Adherence to clinical practice guidelines for using electroconvulsive therapy in elderly depressive patients.

OBJECTIVES: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. METHODS: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. RESULTS: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. CONCLUSION: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

ECT: An essential therapy in psychiatry.

At a time when innovations in psychiatry are booming, particularly in the field of medical devices, we thought it necessary, as members of French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN), to reconsider one of the oldest medical devices in psychiatry: the ECT apparatus. First, we recall the regulatory aspects of ECT. National guidelines define means of implementation and conditions of administration of ECT. Second, we remind of the indications and levels of evidence of ECT in the main psychiatric disorders, including catatonia. Then, we synthetize the place of ECT alongside other brain stimulation therapies, especially repetitive Trancranial Magnetic Stimulation (rTMS). Furthermore, we explain the general effects of ECT: increased neuronal plasticity and neurogenesis, enhancement of the stress axis, resistance to oxidative stress, improved vascular endothelial function, activation of microglia and astrocytes, decrease in inflammatory events by upregulation of neuroinflammatory cytokines, and production of mitochondrial ATP. These effects appear from the first sessions and continue during the course of ECT treatment, suggesting activation of endogenous neuroprotection. Finally, we remember that most patients perform as well or better on neuropsychological assessments after ECT, relative to pre-ECT results, and this improvement continues over the following months. Memory disorders reported post-ECT are not all attributable to ECT. They may be subjective in nature or linked to residual depressive (and possibly comorbid neurogenerative) symptoms later attributed to ECT, on the basis of preexisting negative representations. We urgently need to reemphasize the crucial role of ECT in psychiatric treatment strategies as well as the need to update ECT recommendations.

Glutamatergic and N-Acetylaspartate Metabolites in Bipolar Disorder: A Systematic Review and Meta-Analysis of Proton Magnetic Resonance Spectroscopy Studies.

The exact neurobiological mechanisms of bipolar disorder (BD) remain unknown. However, some neurometabolites could be implicated, including Glutamate (Glu), Glutamine (Gln), Glx, and N-acetylaspartate (NAA). Proton Magnetic Resonance Spectroscopy (1H-MRS) allows one to quantify these metabolites in the human brain. Thus, we conducted a systematic review and meta-analysis of the literature to compare their levels between BD patients and healthy controls (HC). The main inclusion criteria for inclusion were 1H-MRS studies comparing levels of Glu, Gln, Glx, and NAA in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampi between patients with BD in clinical remission or a major depressive episode and HC. Thirty-three studies were included. NAA levels were significantly lower in the left white matter PFC (wmPFC) of depressive and remitted BD patients compared to controls and were also significantly higher in the left dorsolateral PFC (dlPFC) of depressive BD patients compared to HC. Gln levels were significantly higher in the ACC of remitted BD patients compared to in HC. The decreased levels of NAA of BD patients may be related to the alterations in neuroplasticity and synaptic plasticity found in BD patients and may explain the deep white matter hyperintensities frequently observed via magnetic resonance imagery.

[Multidimensional and computational theory of mood]. / Théorie multidimensionnelle et computationnelle de l'humeur.

What is mood? Despite its crucial place in psychiatric nosography and cognitive science, it is still difficult to delimit its conceptual ground. The distinction between emotion and mood is ambiguous: mood is often presented as an affective state that is more prolonged and less intense than emotion, or as an affective polarity distinguishing high and low mood swinging around a baseline. However, these definitions do not match the clinical reality of mood disorders such as unipolar depression and bipolar disorder, and do not allow us to understand the effect of mood on behaviour, perception and cognition. In this paper, we propose a multidimensional and computational theory of mood inspired by contemporary hypotheses in theoretical neuroscience and philosophy of emotion. After suggesting an operational distinction between emotion and mood, we show how a succession of emotions can cumulatively generate congruent mood over time, making mood an emerging state from emotion. We then present how mood determines mental and behavioral states when interacting with the environment, constituting a dispositional state of emotion, perception, belief, and action. Using this theoretical framework, we propose a computational representation of the emerging and dispositional dimensions of mood by formalizing mood as a layer of third-order Bayesian beliefs encoding the precision of emotion, and regulated by prediction errors associated with interoceptive predictions. Finally, we show how this theoretical framework sheds light on the processes involved in mood disorders, the emergence of mood congruent beliefs, or the mechanisms of antidepressant treatments in clinical psychiatry.

