[This corrects the article DOI: 10.3389/fnagi.2025.1613566.].

Background: Subthreshold depression is a prevalent condition among the elderly and often remains untreated due to the limited efficacy and poor tolerability of standard antidepressants. Choline alfoscerate, a cholinergic precursor, is indicated for the treatment of a condition, pseudodepression in the elderly, that is currently clinically classified as subthreshold depression in older adults. Also, choline alfoscerate has shown neuroprotective and antidepressant-like effects. Objective: This pilot study aims to evaluate the efficacy and safety of choline alfoscerate in elderly patients with subthreshold depressive symptoms, using contemporary diagnostic criteria and standardized outcome measures. Methods: Seventeen patients aged ≥65 years were enrolled in an open-label, single-arm study and received 1200 mg/day of choline alfoscerate for 8 weeks. Clinical and neuropsychological assessments were performed at baseline, after 4 weeks, and at the study's end. Results: A statistically significant improvement was observed in depressive symptoms, as reflected by reductions in HAMD-17 (p < 0.001) and GDS-15 scores (p < 0.05), as well as in overall clinical severity assessed by the Clinical Global Impression-Severity scale (CGI-S, p < 0.05). No significant changes were noted in cognitive performance (MOCA) or apathy (AES-I). The treatment was well tolerated. Conclusions: Choline alfoscerate may represent a potentially safe and promising therapeutic option for subthreshold depression in older adults. However, given the exploratory nature of this open-label pilot study, these findings should be considered preliminary and hypothesis-generating and require confirmation in randomized controlled trials.

Background:Seasonal affective disorder (SAD) occurs in two main forms: winter-pattern SAD, associated with depressive symptoms during shorter, darker days; and summer-pattern SAD, linked to mood disturbances during longer, hotter days. SAD may develop into a chronic condition with recurring depressive episodes. Risk factors for SAD include geographic latitude, age, gender, genetic predisposition, and lifestyle. Sleep disturbances, such as insomnia, hypersomnia, and circadian rhythm disruptions, are common and can amplify emotional symptoms. Objective:This review explores the clinical features and management strategies for insomnia associated with SAD, focusing on the potential of benzodiazepines (BZDs), in particular lormetazepam. Results:Controversies surround current nonpharmacological and pharmacological strategies for managing sleep disorders in SAD. This review emphasizes the importance of using more effective treatments for insomnia associated with SAD, currently an unmet need. In particular, clinical evidence supports the potential benefits of intermittent hypnotic BZDs to treat insomnia. Among the BZDs, short-term or intermittent use of lormetazepam is an effective treatment option in the management of insomnia. Conclusion:Insomnia associated with SAD is an important symptom to monitor because it impacts the patient's quality of life. BZDs, including lormetazepam, are a standard short-treatment option for insomnia that could improve the sleep symptoms associated with SAD. Comparative clinical trials of the efficacy and safety of lormetazepam in this patient population are required to confirm this.

Major Depressive Disorder (MDD) is a leading cause of disability worldwide, with significant economic and social burden. However, studies assessing the overall socio-economic burden (direct, indirect and intangible costs) are scarce. This study aims to evaluate the socioeconomic burden imposed by MDD on patients referred to specialist medical centers in Italy. An observational, multicenter, longitudinal cost of illness study was conducted on patients aged 18–65 years with a diagnosis of MDD starting antidepressant therapy. Healthcare resources consumption and productivity loss were collected over 1-year follow-up to estimate per-patients MDD costs. Depressive symptoms were assessed with various clinical scales. Health Related Quality of Life (HRQoL) was assessed with the EQ-5D-5 L. MDD severity decreased during the observational period, as reported by all clinical scales, with a notable improvement in HRQoL scores. The main costs associated with MDD patients were indirect costs, €386.3 per patient-month at baseline, declining to €179.9 in the last 6 months. Direct medical costs peaked in the first 3 months (€155.9 per patient-month), compared to baseline (€55,09 per patient-month), then decreased. Costs were significantly associated with and increased with the number of depressive episodes (129.71;7.59-251.83) and the augmentation of Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR16) score (7.92;2.02–13.82). Our results suggest that MDD is a mental health issue with socio-economic burden that varies with symptoms severity. Indirect costs represent the main expense for MDD patients. These findings highlight the complexity and burden of MDD, emphasizing the importance of prioritizing depressive disorders in public health. • Major Depressive Disorder (MDD) is a leading cause of disabilities worldwide, with significant economic and social impacts. • During the study period, MDD severity decreased as reported by clinical scales and an improvement of HRQoL was observed. • Economic burden was driven by indirect costs. As regard, the direct medical costs, these increased during the first 3 months and then decreased overtime. • The number of depressive episodes and the increase in QIDS-SR16 score were factors that significantly influenced the disease costs. • MDD is associated with high socio-economic burden, emphasizing the importance of including MDD as a public-health priority.

