Cognitive reserve and cognition in mood disorders: A systematic review and meta-analysis.

Cognitive functioning heterogeneity is a well-recognized phenomenon in individuals diagnosed with mood disorders. Cognitive Reserve (CR) has been linked to multiple positive outcomes, including cognitive performance in these patients. This systematic review and meta-analysis aim to provide a comprehensive analysis of the relationship between CR and cognitive functioning in individuals with mood disorders, including bipolar disorder and depressive disorders. Following PRISMA guidelines, a systematic review and meta-analysis was conducted of original research exploring the relationship between CR and cognitive performance in adult individuals with mood disorders. The literature search was conducted on PubMed, Scopus, and Web of Science, from 2002 to September 2023, and the Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. Overall, 17 studies met the inclusion criteria for the systematic review and 11 for the meta-analysis. Both qualitative and quantitative findings suggested a positive relationship between CR measures and cognitive domains. CR emerges as a possible protective factor for cognitive functioning in adult individuals with mood disorders, potentially helping to mitigate the cognitive impairments associated with the disorder. These findings underscore the importance of the fact that promoting and enhancing CR could help in the cognitive prognosis of this population.

The bidirectional interaction between antidepressants and the gut microbiota: are there implications for treatment response?

This review synthesizes the evidence on associations between antidepressant use and gut microbiota composition and function, exploring the microbiota's possible role in modulating antidepressant treatment outcomes. Antidepressants exert an influence on measures of gut microbial diversity. The most consistently reported differences were in ß-diversity between those exposed to antidepressants and those not exposed, with longitudinal studies supporting a potential causal association. Compositional alterations in antidepressant users include an increase in the Bacteroidetes phylum, Christensenellaceae family, and Bacteroides and Clostridium genera, while a decrease was found in the Firmicutes phylum, Ruminococcaceae family, and Ruminococcus genus. In addition, antidepressants attenuate gut microbial differences between depressed and healthy individuals, modulate microbial serotonin transport, and influence microbiota's metabolic functions. These include lyxose degradation, peptidoglycan maturation, membrane transport, and methylerythritol phosphate pathways, alongside gamma-aminobutyric acid metabolism. Importantly, baseline increased α-diversity and abundance of the Roseburia and Faecalibacterium genera, in the Firmicutes phylum, are associated with antidepressant response, emerging as promising biomarkers. This review highlights the potential for gut microbiota as a predictor of treatment response and emphasizes the need for further research to elucidate the mechanisms underlying antidepressant-microbiota interactions. More homogeneous studies and standardized techniques are required to confirm these initial findings.

Facing Life in Old Age: Exploring Resilience in Older Adults with Bipolar Disorder.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long duration of the disease, as seen in this population, could affect the development of resilience strategies, but this remains under-researched. Therefore, this study aims to assess resilience levels within the OABD population and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of these patients. Methods: This study sampled 33 OABD patients from the cohort at the Bipolar and Depressive Disorders Unit of the Hospital Clinic of Barcelona. It was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower psychosocial functioning (p = 0.046), a higher cognitive reserve (p = 0.026), and earlier onset (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may have lower resilience levels which correlate with more psychiatric episodes, especially depressive episodes and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could help in early identification of patients requiring additional support to foster resilience and enhance OABD management.

Emotional intelligence and neurocognition profiles in first-episode psychosis: A two-year follow-up study.

Emotional intelligence (EI) and neurocognition (NC) impairments are common in first-episode psychosis (FEP), yet their evolution over time remains unclear. This study identified patient profiles in EI and NC performance in FEP. 98 adult FEP patients and 128 healthy controls (HCs) were tested on clinical, functional, EI, and NC variables at baseline and two-year follow-up (FUP). A repeated-measures ANOVA compared the effects of group (patients and HCs) and time on EI. Significant EI improvements were observed in both groups. Four groups were created based on NC and EI performance at baseline and FUP in patients: impairment in NC and EI, impairment in NC only, impairment in EI only, and no impairment. At FUP, patients impaired in NC and EI showed less cognitive reserve (CR), greater negative and positive symptoms, and poorer functional outcomes. At FUP, three group trajectories were identified: (I) maintain dual impairment (II) maintain no impairment or improve, (III) maintain sole impairment or worsen. The maintain dual impairment group had the lowest levels of CR. EI and NC impairments progress differently in FEP. Greater CR may protect against comorbid EI/NC impairment. Identifying these patient characteristics could contribute to the development of personalised interventions.

Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression.

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE­TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan­Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.

