Enhanced peripheral levels of BDNF and proBDNF: elucidating neurotrophin dynamics in cocaine use disorder.

Brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF, are known to significantly contribute to brain homeostasis, neuroplasticity, and neuronal remodeling. Although these neurotrophins are thought to have opposing roles, both play a critical part in shaping long-lasting behavioral changes following substance use. In this context, our study sought to explore the implications of these neurotrophins in the pathophysiology of cocaine use disorder (CUD). We conducted a case-control study, which included 28 individuals seeking treatment for CUD and 38 matched healthy participants. We measured peripheral neurotrophin concentrations via an enzyme-linked immunosorbent assay. Additionally, all participants were screened for cocaine-associated pathways (e.g., cocaine intake, craving intensity), along with associated psychopathological data. Our findings highlighted an increased concentration of BDNF and proBDNF in CUD individuals when compared to healthy controls (BDNF: 18092.80 ± 6844.62 vs. 11334.42 ± 5061.85 pg/ml, p < 0.001; proBDNF: 87.03 ± 33.23 vs. 55.70 ± 23.26 ng/ml, p < 0.001). We further corroborated the relationship between neurotrophin levels and CUD using a linear regression model. Nevertheless, there was no significant difference in the proBDNF to BDNF ratio between the two groups. Interestingly, our study also demonstrated the influence of factors like usage of psychotropic medications, history of psychiatric hospitalizations, and psychiatric diagnoses on neurotrophin dynamics. In conclusion, our study underscores the significance of neurotrophin fluctuations in CUD. The observed increase in BDNF and proBDNF levels could play a pivotal role in driving craving and relapse risk. Thus, a nuanced understanding of these neurobiological underpinnings in CUD might contribute to the development of more targeted and effective therapeutic strategies.

Connected minds in disconnected bodies: Exploring the role of interoceptive sensibility and alexithymia in problematic use of the internet.

INTRODUCTION: The ever-increasing prominence of the internet and digital technology in our society requires a deeper examination of how these developments alter perception of our bodies and emotions. One such consequence is the emergence of Problematic Use of the Internet (PUI) - an array of compulsive or addictive behaviors mediated by the web that detrimentally affect an individual's functioning. This suggests that some people may be shifting their consciousness from the physical realm to the digital world. The objective of this study was to investigate how shortcomings in interoception (the sensibility to bodily signals) and alexithymia (an inability to identify and express emotions) might contribute to PUI. METHODS: The Internet Addiction Test (IAT), the Toronto Alexithymia Scale (TAS-20), and the Multidimensional Assessment of Interoceptive Awareness (MAIA) were used to assess a sample of 1076 adolescents and young adults aged between 16 and 26 years via an online survey. Data analysis was based on t-test, correlations and multivariate regression. RESULTS: 26.8% (n = 288) of participants met the criteria for moderate PUI. Individuals with PUI displayed higher levels of alexithymia (p < 0.001) and diminished abilities in certain aspects of interoceptive sensibility, including placing trust in their own bodily signals (p = 0.006), not responding excessively to uncomfortable sensations with worry (p < 0.001), and not denying them (p = 0.006). Multivariate modelling revealed associations between PUI and the following factors: having a boyfriend/girlfriend (aOR = 5.70), substance use (aOR = 1.78), difficulty in identifying feelings (aOR = 1.09), externally oriented thinking (aOR = 1.05), low disposition in perceiving body sensations (aOR = 0.25), tendency to become distracted (aOR = 0.82) or excessively worried (aOR = 0.11) in the face of pain. Furthermore, the analysis indicated how these aspects of body perception may be interrelated, either enhancing or reducing the risk of PUI when examined individually, collectively, or in combination. CONCLUSIONS: This study underlines the potential connection between difficulties in the mind-body interaction and the development of PUI. It suggests a bidirectional relationship between excessive digital device use and distorted bodily interoceptive processes in PUI, reinforcing the notion that individuals struggling with emotion identification and expression may be more prone to excessive internet usage. To further comprehend the relevance of these constructs in PUI, it is necessary to conduct more targeted investigations and longitudinal studies.

Linking Striatal Dopaminergic Asymmetry with Personality Traits: Insights from Gambling Disorder.