Introduction: Current guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as the first-line treatment for chronic insomnia. Pharmacological recommendations by European guidelines for the treatment of insomnia disorder include positive GABAergic modulators such as short and medium acting benzodiazepines and "Z-drugs" (eszopiclone, zaleplon, zolpidem, zopiclone), dual orexin receptor antagonists (DORAs; daridorexant), melatonin receptor agonists (melatonin 2 mg prolonged release- PR). Given the chronic nature of insomnia, the presence of non-responders to some treatments it is often necessary switching between various therapeutic approaches and medications. However, clear guidance regarding safe and effective protocols for switching these medications currently lacks in Europe. Method: To address this gap, we used the RAND/UCLA Appropriateness to evaluate the appropriateness of procedures for switching medications prescribed for insomnia disorder. Following a systematic review of the literature conducted in accordance with the PRISMA guidelines, we then formulated some recommendations. Results: Twenty-one papers were selected. Conclusions: Discontinuation of Hypnotic Benzodiazepines and Z-drugs should be gradual, with dose reductions of 10-25 % each week. Multi-component CBT-I, daridorexant, eszopiclone, and melatonin 2 mg PR were shown to facilitate the gradual discontinuation of hypnotic benzodiazepines/Z-drugs within a cross-tapered program, which can be delayed when necessary. Finally, daridorexant and melatonin 2 mg PR do not require special switching or deprescribing protocols. Several sedative-hypnotic dosage reduction algorithms are proposed in this work for clinical use in real world settings.

OBJECTIVES:Understanding real-life management of mental health disorders is crucial for enabling effective social and healthcare interventions. This retrospective real-world study investigated differences in the management of young adults (<30 years) and adults (≥30 years) starting treatment with second-generation antipsychotics (SGAs) in Italy, Spain and Poland. METHODS:Patients' characteristics, treatment and safety profile and healthcare resource utilisation were analysed from general practitioners' and psychiatrists' electronic medical records and from pharmacy prescription records. The main analysis was stratified by age, but stratification by SGA molecule and a focus on subjects with schizophrenia were also provided. RESULTS:A total of 530,587 subjects started treatment with SGAs. Throughout data sources, young adults accounted for from 17.8% to 30.2%; women were more represented among adults, who also had higher proportions of comorbid conditions. Young adults showed higher frequencies of switches (from 4.7% to 11.0% for young adults and from 2.9% to 8.6% for adults) and add-ons (from 2.5% to 5.6% for young adults and from 1.7% to 5.0% for adults) and exhibited slightly better adherence/persistence with the initial SGA. CONCLUSIONS:Distinct management behaviours were identified depending on age. A nuanced approach integrating tailored therapeutic strategies is needed to optimise long-term outcomes for patients requiring treatment with SGAs.

While mild cognitive impairment (MCI) is a risk factor for dementia, it is currently impossible to predict which patients will go on to develop dementia or Alzheimer’s disease. Given the projected global increase in dementia due to an increasingly aging population, there is an urgent need to develop pharmacological therapies to reduce symptoms of MCI, and to help delay its possible progression to dementia. Choline alphoscerate is a cholinergic precursor naturally found in the brain that has been identified as an essential nutrient and is available as a prescription drug. While the efficacy of choline alphoscerate on cognitive function is well established in patients with MCI, Alzheimer’s disease, and cognitive impairment of vascular origin, emerging evidence suggests that it has neuroprotective effects against β-amyloid injury and may be useful as a preventive therapy against development of Alzheimer’s disease in patients with MCI. Recent data also show that choline alphoscerate may be effective against non-cognitive symptoms of MCI (e.g., depression, anxiety, irritability, aggression, and apathy). Here we review pharmacological and clinical evidence regarding choline alphoscerate in order to highlight its usefulness in patients with MCI. The potential role of choline alphoscerate in promoting healthy sleep architecture is also explored.