Efficacy and tolerability of monoamine oxidase inhibitors for the treatment of depressive episodes in mood disorders: A systematic review and network meta-analysis.

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are considered third-line treatments for treatment resistant depression; however, they are underused in clinical practice. AIMS: This study aimed to assess the efficacy, tolerability, and acceptability of MAOIs for the treatment of depression in comparison with other antidepressant treatments. METHODS: A systematic review and network meta-analysis of randomised clinical trials was performed to compare the efficacy, tolerability and acceptability between MAOIs and other antidepressant treatments for the treatment of depressive episodes. RESULTS: A total of 83 double-blinded, randomised controlled trials were included in the analysis, with 7765 participants assigned to an active treatment and 1844 assigned to placebo. Several MAOIs, including isocarboxazid, phenelzine, tranylcypromine and moclobemide, showed significantly higher efficacy compared with placebo. The tolerability and acceptability of MAOIs was comparable to other antidepressants. LIMITATIONS: A disproportionate number of studies investigating the most commonly used MAOIs, such as moclobemide and phenelzine, and a lack of specific studies focusing on treatment-resistant and atypical depression. CONCLUSIONS: MAOIs are similar in efficacy to other antidepressants for the treatment of depression. However, more studies are needed comparing MAOI treatment in people with treatment-resistant, atypical and bipolar depression.

Is a vegetarian diet beneficial for bipolar disorder? Relationship between dietary patterns, exercise and pharmacological treatments with metabolic syndrome and course of disease in bipolar disorder.

BACKGROUND: Lifestyle factors are being increasingly studied in bipolar disorder (BD) due to their possible effects on both course of disease and physical health. The aim of this study was to jointly describe and explore the interrelations between diet patterns, exercise, pharmacological treatment with course of disease and metabolic profile in BD. METHODS: The sample consisted of 66 euthymic or mild depressive individuals with BD. Clinical and metabolic outcomes were assessed, as well as pharmacological treatment or lifestyle habits (diet and exercise). Correlations were explored for different interrelations and a factor analysis of dietary patterns was performed. RESULTS: Adherence to the Mediterranean diet was low, seen in 37.9% of the patients and was positively associated with perceived quality of life. The amount of exercise was negatively associated with cholesterol levels, with 32.8% of participants rated as low active by International Physical Activity Questionnaire. There was a high prevalence of obesity (40.6%) and metabolic syndrome (29.7%). Users of lithium showed the best metabolic profile. Interestingly, three dietary patterns were identified: "vegetarian," "omnivore" and "Western." The key finding was the overall positive impact of the "vegetarian" pattern in BD, which was associated with reduced depression scores, better psychosocial functioning, and perceived quality of life, decreased body mass index, cholesterol, LDL and diastolic blood pressure. Nuts consumption was associated with a better metabolic profile. CONCLUSIONS: A vegetarian diet pattern was associated with both, better clinical and metabolic parameters, in patients with BD. Future studies should prioritize prospective and randomized designs to determine causal relationships, and potentially inform clinical recommendations.

Wearable Data From Subjects Playing Super Mario, Taking University Exams, or Performing Physical Exercise Help Detect Acute Mood Disorder Episodes via Self-Supervised Learning: Prospective, Exploratory, Observational Study.

BACKGROUND: Personal sensing, leveraging data passively and near-continuously collected with wearables from patients in their ecological environment, is a promising paradigm to monitor mood disorders (MDs), a major determinant of the worldwide disease burden. However, collecting and annotating wearable data is resource intensive. Studies of this kind can thus typically afford to recruit only a few dozen patients. This constitutes one of the major obstacles to applying modern supervised machine learning techniques to MD detection. OBJECTIVE: In this paper, we overcame this data bottleneck and advanced the detection of acute MD episodes from wearables' data on the back of recent advances in self-supervised learning (SSL). This approach leverages unlabeled data to learn representations during pretraining, subsequently exploited for a supervised task. METHODS: We collected open access data sets recording with the Empatica E4 wristband spanning different, unrelated to MD monitoring, personal sensing tasks-from emotion recognition in Super Mario players to stress detection in undergraduates-and devised a preprocessing pipeline performing on-/off-body detection, sleep/wake detection, segmentation, and (optionally) feature extraction. With 161 E4-recorded subjects, we introduced E4SelfLearning, the largest-to-date open access collection, and its preprocessing pipeline. We developed a novel E4-tailored transformer (E4mer) architecture, serving as the blueprint for both SSL and fully supervised learning; we assessed whether and under which conditions self-supervised pretraining led to an improvement over fully supervised baselines (ie, the fully supervised E4mer and pre-deep learning algorithms) in detecting acute MD episodes from recording segments taken in 64 (n=32, 50%, acute, n=32, 50%, stable) patients. RESULTS: SSL significantly outperformed fully supervised pipelines using either our novel E4mer or extreme gradient boosting (XGBoost): n=3353 (81.23%) against n=3110 (75.35%; E4mer) and n=2973 (72.02%; XGBoost) correctly classified recording segments from a total of 4128 segments. SSL performance was strongly associated with the specific surrogate task used for pretraining, as well as with unlabeled data availability. CONCLUSIONS: We showed that SSL, a paradigm where a model is pretrained on unlabeled data with no need for human annotations before deployment on the supervised target task of interest, helps overcome the annotation bottleneck; the choice of the pretraining surrogate task and the size of unlabeled data for pretraining are key determinants of SSL success. We introduced E4mer, which can be used for SSL, and shared the E4SelfLearning collection, along with its preprocessing pipeline, which can foster and expedite future research into SSL for personal sensing.

