INTRODUCTION:The corpus callosum (CC) is critical for inter-hemispheric integration, and its structural abnormalities have been implicated in the neurobiology of schizophrenia (SCZ). Ap-proximately 20-35% of SCZ patients exhibit resistance to antipsychotics and are classified as treat-ment-resistant schizophrenia (TRS). To date, no studies have specifically analyzed CC morphology in TRS compared to healthy controls (HCs) and treatment-responsive SCZ patients (non-TRS). METHODS:The study included 75 HCs and 97 SCZ patients (39 TRS and 58 non-TRS, including cannabis users and non-users). Participants underwent cross-sectional assessment using the Neuro-logical Evaluation Scale (NES), the Brief Assessment of Cognition in Schizophrenia, and the Posi-tive and Negative Syndrome Scale (PANSS). CC volume was measured via MRI and analyzed with a novel artificial intelligence program (MRI-AI) for single-subject assessment, with findings con-firmed through group-level voxel-based morphometry (VBM). RESULTS:TRS patients exhibited significantly higher total PANSS (p < 0.001) and NES (p < 0.001) scores and performed worse on working memory tasks compared to non-TRS patients. MRI-AI identified CC volume reduction in 55.88% of TRS patients (TRS CC: 3.02 mL vs. non-TRS with cannabis use: 3.69 mL; without cannabis use: 3.28 mL; p = 0.002). VBM confirmed significant CC volume reduction in TRS patients relative to HCs (p = 0.004). Cannabis use in non-TRS patients did not significantly affect CC volume or cognitive performance. CONCLUSIONS:TRS is associated with pronounced neurological, cognitive, and clinical dysfunctions. Aberrant CC volume may contribute to TRS pathogenesis and executive function deficits. MRI-AI provides a robust, single-subject approach for characterizing CC abnormalities in schizophrenia, of-fering potential for personalized clinical assessment.

Fetal alcohol spectrum disorders (FASDs) refer to a group of clinical conditions that occur in a person exposed to alcohol before birth. Neuroimaging shows abnormalities in brain structure, cortical development, white matter microstructure, and functional connectivity in individuals with FASD. These abnormalities modify the normal developmental trajectories resulting in deficits in cognition and behavior across several domains, including general intelligence, memory, language, attention, learning, visuospatial abilities, executive functioning, fine and gross motor skills, and social and adaptive functioning. This paper provides a review of the cognitive and behavioral outcomes of prenatal alcohol exposure. Updates data on FASD-specific neurobehavioral profile and its potential as a diagnostic tool will then be presented.

Background. The Addiction Services in Italy are highly heterogeneous as they are coordinated at a regional leved. Therefore, although they must be adapted to local realities, there is a need to standardise the approaches nationally by delining some shared standards. This project aimed to identify and share experts opinions concerning the operative management of the addicted patient to promote a homogeneous approach in Italy and favour appropriate and integrated handling in the phases of reception, care and reintegration of the addicted patient. Methods. A two-round, web-based, Nominal Group Technique (NGT) methodology involving nine Italian experts on addiction has been used. Results. The board agreed on the new goals to promote appropriate and differentiated management according to the stages of the discase and the patient's needs and to encourage carly action on addiction. Three main areas of intervention were identi fied: the optimisation of services (training, multidisciplinary and sharing of pathways); the management of pathways (medical and psychological assessment, patient stratification, differentiation of pathways by target population) aware- ness raising interventions (preventive strategies mainly addressed to the adolescent and high-risk youth population). Conclusions. The conclusions of this study, although resulting from the analysis of the Italian reality, are consistent with international guidelines; these can, therefore, in our opinion, stimulate further discussion on the correct manage ment of addicted patients albio at an international level.

