Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.

One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.

Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.

Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Studies about brain structure in bipolar disorder have reported conflicting findings. These findings may be explained by the high degree of heterogeneity within bipolar disorder, especially if structural differences are mapped to single brain regions rather than networks.

We aim to complete a systematic review and meta-analysis to identify brain networks underlying structural abnormalities observed on T1-weighted magnetic resonance imaging scans in bipolar disorder across the lifespan. We also aim to explore how these brain networks are affected by sociodemographic and clinical heterogeneity in bipolar disorder.

We will include case–control studies that focus on whole-brain analyses of structural differences between participants of any age with a standardised diagnosis of bipolar disorder and controls. The electronic databases Medline, PsycINFO and Web of Science will be searched. We will complete an activation likelihood estimation analysis and a novel coordinate-based network mapping approach to identify specific brain regions and brain circuits affected in bipolar disorder or relevant subgroups. Meta-regressions will examine the effect of sociodemographic and clinical variables on identified brain circuits.

Findings from this systematic review and meta-analysis will enhance understanding of the pathophysiology of bipolar disorder. The results will identify brain circuitry implicated in bipolar disorder, and how they may relate to relevant sociodemographic and clinical variables across the lifespan.

Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.

To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).

In a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.

This trial will advance the understanding of psilocybin's mechanism of antidepressant action.

This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.

To compare supraglottoplasty versus non-surgical treatment in children with laryngomalacia and mild, moderate and severe obstructive sleep apnoea.

Patients were classified based on their obstructive apnoea hypopnoea index on initial polysomnogram, which was compared to their post-treatment polysomnogram.

Eighteen patients underwent supraglottoplasty, and 12 patients had non-surgical treatment. The average obstructive apnoea hypopnoea index after supraglottoplasty fell by 12.68 events per hour (p = 0.0039) in the supraglottoplasty group and 3.3 events per hour (p = 0.3) in the non-surgical treatment group. Comparison of the change in obstructive apnoea hypopnoea index in the surgical versus non-surgical groups did not meet statistical significance (p = 0.09).

All patients with laryngomalacia and obstructive sleep apnoea had a statistically significant improvement in obstructive apnoea hypopnoea index after supraglottoplasty irrespective of obstructive sleep apnoea severity, whereas patients who received non-surgical treatment had more variable and unpredictable results. Direct comparison of the change between the two groups did not find supraglottoplasty to be superior to non-surgical treatment. Larger prospective studies are recommended.

Neuroprogressive models of the trajectory of cognitive dysfunction in patients with bipolar disorder (BD) have been proposed. However, few studies have explored the relationships among clinical characteristics of BD, cognitive dysfunction, and aging.

We conducted a cross-sectional analysis in euthymic participants with the MATRICS Cognitive Consensus Battery, the Trail Making Test B, the Stroop Test, and the Wechsler Test of Adult Reading. Age- and gender-equated control participants without a mental disorder [‘Healthy Controls’ – HC)] were assessed similarly. We compared cognitive performance both globally and in seven domains in four groups: younger BD (age ⩽49 years; n = 70), older BD (age ⩾50 years; n = 48), younger HC (n = 153), and older HC (n = 44). We also compared the BD and HC groups using age as a continuous measure. We controlled for relevant covariates and applied a Bonferroni correction.

Our results support both an early impairment (‘early hit’) model and an accelerated aging model: impairment in attention/vigilance, processing speed, and executive function/working memory were congruent with the accelerated aging hypothesis whereas impairment in verbal memory was congruent with an early impairment model. BD and HC participants exhibited similar age-related decline in reasoning/problem solving and visuospatial memory. There were no age- or diagnosis-related differences in social cognition.

Our findings support that different cognitive domains are affected differently by BD and aging. Longitudinal studies are needed to explore trajectories of cognitive performance in BD across the lifespan.

Several surveys report that post-COVID-19 patients (pts) could be at risk of persistent emotional distress, fatigue and impaired neurocognitive function (NCF).