Increasing prevalence of self-harm, suicidal behavior and suicidal ideation throughout a three-year period in the context of COVID-19 pandemic in Spain.

The COVID-19 pandemic had a great impact on mental health both in the general population and in individuals with preexisting mental disorders. Lockdown, social restrictions, changes in daily habits and limited access to health services led to changes in consultations in mental health services. This study aimed to determine changing trends in psychiatric admissions by the inclusion of adult patients admitted to the Emergency Department (ED) of Hospital Clínic of Barcelona between 2019 and 2021. Acute admissions, social issues and psychiatric diagnoses were compared between years, seasons and considering the interaction between both years and seasons. A total of 13,677 individuals were included in the analysis. An overall reduction in consultations to the ED and a higher proportion of acute admissions was observed in 2020 in context of the COVID-19 outbreak. Increased prevalence of sleeping disorders and substance use disorders was found in 2020. Self-harming behavior, suicidal thoughts and suicidal behavior showed an increasing tendency over time, with their highest rates in 2021. Prevention and management strategies should be considered in order to address increasing needs in mental health care.

Validation of a pregnancy-adapted Mediterranean Diet Adherence Screener (preg-MEDAS): a validation study nested in the Improving Mothers for a better PrenAtal Care Trial BarCeloNa (IMPACT BCN) trial.

BACKGROUND: Non-time-consuming and easy-to-administer dietary assessment tools specific for pregnancy are needed. OBJECTIVES: The aim of this validation study nested in the IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa) trial is to determine the concurrent validity of the 17-item pregnancy-adapted Mediterranean diet score (preg-MEDAS) and to analyze whether changes in the preg-MEDAS score were associated with maternal favorable dietary and cardiometabolic changes after 3 mo of intervention in pregnant women. METHODS: Dietary data was collected in 812 participants using the preg-MEDAS and a 151-item validated food frequency questionnaire (FFQ) at baseline (19-23 wk gestation) and final visit (31-34 wk gestation). Concurrent preg-MEDAS validity was evaluated by Pearson and intraclass correlation coefficients, κ statistic, and Bland-Altman methods. RESULTS: The preg-MEDAS had a good correlation with the FFQ (r = 0.76 and intraclass correlation coefficient 0.75). The agreement of each of the preg-MEDAS items ranged from 40.9% to 93.8% with a substantial agreement mean concordance (κ = 0.61). A 2-point increase in preg-MEDAS was associated with a decrease in maternal mean and systolic blood pressure (ß: -0.51 mmHg; 95% confidence interval [CI]: -0.97, -0.04 mmHg and -0.87 mmHg; 95% CI: -1.48, -0.26 mmHg, respectively). CONCLUSIONS: The preg-MEDAS displays good validity for assessing adherence to the Mediterranean diet, allowing detection of dietary changes over time. In addition, changes observed in preg-MEDAS are significantly associated with a decrease in maternal blood pressure. Therefore, we propose preg-MEDAS as a rapid and simple dietary assessment tool during pregnancy. This trial was registered at clinicaltrials.gov as NCT03166332.

Sleep-wake variations of electrodermal activity in bipolar disorder.