Circuit based anti-correlation, attention orienting, and major depression.

Major depression is a multidimensional disorder producing emotional dysregulation, cognitive impairment, and neuro-vegetative symptoms. A pathophysiological model of depression needs to explain how these dimensions interact to produce specific clinical phenotypes and how these interactions may predict remission to specific treatments. It is unlikely that major depression results from discrete brain lesions. Here we propose to define major depression as a disorder of neural networks. We review evidence suggesting that the dynamics of neural networks involved in allocation of attention resources to the internal and external world contribute to cognitive impairment, increased self-focus, and dysfunctional saliency detection in depression. We describe cognitive and emotional tasks that reveal abnormal cooperation between the Central Executive Network and the Default Mode Network. Finally we suggest that depression is associated with increased social rejection sensitivity. Studies on social rejection will shed light on how attachment relates to impairment in allocation of attention resources to produce depressive symptoms such as rumination and cognitive problems.

Personality and Neuropsychological Profiles in Friedreich Ataxia.

Friedreich ataxia, an autosomal recessive mitochondrial disease, is the most frequent inherited ataxia. Many studies have attempted to identify cognitive and affective changes associated with the disease, but conflicting results have been obtained, depending on the tests used and because many of the samples studied were very small. We investigated personality and neuropsychological characteristics in a cohort of 47 patients with genetically confirmed disease. The neuropsychological battery assessed multiple cognition domains: processing speed, attention, working memory, executive functions, verbal memory, vocabulary, visual reasoning, emotional recognition, and social cognition. Personality was assessed with the Temperament and Character Inventory, and depressive symptoms were assessed with the Beck Depression Inventory. We found deficits of sustained attention, processing speed, semantic capacities, and verbal fluency only partly attributable to motor deficit or depressed mood. Visual reasoning, memory, and learning were preserved. Emotional processes and social cognition were unimpaired. We also detected a change in automatic processes, such as reading. Personality traits were characterized by high persistence and low self-transcendence. The mild cognitive impairment observed may be a developmental rather than degenerative problem, due to early cerebellum dysfunction, with the impairment of cognitive and emotional processing. Disease manifestations at crucial times for personality development may also have an important impact on personality traits.

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression.

BACKGROUND: Many studies have measured central and peripheral γ-aminobutyric acid (GABA) levels in patients with depression. We performed a meta-analysis to provide an objective overview of GABA changes in those with unipolar or bipolar depression. METHODS: After a systematic database search, original data were extracted with the help of seminal authors to calculate standardized mean differences. We compared GABA levels between patients with current major depressive episodes and controls, between euthymic patients and controls, and in patients before and after treatment. We performed meta-regressions to explore the influence of demographic and clinical variables on GABA significant mean differences. RESULTS: For unipolar depression, central and peripheral GABA levels were diminished in currently depressed patients, but normal in euthymic patients, compared with the healthy controls. For bipolar disorder, GABA levels were diminished in medication-free patients, but seemed to be normalized in medicated patients, compared with the healthy controls. We found no significant association with demographic or clinical variables. LIMITATIONS: There was a great heterogeneity across studies, probably because of the substantial variation of clinical characteristics in the included samples. Many subanalyses were performed to assess how the diagnosis, medications, or the type of measurements of peripheral or central GABA levels may affect the main results. CONCLUSION: The GABA levels evolved differentially in patients with unipolar and bipolar disorders. Our results suggest that GABA levels could represent a biomarker of symptomatic states in patients with unipolar disorder and would be normalized by mood stabilizers in those with bipolar disorder.

