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The perception of social exclusion among patients with opioid use disorder (OUD) could be affected by long-term opioid use. This study explores the emotional and cardiac autonomic responses to an experience of ostracism in a sample of participants with OUD on opioid agonist treatment (OAT). Twenty patients with OUD and twenty healthy controls (HC) performed a ball-tossing game (Cyberball) with two conditions: Inclusion and Ostracism. We measured self-reported ratings of perceived threat towards one's fundamental needs and respiratory sinus arrhythmia (RSA) immediately after the game and 10 min after Ostracism (Reflective stage). Following ostracism, participants with OUD self-reported blunted feelings of threat to the fundamental need to belong. RSA levels were significantly suppressed immediately after ostracism and during the Reflective stage in comparison with HC, indicating an autonomic alteration in response to threatening social situations. Finally, only among HC higher perceived threats towards fundamental needs predicted increases in RSA levels, suggesting an adaptive vagal regulation in response to a perceived threat. Conversely, among patients with OUD the subjective response to ostracism was not associated with the autonomic reaction. OAT may have a protective effect against negative feelings of ostracism. However patients with OUD on OAT present poor autonomic regulation in response to social threats, which could reflect their trait hypersensitivity to social rejection., (Copyright © 2023. Published by Elsevier Inc.)

Malignant catatonia is a life-threatening syndrome that could be observed in various psychiatric and neurological conditions. We describe the challenging case of a young woman with relapsing-remitting malignant catatonia, which finally resolve after electroconvulsive therapy (ECT). Details regarding her psychiatric symptoms, dynamics, and EEG features during each acute and post-acute phases of the disease are described and long-term follow-ups are provided. We emphasize the importance of a multidisciplinary cross talk between neurologists and psychiatrists to ensure adequate management of this dangerous condition. Knowledge and gaps in the field of autoimmune psychosis are also discussed.

This review aims to elucidate environmental and genetic factors, as well as their epigenetic and neuroendocrine moderators, that may underlie the association between early childhood experiences and Substance Use Disorders (SUD), through the lens of parental attachment. Here we review those attachment-related studies that examined the monoaminergic systems, the hypothalamic pituitary adrenal stress response system, the oxytoninergic system, and the endogenous opioid system from a genetic, epigenetic, and neuroendocrine perspective. Overall, the selected studies point to a moderating effect of insecure attachment between genetic vulnerability and SUD, reasonably through epigenetic modifications. Preliminary evidence suggests that vulnerability to SUDs is related with hypo-methylation (e.g. hyper-expression) of high-risk polymorphisms on the monoaminergic and hypothalamic pituitary adrenal system and hyper-methylation (e.g. hypo-expressions) of protective polymorphisms on the opioid and oxytocin system. These epigenetic modifications may induce a cascade of neuroendocrine changes contributing to the subclinical and behavioural manifestations that precede the clinical onset of SUD. Protective and supportive parenting could hence represent a key therapeutic target to prevent addiction and moderate insecure attachment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Individuals with Borderline Personality Disorder (BPD) feel rejected even when socially included. The pathophysiological mechanisms of this rejection bias are still unknown. Using the Cyberball paradigm, we investigated whether patients with BPD, display altered physiological responses to social inclusion and ostracism, as assessed by changes in Respiratory Sinus Arrhythmia (RSA)., Methods: The sample comprised 30 patients with BPD, 30 with remitted Major Depressive Disorder (rMDD) and 30 Healthy Controls (HC). Self-report ratings of threats toward one's fundamental need to belong and RSA reactivity were measured immediately after each Cyberball condition., Results: Participants with BPD showed lower RSA at rest than HC. Only patients with BPD, reported higher threats to fundamental needs and exhibited a further decline in RSA after the Inclusion condition., Conclusions: Individuals with BPD experience a biased appraisal of social inclusion both at the subjective and physiological level, showing higher feelings of ostracism and a breakdown of autonomic regulation to including social scenarios., (© 2021. The Author(s).)