The role of dopamine in the pathophysiology of gambling disorder (GD) remains incompletely understood, with disparate research findings concerning presynaptic and postsynaptic structures and dopaminergic synthesis. The aim of this study was to investigate potential correlations between striatal dopamine transporter (DAT) lateralization and asymmetry index, as assessed by 123I-FP-CIT SPECT, and temperamental traits, as measured by Cloninger's Temperament and Character Inventory (TCI), in GD subjects. Significant associations were found between DAT binding asymmetries in the caudate and putamen and the temperamental dimensions of harm avoidance and novelty seeking. Specifically, high novelty seeking scores correlated with increased DAT binding in the left caudate relative to the right, whereas higher harm avoidance scores corresponded to increased DAT binding in the right putamen relative to the left. These observations potentially imply that the asymmetry in DAT expression in the basal ganglia could be an outcome of hemispheric asymmetry in emotional processing and behavioural guidance. In summary, our study provides evidence supporting the relationship between DAT asymmetries, temperamental dimensions and GD. Future investigations could be directed towards examining postsynaptic receptors to gain a more comprehensive understanding of dopamine's influence within the basal ganglia circuit in disordered gambling. If confirmed in larger cohorts, these findings could have substantial implications for the tailoring of individualized neuromodulation therapies in the treatment of behavioural addictions.

Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia.

PURPOSE/BACKGROUND: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. METHODS/PROCEDURES: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. FINDINGS/RESULTS: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. IMPLICATIONS/CONCLUSIONS: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

Treating bipolar depression with esketamine: Safety and effectiveness data from a naturalistic multicentric study on esketamine in bipolar versus unipolar treatment-resistant depression.

BACKGROUND: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD. OBJECTIVES: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch. METHODS: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up. RESULTS: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch. CONCLUSIONS: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment.

Investigating the Effectiveness and Tolerability of Intranasal Esketamine Among Older Adults With Treatment-Resistant Depression (TRD): A Post-hoc Analysis from the REAL-ESK Study Group.

INTRODUCTION: Treatment-resistant depression (TRD) is a serious and debilitating psychiatric disorder that frequently affects older patients. Esketamine nasal spray (ESK-NS) has recently been approved as a treatment for TRD, with multiple studies establishing its efficacy and tolerability. However, the real-world effectiveness, tolerability, and safety of this treatment in older adults is still unclear. OBJECTIVES: To evaluate the efficacy and tolerability of ESK-NS in older subjects with TRD. METHODS: This is a post-hoc analysis of the REAL-ESK study, a multicenter, retrospective, observational study. Participants here selected were 65 years or older at baseline. The Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) were used to assess depressive and anxiety symptoms, respectively. Data were collected at three-time points: baseline, 1 month after the start of treatment (T1), and 3 months after treatment (T2). RESULTS: The sample included older adults with TRD (n = 30). MADRS and HAM-A values decreased significantly at T1 (T0 versus T1: pholm <0.001, Cohen's d = 0.840) and T2 follow-ups (T0 versus T2: pholm <0.001, Cohen's d = 1.419). At T2, 53.3% of subjects were responders (MADRS score reduced ≥50%), while 33.33% were in remission (MADRS<10). ESK-NS-related adverse effects were in order of frequency dizziness (50%), followed by dissociation (33.3%), sedation (30%), and hypertension (13.33%). Six out of 30 participants (20%) discontinued treatment. CONCLUSIONS: Our findings provide preliminary evidence of ESK-NS effectiveness in older adults with TRD, a highly debilitating depressive presentation. Furthermore, we observe high levels of treatment-emergent adverse events, which, in the majority of instances, did not require treatment suspension.

Evaluating Craving in Alcohol Use Disorder: Psychometric Characteristics of the Craving Typology Questionnaire-15 (CTQ-15).