The aim was to assess emotional distress, fatigue and NCF in order to provide adequate care.

Patients with persistent physical or mental symptoms, at least 8 weeks post-COVID-19, were eligible for this ongoing prospective longitudinal single center trial. Data on depression, anxiety, cognition, post-traumatic stress symptoms (PTSS) and fatigue were collected using 4 validated questionnaires at study entry (T0) and at 6 months (T1).

Ninety-three pts were recruited between November 2020-March 2021. Test results from 64 eligible pts (15 male pts) were analyzed at T0; 63 pts (98%) were treated in outpatient settings. Median age was 47 years [range 27-75]). Median time since COVID-19 was 29 weeks [range 8-53]. Twenty-two pts (34%) had a history of psychiatric disorders. According to the Hospital Anxiety Depression Scale (HADS), 44 pts (73%) reported anxiety symptoms and 26 pts (41%) reported depressive symptoms; 48 pts (69%) reported cognitive complaints according to the Cognitive Failure Questionnaire and 29 pts (45%) suffered from PTSS, according to the Post-Traumatic Stress Disorder Checklist-Civilian Version (PCL-C). Fifty-five pts (86%) had an elevated score on the Fatigue Severity Scale, indicating severe fatigue. Twenty-seven pts (42%) were still on sick leaf. Diminished social support and psychiatric history were predictive factors for neurocognitive dysfunction and PTSS.

A majority of patients who recovered physically from COVID-19, are at risk for suffering from persistent anxiety, PTSS and neurocognitive dysfunction.

No significant relationships.

The placebo response in depression clinical trials is a major contributing factor for failure to establish the efficacy of novel and repurposed treatments. However, it is not clear as to what the placebo response in treatment-resistant depression (TRD) patients is or whether it differs across treatment modalities. Our objective was to conduct a systematic review and meta-analysis of the magnitude of the placebo response in TRD patients across different treatment modalities and its possible moderators.

Searches were conducted on MEDLINE and PsychInfo from inception to January 24, 2020. Only studies that recruited TRD patients and randomization to a placebo (or sham) arm in a pharmacotherapy, brain stimulation, or psychotherapy study were included (PROSPERO 2020 CRD42020190465). The primary outcome was the Hedges’ g for the reported depression scale using a random-effects model. Secondary outcomes included moderators assessed via meta-regression and response and remission rate. Heterogeneity was evaluated using the Egger's Test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks.

46 studies met our inclusion criteria involving a total of 3083 participants (mean (SD) age: 45.7 (6.2); female: 52.4%). The pooled placebo effect for all modalities was large (N = 3083, g = 1.08 ,95% CI [0.95-1.20)I 2 = 0.1). The placebo effect in studies of specific treatment modalities did not significantly differ: oral medications g = 1.14 (95%CI:0.99-1.29); parenteral medications g = 1.32 (95%CI:0.59-2.04); ayahuasca g = 0.47 (95%CI:-0.28-1.17); rTMS g = 0.93 (95%CI:0.63-1.23); tDCS g = 1.32 (95%CI:0.52-2.11); invasive brain stimulation g = 1.06 (95%CI:0.64-1.47). There were no psychotherapy trials that met our eligibility criteria. Similarly, response and remission rates were comparable across modalities. Heterogeneity was large. Two variables predicted a lager placebo effect: open-label prospective design (B:0.32, 95%CI: 0.05-0.58; p:0.02) and sponsoring by a pharmaceutical or medical device company (B:0.39, 95%CI:0.13-0.65, p:0.004)). No risk of publication bias was found.

The overall placebo effect in TRD studies was large (g = 1.08) and did not differ among treatment modalities. A better understanding of the placebo response in TRD will require: standardizing the definition of TRD, head-to-head comparisons of treatment modalities, an assessment of patient expectations and experiences, and standardized reporting of outcomes.