Both genetic and early environmental factors contribute to the pathogenesis of Alcohol Use Disorder (AUD). Gender and psychopathology symptoms might further moderate this association, resulting in an impairment of both the dopaminergic and serotoninergic pathways that sustain the binge, withdrawal and craving cycle. In a sample of of adult children of alcoholic parents (ACOAs) (n = 107) we compared those with and without an AUD, on socio-demographic variables, adverse childhood experiences, psychopathology symptoms and two polymorphisms associated with an impaired serotoninergic and dopaminergic neurotransmission (5HTTLPR and Taq1A/DRD2). A logistic regression revealed that an early caring environment might lower the risk of developing an AUD. When controlling for the actual psychopathology symptoms, being male and having the genotype associated with an impaired dopaminergic neurotransmission were still associated with AUD. Results were confirmed by an unsupervised approach that showed how the clusters characterised by being male and having the high risk genotypes were still associated with AUD compared to being female without the unfavourable dopamine genotype.Our results point to the need for implementing prevention strategies aimed at creating a caring environment especially in those families with an alcoholic parent. We further suggest that psycho-education as a symptom recognition and avoiding self-medication could improve the outcome in those subjects at higher risk, especially males., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Even though most of the systematic reviews suggest that depression and anxiety are related to poor neonatal outcomes, it is not yet clear whether a dose-response effect exists., Aim: The aim of the present study is to evaluate the amount of depressive and anxiety symptoms in a cohort of pregnant women and its effect on their newborns., Methods: Two hundred ninety-nine women were assessed for anxiety and depressive disorders and anxious and depressive symptoms at near monthly intervals throughout pregnancy. At the time of delivery, we collected the newborns' gestational age, birth weight and the Apgar score at 1 and 5 min., Results: Sixty-seven women were diagnosed as depressed and 43 had an anxious disorder. After controlling for confounding variables only the overall levels of anxiety during pregnancy were negatively associated with birth weight ( B = -5.76; 95% CI = -10.96, -2.81), suggesting the existence of a "dose-response" effect. The birth outcomes in mildly depressed pregnant women were similar to those of nondepressed women., Conclusion: Anxiety symptoms, beyond a categorical diagnosis, are associated with low birth weight and should be recognized and properly treated during pregnancy.

Objectives: Incident depression, occurring after an acute coronary syndrome (ACS) in never depressed patients, exerts a negative effect on the cardiac prognosis. Nonetheless only a few studies have evaluated the risk factor for incident depression and, particularly, no study have investigated the role of personality disorders. Therefore, the aim of this study is to verify if personality disorders represent a risk for incident depression in patients at their first ACS. Method: The study sample was selected among never depressed patients who were consecutively admitted to the Coronary Intensive Care Unit, from January 2009 to March 2012, for the first ACS. The study sample included 262 patients. The presence of depressive disorder was assessed with the Primary Care Evaluation of Mental Disorders (DSM-IV criteria), whereas its severity was evaluated with the Hospital Anxiety and Depression Scale. Evaluations were collected at baseline and at 1, 2, 4, 6, 9, 12 and 24 months of follow-up. Moreover, at baseline personality disorders were investigated with the Structured Clinical Interview for DSM-IV Axis II disorders. Results: Out of 262 subjects, a depressive disorder was diagnosed in 56 patients (21%). At baseline risk factors for incident depression were being widowed, having a distress reaction and narcissistic personality traits. Conclusion: Clinicians should keep in mind these characteristics when facing patients at their first ACS, given the detrimental effect of depression on cardiac prognosis. A psychological support should prevent the onset of incident depression in these patients.

