Andrea Escelsior

Esketamine has demonstrated efficacy in treatment-resistant depression (TRD), but medium-term real-world functional outcomes remain understudied. This study described 6-month depressive symptoms and functional trajectories during routine esketamine treatment, focusing on functional outcomes and remission correlates. In this prospective multicenter study, 60 patients with TRD initiating intranasal esketamine augmentation were assessed at baseline, Month 1, Month 3, and Month 6 using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Sheehan Disability Scale (SDS). Mixed-effects models, Turnbull interval-censored time-to-remission analysis, logistic regression, and ROC analyses were performed. MADRS and SDS improved significantly at all follow-up time points (p < 0.001). At Month 6, symptomatic response and remission rates were 78.3 and 46.7%, while functional response and remission rates were 78.3 and 33.3%, respectively. Turnbull estimates showed cumulative functional remission rates of 5.0, 15.0, and 33.3% at Months 1, 3, and 6, respectively. MADRS-SDS correlations decreased over time, supporting partial symptomatic-functional dissociation. Higher baseline SDS (OR = 0.73, 95% CI: 0.59–0.89) and more previous antidepressant trials (ADTs; OR = 0.53, 95% CI: 0.35–0.82) were associated with lower odds of Month 6 functional remission; bootstrap internal validation supported coefficient stability. ROC-derived thresholds were considered sample-dependent and not clinically validated. Cumulative esketamine dosage was associated with functional response but not remission. Depressive symptoms and functioning improved progressively over 6 months during esketamine treatment in routine clinical care. Functional remission followed a slower trajectory than symptomatic remission and had partly distinct correlates, supporting functional monitoring as a distinct TRD outcome.

Visual illusions serve as a window into the altered perceptual experiences of individuals with psychiatric disorders. One such is the induced Roelofs effect, where the perceived position of a small stimulus is shifted toward the midline of a distractor frame surrounding the stimulus, as the shift is more pronounced in individuals with schizophrenia. The present work extends the induced Roelofs effect assessment to bipolar disorder. Healthy controls, patients with bipolar disorder, and patients with schizophrenia were shown a dot stimulus placed inside a frame whose horizontal position could vary, and they were asked to determine whether the dot position was to their left or to their right. The induced Roelofs effect was minimal in healthy controls, large in schizophrenia, and intermediate in bipolar disorder. No association between the effect size and psychotic symptomatology or cognitive abilities was found. Yet, a nonlinear, concave association was found between the total pharmacological load and the illusion size. The results suggest that the illusion is related to alterations in sensory processing, which are common to both bipolar disorder and schizophrenia, hence showing their potential utility in clinical evaluations, which currently tend to overlook the sensory domain.

Innate immune dysfunction is implicated in schizophrenia (SZ) and bipolar disorder (BD). Alterations in natural killer (NK) cells, monocytes and macrophages occur in both disorders across peripheral and central compartments. This systematic review synthesises current evidence by clinical stage and illness phase. Following PRISMA guidelines, PubMed, Scopus and PsycINFO were searched to May 2025. Eligible studies reported peripheral blood, cerebrospinal fluid (CSF) or post-mortem brain findings. Eighty-one studies met inclusion criteria. In SZ, peripheral data showed altered NK cell subsets and monocyte abnormalities, including elevated counts and inflammatory ratios, particularly in early or acute stages. CSF studies found increased monocyte chemoattractants, and post-mortem analyses revealed macrophage upregulation in frontal and temporal cortices. In BD, NK cell results were limited and inconsistent. Monocyte activation was most evident during symptomatic phases, particularly mania. CSF analyses detected increased monocyte- and macrophage-associated proteins, while post-mortem findings indicated microglial activation in selected cortical and subcortical regions, less consistently than in SZ. Innate immune alterations in SZ and BD partly overlap yet remain disorder- and state-specific. Central compartments and NK cells are underexplored. Stratification by stage and phase may improve interpretability and guide longitudinal, multimodal, cell-specific research for precision immunopsychiatry.