Transdiagnostic group cognitive-behavioral therapy (tCBT) is a delivery model that could help overcome barriers to large-scale implementation of evidence-based psychotherapy for anxiety disorders. The aim of this study was to assess the effectiveness of combining group tCBT with treatment-as-usual (TAU), compared to TAU, for the treatment of anxiety disorders in community-based mental health care.

In a multicenter single-blind, two-arm pragmatic superiority randomized trial, we recruited participants aged 18–65 who met DSM-5 criteria for principal diagnoses of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Group tCBT consisted of 12 weekly 2 h sessions. There were no restrictions for TAU. The primary outcome measures were the Beck Anxiety Inventory (BAI) and clinician severity rating from the Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5) for the principal anxiety disorder at post-treatment, with intention-to-treat analysis.

A total of 231 participants were randomized to either tCBT + TAU (117) or TAU (114), with outcome data available for, respectively, 95 and 106. Results of the mixed-effects regression models showed superior improvement at post-treatment for participants in tCBT + TAU, compared to TAU, for BAI [p < 0.001; unadjusted post-treatment mean (s.d.): 13.20 (9.13) v. 20.85 (10.96), Cohen's d = 0.76] and ADIS-5 [p < 0.001; 3.27 (2.19) v. 4.93 (2.00), Cohen's d = 0.79].

Our findings suggest that the addition of group tCBT into usual care can reduce symptom severity in patients with anxiety disorders, and support tCBT dissemination in routine community-based care.

Mood disorders, i.e. major depressive disorder (MDD) and bipolar disorders, are leading sources of disability worldwide. Currently available treatments do not yield remission in approximately a third of patients with a mood disorder. This is in part because these treatments do not target a specific core pathology underlying these heterogeneous disorders. In recent years, abnormal inflammatory processes have been identified as putative pathophysiological mechanisms and treatment targets in mood disorders, particularly among individuals with treatment-resistant conditions.

In this selective review, we aimed to summarise recent advances in the field of immunopsychiatry, including emerging pathophysiological models and findings from treatment ttrials of immunomodulatory agents for both MDD and bipolar disorders.

We performed a literature review by searching Medline for clinical trials of immunomodulating agents as monotherapy or adjunctive treatments in MDD and bipolar disorders. Included studies are randomised controlled trials (RCTs), cluster RCTs or cross-over trials of immunomodulating agents that had an active comparator or a placebo-arm.

Current evidence shows an association between inflammation and mood symptoms. However, there is conflicting evidence on whether this link is causal.

Future studies should focus on identifying specific neurobiological underpinnings for the putative causal association between an activated inflammatory response and mood disorders. Results of these studies are needed before further treatment trials of immunomodulatory agents can be justified.

Chronic social isolation in the elderly may be related with diverse psychiatric disorders: chronic depressive episode, paranoia-type personality, and late non-schizophrenic psychosis.

In order to separate psychotic depression and non-schizophrenic psychosis with depressive mood, there is a need for more clearly defined criteria.

We report the case of a 68 yrs. women living alone at home for more than twenty years, with a complete social isolation for two years. This behaviour was found associated with severe delusion: she unreasonably felt persecuted by her flat's owner and she dissimulated an extensive basocellular carcinoma on her face threatening her life. A history of a short depressive episode at the time of her divorce was only found, as she demonstrated at initial assessment many paranoia personality traits. A review of literature on this disorders’ association was therefore undertaken.

Evolution after admission revealed the lack of effectiveness of antipsychotic treatment on delusion, but some efficiency of antidepressant. Nevertheless, personality traits remained unaffected by care. Literature on the association between mood disorders and non-schizophrenic psychosis is rare, and we suggest some criteria that may account for psychotic depression and be useful to treatment choice.

In the absence of a history of chronic mood or psychotic disorder, it is hypothesised that paranoia symptoms may account more for a psychotic depression than for late paranoid schizophrenia. This may have consequences for therapeutic strategy.