Background and Objectives: Subthreshold depression (StD) presents with depressive symptoms similar to major depressive disorder (MDD) but of lower intensity. Despite its milder form, StD is significantly prevalent in the older population, affecting up to 12.9%. StD is associated with adverse outcomes, such as an increased risk of MDD and mild cognitive impairment (MCI). Treating StD in older adults is challenging due to the limited efficacy and side effects of traditional antidepressants. As a result, clinicians often adopt a “watchful waiting” strategy, which increases the risk of StD progressing into MDD or MCI. Choline alphoscerate (α-GPC), a cholinergic drug, is indicated in the treatment of pseudodepression in the elderly, a condition that corresponds to the actual definition of StD. This review highlights the role of α-GPC in the treatment of StD in older subjects. Methods: A comprehensive review of preclinical and clinical studies was conducted, focusing on the efficacy of α-GPC in improving cognitive and behavioral functions in mental conditions and in modulating neurotransmitter systems involved in depression, such as dopamine and serotonin. Results: Evidence points to the therapeutic benefits of using α-GPC in StD as it acts on cholinergic dysfunction and cognitive impairment. Additionally, it may improve mood regulation and motivation, key factors in StD and in depressive disorders. These findings suggest that α-GPC may reduce the risk of progression from StD to MDD or MCI. Conclusions: α-GPC represents an effective and safe therapeutic option for the treatment of StD in the older population, improving clinical outcomes and enhancing the quality of life in this high-risk group.

Background Cognitive deficits are difficult to treat and negatively influence quality of life and functional outcomes of persons with schizophrenia. In the last twenty years, extensive literature demonstrated that persons with diabetes and insulin resistance (IR) also display cognitive deficits. Being type 2 diabetes (T2DM) and IR highly frequent in persons with schizophrenia, it is plausible to hypothesize that these conditions might play a role in determining dyscognition. If that is the case, acting on glucose dysmetabolism may eventually improve cognitive functioning. This review aims at: 1. evaluating the association between IR or T2DM and cognitive dysfunction in schizophrenia; 2. reviewing the evidence that pharmacological treatment of IR or T2DM may improve dyscognition in schizophrenia. Methods Two systematic searches were conducted in PubMed, PsycInfo, and Scopus. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Results From the first search we included 17 studies, 8 on the effects of T2DM and 9 on the effects of IR-other prediabetes measures on cognition in persons with schizophrenia. From the second search we included 12 studies investigating the effect on cognition of glucose (4 studies), insulin (2 studies), metformin (2 studies), PPAR-γ agonists (2 studies), GLP-1 agonist (1 study), bromocriptine (1 study). Conclusions T2DM was associated with worse cognitive function in persons with schizophrenia, while IR was less strongly associated with cognitive dysfunction. Evidence regarding the efficacy of glucose-lowering medications on cognition in schizophrenia is inconclusive, yet methodological issues likely contribute to explain conflicting results.

Important sex-related differences have been observed in the onset, prevalence, and clinical phenotype of depression, based on several epidemiological studies. Social, behavioural, and educational factors have a great role in underlying this bias; however, also several biological factors are extensively involved. Indeed, sexually dimorphic biological systems might represent the underlying ground for these disparities, including cerebral structures and neural correlates, reproductive hormones, stress response pathways, the immune system and inflammatory reaction, metabolism, and fat distribution. Furthermore, in this perspective, it is also important to consider and focus the attention on specific ages and life stages of individuals: indeed, women experience during their life specific periods of reproductive transitional phases, which are not found in men, that represent windows of particular psychological vulnerability. In addition to these, other biologically related risk factors, including the occurrence of sleep disturbances and the exposure to childhood trauma, which are found to differentially affect men and women, are also putative underlying mechanisms of the clinical bias of depression. Overall, by taking into account major differences which characterize men and women it might be possible to improve the diagnostic process, as well as treat more efficiently depressed individuals, based on a more personalized medicine and research.

