (HF) and delta power bands was studied using coherence analysis. RESULTS: Patients showed increased sleep latency, stage 1 and wake durations. No differences in heart rate variabilities were observed: Total power, HF and RR-interval decreased from NREM to REM sleep and wakefulness in both groups. Gain value was lower in patients while coherence and phase shift were similar between groups. Modifications in HF appear 8 min before modifications in delta. CONCLUSION: Major depressive disorder is related to an altered link between cardiac vagal influence and delta sleep, suggesting disorders in cardiovascular controls and an altered neuroplasticity.

[Confirmatory factor analysis of the French version of the emotional intelligence inventory]. / Analyse confirmatoire de la version française de l'inventaire d'intelligence émotionnelle.

BACKGROUND: In the context of the increasing interest in the study and assessment of emotional abilities in psychology, we translated into French and evaluated the construct validity of the emotional intelligence inventory (EII) designed in English [Psychol Rep; 88 (2001):353-64]. This self-rating scale is modelled along the theoretical constructs of the Mayer, Caruso and Salovey's model [Intelligence; 27 (1999):267-98]; it comprises 41 items tapping the four following factors: (1) empathy; (2) utilization of feelings, (3) handling relationships and; (4) self-control. METHODS: One thousand three hundred and thirty-five students (42.7% men) with a mean age of 19.6 years and affiliated to several school and faculties participated to this Belgian interuniversity study. They were administered the French version of the EII, as well as a series of related questionnaires. Confirmatory factor analyses (CFA) were applied to these data and various fit indices examined in order to assess the factorial adjustment to the data of the four-factor a priori structure. RESULTS: CFA did not support the original 41-item four-factor structure for the scale in French, but a good statistical fit to the data could be obtained with the reduction of the scale to 20 items. The content of the resulting item set, keeping Tapia's four factors, encourages a revision of the domain covered by the subscales. CONCLUSION: Further efforts should be directed at assessing the content validity of the proposed revised scale as a reliable tool in measuring emotional intelligence by self-report.

The modifications of the long-range temporal correlations of the sleep EEG due to major depressive episode disappear with the status of remission.

OBJECTIVE: The aim of the present study is to investigate the scaling properties of the sleep electroencephalogram (EEG) in remitted depressed men, and to evaluate if a past history of major depressive disorder (MDD) could modify significantly and definitively, as a "scar marker," the dynamics of the sleep EEG time series. METHODOLOGY: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated depressed men in full to partial remission (42.43+/-5.62 years) and 14 healthy subjects (42.8+/-8.55 years). Scaling properties in these time series were investigated with detrended fluctuation analysis (DFA) (time range: 0.16-2.00 s). The scaling exponent alpha was determined in stage 2, in slow wave sleep (stages 3 and 4), and during rapid eye movement (REM) sleep. Forty-five epochs of 20 s were chosen randomly in each of these stages for each subject in both groups. RESULTS: We did not observe a significant difference and deviation of the scaling exponents between the two groups during the three sleep stages of interest. CONCLUSION: In this study, we do not observe any functional sequelae of a past history of one or more unipolar major depressive episode on the fluctuation properties of the sleep EEG. This finding is a sign of similar underlying neuronal dynamics in healthy controls and patients with a lifetime history of MDD. This study gives an additional argument to the theory that depression does not modify definitively the dynamics of the neuronal networks and is therefore against the "depressive scar hypothesis," in which permanent residual deficit is created by the acute state of the depressive disease.

Characterization of the sleep EEG in acutely depressed men using detrended fluctuation analysis.

OBJECTIVE: The aim of the present paper is to study the fluctuations of the sleep EEG over various time scales during a specific pathological condition: major depressive episode. Focus is made on scaling behaviour, which is the signature of the absence of characteristic time scale, and the presence of long-range correlations associated to physiological constancy preservation, variability reduction and mostly adaptability. METHODS: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated patients with a major depressive episode (41.70+/-8.11 years) and 14 healthy subjects (42.43+/-5.67 years). Scaling in these time series was investigated with detrended fluctuation analysis (time range: 0.16-2.00s). Scaling exponents (alpha) were determined in stage 2, slow wave sleep (stages 3 and 4) and during REM sleep. Forty-five epochs of 20s were chosen randomly in each of these stages. RESULTS: The median values of alpha were lower in patients during stage 2 and SWS. CONCLUSIONS: Major depressive episodes are characterized by a modification in the correlation structure of the sleep EEG time series. The finding which shows decreasing rate of the temporal correlations being different within the two groups in stage 2 and SWS provides an electrophysiologic argument that the underlying neuronal dynamics are modified during acute depression. SIGNIFICANCE: The observed modifications in scaling behaviour in acutely depressed patients could be an explanation of the sleep fragmentation and instability found during major depressive episode.