Severe depression after mid-life has significant clinical, cognitive or functional consequences. These related dimensions may have a different evolution under treatment, and their assessment may be useful to evaluate treatment efficiency.

To measure differential treatment effect on clinical, cognitive and functional dimensions in elderly severe depression.

The relation between these three dimensions has been examined from the inclusion through six weeks of treatment

Three different treatment (antidepressant, ECT and rTMS) were proposed to ten patients aged more than 60. The clinical, cognitive and functional dimensions were compared at inclusion and J42, and their evolution was also measured. At the end, we tried to assess trends for difference between the three types of treatment. Three types of evaluation were performed: clinical (depression, anxiety and apathy), neuropsychological (memory, attentional and executive functioning) and functional (activities of daily life, autonomy).

This preliminary study put in evidence a common pre-treatment profile of depressive symptoms (mood disorder), cognitive (executive difficulties) and functional (loss of autonomy, physical problems) abilities. Clinical improvement was associated with similar cognitive and functional progression, whatever therapeutic method was proposed.

Repetitive evaluation of symptomatology, cognitive performance and everyday life functioning seems to have a major importance in post midlife depressive episodes. It might be useful to determine if non-pharmacological treatment may result in a different evolution of these dimensions.

White-matter abnormalities are sometimes associated with mood disorders, and atypical depression may be related with a leukodystrophy.

A case report of a treatment-resistant depression with cognitive deficits and extensive white-matter hyperintensities suggested a literature review on this unattended association.

A 33 yrs. woman was recovered in our psychiatric ward with a recurrent depressive disorder, partially resistant to antidepressant for eleven years. MADRS score was 26 at admission, without significant anxiety or psychotic symptoms. After 12 days, she presented delirium with neurological localisation symptoms. MRI examination put in evidence confluent hypersignal of white matter with demyelinisation, without grey-matter lesion. No biological or enzymatic abnormalities were detected. A severe executive dysfunction with information slowing was detected on neuropsychological assessment. We performed a literature review on the association of depression and leukodystrophy.

The presented case is a probable Childhood Ataxia with Cerebral Hypomyelination (CACH) syndrome lately revealed by treatment-resistant depression. It represents 30% of all causes of leukodystrophy, and as it is described typically in a childhood form, an onset at adulthood has also been reported, sometimes with foreground behavioural and affective disorders. in that form, it may present with a treatment-resistant and atypical depression.

Treatment-resistant depression in young people with an atypical presentation may be related with an extensive white-matter disease, and a complete evaluation including MRI, biological, enzymatic, neuropsychological assessments, is therefore recommended.

The role of social factors in suicidal behaviour is long established. There is growing evidence supporting the Interpersonal Theory of Suicide (ITS), as developed by Joiner et al., which postulates that two psychological dimensions linked to thwarted fundamental interpersonal needs, perceived burdensomeness and thwarted belongingness are linked to the onset of suicidal desire. The Interpersonal Needs Questionnaire (INQ) has been designed to assess those dimensions for use in research on the aetiology of suicidal behaviour and as a component of risk assessment in clinical settings. There is currently no available French version.

Our objective was to provide a French adaptation of the INQ. We translated the INQ, and then examined the construct validity of INQ-F in a clinical setting.

The INQ was translated and administered to 50 patients admitted for suicide attempt or suicidal ideation. Scales with validated French versions were used to assess the following dimensions: suicide risk (Ducher Suicide Risk Assessment Scale (RSD), depression (BDI-SF and MADRS), hopelessness (Beck Hopelessness Scale (BHS) and social vulnerability (EPICES).

INQ-F was significantly correlated with suicide risk (rho= .737, p < .001), depression, hopelessness and social isolation. Internal consistency was high (Cronbach's alpha = .9137).

Our results support the construct validity of the INQ-F, although complementary studies are needed to further establish it, as well as the relevance of the ITS for suicide risk assessment in clinical settings.