AIMS: The Craving Typology Questionnaire (CTQ) is a psychometric instrument used to assess alcohol craving in normal controls and subjects with alcohol use disorder (AUD). It allows a dimensional self-rating assessment of craving according to a three-pathway psychobiological model of craving distinguishing craving into a reward, relief and obsessive component. The aim of the present study is to evaluate psychometric properties of the CTQ-15, a revised version of CTQ with 15 items. METHODS: The CTQ-15 was firstly administered to two groups of control subjects, one (414 subjects) used for the exploratory factor analysis and the other one (415 subjects) for the confirmatory factor analysis. A three-factor model was assessed and compared to alternative models. RESULTS: The resulting structure was in line with the original scale CTQ. Obsessive craving accounted for 15.20% of the total variance, relief craving for the 13.99% and reward craving for 13.13% of the total variance. The three-factor model (M1) reached good fit indices (CFI = 0.96, TLI = 0.95, RMSEA = 0.06 and SRMR = 0.05) and was significantly better than other alternative models. Reliability showed good internal consistency for each scale, i.e. obsessive craving (α = 0.92), relief craving (α = 0.82) and reward craving (α = 0.81). CONCLUSIONS: The CTQ-15 proved to be reliable and practical for identifying the three dimensions of craving in clinical practice. Craving plays a crucial role in the mechanisms of dependence and relapse; thus, characterizing the craving can be fundamental to a targeted drug therapy.

High-Risk Gaming Is Associated with Frequent Substance Use: An Exploratory Survey among Young Adults.

INTRODUCTION: Internet gaming disorder (IGD) is an emerging condition within the field of behavioural addictions. IGD has been demonstrated to be highly comorbid with many other mental health disorders. Among these, substance use has been associated with IGD, and there are underlying similarities between behavioural addictions and substance use disorders. The main aims of the present study were (i) to investigate the association between high-risk gaming and substance use among young adults drawn from the general Italian population; and (ii) to explore the psychopathological correlates of high-risk gaming. METHODS: Lifetime substance use, type of substances consumed, and frequency of use were investigated through an online survey in a sample of 913 adults aged 18-40 years. High-risk gaming was assessed using the ten-item Internet Gaming Disorder Test (IGDT-10). Psychopathology was assessed using the Revised 90-item Symptom Checklist (SCL-90-R). RESULTS: High-risk gaming prevalence rate was 4.4%. High-risk gamers scored higher on all dimensions of psychopathology, confirming the association between high-risk gaming and psychiatric distress. Regarding substance use, high-risk gamers were more commonly polysubstance users and more commonly made use of psychodysleptic substances. High-risk gamers were more commonly frequent substance users, and 32.5% of high-risk gamers used or had used psychoactive substances often or everyday throughout their lives. DISCUSSION AND CONCLUSION: The findings are in line with the concept of a common neurobiological vulnerability for both gaming and substance use. There is the need for more research to examine the phenomenology of gaming and its interplay with substance use to help develop effective interventions and prevention strategies.

What role for cognitive remediation in the treatment of depressive symptoms? A superiority and noninferiority meta-analysis for clinicians.

BACKGROUND: Cognitive remediation (CR) is a promising technique in the treatment of the cognitive dimension of depression. The present study evaluated the potential of CR in treating depressive symptoms and provides practical information about its usefulness in clinical settings. METHODS: We performed two meta-analyses of published randomized (and nonrandomized) clinical trials, comparing CR to control conditions in subjects with current depressive symptomatology. The superiority meta-analysis aimed to determine the superiority of CR when compared with placebo/waiting list interventions and its efficacy when used as an augmentation therapy. The noninferiority meta-analysis determined whether CR had noninferior efficacy compared with standard antidepressant interventions. RESULTS: CR was found to significantly improve depressive symptomatology in the superiority meta-analysis (CR: n = 466, control n = 478). Moreover, CR seemed to be noninferior to standard antidepressant interventions (CR: n = 230, control n = 235). CR was more effective when addressing hot (vs. cold) cognition, when involving younger patients (i.e., <30 years), and in the case of mild-moderate (vs. severe) depression. CONCLUSIONS: CR should be considered an augmentation treatment to improve treatment outcomes in depressed subjects, especially among young individuals. Interventions addressing hot cognition seem to be the most promising.

Substance-related exogenous psychosis: a postmodern syndrome.