BACKGROUND:Work functioning impairment is a key diagnostic and prognostic criterion in patients with psychiatric disorders and work inclusion is a major goal of their therapeutic pathway. Since 2009, the Regional Innovative Program (PIR) TR106, promoted by ASST Fatebenefratelli-Sacco of Milan in collaboration with other Departments of Mental Health and Addictions (DSMDs) in the town of Milan (Italy), has been developing the employment inclusion of psychiatric patients. AIMS:The objective of this study is to evaluate its outcomes over 8 years of observation. METHOD:We reported the results of a retrospective epidemiologic analysis on 2,142 interventions on 1,066 patients recruited, investigating PIR TR106 outcomes per year focusing on different subgroups. We focused on 'positive', 'negative', and 'other' outcomes. RESULTS:We preliminary calculated job maintenance interventions (5%, 107) and excluded these interventions from the overall. We observed 29 job firing (1.4%) and 15 job resignations (0.7%) as negative results (equal to 2.2% of the total) and 388 job hiring (16.6%), 647 traineeships (31.8%), and 413 work formation (20.3%) as positive outcomes (equal to 68.75%). In other outcomes (29.1%) we found 305 dismissals from PIR TR 106 (15%) and transitory outcomes (14.1%).Job hiring increased from 8.9% in 2012 to 23.8 % in 2019 (p < .001), while the dismissals diminished from 26.7% to 13.3% (p < .001). The effectiveness of traineeships in terms of job hiring increased in the ratio of annual job hiring versus job traineeship (+48.8%). The majority of hired patients (15.1%) were affected by a psychotic disorder. A significant hiring increase was observed in patients with psychotic disorders and personality disorders (p < .005). CONCLUSIONS:PIR-TR106 represents a territorial employment inclusion program with progressively increasing effectiveness and specificity, as suggested by changes in outcomes during the 8-year observation. The adaptive capacity and sustainability of the intervention are worth further investigation.

This randomized-controlled study evaluates the effectiveness of a newly developed social cognition rehabilitation intervention, the modified Social Cognition Individualized Activity Lab (mSoCIAL), in improving social cognition and clinical and functional outcomes of persons with schizophrenia recruited in two Italian sites: University of Campania “Luigi Vanvitelli” in Naples and ASST Fatebenefratelli-Sacco in Milan. mSoCIAL consists of a social cognitive training module focusing on different domains of social cognition and of a narrative enhancement module. We assessed changes in social cognition, clinical characteristics and functional variables in patients with schizophrenia who participated in 10 weekly sessions of mSoCIAL or received treatment as usual (TAU). A paired-sample t test and a repeated-measures MANOVA were used to investigate respectively within and between-group differences. Twenty people with schizophrenia were blindly assigned to mSoCIAL and 20 to TAU. After 10 weeks, mSoCIAL significantly improved disorganization, emotion recognition, functional capacity and real-life functioning. As compared to TAU, the mSoCIAL group showed a significant improvement in minimal and enriched social inference domain of theory of mind, and in key domains of real-life functioning (interpersonal relationships, everyday life skills, and work skills). mSoCIAL improved social cognition and real-life functioning of people with schizophrenia. These results highlight the importance of social cognition deficit treatment in schizophrenia and the necessity for these interventions to be multifaced and personalized. Such an approach ensures that improvements in social cognition translate into enhanced functional outcomes. Trial registration NCT05130853, registered on 24 November 2021.