BACKGROUND: Affective states influence the sympathetic nervous system, inducing variations in electrodermal activity (EDA), however, EDA association with bipolar disorder (BD) remains uncertain in real-world settings due to confounders like physical activity and temperature. We analysed EDA separately during sleep and wakefulness due to varying confounders and potential differences in mood state discrimination capacities. METHODS: We monitored EDA from 102 participants with BD including 35 manic, 29 depressive, 38 euthymic patients, and 38 healthy controls (HC), for 48 h. Fifteen EDA features were inferred by mixed-effect models for repeated measures considering sleep state, group and covariates. RESULTS: Thirteen EDA feature models were significantly influenced by sleep state, notably including phasic peaks (p < 0.001). During wakefulness, phasic peaks showed different values for mania (M [SD] = 6.49 [5.74, 7.23]), euthymia (5.89 [4.83, 6.94]), HC (3.04 [1.65, 4.42]), and depression (3.00 [2.07, 3.92]). Four phasic features during wakefulness better discriminated between HC and mania or euthymia, and between depression and euthymia or mania, compared to sleep. Mixed symptoms, average skin temperature, and anticholinergic medication affected the models, while sex and age did not. CONCLUSION: EDA measured from awake recordings better distinguished between BD states than sleep recordings, when controlled by confounders.

Physical comorbidities of older age bipolar disorder (OABD) patients: A global replication analysis of prevalence and sex differences.

OBJECTIVES: To compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence. METHODS: OABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women). RESULTS: After controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled. CONCLUSIONS: This replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women.

The Mediterranean Diet in Pregnancy: Implications for Maternal Brain Morphometry in a Secondary Analysis of the IMPACT BCN Randomized Clinical Trial.

INTRODUCTION: A Mediterranean diet has positive effects on the brain in mid-older adults; however, there is scarce information on pregnant individuals. We aimed to evaluate the effect of a structured Mediterranean diet intervention on the cortical structure of the maternal brain during pregnancy. METHODS: This study was a secondary analysis of the IMPACT BCN, a randomized clinical trial with 1221 high-risk pregnant women randomly allocated into three groups at 19-23 weeks of gestation: Mediterranean diet intervention, a mindfulness-based stress reduction program, or usual care. Maternal brain magnetic resonance imaging was performed during the third trimester of pregnancy in a random subgroup of participants. For this study, data from the Mediterranean diet and usual groups were analyzed. Maternal dietary intake, adherence to the Mediterranean diet and metabolite biomarkers were evaluated using a food frequency questionnaire, a 17-item dietary screener and plasma/urine samples, respectively. RESULTS: The cluster-wise analysis showed that the Mediterranean diet group participants (n = 34) had significantly larger surface areas in the right precuneus (90%CI: <0.0001-0.0004, p < 0.001) and left superior parietal (90%CI: 0.026-0.033, p = 0.03) lobules compared to the usual care group participants (n = 37). A larger right precuneus area was associated with high improvements in adherence to the Mediterranean diet, a high intake of walnuts and high concentrations of urinary hydroxytyrosol. A larger left superior parietal area was associated with a high intake of walnuts and high concentrations of urinary hydroxytyrosol. CONCLUSIONS: The promotion of a Mediterranean diet during pregnancy has a significant effect on maternal brain structure.

Clinical, sociodemographic and environmental predicting factors for relapse in bipolar disorder: A systematic review.

INTRODUCTION: Bipolar disorder (BD) is a chronic and recurrent illness characterized by manic, mixed or depressive episodes, alternated with periods of euthymia. Several prognostic factors are associated with higher rates of relapse, which is crucial for the identification of high-risk individuals. This study aimed at systematically reviewing the existing literature regarding the impact of sociodemographic, clinical and environmental factors, in clinical relapses, recurrences and hospitalizations due to mood episodes in BD. METHODS: A systematic search of electronic databases (PubMed, Cochrane library and Web of Science) was conducted to integrate current evidence about the impact of specific risk factors in these outcomes. RESULTS: Fifty-eight articles met the inclusion criteria. Studies were grouped by the type of factors assessed. Family and personal psychiatric history, more severe previous episodes, earlier age of onset, and history of rapid cycling are associated with clinical relapses, along with lower global functioning and cognitive impairments. Unemployment, low educational status, poorer social adjustment and life events are also associated with higher frequency of episodes, and cannabis with a higher likelihood for rehospitalization. LIMITATIONS: Small sample sizes, absence of randomized clinical trials, diverse follow-up periods, lack of control for some confounding factors, heterogeneous study designs and diverse clinical outcomes. CONCLUSIONS: Although current evidence remains controversial, several factors have been associated with an impaired prognosis, which might allow clinicians to identify patients at higher risk for adverse clinical outcomes and find modifiable factors. Further research is needed to elucidate the impact of each risk factor in the mentioned outcomes.

