Leo program, a short multi-family skill-based psychoeducational program for caregivers of relatives living with a severe mental disorder: a retrospective pilot study.

Background: Caring for a relative with a severe mental disorder (SMD) is associated with high levels of burden and poor physical and mental health. There is a dire need for family psychoeducational programs that can be provided as early as possible. This manuscript describes the pilot testing of "Leo" a motivational-based psychoeducational program for caregivers of individuals with a SMD. The Leo program aims to provide caregivers with skills to best support their relative and to adopt self-care behaviors. Methods: We retrospectively analyzed medical records of caregivers who enrolled in a short, multi-family, skill-based psychoeducational program, consisting of eight 3-hour sessions over 8 weeks. Outcomes of interest included: i) adherence to the program, ii) satisfaction and perceived usefulness, and iii) pre-post changes in self-reported levels of depression (CES-D), burden (ZBI), and skills (10 Likert-scaled items). A network analysis was used to investigate the relationships between pre-post changes in self-evaluated skills and pre-post changes in burden and depression levels. Results: Over the 91 enrolled participants, 87 (95.6%) completed the program attending at least 5/8 sessions, 80.5% attending all sessions. Seventy-six caregivers fulfilled the questionnaires at baseline and after the program, and were included in the analysis. Although there was no evidence for significant change in self-reported depression levels (Cohen's d=0.19, p=0.210), burden scores and all evaluated skills were improved post-intervention, with medium to strong effect size (Cohen's ds from 0.47 to 0.87; p<0.001). Network output indicated that increased self-evaluated competence in 5 skills were associated with a global improvement in caregivers' burden and/or depression scores. Post-intervention, 89.7% of caregivers were "very satisfied" and 82.1% found the program "extremely useful". Conclusion: This pilot retrospective study shows high levels of satisfaction, perceived usefulness, and adherence to "Leo", a short, multi-family, skill-based psychoeducational program with promising results in improving caregivers' burden, self-evaluated competence in coping with caregiving demands and in self-care behaviors. This study provides preliminary insights into the mechanisms by which family psychoeducation might alleviate burden of care. A larger-scaled, controlled, randomized study with follow-up assessments is warranted to determine how burden, depression, and skills, as well as their inter-relationships, evolve over time.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

INTRODUCTION: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship. METHOD: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire. RESULTS: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable. CONCLUSION: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety.

Clinical and cognitive characteristics of subjects with schizophrenia and childhood attention-deficit/hyperactivity disorder: Results from the multicentric FACE-SZ cross-sectional dataset.

BACKGROUND: Childhood Attention-deficit/hyperactivity disorder (C-ADHD) is a neurodevelopmental disorder, associated with an increased risk of subsequent schizophrenia. The objective of the present study was to determine the prevalence of C-ADHD in schizophrenia and the clinical and cognitive characteristics associated with C-ADHD history in schizophrenia. METHODS: 569 subjects with schizophrenia (74 % men, mean age 30.8) were included in ten expert centers at a national level and tested with a comprehensive battery of clinician-rated, patient-reported scales and cognitive tests. C-ADHD was assessed with the WURS (Wender Utah Rating Scale) self-report questionnaire. Multivariate, correlation, and principal component analyses (PCA) were conducted. RESULTS: Thirty-nine subjects (N = 39, 6.9 %) were classified in the C-ADHD group. Compared to those without C-ADHD, subjects with C-ADHD were more frequently male, had lower education levels, more severe positive clinical symptoms, more subjective cognitive deficits complaints, and lower medication adherence with small to medium effect sizes. Two cognitive components emerged from the PCA, one component including perceptual reasoning and working memory, and another component including visuospatial search and graphomotor speed, cognitive inhibition/flexibility and central executive functioning. Both components were associated with lower performances in the C-ADHD group. CONCLUSIONS: C-ADHD is frequent in schizophrenia and associated with more severe positive symptoms and impaired cognitive performances compared to those without C-ADHD. This suggests that the pathophysiological mechanisms contributing to these disorders may lead to the worsening of the cognitive functioning in patients with both disorders. C-ADHD is a relevant clinical marker to discriminate subgroups of schizophrenia with different profiles for a precision-psychiatry approach.