There is growing recognition that substance use is associated with the emergence of psychosis.Elements of post-modernity dominate contemporary social contexts and operate as existential background factors that contribute to the emergence of substance-related psychotic phenomena, particularly use of potent and highly rewarding novel psychoactive substances (NPS). About 25% of first-episode psychoses are substance-induced (SIP). DSM-5 SIP diagnosis is based on the assumption that symptoms are transient and disappear after sustained abstinence. This narrowed definition does not consider the issue of persistent SIP. There is a clear need for a new diagnostic framework that provides reliable, unambiguous clinical criteria to differentiate between comorbid conditions (i.e., schizophrenia patients with a substance use disorder) and substance-related psychoses. In the present contribution, we aim to outline a novel and separate clinical entity: substancerelated exogenous psychosis (SREP). Within this diagnostic category, we refer to both transientand persistent psychoses associated with substance use. SREP is conceived as a distinct psychoticdisorder with psychopathological specificities that clearly differentiate it from schizophrenia. We address differences in terms of clinical presentation, epidemiology, etiological models and treatment response. SREP is characterized by altered states of consciousness, persecutory delusions, visual and cenesthetic hallucinations, impulsivity and psychomotor agitation, affectiveand negative symptoms, a pervasive feeling of unreality and intact insight. Delusions are typically secondary to abnormal perception resulting from a characteristic "sensorialization" of the world. Longitudinal studies are warranted to substantiate our hypothesis of a novel diagnostic categoryand support the clinical validity of SREP. This may have important implications in terms of early differential diagnosis and staging (i.e., between comorbid conditions, persistent and transientsubstance-related psychotic states) as well as choice of treatment interventions.

Characterizing the building blocks of Problematic Use of the Internet (PUI): The role of obsessional impulses and impulsivity traits among Italian young adults.

BACKGROUND: Problematic Use of the Internet (PUI) is a considerable issue of the modern era, but its risk factors are still poorly understood. Impulsivity and obsessive-compulsive symptoms have been associated with PUI, but this relationship is still debated. In this article we focus on the relationships of PUI with obsessive-compulsive and impulsive symptoms in a cohort of Italian young adults, in order to identify possible vulnerability factors for PUI. METHODS: A sample of 772 Italian individuals aged 18-30 (mean age 23.3 ± 3.3 years old; 38% males and 62% females) was assessed via online survey using the Internet Addiction Test (IAT), the Mini International Neuropsychiatric Interview (MINI) Screen, the Padua Inventory-Washington State University Revision (PI-WSUR) and the Barratt Impulsiveness Scale (BIS-11). RESULTS: Ninety-seven subjects (12.6% of the sample) reported IAT scores at risk for PUI. PUI participants reported higher levels of impulsivity, obsessive-compulsive symptoms and a higher burden of co-occurrent psychiatric symptoms. In a logistic regression model, obsessional impulses to harm (OR = 1.108, p < 0.001), attentional impulsivity (OR = 1.155, p < 0.001) and depressive symptomatology (OR = 1.246, p = 0.012) had significant association with PUI. Finally, higher severity of PUI has been associated with manic/psychotic symptoms and with attentional impulsivity. CONCLUSIONS: Our findings confirmed the role of impulsivity in PUI, while also underling the association of obsessional impulses with this pathological behavior. We could hypothesize a trigger role of obsessive impulses for the engagement in PUI, together with factors as negative affective states. Further research is needed with respect to more severe forms of PUI, also for establishing tailored interventions.

Telepsychiatry and other cutting-edge technologies in COVID-19 pandemic: Bridging the distance in mental health assistance.

BACKGROUND: At the end of 2019, a novel coronavirus (COVID-19) was identified in China. The high potential of human-to-human transmission led to subsequent COVID-19 global pandemic. Public health strategies including reduced social contact and lockdown have been adopted in many countries. Nonetheless, social distancing and isolation could also represent risk factors for mental disorders, resulting in loneliness, reduced social support and under-detection of mental health needs. Along with this, social distancing determines a relevant obstacle for direct access to psychiatric care services. The pandemic generates the urgent need for integrating technology into innovative models of mental healthcare. AIMS: In this paper, we discuss the potential role of telepsychiatry (TP) and other cutting-edge technologies in the management of mental health assistance. We narratively review the literature to examine the advantages and risks related to the extensive application of these new therapeutic settings, along with the possible limitations and ethical concerns. RESULTS: Telemental health services may be particularly feasible and appropriate for the support of patients, family members and healthcare providers during this COVID-19 pandemic. The integration of TP with other technological innovations (eg, mobile apps, virtual reality, big data and artificial intelligence (AI)) opens up interesting future perspectives for the improvement of mental health assistance. CONCLUSION: Telepsychiatry is a promising and growing way to deliver mental health services but is still underused. The COVID-19 pandemic may serve as an opportunity to introduce and promote, among numerous mental health professionals, the knowledge of the possibilities offered by the digital era.