Background: This cohort study was aimed to verify whether subjects at their first acute coronary syndrome (ACS) were more alexithymic than healthy controls (HC) and whether alexithymia can predispose patients with coronary artery disease to new major adverse cardiac events (MACE) during a 24-month follow-up period., Methods: The sample included 100 HC with no history of depression or ACS and 304 never depressed patients with a first-ever ACS. A total of 266 patients completed the 2-year follow-up., Results: Patients and HC reported similar Toronto Alexithymia Scale (TAS-20) scores. During the follow-up, 69 (22.69%) patients developed incident depression and 57 (18.75%) developed a new MACE. In a proportional hazard model, developing a first-ever depressive episode, but not alexithymia (hazard ratio = 1.008, 95% confidence interval = 0.984-1.033; p = 0.500), was associated with almost 3 times the risk of a recurrent cardiac event., Conclusion: Incident depression, but not TAS-20 scores, represented risk factor for MACE.

Few studies assess the role of personality styles in predicting the onset of depression among cardiac patients. This study evaluates whether temperament and character can represent a risk factor for the development of incident first-ever depressive episodes in patients at their first acute coronary syndrome (ACS). Two hundred sixty-seven (72.1%) subjects (male) completed the Temperament and Character Inventory (TCI) a few days after the cardiac event. At baseline and after 1, 2, 4, 6, 9, 12, and 24 months of follow-up, the participants completed the Primary Care Evaluation of Mental Disorder (PRIME-MD) and the Hospital Anxiety and Depression Scale to establish the presence of a depressive episode and its severity. During the follow-up, 61 (22.8%) participants developed a depressive episode. Temperamental risk factors for incident depression were scored high on novelty seeking and harm avoidance at the TCI. Given the detrimental effect of depression on cardiac prognosis, clinicians should take temperament variables into account when determining the treatment plans of their patients with ACS.

Objective: Depression is an established risk factor for acute coronary syndrome (ACS), with an impact on cardiac prognosis; nonetheless, the literature disagrees on the role played by anxiety. No study has evaluated this relationship in a cardiac population with no history of depression and after their first diagnosis of ACS. The aim of this study is to explore these associations without the confounding role of long-lasting heart disease or psychiatric illnesses., Method: Two hundred sixty-six patients with no history of depression completed the Hospital Anxiety and Depression Scale and the Primary Care Evaluation of Mental Disorder at baseline and at 1, 2, 4, 6, 9, 12, and 24 months follow-up after their first diagnosis of ACS. During the follow-up period, we collected information regarding the major adverse cardiac events., Results: Developing a first-ever depressive episode, in a proportional hazard model, was associated with almost 3 times the risk of a recurrent cardiac event (odds ratio = 2.590, 95% confidence interval [CI] [1.321, 5.078], p = .006). Furthermore, a moderation analysis revealed that increasing levels of baseline anxiety had opposing effects on cardiac outcomes, being protective only in those who did not develop incident depression (B = -0.0824, 95% CI [-0.164, -0.005], p = .048). No dose-response effect between depressive or anxious symptoms and cardiac outcomes emerged., Conclusion: Our results confirm the detrimental effect of depression on cardiac prognosis in a selected population and suggest that anxiety after the first diagnosis of ACS might have different roles depending on the illness' course. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Objective: This work tested the hypothesis that patients with high negative affectivity (NA) would have a better response to a serotonergic agent (escitalopram) than to one not thought to act directly on serotonin (bupropion)., Method: Data from a study conducted between August 2007 and July 2011 were reanalyzed retrospectively. Patients (N = 245) meeting criteria for major depressive disorder (MDD), diagnosed with DSM-IV-TR, were randomly assigned to double-blind treatment with bupropion extended-release, escitalopram, or the combination. Negative affectivity score was estimated using the guilt, hostility/irritability, and fear/anxiety items of the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Quick Inventory of Depressive Symptoms, and the Social Adjustment Scale. We felt that these items captured published descriptions of the NA construct. A Clinical Global Impressions-Severity of Illness (CGI-S) score ≤ 2 defined response. Because combined treatment addressed both serotonin and non-serotonin systems, patients treated with both medications did not test the hypothesis and so were excluded from the analyses., Results: Analysis of covariance with treatment as a grouping variable, NA as covariate, and CGI-S as dependent variable showed a significant 2-way interaction between treatment and NA (F₁,₁₅₆ = 4.82, P < .03). In the low-NA group, response rates were similar between treatments (escitalopram: 28/42 [67%]; bupropion: 23/40 [58%]; NS), while there was a significant advantage for escitalopram in patients with high NA (escitalopram: 24/40 [60%]; bupropion = 14/41 [34%]; P = .017)., Conclusions: These data suggest that patients with high negative affectivity respond preferentially to antidepressants that selectively enhance serotonin neurotransmission. Although patients with low NA appear to benefit from serotonin enhancement as well, they also improved with bupropion, an antidepressant not thought to directly affect serotonin neurotransmission. These findings come from retrospective analyses using unproven approximation of NA, so no clinical inferences should be made before independent replication utilizing accepted NA measurement., Trial Registration: ClinicalTrials.gov identifier: NCT00519428., (© Copyright 2014 Physicians Postgraduate Press, Inc.)