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.

BACKGROUND: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. METHODS: This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. RESULTS: Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p = 0.008). CONCLUSIONS: This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.

Molecular mapping of a core transcriptional signature of microglia-specific genes in schizophrenia.

Besides playing a central role in neuroinflammation, microglia regulate synaptic development and is involved in plasticity. Converging lines of evidence suggest that these different processes play a critical role in schizophrenia. Furthermore, previous studies reported altered transcription of microglia genes in schizophrenia, while microglia itself seems to be involved in the etiopathology of the disease. However, the regional specificity of these brain transcriptional abnormalities remains unclear. Moreover, it is unknown whether brain and peripheral expression of microglia genes are related. Thus, we investigated the expression of a pre-registered list of 10 genes from a core signature of human microglia both at brain and peripheral levels. We included 9 independent Gene Expression Omnibus datasets (764 samples obtained from 266 individuals with schizophrenia and 237 healthy controls) from 8 different brain regions and 3 peripheral tissues. We report evidence of a widespread transcriptional alteration of microglia genes both in brain tissues (we observed a decreased expression in the cerebellum, associative striatum, hippocampus, and parietal cortex of individuals with schizophrenia compared with healthy controls) and whole blood (characterized by a mixed altered expression pattern). Our results suggest that brain underexpression of microglia genes may represent a candidate transcriptional signature for schizophrenia. Moreover, the dual brain-whole blood transcriptional alterations of microglia/macrophage genes identified support the model of schizophrenia as a whole-body disorder and lend weight to the use of blood samples as a potential source of biological peripheral biomarkers.

Poverty and inequality in real-world schizophrenia: a national study.

Background: Schizophrenia has high socioeconomic impact among severe psychiatric disorders. Aims: To explore clinician-reported and patient-reported inequities between patients under the poverty threshold vs. the others. Method: 916 patients consecutively recruited in 10 national centers received a comprehensive standardized evaluation of illness severity, addictions and patient-reported outcomes. Results: 739 (80.7%) of the patients were classified in the poverty group. This group had poorer objective illness outcomes (lower positive, negative, cognitive, excitement/aggressive and self-neglect symptoms and lifetime history of planned suicide) in multivariate analyses. While they had similar access to treatments and psychotherapy, they had lower access to socially useful activities, couple's life, housing and parenthood. They had also more disturbed metabolic parameters. On the contrary, the poverty group reported better self-esteem. No significant difference for depression, risky health behavior including addictions and sedentary behavior was found. Interpretation: The equity in access to care is attributed to the French social system. However, mental and physical health remain poorer in these patients, and they still experience poor access to social roles independently of illness severity and despite healthcare interventions. These patients may have paradoxically better self-esteem due to decreased contact with society and therefore lower stigma exposure (especially at work). Schizophrenia presents itself as a distinct impoverished population concerning health-related outcomes and social integration, warranting focus in public health initiatives and improved treatment, including tailored interventions, collaborative care models, accessible mental health services, housing support, vocational training and employment support, community integration, education and awareness, research and data collection, culturally competent approaches, and long-term support.

Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset.

Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.

Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs.

QUESTION: This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia. STUDY SELECTION AND ANALYSIS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed. FINDINGS: Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio. CONCLUSIONS: The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.

Evolution of Cognitive Impairments in Treatment-Resistant Depression: Results from the Longitudinal French Centers of Expertise for Treatment-Resistant Depression (FACE-DR) Cohort.

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients (n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded (n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning.

Network analysis of the associations between personality traits, cognitive functioning, and inflammatory markers in elderly individuals without dementia.

Introduction: Lower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia. Methods: This study utilizes a network analysis approach, a statistical method that allows visualization of the data's unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1ß, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test. Results: Openness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified. Discussion: In elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively.

Long-term benzodiazepine prescription in treatment-resistant depression: A national FACE-TRD prospective study.

BACKGROUND: Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD). OBJECTIVE: To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year. RESULTS: At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028). CONCLUSION: Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible.

Clinical and pharmacological correlates of caffeine consumption in subjects with schizophrenia - Data from the FACE-SZ cohort.

Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = -0.12) but significant.

Diurnal symptoms of sleepiness and dysfunction predict future suicidal ideation in a French cohort of outpatients (FACE-DR) with treatment resistant depression: A 1-year prospective study about sleep markers.

BACKGROUND: Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide. METHODS: Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires. RESULTS: Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1-3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16-2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56-0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments. LIMITATIONS: Sleep assessments were based on self-reported questionnaires rather than objective measures. CONCLUSIONS: Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD.

Clinical characteristics associated with discrepancies between self- and clinician-rated suicidal ideation in patients with bipolar disorder (FACE-BD cohort).

Suicidal ideation (SI) is a major suicide risk factor; therefore, it is crucial to identify individuals with SI. Discrepancies between the clinicians and patients' estimation of SI may lead to under-evaluating the suicide risk. Yet, studies on discrepancies between self- and clinician-rated SI are lacking, although identifying the patients' sociodemographic and clinical characteristics associated with such discrepancies might help to reduce the under-evaluation risk. Therefore, the aim of this study was to identify features associated with SI rating discrepancies in patients with bipolar disorder (BD) because of the high prevalence of suicide in this population. Among the patients recruited by the French network of FondaMental expert centers for BD, patients with SI (i.e. ≥2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report and/or ≥3 for item 10 of the clinician-rated Montgomery and Åsberg Depression Rating Scale) were selected and divided in concordant (i.e. SI in both self- and clinician-rated questionnaires; n = 130; 25.6%), and discordant (i.e. SI in only one questionnaire; n = 377; 74.4%). Depression severity was the feature most associated with SI evaluation discrepancy, especially in patients with SI identified only with the self-rated questionnaire. Clinician may under-evaluate SI presence in patients with low depression level.

History of learning disorders is associated with worse cognitive and functional outcomes in schizophrenia: results from the multicentric FACE-SZ cross-sectional dataset.

Schizophrenia is associated with early neurodevelopmental disorders, including most frequently learning disorders (LD), among them dyslexia and dyspraxia. Despite the demonstrated links between schizophrenia and LD, specific clinical patterns of the schizophrenia with a history of LD subgroup remain unknown. The aim of the present study was to investigate cognitive impairment, symptoms and functional outcome associated with a history of LD in a large cross-sectional, multicentric, sample of schizophrenia subjects. 492 community-dwelling subjects with schizophrenia (75.6% male, mean age 30.8 years) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. The 51 (10.4%) subjects identified with a history of LD had significantly impaired general cognitive ability (Wechsler Adult Intelligence Scale Full Scale Total IQ: Cohen's d = 0.50, p = 0.001), processing speed (d = 0.19), verbal comprehension (d = 0.29), working memory (d = 0.31), cognitive inhibition and flexibility (d = 0.26), central executive functioning (d = 0.26), phonemic verbal fluency (d = 0.22) and premorbid intellectual ability (d = 0.48), as well as with a worse functional outcome (Global Assessment of Functioning, d = 0.21), independently of age, sex, education level, symptoms, treatments, and addiction comorbidities. These results indicate that a history of LD is associated with later cognitive impairment and functional outcome in schizophrenia. This suggests that history of LD is a relevant clinical marker to discriminate subgroups of patients with schizophrenia with different profiles in a precision psychiatry framework.

Caregiving-related experiences associated with depression severity and its symptomatology among caregivers of individuals with a severe mental disorder: an online cross-sectional study.

Caring for a relative with a severe mental disorder puts family caregivers to a great risk of depression. While overall caregiving burden is a strong predictor of depression, the contribution of the various dimensions of burden to caregivers' depression as well as their relationships with depressive symptoms has received little attention. 384 family caregivers completed a cross-sectional online survey including the Center for Epidemiological Studies Depression (CES-D) scale, the Zarit Burden Interview (ZBI), and the Brief Experience of Caregiving Inventory (BECI), measuring caregiving burden and experience. We estimated the structure of the relationships between caregiving experiences (i.e., ZBI and BECI subscales) and CES-D symptoms using a network approach. Negative Emotion/Consequences, (lack of) Positive Personal Experience, and Stigma/Effects on Family were the most connected caregiving dimensions to depression. To untangle the role of the Negative Emotion/Consequences component (by far the most central node in estimated networks), a secondary analysis incorporating its composing items was estimated. Losing control over life, feeling strained around the relative and impaired self-perceived health emerged as central nodes. Interestingly, these caregiving-related dimensions or experiences were differentially connected to depressive symptoms. We discuss how these findings might help future research and inform tailored psychoeducational interventions for family caregivers of people with a severe mental disorder.

