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The clinical presentation of schizophrenia encompasses symptoms divided into three dimensions: positive, negative, and cognitive. Negative symptoms (NS), in particular, have a major impact on the quality of life of the affected subject, and, differing from positive symptoms, are often associated with a limited response to pharmacotherapy. To date, studies specifically investigating NS in schizophrenia are scant; therefore, proper selection of therapy for NS remains a major unmet medical need. Given the heterogeneity of the clinical presentation of schizophrenia, the treatment of NS, as well as therapy for other associated symptoms, should be largely individualized according to a patient's specific characteristics. In this paper, we review current knowledge on NS and construct a clinical algorithm for the treatment of schizophrenic conditions with pronounced NS. Overall, data from the literature suggest that second-generation antipsychotics, such as cariprazine and amisulpride, should be preferred over first-generation antipsychotics (FGAs), as they are associated with better functional outcomes and lower cognitive impairment. The combination of antipsychotics and antidepressants may also improve NS while addressing some affective disorders associated with schizophrenia; however, no clear information is available on the effects of this combination on primary NS or on the mechanism of action of the combination. In the proposed clinical algorithm, we suggest that cariprazine should be used as first-line treatment for patients with predominant NS, and that amisulpride should be considered as an alternative in cases of cariprazine failure. Further treatment lines may include the use of olanzapine and quetiapine, and add-on therapy with antidepressants.

Graphical AbstractDiagram illustrating the effects of choline alphoscerate on the brain. It highlights benefits like enhancement of cognitive functions and synaptic signaling. Key aspects include epigenetic regulation, acetylcholine neurotransmission, and membrane lipid composition. The diagram shows interactions with enzymes and neurotransmitters in the synaptic cleft, and includes references to Alzheimer's disease and healthy aging. Various compounds and neurotransmitters like acetylcholine, SAM, and Co-A are labeled, with processes such as the modulation of gene expression and enhancement of cholinergic tone noted. The image includes a legend for anti-cholinesterases.

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.

Depression and obesity represent two of the most common complications during pregnancy and are associated with severe health risks for both the mother and the child. Although several studies have analysed the individual effects of depression or obesity on the mothers and their children, the effects associated with the co-occurrence of both disorders have so far been poorly investigated. The relationship between depression and obesity is very complex and it is still unclear whether maternal depression leads to obesity or vice versa. It is well known that the intrauterine environment plays an important role in mediating the effects of both depression and obesity in the mother on the fetal programming, increasing the child’s risk to develop negative outcomes.

Antidepressant Drugs (ADs) are among the most commonly prescribed medications in developed countries. The available epidemiological evidence suggests an association between AD use and higher risk of developing type 2 diabetes mellitus. However, some methodological issues make the interpretation of these results difficult. Moreover, very recent studies provided conflicting results. Given the high prevalence of both diabetes and AD use in many countries, clarifying whether this association is causal is of extreme relevance for the public health. The aim of the present study is to provide an up-to-date evaluation of the evidence in support of a causal role of ADs in inducing diabetes. A systematic literature search was conducted to identify relevant studies in MEDLINE (PubMed), PsycINFO, and International Pharmaceutical Abstracts (IPA) through 31st December 2016. Only studies assessing the incidence of new-onset diabetes in subjects treated with ADs were included. Results were pooled using a random-effects meta-analysis. Moreover, we extensively reviewed the role of the different sources of bias that have been proposed to explain the association between AD and diabetes. Twenty studies met the inclusion criteria. In the meta-analysis, the association between AD use and diabetes was still evident after the inclusion of the recent negative studies [pooled relative risk = 1.27, 95% confidence interval (CI), 1.19-1.35; p<0.001]. None of the biases proposed by previous authors seemed able to fully explain the observed association. This updated meta-analysis confirms the association between AD use and incident diabetes. It still remains a matter of debate whether single ADs exert a different effect on the risk of diabetes. Given the possible heterogeneity, we suggest that a classification of ADs according to their pharmacological profiles could be useful in better elucidating the nature of this association.

Autism Spectrum Disorder (ASD) is often unrecognized, especially in mild forms and in women. Studies evaluating features associated with missed/misdiagnosis in men and women with ASD are warranted. 61 subjects (22 females, 39 males, age 28.5 ± 10.8 years) with ASD with no language/intellectual deficit were enrolled in the service for the treatment of psychiatric comorbidities in adults with ASD of the ASST Fatebenefratelli-Sacco in Milan (Italy). A detailed clinical history was gathered, and two self-report questionnaires (Autism Spectrum Quotient-AQ and Adult Autism Subthreshold Spectrum-AdAS Spectrum) were administered. 75.4% received their ASD diagnosis average eight years later than the first evaluation by mental health services. Compared to males, females showed a significantly greater delay in referral to mental health services and a significantly higher age at diagnosis of ASD. Among men, diagnostic delay inversely correlated with scores on the AdAS Spectrum total, Verbal communication, Empathy and Inflexibility and adherence to routine domains. Among women, diagnostic delay positively correlated with the Attention to detail score while the age at diagnosis of ASD positively correlated with the AdAS Spectrum Verbal communication and Restricted interests and rumination domain scores. Females were less likely to be correctly diagnosed and more likely to be misdiagnosed at first evaluation than men. Females reported significantly higher scores than men in the Hyper/Hyporeactivity to sensory input domain only among subjects who were misdiagnosed. Our findings provide gender-specific information about ASD patients seeking help for comorbid conditions and might be a primary ground for future research.

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.

Patients with severe mental illness (SMI), such as schizophrenia or bipolar disorders, are more frequently affected by metabolic syndrome and cardiovascular (CV) diseases than the general population, with a significant reduction in life expectancy. Beyond metabolic syndrome, quantifying the risk of CV morbidity in the long-term may help clinicians to put in place preventive strategies. In this study, we assessed 10-year CV risk in patients with SMI and healthy individuals using an algorithm validated on the Italian general population. Patients aged 35-69 years diagnosed with SMI were consecutively recruited from psychiatric acute care units. Single CV risk factors were assessed, and 10-year CV risk calculated by means of the CUORE Project 10-year CV risk algorithm, based on the combination of the following risk factors: age, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking habit, and hypertensive treatment. Patients' data were compared with those from the general population. The 10-year CV risk was log-transformed, and multivariable linear regression was used to estimate mean ratios, adjusting for age, and education. Three hundred patients and 3,052 controls were included in the analysis. Among men, the 10-year CV risk score was very similar between patients with SMI and the general population (mean ratio [MR]: 1.02; 95%CI 0.77-1.37), whereas a 39% increase in 10-year CV risk was observed in women with SMI compared to the general population (MR: 1.39; 95%CI 1.16-1.66). In our study, women with SMI were consistently more at risk than the general population counterpart, even at younger age.

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.

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.