The relation between rumination and temporal features of emotion intensity.

Intensity profiles of emotional experience over time have been found to differ primarily in explosiveness (i.e. whether the profile has a steep vs. a gentle start) and accumulation (i.e. whether intensity increases over time vs. goes back to baseline). However, the determinants of these temporal features remain poorly understood. In two studies, we examined whether emotion regulation strategies are predictive of the degree of explosiveness and accumulation of negative emotional episodes. Participants were asked to draw profiles reflecting changes in the intensity of emotions elicited either by negative social feedback in the lab (Study 1) or by negative events in daily life (Study 2). In addition, trait (Study 1 & 2), and state (Study 2) usage of a set of emotion regulation strategies was assessed. Multilevel analyses revealed that trait rumination (especially the brooding component) was positively associated with emotion accumulation (Study 1 & 2). State rumination was also positively associated with emotion accumulation and, to a lesser extent, with emotion explosiveness (Study 2). These results provide support for emotion regulation theories, which hypothesise that rumination is a central mechanism underlying the maintenance of negative emotions.

Default mode and task-positive networks connectivity during the N-Back task in remitted depressed patients with or without emotional residual symptoms.

Clinical remission of depression may be associated with emotional residual symptoms. We studied the association of emotional blunting, rumination with neural networks dynamics in remitted depressed patients and cognitive performance during an N-Back task. Twenty-six outpatients in remission of depression (Hamilton Depressive rating scale score <7) performed an N-Back task during fMRI assessment. All patients had been treated by paroxetine for a minimum of 4 months. Two subgroups of patients [Nonemotionally blunted (NEB) = 14 and emotionally blunted (EB) = 12] were determined. To identify functional network maps across participants, the Network Detection using Independent Component Analysis approach was employed. Within and between Task Positive Network (TPN) and Default Mode Network (DMN) connectivity were assessed and related to variability of performance on the N-Back task and rumination. EB and NEB patients were not different for the level of accurate responses at the N-Back. However over the entire working memory task, the negative correlation between DMN and TPN was significantly lower in the EB than NEB group and was differently related to cognitive performance and rumination. The stronger the negative correlation between DMN and TPN was, the less variable the reaction time during 3-Back task in NEB patients. Moreover the greater the negative correlation between DMN and TPN was, the lower the rumination score in EB patients. Emotional blunting may be associated with compromised monitoring of rumination and cognitive functioning in remitted depressed patients through altered cooperation between DMN and TPN. The study suggests clinical remission in depression is associated with biological heterogeneity. Hum Brain Mapp 38:3491-3501, 2017. © 2017 Wiley Periodicals, Inc.

Self-reference in suicidal behaviour.

INTRODUCTION: Several lines of evidence suggest a perturbed sense of self in people who attempt suicide, but it has rarely been experimentally studied. Here, we aimed to explore in this population the narrative self through explicit self-perception and the self-reference effect in memory. METHODS: Forty-seven patients with a mood disorder, including 20 with a personal history of suicide attempt, completed a self-referential task. During the encoding phase, they were presented with personality traits and had to successively judge whether each trait described themselves ("self condition") or was a desirable trait, in general ("general condition"). Then, they were unexpectedly asked to retrieve as many previously presented traits as possible (free recall phase). RESULTS: Suicide attempters did not differ from non-attempter patients in any self-reference measures. Moreover, none of these measures correlated with current suicidal ideas. During the encoding phase, patients in both groups attributed negative traits to themselves more often than they considered them to be desirable, in general, with an opposite pattern for positive traits. The number of negative traits during the self but not the general condition was correlated with depression, anxiety, and mental pain levels, whereas depression and mental pain levels were correlated with suicidal ideas. No self-reference effect in memory was found. CONCLUSIONS: Overall, measures of the narrative self were not directly associated with suicidality. However, biased self-perception was related to painful and depressive feelings, which were in turn related to suicidal ideas. More research on self-related processing during the suicidal process is warranted.