Background: Opioid agonist therapy (OAT) is a crucial tool for leading drug-dependent patients to abstinence from sub-stances. Among the currently available treatment options, levomethadone appears to demonstrate excellent therapeutic potential in the long term. Yet, much can still be learned from levomethadone application in complex clinical cases. This article describes two clinical cases of patients with severe opioid dependence and psychiatric comorbidities who switched from racemic methadone to levomethadone. Methods. We present a description of the therapeutical history of these two patients and report the outcomes of various psychometric tests (i.e., HAM-D, HAM-A, BPRS, GAF, OOWS, SOWS, OC-VAS, SF-36, SDS, CGI) performed at the beginning of levomethadone therapy, four weeks later, and 12 weeks later. Results. Both patients have complex treatment histories characterised by successes and failures from previous therapies. At the time of initiation of levomethadone therapy, the clinical status of both patients was characterised by a high degree of psychopathological symptoms, distress, substance abuse, and poor levels of functioning. The re-evaluation of patients after 4 and 12 weeks of treatment with levomethadone showed a significant improvement in all psychometric tests admin-istered. Conclusions. The transition from racemic methadone to levomethadone appears to occur smoothly without any particular psychophysical relapses. The data from these two complex cases confirm the long-term therapeutical benefit of levomethadone.

Background: Fetal alcohol spectrum disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with fetal alcohol syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. Hypothesis/Objective: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF- α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

INTRODUCTION:Although women belonging to sexual and gender minorities are more at risk of gynecological and breast cancer, pieces of evidence have been provided that this population finds hardships getting involved in cancer screening programs. This happens because they tend to avoid clinical settings because of fear of discrimination, heteronormative assumptions, heterosexism, classism, and homophobic slurs by healthcare professionals. On the other hand, medical programs that allow healthcare providers to have experience with LGBTQ people are scarce and there are no specific tools to assess sexual cancer risks in this population.EVIDENCE ACQUISITION:Studies included were obtained searching MEDLINE with keywords "lesbians," "queer women," "trans women," "LGBTQ women," "cervical cancer screening," "pap test," "oncology screening," "mammogram" and "prevention." Furthermore, 1577 papers were found. After filtering for species, sex, language, and time range, 820 papers were left. The number of works included was 24 after title screening and 20 after abstract screening and full-text screening.EVIDENCE SYNTHESIS:More research will be needed to develop tools with an inclusive, non-judgmental, and open language capable of engaging the LGBTQ community. Cancer screening programs involve a large variety of healthcare providers including midwives.CONCLUSIONS:Midwives are multifaceted healthcare professionals whose large competence spectrum includes a variety of knowledge and skills going from antenatal care to education and research and they may efficiently provide cancer screenings. Midwives have been asking for more specialistic roles and calling for specific instruction to face the complex and ever-changing reality.

Patients with alcohol use disorder (AUD) do not manifest homogeneous clinical symptoms. Various studies described both cognitive impairments and psychiatric disorders among people with AUD. This disorder is one of the most frequent mental disorders in developed countries, due to excessive alcohol consumption. Alcohol is toxic as it increases the production of reactive oxygen species (ROS) and can cause dependence. This causes negative effects on brain development and cognitive functions that affect the individual's work, health, and social life. Current pharmacology treatment for alcohol addiction is based on direct action against the neurotransmitters involved in alcohol dependence. AUD patients without comorbid psychiatric disorders or severe cognitive deficits are defined as "pure alcoholics". To date, poor is known about effective treatments for this typology of AUD patients. Psychotherapy is largely used in resolving many psychiatric disorders, including substance use disorders. Motivational enhancement therapy (MET) and cognitive-behavioral therapy (CBT) are two psychotherapies used to achieve and maintain abstinence in patients affected by substance use disorders. This short review aims to describe two CBT and MET and to present the advantages and disadvantages of these two psychotherapies in the treatment of AUD.

•30% of patients with schizophrenia develop treatment-resistance (TRS).•Patients with early onset (EOTRS) may differ from adult-onset (AOTRS) and controls.•EOTRS did not differ from AOTRS in spectrometry, DTI and cognition.•Both EOTRS and AOTRS were impaired compared to healthy controls.•Neuroimaging and cognition measures may be impaired at the beginning of TRS.