Almost a third of bariatric surgery patients present suboptimal weight loss or important weight regain in the first five postoperative years. While the reasons underlying this are not fully understood, it is known that pathological eating styles (such as emotional or binge eating) can thwart efforts to maintain weight loss. However, detailed characterization and understanding of these eating styles have yet to be achieved. In particular, research on gender differences in pathological eating styles and psychiatric symptoms before bariatric surgery is lacking. To characterize gender differences in eating styles and their association with clinical symptoms, we prospectively enrolled 110 bariatric surgery candidates, collecting eating styles and clinical scores. Women displayed a higher frequency of emotional eating as compared to men (x2 = 9.07, p = 0.003), while men showed a higher frequency of quantitative eating behavioral style (x2 = 4.58, p = 0.044). Binge eating style was associated with higher Difficulties in Emotion Regulation Scale (DERS), Hamilton Depression Scale (HAM-D), and Hamilton Anxiety Scale (HAM-A) scores (p < 0.05). Emotional eating style was associated with higher HAM-D and HAM-A scores (p < 0.05). The present findings highlight the importance of understanding the role of gender differences in emotion regulation processes involved in the development and maintenance of pathological eating styles in bariatric surgery candidates. This paves the way to gender- and symptoms-specific interventions on eating behaviors to improve surgery long-term outcomes.

Study question Is there an association between mitochondrial DNA (mtDNA) content and Ongoing Pregnancy Rate (OPR) in D5 or D6 euploid blastocyst? Summary answer Day6 OPR is decreased in high mtDNA content blastocyst. Day5 and Day6 mtDNA levels are independent of maternal age or standard morphology. What is known already Preimplantation development is an energy-demanding process and mitochondrial ATP production is crucial for cellular activity in fast replicating cells. Mitochondrial content in preimplantation embryo has been proposed as a marker of embryo potential in term of viability and implantation success though the dynamics and distribution of mitochondria in human embryo is still debated. In recent years, it has been suggested that low mtDNA levels were associated with euploid chromosomal complement and higher implantation rate while other studies failed to find a correlation between mtDNA content and reproductive outcome. Study design, size, duration This study is a retrospective cohort analysis from 2020 to 2022 including 343 Day5 and 187 D6 single euploid blastocyst transfer. Primary endpoint was OPR beyond pregnancy week 16. Day5 and Day6 frozen-thawed transfer were divided based on blastocyst mtDNA content in four groups: Day5-high, Day5-low, D6-high, D6-low. Secondary endpoints were relationship between mtDNA content, maternal age and standard morphology in all obtained blastocysts. Statistical differences were compared by Chi-Square test. Participants/materials, setting, methods 771 couples performed IVF cycles with next-generation sequencing (NGS)-preimplantation genetic testing of aneuploidy (PGT-A) (age 19-47yrs; Mean age 37.8yrs). Following culture in sequential media 700 euploid blastocyst were obtained and mitochondrial and chromosomal DNA copy number variation were examined simultaneously with next generation sequencing (NGS) methodology. mtDNA copy numbers was based on the observed ratios of sequence coverages between mtDNA and nuclear DNA. Main results and the role of chance In our clinical setting OPR is similar in Day5 vs. Day6 transfers (55% vs. 49% n.s.). However when mtDNA content is considered D6-low OPR is comparable to D5-high or low (57.3%; 53.3%; 57,3% respectively n.s.) while D6-high transfers yield significantly decreased OPR (31,2% p < 0.05). When stratified by age only Advanced Maternal Age (AMA) patients ( > = 38yrs) showed this decrease at a significant level (Day6 high OPR 20% p < 0,05).This result in transferred blastocyst is obtained despite high:low ratio of all biopsied blastocyst is constant in Day5 (1:1) (47%-53%) and markedly decreased in Day6 (1:4) (25%-75%) either overall or in younger (n.s.) and AMA patients (n.s.). Moreover when standard morphology distribution is evaluated according to Gardner classification criteria top, fair and poor quality blastocysts display the same 1:1 high:low blastocysts mtDNA ratio in Day5 and 1:4 in Day 6 overall and in younger and AMA patients. Hence, the mtDNA blastocyst content is independent of patients’ age and blastocyst quality. The origin of Day6 OPR decrease could therefore depend on the number of Day6-high blastocyst transferred in AMA patients and ultimately in the number of blastocyst available to transfer for each patient. Limitations, reasons for caution Due to the small numbers of Day6-high mtDNA blastocyst, a larger sample size is required to confirm these preliminary findings. Moreover, the retrospective nature of the study may introduce some bias mainly in patients’ characteristics and the strategy of embryo selected for transfer. Wider implications of the findings While Day5-high blastocyst yield higher OPR the persistence of higher mtDNA levels in Day6 blastocyst may hamper their implantation potential. Our findings may help to select the embryo to transfer to maximize transfer success. D6 blastocysts with low mtDNA content should be preferred whenever a choice is possible. Trial registration number Not Applicable