Objective: Time distortions characterise severe mental disorders, exhibiting different clinical and neurobiological manifestations. This systematic review aims to explore the existing literature encompassing experimental studies on time perception in patients with bipolar disorder (BD), considering psychopathological and cognitive correlates. Methods: Studies using an experimental paradigm to objectively measure the capacity to judge time have been searched for. Selected studies have been described based on whether i) explicit or implicit time perception was investigated, ii) the temporal intervals involved were sub-second or supra-second, and iii) a perceptual or motor timing paradigm was used. Results: Only 11 met the criteria for inclusion in the review. The available literature shows that the performance of BD patients mostly aligns with controls within sub-second timeframes (six articles), while a different pattern emerges within supra-second intervals based on the clinical phase of the disease (seven articles). Specifically, for longer temporal spans, BD patients tend to overestimate the duration during manic states and underestimate it during depressive states. Notably, no studies have directly investigated the neurobiological mechanisms associated with time perception. Conclusion: This review indicates that BD patients exhibit time perception similar to controls within sub-second intervals, but tend to overestimate time and underestimate it based on the clinical phase within supra-second intervals. Expanding the understanding of time perception in BD, particularly in relation to clinical phases and cognitive function, is of great importance. Such insights could deepen our understanding of the disorder, refine diagnostic processes, and guide the development of innovative therapeutic interventions.

Background/Objectives: Anorexia nervosa (AN) is a complex psychiatric disorder characterized by an extreme fear of gaining weight, leading to severe calorie restriction and weight loss. Beyond its psychiatric challenges, AN has significant physical consequences affecting multiple organ systems. Recent research has increasingly focused on the interplay between autoantibodies, oxidative stress, and nutritional state in this condition. Methods: Ninety-six subjects were evaluated: forty-eight with AN and forty-eight normal-weight control subjects. The serum levels of IgG reactive to hypothalamic antigens, uric acid, and total antioxidant capacity were evaluated by laboratory assays. Results: Anti-hypothalamic autoantibodies were found in AN patients. Furthermore, increased levels of oxidative stress were reported, as measured by decreased serum uric acid and total antioxidant capacity (TAC), and they reduced with the disease duration and the restoration of body mass index (BMI). Finally, a decrease in both autoantibodies and oxidative stress was observed as patients’ clinical condition improved, as measured by time since diagnosis and BMI recovery. Conclusions: The clinical improvement of AN patients seems to be associated with a decrease in the autoimmune response to hypothalamic cellular antigens and a reduction in oxidative stress. Dysregulation of the immune system and oxidative stress appear to be interconnected in various diseases, including autoimmune and psychiatric disorders. These findings, although preliminary, may offer potential avenues for the treatment of this challenging condition.

Structuring sensory events in time is essential for interacting with the environment and producing adaptive behaviors. Over the past years, the microstructure of temporality received increasing attention, recognized as a fundamental factor influencing cognitive, affective, and social abilities, whose alteration can underlie the etiopathogeneses of some clinical symptoms in psychiatric disorders. The present research investigated multisensory temporal processing in individuals with schizophrenia (N = 21), bipolar disorder (N = 20) and healthy controls (N = 21) in order to explore a plausible link between multisensory alterations in the temporal order of events and the psychopathological dimensions underlying psychosis. We asked participants to temporally order audio-tactile, visual-tactile, and audio-visual stimuli, and we administered different psychopathological scales to explore depressive, manic and psychotic symptoms. Results demonstrated that both subjects with schizophrenia and bipolar disorder are less precise in temporal order judgment independently of the sensory modalities involved. Interestingly, reduced precision in temporal processing of patients is positively associated with the presence and severity of positive symptoms. Our findings support the hypothesis that low-level sensory alterations in temporal structure may contribute to the emergence of clinical symptoms such as delusions, hallucinations, and disorganized behaviors.

Sensory processing is a fundamental aspect of human experience, and varies significantly between individuals, potentially affecting individual functioning, behaviour, and mental health. This study investigated the associations between sensory processing and psychopathology in a sample of the general population. Participants responded to a general psychiatric screening tool (DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure-Adult) and to the Adolescent/Adult Sensory Profile (AASP) questionnaire. The sample comprised 1108 young adults (77.25% females, mean age 22.6). Data were analysed using item response theory and Bayesian network analyses, revealing specific associations between sensory profiles and psychopathological dimensions. Specifically, we detected associations between the low registration sensory profile and the dimensions of psychosis, substance use, and mania. Sensation seeking was associated with mania. Sensory sensitivity was related to depression and mania, while sensation avoiding was inversely correlated with mania. These findings suggest that reduced external sensory awareness may be linked to a predisposition to psychosis, while a multifaceted sensory processing pattern may indicate vulnerability to mood disorders. Assessing sensory processing could yield crucial insights into individual susceptibilities to mental disorders and help identify targeted preventive and therapeutic strategies