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently, the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human and animal models have demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, PPAC may induce changes in behavior, cognitive functions, and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine, and immune alterations, reduced physical growth, placental disruptions, and metabolic alterations. Neurobiological studies on PPAC have also disclosed changes in brain function and structure by disrupting the growth factors pathways. In particular, as shown in animal model studies, PPAC alters brain nerve growth factor (NGF) and brainderived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women), during pregnancy, and lactation cannot be established, the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

Introduction COVID-19 is a complex syndrome caused by SARS-Cov-2. It mainly affects the respiratory system, but it could cause serious harm during pregnancy. An increase in stillbirths and preterm births has been highlighted by many authors. Although WHO and Royal College of Obstetrics and Gynecology don’t recommend elective caesarean section in women with confirmed infection, caesarean sections were performed by many clinicians. The aim of this short narrative review is to analyze pieces of evidence found in literature about the effectiveness of caesarean section in preventing stillbirths in COVID-19 positive mothers. Methods Studies included in the present review were retrieved searching MEDLINE (last access January 28th, 2021) with the following keywords: “pregnant woman with covid-19”, “Caesarean section”, “Abdominal Delivery” and “Stillbirth”. Studies regarding the mode of delivery in pregnant women infected with COVID-19 and neonatal outcomes were included. Studies about biology, anesthesiology and necroscopy were excluded. Filters for “human” and “English” were applied. Results Searching MEDLINE, 22 references were found. Other 103 articles were found searching bibliography. Two references were excluded after duplicate removal, 77 references after the title screen and 46 after the abstract screen. The final number of references included is 21. Most of the included studies were case reports. Most of them were from China. Discussion Many authors highlighted the increased risk of fetal death in pregnancies complicated with SARS-Cov-2 infection, but it is not clear if Caesarean Section could reduce this risk. Pieces of evidence show that most clinicians choose to perform an elective caesarean section mostly because of maternal conditions or the fear of possible vertical transmission. Data show that mode of delivery doesn’t affect the neonatal outcome and Caesarean Section doesn’t reduce the positivity rate among neonates. Different opinions were found about the possible infection of amniotic fluid, cord blood and placenta. The risk of vertical transmission is considered moderate or low by most of the authors. Positivity to SARS-Cov-2 isn’t an indication of elective caesarean section by itself, but this mode of delivery should be optioned in patients with other obstetrical indication or with severe conditions due to COVID. The recent increase in stillbirths could be related to the overall deterioration of maternal conditions.

Kratom or Mitragyna speciosa (Korth.) is an evergreen tree of the coffee family native to South-East Asia and Australasia. It is used by locals recreationally to induce stimulant and sedative effects and medically to soothe pain and opiate withdrawal. Its leaves are smoked, chewed, or infused, or ground to yield powders or extracts for use as liquids. It contains more than 40 alkaloids; among these, mitragynine and 7-hydroxymitragynine are endowed with variable mu, delta, and kappa opioid stimulating properties (with 7-hydroxymitragynine having a more balanced affinity), rhynchophylline, which is a non-competitive NMDA glutamate receptor antagonist, but is present in negligible quantities, and raubasine, which inhibits α1-adrenceptors preferentially over α2-adrenceptors, while the latter are bound by 7-hydroxymitragynine, while mitragynine counters 5-HT2A receptors. This complexity of neurochemical mechanisms may account for kratom's sedative-analgesic and stimulant effects. It is commonly held that kratom at low doses is stimulant and at higher doses sedative, but no cut-off has been possible to define. Long-term use of kratom may produce physical and psychological effects that are very similar to its withdrawal syndrome, that is, anxiety, irritability, mood, eating, and sleep disorders, other than physical symptoms resembling opiate withdrawal. Kratom's regulatory status varies across countries; in Italy, both mitragynine and the entire tree and its parts are included among regulated substances. We describe the case of a patient who developed anxiety and dysphoric mood and insomnia while using kratom, with these symptoms persisting after withdrawal. He did not respond to a variety of antidepressant combinations and tramadol for various months, and responded after 1 month of clomipramine. Well-being persisted after discontinuing tramadol.