Abstract Study question Is there an association between mitochondrial DNA (mtDNA) content and Ongoing Pregnancy Rate (OPR) in D5 or D6 euploid blastocyst? Summary answer Day6 OPR is decreased in high mtDNA content blastocyst. Day5 and Day6 mtDNA levels are independent of maternal age or standard morphology. What is known already Preimplantation development is an energy-demanding process and mitochondrial ATP production is crucial for cellular activity in fast replicating cells. Mitochondrial content in preimplantation embryo has been proposed as a marker of embryo potential in term of viability and implantation success though the dynamics and distribution of mitochondria in human embryo is still debated. In recent years, it has been suggested that low mtDNA levels were associated with euploid chromosomal complement and higher implantation rate while other studies failed to find a correlation between mtDNA content and reproductive outcome. Study design, size, duration This study is a retrospective cohort analysis from 2020 to 2022 including 343 Day5 and 187 D6 single euploid blastocyst transfer. Primary endpoint was OPR beyond pregnancy week 16. Day5 and Day6 frozen-thawed transfer were divided based on blastocyst mtDNA content in four groups: Day5-high, Day5-low, D6-high, D6-low. Secondary endpoints were relationship between mtDNA content, maternal age and standard morphology in all obtained blastocysts. Statistical differences were compared by Chi-Square test. Participants/materials, setting, methods 771 couples performed IVF cycles with next-generation sequencing (NGS)-preimplantation genetic testing of aneuploidy (PGT-A) (age 19-47yrs; Mean age 37.8yrs). Following culture in sequential media 700 euploid blastocyst were obtained and mitochondrial and chromosomal DNA copy number variation were examined simultaneously with next generation sequencing (NGS) methodology. mtDNA copy numbers was based on the observed ratios of sequence coverages between mtDNA and nuclear DNA. Main results and the role of chance In our clinical setting OPR is similar in Day5 vs. Day6 transfers (55% vs. 49% n.s.). However when mtDNA content is considered D6-low OPR is comparable to D5-high or low (57.3%; 53.3%; 57,3% respectively n.s.) while D6-high transfers yield significantly decreased OPR (31,2% p < 0.05). When stratified by age only Advanced Maternal Age (AMA) patients ( > = 38yrs) showed this decrease at a significant level (Day6 high OPR 20% p < 0,05).This result in transferred blastocyst is obtained despite high:low ratio of all biopsied blastocyst is constant in Day5 (1:1) (47%-53%) and markedly decreased in Day6 (1:4) (25%-75%) either overall or in younger (n.s.) and AMA patients (n.s.). Moreover when standard morphology distribution is evaluated according to Gardner classification criteria top, fair and poor quality blastocysts display the same 1:1 high:low blastocysts mtDNA ratio in Day5 and 1:4 in Day 6 overall and in younger and AMA patients. Hence, the mtDNA blastocyst content is independent of patients’ age and blastocyst quality. The origin of Day6 OPR decrease could therefore depend on the number of Day6-high blastocyst transferred in AMA patients and ultimately in the number of blastocyst available to transfer for each patient. Limitations, reasons for caution Due to the small numbers of Day6-high mtDNA blastocyst, a larger sample size is required to confirm these preliminary findings. Moreover, the retrospective nature of the study may introduce some bias mainly in patients’ characteristics and the strategy of embryo selected for transfer. Wider implications of the findings While Day5-high blastocyst yield higher OPR the persistence of higher mtDNA levels in Day6 blastocyst may hamper their implantation potential. Our findings may help to select the embryo to transfer to maximize transfer success. D6 blastocysts with low mtDNA content should be preferred whenever a choice is possible. Trial registration number Not Applicable

Definition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient's characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia.