Gut Microbiota and Bipolar Disorder: An Overview on a Novel Biomarker for Diagnosis and Treatment.

The gut microbiota is the set of microorganisms that colonize the gastrointestinal tract of living creatures, establishing a bidirectional symbiotic relationship that is essential for maintaining homeostasis, for their growth and digestive processes. Growing evidence supports its involvement in the intercommunication system between the gut and the brain, so that it is called the gut-brain-microbiota axis. It is involved in the regulation of the functions of the Central Nervous System (CNS), behavior, mood and anxiety and, therefore, its implication in the pathogenesis of neuropsychiatric disorders. In this paper, we focused on the possible correlations between the gut microbiota and Bipolar Disorder (BD), in order to determine its role in the pathogenesis and in the clinical management of BD. Current literature supports a possible relationship between the compositional alterations of the intestinal microbiota and BD. Moreover, due to its impact on psychopharmacological treatment absorption, by acting on the composition of the microbiota beneficial effects can be obtained on BD symptoms. Finally, we discussed the potential of correcting gut microbiota alteration as a novel augmentation strategy in BD. Future studies are necessary to better clarify the relevance of gut microbiota alterations as state and disease biomarkers of BD.

Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease.

Schizophrenia is a major psychotic disorder affecting nearly 23.6 million people globally and greatly impacting the cognitive and social functioning of individuals. Multiple risk factors, including genetic, environmental, and epigenetic factors have been identified. However, the exact mechanism by which some factors aid in the development of schizophrenia is still uncertain. Acute and/or long-standing inflammation has been implicated as both a cause and effect of schizophrenia. Heightened immune responses have been documented in large cohorts of individuals with schizophrenia. While not completely known, multiple hypotheses, such as disruption of the blood-brain barrier, alterations in the kynurenine/tryptophan pathway, and increased microglial activation, have been presented to correlate inflammation with schizophrenic symptoms. Measurement of C-reactive protein (CRP) is a commonly performed and inexpensive test on patients' serum to determine levels of systemic inflammation in the body. Multiple studies have reported an elevated CRP level in different stages of schizophrenia, indicating its potential to be used as a viable biomarker in the diagnosis and monitoring of schizophrenia along with assessing treatment response to conventional and non-conventional treatment regimens. This review aims to evaluate the role of inflammation, in general, and CRP, in particular, in the pathogenesis of schizophrenia and its potential significance in diagnostic, therapeutic, and preventative approaches towards schizophrenia and psychosis.

New Psychoactive Substances and Suicidality: A Systematic Review of the Current Literature.

Background and Objectives: Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated with health-related risks, especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self-injurious behavior. This paper aims at providing an overview of NPS abuse and the effects on mental health and suicidality issues, by performing a literature review of the current related knowledge, thereby identifying those substances that, more than others, are linked to suicidal behaviors. Materials and Methods: A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been undertaken. An electronic search was performed, including all papers published up to March 2021, using the following keywords "NPS" OR "new psychoactive substances" OR "novel psychoactive substances" OR "synthetic cannabinoids" OR "phenethylamines" OR "synthetic cathinones" OR "tryptamines" OR "piperazines" OR "new synthetic opioids" OR "designer benzodiazepines" AND ("suicide" OR "suicidality") NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. Results: Suicidality and self-injurious behavior appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. The results are organized according to the substances recorded. Conclusion: The growing use of NPS has become a significant clinical issue, causing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviors, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring, and restriction of NPS.

Multiple Sessions of High-Frequency Repetitive Transcranial Magnetic Stimulation as a Potential Treatment for Gambling Addiction: A 3-Month, Feasibility Study.