Background Age-at-onset (AAO) affects psychiatric disorder outcome; substance (SUDs) or alcohol use disorders (AUDs) may influence their onset. Affective temperaments may affect early AAO and drug-use proneness. Objectives: To investigate whether SUD/AUD moderated temperamental effects in determining AAO of mental disorders. Methods: We included 300 post-acute inpatients with schizophrenia-spectrum and other psychotic (SSOPDs), major depressive (MDD) or bipolar (BD) disorders (168 men; mean age, 40.63 years +/- 11.82 men, 43.21 years +/- 12.69 women) with (N = 110) or without (N = 190) SUD/AUD. Patients completed cross-sectionally TEMPS-A. We carried moderation analysis with each regression-significant TEMPS temperament as independent variable, SUD/AUD presence/absence as dichotomous moderator, and AAO as dependent variable. Significance was set at p < 0.05. Results: AAO was lower in patients with SUD/AUD diagnosis than in patients without (23.74 +/- 10.09 vs. 27.73 +/- 10.35, respectively, p = 0.001, eta 2 = 0.034). SUD/AUD patients scored higher on the hyperthymic (10.22 +/- 4.08, p < 0.001, eta 2 = 0.069) and irritable (8.26 +/- 4.69, p < 0.01, eta 2 = 0.026) temperaments than nonSUD/AUD patients. Moderation analysis showed only direct effects of irritable (beta = -0.55, p < 0.005) and hyperthymic (beta = -0.95, p < 0.001) temperaments on AAO and no significant SUD/AUD and interaction effects. Limitations. Cross-sectional design. Conclusions: When irritable and hyperthymic traits prevail over other temperaments, AAO is earlier in SSOPDs, MDD, and BD. SUD/AUD presence/absence does not moderate the relationship between temperament and AAO.

© 2021 Vento, de Persis, De Filippis, Schifano, Napoletano, Corkery and Kotzalidis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/

BACKGROUND Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability. AIM The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice. RESULTS Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced. DISCUSSION The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life. CONCLUSIONS PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings.

Background: To overcome nonadherence in patients with psychosis switch to long-acting injectable (LAI) antipsychotic formulations is adopted. Most oral versus LAI comparisons showed similar antipsychotic responses. Psychoses often overlap with substance use disorder (SUD). Head-to-head LAI comparisons have hitherto focused only on non-comorbid populations. Objective: The objective of this study was to compare two LAIs, administered for 12 months, in initially hospitalized patients with psychosis comorbid with SUD in their clinical and quality of life (QoL) outcomes. Patients and methods: Inpatients were recruited during 2016 and switched randomly to 400 mg intramuscular aripiprazole monohydrate (AM) (N=50) or to 100 mg intramuscular paliperidone palmitate (PP) once-monthly (N=51); patients were discharged and followed up for 12 months. Patients were rated at baseline and after 1 year through the Clinical Global Impression scale - severity (CGIs), substance craving intensity was rated through a visual analog scale for substance craving, and QoL through the World Health Organization (WHOQOL-BREF) scale. We addressed confounders with backward stepwise logistic regression and three-way analysis of variance. Results: PP were older and had more cases of schizophrenia spectrum and less bipolar disorders than AM, but AM had a stronger craving for substances at baseline. Both LAIs were associated with significant improvements in all outcomes, with AM displaying stronger effect sizes than PP. The two groups did not differ on baseline WHOQOL-BREF scores in any domain, but at the 1-year follow-up, AM fared better on all domains. The two groups did not differ in final severity, but PP scored higher than AM in craving at the 1-year endpoint. Limitation: The CGIs is not a refined tool for severity and the substance craving may be subject to recall bias. Conclusion: 1-year AM and PP was followed by improved clinical status and QoL and reduced substance craving in a population with psychosis and SUD comorbidity. AM, compared to PP, improved craving and QoL at the 1-year follow-up.