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

Linear and non-linear brain-heart and brain-brain interactions during sleep.

In this study, the physiological networks underlying the joint modulation of the parasympathetic component of heart rate variability (HRV) and of the different electroencephalographic (EEG) rhythms during sleep were assessed using two popular measures of directed interaction in multivariate time series, namely Granger causality (GC) and transfer entropy (TE). Time series representative of cardiac and brain activities were obtained in 10 young healthy subjects as the normalized high frequency (HF) component of HRV and EEG power in the δ, θ, α, σ, and ß bands, measured during the whole duration of sleep. The magnitude and statistical significance of GC and TE were evaluated between each pair of series, conditional on the remaining series, using respectively a linear model-based approach exploiting regression models, and a nonlinear model-free approach combining nearest-neighbor entropy estimation with a procedure for dimensionality reduction. The contribution of nonlinear dynamics to the TE was also assessed using surrogate data. GC and TE consistently detected structured networks of physiological interactions, with links directed predominantly from HRV to the EEG waves in the brain-heart network, and from the σ and ß EEG waves to the δ, θ, and α waves in the brain-brain network. While these common patterns supported the suitability of a linear model-based analysis, we also found a significant contribution of nonlinear dynamics, particularly involving the information transferred out of the δ node in the two networks. This suggested the importance of nonparametric TE estimation for evidencing the fine structure of the physiological networks underlying the autonomic regulation of cardiac and brain functions during sleep.

Tropism of AAV-2 vectors for neurons of the globus pallidus.

A recombinant AAV-2 vector encoding the green fluorescent protein (gfp) under the control of the cytomegalovirus (CMV) promoter was injected into the striatum at varying antero-posterior coordinates. When the virus was delivered to the anterior part of the striatum, transduction efficiency was low and limited to the vicinity of the needle tract. In contrast, after injection into the posterior part of the striatum, in addition to a localized transduced area in the striatum, efficient and widespread transduction was observed at distance from the injection site, in the globus pallidus. In the latter case, labelled cells were also detected in the internal capsule and in the stria terminalis. The number of transduced cells in the striatum increased up to I month and then decreased whereas in the globus pallidus, transduction was maximal as early as 2 weeks post-injection. In the striatum and in the globus pallidus, the labelled cells had a neuron-like morphology. In contrast, in the internal capsule, labelled cells had a glial-like morphology.

A study of the dynamic interactions between sleep EEG and heart rate variability in healthy young men.

OBJECTIVE: We investigated the interactions between heart rate variability and sleep electroencephalogram power spectra. METHODS: Heart rate and sleep electroencephalogram signals were recorded in 8 healthy young men. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. Spectral components of RR intervals were studied across sleep stages. The cross-spectrum maximum was determined as well as coherencies, gains and phase shifts between normalized high frequency of RR intervals and all electroencephalographic frequency bands, calculated over the first 3 NREM-REM cycles. RESULTS: RR intervals increased from awake to NREM and decreased during REM. Normalized low frequency decreased from awake to NREM and increased during REM while normalized high frequency evolved conversely. Low to high frequency ratio developed in opposition to RR intervals. Coherencies between normalized high frequency and power spectra were high for all bands. The gain was highest for delta band. Phase shift between normalized high frequency and delta differed from zero and modifications in normalized high frequency preceded changes in delta by 41+/-14 degrees. CONCLUSIONS: Our study demonstrates that: (1) all electroencephalographic power bands are linked to normalized high frequency; (2) modifications in cardiac vagal activity show predominantly parallel changes and precede changes in delta band by a phase shift corresponding to a lead of 12+/-5 min.

The impact of chronic primary insomnia on the heart rate--EEG variability link.