Gambling disorder (GD) is a behavioral addiction, in which dysfunctions in prefrontal activity have been proposed as relevant pathophysiological correlates. The aim of the present study was to preliminarily investigate the feasibility of a noninvasive neuromodulation intervention targeting the prefrontal cortex to treat GD in an open-label setting. We included 8 treatment-seeking patients with GD (7 males; 1 female; mean age: 40.6 ± 11.2). The study consisted of 3 phases: (1) outpatient screening phase, (2) 2-week intensive repetitive transcranial magnetic stimulation (rTMS) treatment phase (twice daily, 5 days/week for 2 weeks); and (3) 3-month maintenance follow-up phase (twice daily, once a week). Each high-frequency (15 Hz) rTMS session was delivered targeting the left dorsolateral prefrontal cortex. GD severity and treatment response were assessed at the baseline and during the follow-up. No relevant side effect was reported. We found a 71.2% Gambling Symptom Assessment Scale mean score reduction after 2 weeks of rTMS treatment; the days spent gambling decreased from 19.63 ± 7.96 to 0.13 ± 0.35 days. Clinical improvements were maintained throughout the study period. The lack of a control group limits the interpretation of these results. In conclusion, these results consolidate the rationale that rTMS interventions deserve further investigation as a potential treatment for GD. These protocols should be tested in larger randomized controlled studies, to determine the real benefits of neuromodulation in the clinical course of patients with GD. Registration Number: ClinicalTrials.gov Identifier NCT03336879.

Treating schizophrenia with cariprazine: from clinical research to clinical practice. Real world experiences and recommendations from an International Panel.

BACKGROUND: Management of schizophrenia is sub-optimal in many patients. Targeting negative symptoms, among the most debilitating aspects of schizophrenia, together with positive symptoms, can result in significant functional benefits and dramatically improve quality of life for patients and their carers. Cariprazine, a partial agonist of the dopamine receptors D2/D3 has demonstrated effectiveness across symptom domains in clinical trials, particularly on negative symptoms. OBJECTIVE: To obtain a broader insight from clinicians with specific experience with cariprazine, on how it affects patient populations outside the clinical trial setting. METHODS: The panel addressed a series of psychopharmacologic topics not comprehensively addressed by the evidence-based literature, including characteristics of patients treated, dosing and switching strategies, duration of therapy, role of concomitant medications and tolerability as well as recommendations on how to individualize cariprazine treatment for patients with schizophrenia. RESULTS: Patients recommended for cariprazine treatment are those with first episodes of psychosis, predominant negative symptoms (maintenance/acute phase) and significant side effects (metabolic side effects, hyperprolactinemia, sedation) with other antipsychotics. When the long-term treatment of a lifetime illness is adequately weighted, cariprazine becomes one of the first-line medications, not only for patients with predominant negative symptoms but also for those with relatively severe positive symptoms, especially if they are at the first episodes and if a specific medication is added for symptoms such as agitation or insomnia. For instance, patients with agitation may also benefit from the combination of cariprazine and a benzodiazepine or another sedating agent. Cariprazine may be prescribed as add-on to medications such as clozapine, when that medication alone is ineffective for negative symptoms, and sometimes the first may be discontinued or its dose lowered, after a period of stability, leaving the patient on a better tolerated antipsychotic regimen. CONCLUSIONS: Based on real-world clinical experience, the panel considered that cariprazine, with its distinct advantages including pharmacokinetics/pharmacodynamics, good efficacy and tolerability, represents a drug of choice in the long-term management of schizophrenia not only for patients with predominant negative symptoms but also for those with positive symptoms.

Striatal presynaptic dopaminergic dysfunction in gambling disorder: A 123 I-FP-CIT SPECT study.

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward-based decision making. We performed 123 I-FP-CIT Single-photon emission computed tomography (SPECT) and correlated DAT binding ratios in the bilateral caudate and putamen with gambling symptoms (G-SAS, PG-YBOCS) and behaviors, as well as other psychometric variables (anhedonia and impulsivity). Gambling disorder (GD) subjects were also administered a computerized version of the Iowa gambling task (IGT) to assess reward-based decision making. We found reduced DAT availability in GD subjects compared with healthy controls (-13.30% in right caudate, -11.11% in right putamen, -11.44% in left caudate, and -11.46% in the left putamen). We also found that striatal DAT availability was inversely correlated with days spent gambling and IGT performance in GD subjects. These results provide evidence for a presynaptic dopaminergic dysfunction in striatal regions of GD subjects. Functional DAT down-regulation possibly sustains the transition towards compulsive gambling addiction, characterized both by hyperdopaminergic and hypodopaminergic states in the context of a sensitized dopaminergic system.

Transcranial Direct Current Stimulation Reduces Craving in Substance Use Disorders: A Double-blind, Placebo-Controlled Study.

OBJECTIVES: The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms. METHODS: In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1). RESULTS: Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found. CONCLUSIONS: Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.