Nalmefene is the first drug to be approved for reducing alcohol consumption in alcohol use disorder (AUD) patients at high drinking risk. In real-world settings, there is a high prevalence of concurrent psychiatric disorders in AUD subjects, with associated increased morbidity and worse prognosis. This study evaluated the use of nalmefene in AUD patients with stabilized psychiatric comorbidity previously treated unsuccessfully for alcohol dependence, and assessed craving reduction and safety.

1Centro Riferimento Alcologico Regione Lazio (CRARL), Dipartimento di Medicina Clinica, Sapienza Universita di Roma 2UOC delle Dipendenze e Patologie d’Abuso, ASL Rieti 3Casa di Cura Villa Von Siebenthal, Genzano di Roma 4Dipartimento di Neuroscienze, Mental Health, and Sensory Organs (NESMOS), Scuola di Medicina e Psicologia, Sapienza Universita di Roma 5Dipartimento di Radiologia, Fondazione Santa Lucia, Roma

Gambling disorder is a frequently underdiagnosed and disabling disorder with a prevalence greatly increased in recent decades. For various reasons, only a small part of pathological gamblers seek a support making difficult an early identification and delaying the administration of appropriate treatment. In DSM-5, the disorder has been reclassified from an "Impulse-Control Disorder not elsewhere classified" to one of the "Substance-Related and Addictive Disorders" with the intention of improve the diagnosis, to better targeting the treatment and to stimulating further research efforts directed to the disorder. This article reviews assessment techniques, psychosocial and neurobiological factors in the development of pathological gambling and treatment strategies.

Il disturbo da gioco d’azzardo è frequentemente sottodiagnosticato e disabilitante con una prevalenza enormemente aumentata negli ultimi anni. Per varie ragioni, solo una piccola parte dei giocatori patologici cerca un supporto, rendendo difficile una precoce individuazione e ritardando quindi la messa in atto di un trattamento appropriato. Nel DSM-5, il disordine è stato riclassificato da un disturbo del controllo degli impulsi non altrimenti specificato in un disturbo di dipendenza e collegato all’uso di sostanze, al fine di migliorare la diagnosi, indirizzare meglio al trattamento e stimolare ulteriori ricerche nel settore. Questo articolo passa in rassegna le tecniche di valutazione, i fattori psicosociali e neurobiologici nello sviluppo del disturbo da gioco d’azzardo e le strategie di trattamento.

Study Objective To assess acute efficacy and safety of 9.75mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation. Design Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation. Partial analysis of blood levels of the administered drug to correlate with clinical response. Setting Acute psychiatric care wards in a single university hospital. Patients A total of 201 acutely agitated patients (79 with schizophrenia and 122 with bipolar disorder I). Intervention Aripiprazole 9.75mg IM injection. Measurements and Main Results We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation/Calmness Evaluation Scale (ACES), and the Clinical Global Impressions scale (CGI). Assessments were conducted 30, 60, 90, and 120minutes and 24hours after the first injection for PANSS-EC and ACES, and 2, 4, 6, and 24hours for CGI. Response was at least a 40% decrease in PANSS-EC scores. We measured serum aripiprazole and dehydroaripiprazole levels in a subsample. IM aripiprazole significantly improved clinical measures. PANSS-EC improved progressively, starting after 30minutes. ACES improved after 90minutes and continued thereafter. Effects were sustained, with steadily decreasing CGI scores, until the 24th hour. Response rate was 83.6% after 2hours, but with repeat injections, it rose to over 90% with no differences among diagnostic groups. Although there were gender differences in the response to individual PANSS-EC items, the responses were similar overall. Neither clinical monitoring nor patient reporting revealed any side effects. No therapeutic window was identified, and levels did not correlate with any clinical measure. Conclusion Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia. Our results compare favorably to double-blind trials, probably due to higher expectations in trials involving no placebo arm. Absence of side effects could be related to the short observation time.