OBJECTIVE: To determine if chronic insomnia alters the relationship between heart rate variability and delta sleep determined at the EEG. METHODS: After one night of accommodation, polysomnography was performed in 14 male patients with chronic primary insomnia matched with 14 healthy men. ECG and EEG recordings allowed the determination of High Frequency (HF) power of RR-interval and delta sleep EEG power across the first three Non Rapid Eye Movement (NREM)-REM cycles. Interaction between normalized HF RR-interval variability and normalized delta sleep EEG power was studied by coherency analysis. RESULTS: Patients showed increased total number of awakenings, longer sleep latency and wake durations and shorter sleep efficiency and REM duration than controls (p<.01). Heart rate variability across first three NREM-REM cycles and sleep stages (NREM, REM and awake) were similar between both groups. In each group, normalized HF variability of RR-interval decreased from NREM to both REM and awake. Patients showed decreased linear relationship between normalized HF RR-interval variability and delta EEG power, expressed by decreased coherence, in comparison to controls (p<.05). Gain and phase shift between these signals were similar between both groups. CONCLUSIONS: Interaction between changes in cardiac autonomic activity and delta power is altered in chronic primary insomniac patients, even in the absence of modifications in heart rate variability and cardiovascular diseases. SIGNIFICANCE: This altered interaction could reflect the first step to cardiovascular disorders.

The link between cardiac autonomic activity and sleep delta power is altered in men with sleep apnea-hypopnea syndrome.

We hypothesize that sleep apnea-hypopnea alters interaction between cardiac vagal modulation and sleep delta EEG. Sleep apnea-hypopnea syndrome (SAHS) is related to cardiovascular complications in men. SAHS patients show higher sympathetic activity than normal subjects. In healthy men, non-rapid eye movement (NREM) sleep is associated with cardiac vagal influence, whereas rapid eye movement (REM) sleep is linked to cardiac sympathetic activity. Interaction between cardiac autonomic modulation and delta sleep EEG is not altered across a life span nor is the delay between appearances of modifications in both signals. Healthy controls, moderate SAHS, and severe SAHS patients were compared across the first three NREM-REM cycles. Spectral analysis was applied to ECG and EEG signals. High frequency (HF) and low frequency (LF) of heart rate variability (HRV), ratio of LF/HF, and normalized (nu) delta power were obtained. A coherency analysis between HF(nu) and delta was performed, as well as a correlation analysis between obstructive apnea index (AI) or hypopnea index (HI) and gain, coherence, or phase shift. HRV components were similar between groups. In each group, HF(nu) was larger during NREM, while LF(nu) predominated across REM and wake stages. Coherence and gain between HF(nu) and delta decreased from controls to severe SAHS patients. In SAHS patients, the delay between modifications in HF(nu) and delta did not differ from zero. AI and HI correlated negatively with coherence, while HI correlated negatively with gain only. Apneas-hypopneas affect the link between cardiac sympathetic and vagal modulation and delta EEG demonstrated by the loss of cardiac autonomic activity fluctuations across shifts in sleep stages. Obstructive apneas and hypopneas alter the interaction between both signals differently.

Cellular contaminants of adeno-associated virus vector stocks can enhance transduction.

Transduction efficiency of different types of recombinant (r)AAV-2 based vectors preparations markedly differed, with apparently no correlation with the replicative titers. Using HeLa cells as target for transduction, 105 and 30 infectious units were necessary to observe one transductant using respectively cesium-chloride-purified rAAV and crude lysates of producer cells obtained by sonication. The purified vectors were however able to transduce HEK-193 cells efficiently, but transgene expression was detected with some delay compared with crude lysates. The unexpected high transduction efficiency of sonicated crude lysates was due to virally mediated gene transfer, since similar sonicated crude lysates, but with no AAV rep and cap genes, did not lead to detection of transgene products after incubation with HeLa cells. Furthermore, sonicated cellular extracts of 293 or 293/T cells given in trans stimulate transduction of HeLa cells by purified rAAV. In contrast, neither extracts from the adenovirus E1-transformed 911 cell line, nor from other cell lines not harboring any adenovirus gene, had enhancing effect on rAAV-mediated transduction. These data suggest that 293 sonicated extracts contain factors which stimulate rAAV-mediated transduction of cells that are normally poorly transduced and offer a system to identify such factors and to characterize further the steps limiting the transfer of gene by AAV vectors.