A critical role for the hippocampus in the valuation of imagined outcomes.

Many choice situations require imagining potential outcomes, a capacity that was shown to involve memory brain regions such as the hippocampus. We reasoned that the quality of hippocampus-mediated simulation might therefore condition the subjective value assigned to imagined outcomes. We developed a novel paradigm to assess the impact of hippocampus structure and function on the propensity to favor imagined outcomes in the context of intertemporal choices. The ecological condition opposed immediate options presented as pictures (hence directly observable) to delayed options presented as texts (hence requiring mental stimulation). To avoid confounding simulation process with delay discounting, we compared this ecological condition to control conditions using the same temporal labels while keeping constant the presentation mode. Behavioral data showed that participants who imagined future options with greater details rated them as more likeable. Functional MRI data confirmed that hippocampus activity could account for subjects assigning higher values to simulated options. Structural MRI data suggested that grey matter density was a significant predictor of hippocampus activation, and therefore of the propensity to favor simulated options. Conversely, patients with hippocampus atrophy due to Alzheimer's disease, but not patients with Fronto-Temporal Dementia, were less inclined to favor options that required mental simulation. We conclude that hippocampus-mediated simulation plays a critical role in providing the motivation to pursue goals that are not present to our senses.

Single-voxel (1)H spectroscopy in the human hippocampus at 3 T using the LASER sequence: characterization of neurochemical profile and reproducibility.

The hippocampus is crucial for long-term episodic memory and learning. It undergoes structural change in aging and is sensitive to neurodegenerative and psychiatric diseases. MRS studies have seldom been performed in the hippocampus due to technical challenges. The reproducibility of MRS in the hippocampus has not been evaluated at 3 T. The purpose of the present study was to quantify the concentration of metabolites in a small voxel placed in the hippocampus and evaluate the reproducibility of the quantification. Spectra were measured in a 2.4 mL voxel placed in the left hippocampus covering the body and most of the tail of the structure in 10 healthy subjects across three different sessions and quantified using LCModel. High-quality spectra were obtained, which allowed a reliable quantification of 10 metabolites including glutamate and glutamine. Reproducibility of MRS was evaluated with coefficient of variation, standard errors of measurement, and intraclass correlation coefficients. All of these measures showed improvement with increased number of averages. Changes of less than 5% in concentration of N-acetylaspartate, choline-containing compounds, and total creatine and of less than 10% in concentration of myo-inositol and the sum of glutamate and glutamine can be confidently detected between two measurements in a group of 20 subjects. A reliable and reproducible neurochemical profile of the human hippocampus was obtained using MRS at 3 T in a small hippocampal volume.

Mirror Neuron System and Mentalizing System connect during online social interaction.

Two sets of brain areas are repeatedly reported in neuroimaging studies on social cognition: the Mirror Neuron System and the Mentalizing System. The Mirror System is involved in goal understanding and has been associated with several emotional and cognitive functions central to social interaction, ranging from empathy to gestural communication and imitation. The Mentalizing System is recruited in tasks requiring cognitive processes such as self-reference and understanding of other's intentions. Although theoretical accounts for an interaction between the two systems have been proposed, little is known about their synergy during social exchanges. In order to explore this question, we have recorded brain activity by means of functional MRI during live social exchanges based on reciprocal imitation of hand gestures. Here, we investigate, using the method of psychophysiological interaction, the changes in functional connectivity of the Mirror System due to the conditions of interest (being imitated, imitating) compared with passive observation of hand gestures. We report a strong coupling between the Mirror System and the Mentalizing System during the imitative exchanges. Our findings suggest a complementary role of the two networks during social encounters. The Mirror System would engage in the preparation of own actions and the simulation of other's actions, while the Mentalizing System would engage in the anticipation of the other's intention and thus would participate to the co-regulation of reciprocal actions. Beyond a specific effect of imitation, the design used offers the opportunity to tackle the role of role-switching in an interpersonal account of social cognition.