A 1-Day Training Course to Disseminate the BREF Psychoeducational Program to Caregivers and Promote Network Establishment between Psychiatry Departments and Family Associations.

OBJECTIVE: Although international guidelines state that psychoeducation to caregivers should be provided systematically, it remains insufficiently available in psychiatry. This study reports the development and evaluation of an original training course aimed to provide participants with the knowledge and skills to implement "BREF," a psychoeducational program for caregivers. METHODS: The BREF program training course, a free, 1-day course incorporating peer role-play was developed. In addition to psychiatrists, nurses, and psychologists, caregivers were involved as preceptors. Participants were mental health professionals and volunteer caregivers. Participants to the first 28 sessions of the course (n=467) completed a post-course questionnaire (n=341) and a cross-sectional questionnaire (n=56). Quantitative data on satisfaction, learning, and behavior changes following the course were collected equating to levels 1, 2, and 3 of Kirkpatrick's model. RESULTS: After the course, high levels of satisfaction and commitment were observed with 100% of responders recommending the course and 81% intending to implement the BREF program. Confidence mean score to implement BREF was 7.9/10 (±1.4) with no significant effect of course session. At cross-sectional evaluation, 73% of responders reported improvements in skills related to providing psychoeducation to caregivers, 64% stated that the BREF program was implemented/under implementation, and 66% stated that their department had connected with a family association. CONCLUSIONS: Training course sessions alone can increase psychoeducational programs for caregivers and network establishment. The BREF program training course demonstrates a high level of participant satisfaction and is a promising method to disseminate psychoeducation to caregivers, thus addressing a major shortage in mental health organization.

Current (but not ex) cigarette smoking is associated with worse cognitive performances in schizophrenia: results from the FACE-SZ cohort.

BACKGROUND: Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects. METHODS: In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used. RESULTS: In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41-0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001). CONCLUSIONS: This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.

Association Between Mild Neurocognitive Disorder Due to Alzheimer's Disease and Possible Attention-deficit/Hyperactivity Disorder: A Case Report.

Recent literature concerning attention-deficit/hyperactivity disorder (ADHD) underlines the persistence of this neurodevelopmental illness in older patients. Comorbidity with a neurodegenerative disease is thus possible. However, few studies have investigated this topic. To our knowledge, this is the first case report of such a possible association, which raises important questions about clinical presentation, symptoms, diagnosis, and treatment. A 72-year-old man, without any psychiatric history, presented with depression, subjective memory loss, and attention deficit and anxious symptoms, and was diagnosed with mild neurocognitive disorder due to Alzheimer's disease. However, the patient's attentional symptoms appeared to have been present since childhood. A formalized diagnostic interview assessing for ADHD did not allow for a clear diagnosis, possibly due to recall bias. The patient's anxiety symptoms also did not respond well to cognitive behavioral therapy coupled with different antidepressants. We hypothesized the presence of ADHD, with the symptoms balanced until now by the patient's high cognitive capacities, and we postulated that the onset of a neurogenerative process may have disrupted this balance. In this case report, we discuss symptom dimensionality, the interplay between neurodegenerative and neurodevelopmental diseases, and various treatment options. Attentional deficits and anxiety symptoms are frequent in mild neurocognitive disorders due to neurodegenerative illnesses. It is important to explore the time of onset of such symptoms since neurodegenerative processes can worsen neurodevelopmental conditions. Moreover, identification of a pre-existing neurodevelopmental condition can lead to alternative care and treatment options. In addition, the unexplained worsening of ADHD symptoms should prompt clinicians to assess for a neurodegenerative process.

Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort.

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific "immuno-metabolic" profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.