Impact of air pollution and climate change on mental health outcomes: an umbrella review of global evidence.

The impact of air pollution and climate change on mental health has recently raised strong concerns. However, a comprehensive overview analyzing the existing evidence while addressing relevant biases is lacking. This umbrella review systematically searched the PubMed/Medline, Scopus and PsycINFO databases (up to June 26, 2023) for any systematic review with meta-analysis investigating the association of air pollution or climate change with mental health outcomes. We used the R metaumbrella package to calculate and stratify the credibility of the evidence according to criteria (i.e., convincing, highly suggestive, suggestive, or weak) that address several biases, complemented by sensitivity analyses. We included 32 systematic reviews with meta-analysis that examined 284 individual studies and 237 associations of exposures to air pollution or climate change hazards and mental health outcomes. Most associations (n=195, 82.3%) involved air pollution, while the rest (n=42, 17.7%) regarded climate change hazards (mostly focusing on temperature: n=35, 14.8%). Mental health outcomes in most associations (n=185, 78.1%) involved mental disorders, followed by suicidal behavior (n=29, 12.4%), access to mental health care services (n=9, 3.7%), mental disorders-related symptomatology (n=8, 3.3%), and multiple categories together (n=6, 2.5%). Twelve associations (5.0%) achieved convincing (class I) or highly suggestive (class II) evidence. Regarding exposures to air pollution, there was convincing (class I) evidence for the association between long-term exposure to solvents and a higher incidence of dementia or cognitive impairment (odds ratio, OR=1.139), and highly suggestive (class II) evidence for the association between long-term exposure to some pollutants and higher risk for cognitive disorders (higher incidence of dementia with high vs. low levels of carbon monoxide, CO: OR=1.587; higher incidence of vascular dementia per 1 µg/m3 increase of nitrogen oxides, NOx: hazard ratio, HR=1.004). There was also highly suggestive (class II) evidence for the association between exposure to airborne particulate matter with diameter ≤10 µm (PM10) during the second trimester of pregnancy and the incidence of post-partum depression (OR=1.023 per 1 µg/m3 increase); and for the association between short-term exposure to sulfur dioxide (SO2) and schizophrenia relapse (risk ratio, RR=1.005 and 1.004 per 1 µg/m3 increase, respectively 5 and 7 days after exposure). Regarding climate change hazards, there was highly suggestive (class II) evidence for the association between short-term exposure to increased temperature and suicide- or mental disorders-related mortality (RR=1.024), suicidal behavior (RR=1.012), and hospital access (i.e., hospitalization or emergency department visits) due to suicidal behavior or mental disorders (RR=1.011) or mental disorders only (RR=1.009) (RR values per 1°C increase). There was also highly suggestive (class II) evidence for the association between short-term exposure to increased apparent temperature (i.e., the temperature equivalent perceived by humans) and suicidal behavior (RR=1.01 per 1°C increase). Finally, there was highly suggestive (class II) evidence for the association between the temporal proximity of cyclone exposure and severity of symptoms of post-traumatic stress disorder (r=0.275). Although most of the above associations were small in magnitude, they extend to the entire world population, and are therefore likely to have a substantial impact. This umbrella review classifies and quantifies for the first time the global negative impacts that air pollution and climate change can exert on mental health, identifying evidence-based targets that can inform future research and population health actions.

New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview.

Over the last six decades, lithium has been considered the gold standard treatment for the long-term management of bipolar disorder due to its efficacy in preventing both manic and depressive episodes as well as suicidal behaviors. Nevertheless, despite numerous observed effects on various cellular pathways and biologic systems, the precise mechanism through which lithium stabilizes mood remains elusive. Furthermore, there is recent support for the therapeutic potential of lithium in other brain diseases. This review offers a comprehensive examination of contemporary understanding and predominant theories concerning the diverse mechanisms underlying lithium's effects. These findings are based on investigations utilizing cellular and animal models of neurodegenerative and psychiatric disorders. Recent studies have provided additional support for the significance of glycogen synthase kinase-3 (GSK3) inhibition as a crucial mechanism. Furthermore, research has shed more light on the interconnections between GSK3-mediated neuroprotective, antioxidant, and neuroplasticity processes. Moreover, recent advancements in animal and human models have provided valuable insights into how lithium-induced modifications at the homeostatic synaptic plasticity level may play a pivotal role in its clinical effectiveness. We focused on findings from translational studies suggesting that lithium may interface with microRNA expression. Finally, we are exploring the repurposing potential of lithium beyond bipolar disorder. These recent findings on the therapeutic mechanisms of lithium have provided important clues toward developing predictive models of response to lithium treatment and identifying new biologic targets. SIGNIFICANCE STATEMENT: Lithium is the drug of choice for the treatment of bipolar disorder, but its mechanism of action in stabilizing mood remains elusive. This review presents the latest evidence on lithium's various mechanisms of action. Recent evidence has strengthened glycogen synthase kinase-3 (GSK3) inhibition, changes at the level of homeostatic synaptic plasticity, and regulation of microRNA expression as key mechanisms, providing an intriguing perspective that may help bridge the mechanistic gap between molecular functions and its clinical efficacy as a mood stabilizer.