Mapping expectancy-based appetitive placebo effects onto the brain in women.

Suggestions about hunger can generate placebo effects on hunger experiences. But, the underlying neurocognitive mechanisms are unknown. Here, we show in 255 women that hunger expectancies, induced by suggestion-based placebo interventions, determine hunger sensations and economic food choices. Functional magnetic resonance imaging in a subgroup (n = 57/255) provides evidence that the strength of expecting the placebo to decrease hunger moderates medial prefrontal cortex activation at the time of food choice and attenuates ventromedial prefrontal cortex (vmPFC) responses to food value. Dorsolateral prefrontal cortex activation linked to interference resolution formally mediates the suggestion-based placebo effects on hunger. A drift-diffusion model characterizes this effect by showing that the hunger suggestions bias participants' food choices and how much they weigh tastiness against the healthiness of food, which further moderates vmPFC-dlPFC psychophysiological interactions when participants expect decreased hunger. Thus, suggestion-induced beliefs about hunger shape hunger addressing economic choices through cognitive regulation of value computation within the prefrontal cortex.

Whole-brain gray matter maturation trajectories associated with autistic traits from adolescence to early adulthood.

A growing number of evidence supports a continued distribution of autistic traits in the general population. However, brain maturation trajectories of autistic traits as well as the influence of sex on these trajectories remain largely unknown. We investigated the association of autistic traits in the general population, with longitudinal gray matter (GM) maturation trajectories during the critical period of adolescence. We assessed 709 community-based adolescents (54.7% women) at age 14 and 22. After testing the effect of sex, we used whole-brain voxel-based morphometry to measure longitudinal GM volumes changes associated with autistic traits measured by the Social Responsiveness Scale (SRS) total and sub-scores. In women, we observed that the SRS was associated with slower GM volume decrease globally and in the left parahippocampus and middle temporal gyrus. The social communication sub-score correlated with slower GM volume decrease in the left parahippocampal, superior temporal gyrus, and pallidum; and the social cognition sub-score correlated with slower GM volume decrease in the left middle temporal gyrus, the right ventromedial prefrontal and orbitofrontal cortex. No longitudinal association was found in men. Autistic traits in young women were found to be associated with specific brain trajectories in regions of the social brain and the reward circuit known to be involved in Autism Spectrum Disorder. These findings support both the hypothesis of an earlier GM maturation associated with autistic traits in adolescence and of protective mechanisms in women. They advocate for further studies on brain trajectories associated with autistic traits in women.

Reciprocal imitation: toward a neural basis of social interaction.

Social interaction is a coregulated coupling activity that involves at least 2 autonomous agents. Numerous methodological and technical challenges impede the production of natural social interaction within an Magnetic Resonance Imaging environment under controlled conditions. To overcome the obstacle, we chose a simple format of social interaction, namely "interactive imitation" through a double-video system. We registered blood oxygen level-dependent activity of 23 participants during 2 imitative conditions: free (F) and instructed (I) episodes of imitating (i) and of being imitated (bi). In addition to the areas classically reported in instructed imitation tasks, 2 activation patterns were found, which differentiate the subconditions. Firstly, brain areas involved during decisional and attentional processes (dorsolateral prefrontal cortex , dorsal part of anterior cingulate gyrus [dACC], pre-SMA) were activated during all conditions except for instructed imitation-classically used in neuroimaging studies of imitation. Second, a greater activation in dACC and insula combined with an increased deactivation in the default mode network was observed when subjects were imitated compared with when they imitated. We suggest that these 2 patterns reflect the anticipation of the other's behavior and the engagement with others required by social interaction.

Autobiographical memory, mental disorders, and emotional valence: comment on Young, et al. (2012).