Introduction Schizophrenia is a severe and disabling psychiatric disorder probably based on complex pathophysiological mechanisms of reduced inhibition, impaired connectivity and reduced plasticity in neural networks. Beside clinical symptomatology, a core feature of schizophrenia is a global cognitive and social disability, which strongly affect patients’ lives and their quality of life. The cognitive impairment involves memory, attention, executive functions, language, facial emotion recognition and theory of mind abilities. Cognitive remediation strategies, in addition to pharmacological and psychological treatments, has received increasing attention in recent years, as well as the use of non-invasive brain stimulation techniques such as TMS, which have demonstrated promising therapeutic potential. Objectives The present study aimed to evaluate the efficacy of TMS to induce improvements in cognitive functioning in schizophrenia. It also aimed to test the effects of a combined approach to rehabilitation, using both TMS and cognitive remediation strategies. Methods 16 patients were submitted to effective or sham iTBS over the left dorsolateral prefrontal cortex during 3 consecutive weeks. In half of patients the neuromodulation was combined with daily cognitive remediation training (Cogpack software), administered immediately after the application of TMS. Clinical, cognitive and social functioning were tested at baseline and at different timepoints after conclusion of the rehabilitation protocol (immediately after the 3 weeks protocol, and after 1, 3 and 6 months). Results The preliminary results indicate that the proposed TMS protocol induced significant improvements in global cognition. In addition, patients submitted to TMS, even without combined cognitive rehabilitation training, showed major benefits after 1 month from brain stimulation. Conclusions These preliminary data suggest that TMS can induce long-lasting plastic changes in the prefrontal cortex of schizophrenic patients, improving their cognitive perfomances. TMS could be therefore considered in the treatment of schizophrenia to reduce cognitive impairments. Disclosure of Interest None Declared

Subjects affected by schizophrenia present significant deficits in various aspects of social cognition, such as emotion processing, social perception and theory of mind (ToM). These deficits have a greater impact than symptoms on occupational and social functioning. Therefore, social cognition represents an important therapeutic target in people with schizophrenia. Recent meta-analyses showed that social cognition training (SCT) is effective in improving social cognition in subjects with schizophrenia; however, real-life functioning is not always ameliorated. Integration of SCT with an intervention targeting metacognitive abilities might improve the integration of social cognitive skills to daily life functioning. Our research group has implemented a new individualized rehabilitation program: the Social Cognition Individualized Activities Lab, SoCIAL, which integrates SCT with a module for narrative enhancement, an intervention targeting metacognitive abilities. The present multi-center randomized controlled study will compare the efficacy of SoCIAL and treatment as usual (TAU) in subjects diagnosed with a schizophrenia-spectrum disorder. The primary outcome will be the improvement of social cognition and real-life functioning; while the secondary outcome will be the improvement of symptoms, functional capacity and neurocognition. The results of this study will add empirical evidence to the benefits and feasibility of SCT and narrative enhancement in people with schizophrenia-spectrum disorders.

Background: Work functioning impairment is a key diagnostic and transnosographic criterion for psychiatric disorders in both DSM-5 and ICD-11. Occupational inclusion is a fundamental aspect of the care path for patients attending the territorial services provided by the Italian Mental Health and Addiction Departments (DSMDs). Since 2009, the Regional Innovative Programme (PIR) TR106, promoted by the Fatebenefratelli-Sacco hospital of Milan, Italy, in collaboration with six other metropolitan DSMDs, was created to promote integration for people suffering from mental health problems in the city of Milan. Method: Here we present the results of a retrospective epidemiologic analysis on 2,142 interventions on 1,066 patients, conducted between 2012 and 2019. Results: Most of the interventions were conducted with people with psychotic disorders (39%), followed by personality disorders (25.2%) and affective disorders (22.2%). The age range of 25 to 54 years represented 91.5% of the whole sample, mainly in the 35 to 44 years range (36.4%). Significant age group-related changes in interventions were observed in the observation period, with a reduction in the interventions provided to subjects of the 35 to 44 age group, and an increase in the 25 to 34 age group. Conclusions: PIR TR106 provided the most accurate assessment and data collection so far for the city of Milan. Our data characterised psychiatric groups in order to develop specific treatment plans and work inclusion interventions.