Neuroprogression in bipolar disorder: why right is wrong.

The controversy on whether bipolar disorder is a neurodevelopmental versus a neuroprogressive illness is still around, despite some reductionistic claims that only one model is right. The current diagnostic classifications are not helpful to address this issue, and there is conflicting evidence in favor and against either model. In practice, though, understanding that many patients may show a progressive cognitive and functional decline which may be correlated with the number and severity of episodes may lead to better outcomes through early intervention strategies.

Assessing the patient's affective perception of their psychotherapist: validation of the in-Session Patient Affective Reactions Questionnaire.

Background: Psychotherapists need effective tools to monitor changes in the patient's affective perception of the therapist and the therapeutic relationship during sessions to tailor therapeutic interventions and improve treatment outcomes. This study aims to evaluate the factor structure, reliability, and validity of the in-Session Patient Affective Reactions Questionnaire (SPARQ), a concise self-report measure designed for practical application in real-world psychotherapy settings. Methods: Validation data was gathered from (N = 700) adult patients in individual psychotherapy. These patients completed the SPARQ in conjunction with additional measures capturing sociodemographic details, characteristics of therapeutic interventions, individual personality traits, mental health symptom severity, elements of the therapeutic relationship, and session outcomes. This comprehensive approach was employed to assess the construct and criterion-related validity of the SPARQ. Results: The SPARQ has a two-factor structure: Positive Affect (k = 4, ω total = .87) and Negative Affect (k = 4, ω total = .75). Bifactor confirmatory factor analysis (CFA) yielded the following fit indices: X2[df] = 2.53, CFI = .99; TLI = .98; RMSEA = .05; and SRMR = .02. Multi-group CFAs demonstrated measurement invariance (i) across patients who attended psychotherapy sessions in person versus in remote mode, and (ii) across patients with and without psychiatric diagnoses confirmed metric invariance. Furthermore, the SPARQ showed meaningful correlations with concurrently administered measures. Discussion: The SPARQ proves to be a valuable instrument in clinical, training, and research contexts, adept at capturing patients' session-level affective responses towards their therapist and perceptions of the therapeutic alliance. Comprehensive descriptive statistics and a range of score precision indices have been reported, intended to serve as benchmarks for future research.

Neuropsychological functioning and its correlates at 1 year follow-up of severe COVID-19.

BACKGROUND: Short-term cognitive impairment is associated with SARS-CoV-2 infection but the long-term impact is yet to be examined in detail. We aim to study the evolution of these symptoms in severe COVID-19 patients admitted to the intensive care unit (ICU) between April and December 2020 1 year after hospital discharge and to analyze its clinical correlates. METHOD: A total of 58 patients agreed to participate in the 6 months follow-up and 30 at 1 year after hospital discharge. Demographic, clinical and laboratory data were collected and a comprehensive neuropsychological battery including validated tests for the main cognitive domains was administered. To test the magnitude of neurocognitive sequelae, two standard deviations below normative group were considered. To compare the neuropsychological performance at 6 and 12 months follow-up we used repeated measures tests. Finally, regression analyses were performed to test the main effects of medical and psychological factors on multiple cognition. RESULTS: Almost half of the sample continued to have impaired performance on neuropsychological tests at 12 months follow-up. In comparison with the results obtained at 6 months, significant improvements were found in immediate recall (d = 0.49), delayed recall (d = 0.45), and inhibitory control (d = 0.53). Medical variables predicted cognitive performance at 6 months but not at 12 months follow-up, while anxiety and depression predicted cognitive deficits in the long-term. CONCLUSIONS: A generalised improvement was observed in severe COVID-19 patients at follow-up. This improvement was particularly notable in verbal memory and executive functioning. However, a considerable proportion of the sample continued to present deficits at 1 year follow-up.