Young, Erickson, and Drevets (2012) reported that positive and neutral cue words elicited less positive memories among patients with major depression than among healthy controls, while memories from patients were less specific than those from controls, regardless of their intrinsic valence. These results suggested methodological refinements that may shed light on several aspects of autobiographical memory impairment in mental disorders.

[Theoretical and clinical implications of trauma]. / Le concept de traumatisme et ses conséquences théoriques et cliniques.

Usually, trauma is defined as exposure to an event that threatens death or induces serious injury or sexual violence. Beyond post-traumatic stress disorder (PTSD), trauma may increase the risk for severe mental disorders including mood disorders and psychotic disorder. PTSD, following exposure to a traumatic event, is strongly linked to dissociation. However, in contrast convergent findings indicated that, despite the relationship between peri-traumatic dissociation and later PTSD, many people who develop PTSD do not display dissociative responses in the acute phase after the event. Several risk factors are described for PTSD including previous history of traumatic event, previous mental disorders, genetic factors and gender. It is now proposed to distinguish PTSD with or without dissociative symptoms with some specific neural signature for each syndrome. Dissociation may also lead to change in cultural belief and worldview. According to the terror management theory (TMT), it is suggested that cultural worldviews, self-esteem, and interpersonal relationships work together to protect individuals from death anxiety. The trauma, by disrupting this anxiety buffering system, contributes to change beliefs in victims and exposes them to a feeling of social exclusion.

Title: Le concept de traumatisme et ses conséquences théoriques et cliniques. Abstract: Le traumatisme, conçu comme un choc violent, imprévu et qui expose l'individu à sa propre mort, est pourvoyeur de nombreuses pathologies. Dans ce travail, nous discutons principalement le trouble de stress post-traumatique (TSPT), ses spécificités cliniques en fonction du type de traumatisme ainsi que son rapport étroit avec la notion de dissociation. Le traumatisme, par sa violence, bouleverse totalement les croyances fondamentales de l'individu sur les autres, le monde et son rapport à la mort.

[Ketamine in antidepressant treatment: a revolution?] / Évolution ou révolution dans le traitement des dépressions avec la kétamine ?

Thirty percent of depressed patients are treatment resistant (TRD) suggesting the need of new therapeutic strategy. Recently, it has been shown that ketamine, an anesthetic agent with dissociative effects, has potent and rapid antidepressant properties. Ketamine is a ionotropic glutamatergic NMDA antagonist that inhibits gabaergic neurons. Its antidepressant effect peaks at 24 h post-treatment. Several meta-analyses of placebo randomized clinical trials emphasized its efficacy. More recently, a meta-analysis showed its efficiency in real-world population of TRD patients. Although there is no clear biological or clinical predictors of response or remission to ketamine, patients with high level of resistance were found to remit less often. Restoring both the optimism bias and the asymmetry in belief updating mediates the antidepressant ketamine's effect. Consistent with predictive bayesian model and terror management theory, this suggests that dissociation induced by ketamine may contribute to its clinical antidepressant action. Although increasing access to ketamine and esketamine is welcome, legitimate concerns have been raised with respect to long-term safety and abuse risk.

Title: Évolution ou révolution dans le traitement des dépressions avec la kétamine ? Abstract: Définie par l'échec d'au moins deux antidépresseurs de mécanismes d'action différents, la dépression résistante est fréquente et concerne 30 % des patients déprimés. Elle justifie le recours à des stratégies thérapeutiques innovantes. Depuis quelques années, on utilise un agent anesthésiant et dissociatif, la kétamine, et ses dérivés, dans le traitement de la dépression résistante. Dans cette brève revue de la littérature, nous rapportons les données attestant de l'efficacité et de l'efficience de la kétamine dans cette indication. Certains patients bénéficient plus que d'autres de la kétamine qui est recommandée pour un niveau modéré de résistance. Même si cela reste débattu, la dissociation pourrait contribuer aux effets bénéfiques de la kétamine.