The goals of this study were to investigate differences in neurocognitive performance between groups of patients with unipolar major depressive disorder (MDD) or bipolar I disorder (BD-I) in a euthymic state, and to analyze associations among cognitive performance, sociodemographic and clinical variables, and global functioning. The study evaluated 25 outpatients with MDD and 25 outpatients with BD-I. Controls consisted of a sample of 29 healthy adult volunteers. All of the subjects were administered a battery of neuropsychological tests (Babcock Story Recall Test, Wisconsin Card Sorting Test, Trail Making Test Part B, Stroop Color and Word Test, Symbol- Number Association Test, and Digit Span). Patients demonstrated reduced performance on tasks involving executive functions (Trail Making Test Part B and Wisconsin Card Sorting Test) and attention (Digit Span and Symbol-Number Association Test) compared with healthy controls. Performance on neurocognitive tasks did not differentiate patients with MDD from those with BD-I. Improved performance on tasks that assessed executive functions by patients with BDI and MDD, considered as a single group, was associated with better global functioning, even when controlling for several sociodemographic and clinical confounders. Patients with MDD and BD-I showed a similar profile of information-processing deficits and similar global functioning. Global functioning was also moderately associated with performance on executive function tasks.

Aim of this paper is to investigate the psychobiological reactions to experimentally induced negative emotional states in active marijuana-dependent smokers and whether changes in emotional reactivity were reversed by prolonged abstinence. Twenty-eight patients were randomly included into group A (fourteen active marijuana-dependent smokers) or group B (fourteen abstinent marijuana-dependent subjects). Emotional response evaluation of group B subjects was assessed after 6 months of abstinence. Fourteen healthy volunteers, matched for age and sex, were used as controls. Psychometric and emotional response evaluations were performed by administering Symptoms Check List-90 and State-Trait Anxiety Inventory Y-1 (STAI). Neutral and unpleasant set of pictures selected from the international affective picture system and the Self-Assesment Manikin procedure (SAM) have been used to determine ratings of pleasure and arousal. Before and after the experimental session, blood samples were collected to determine ACTH and cortisol plasma levels. Active cannabis users displayed significantly higher levels of pleasantness SAM scores and lower levels of arousal SAM scores compared to abstinent cannabis users and controls in response to emotional task. In a close parallel with psychological data, hormonal findings indicate a persistent hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in cannabis users, particularly among active marijuana smokers, and an impaired hormonal reaction to negative emotions, in comparison with healthy subjects. The capacity of the HPA axis to respond to stressful stimuli/negative emotions seems to be only partially recovered after 6 months of abstinence. Ours findings, although obtained in a small number of subjects, suggest an association between active cannabis use, subjective reduced sensitivity to negative emotions and threat and HPA axis dysfunction.

Epidemiological and clinical data show frequent associations between adverse childhood experiences (ACEs) and substance abuse susceptibility particularly in adolescents. A large body of evidences suggests that the possible dysregulation of neuroendocrine responses as well as neurotransmitters function induced by childhood traumatic experiences and emotional neglect could constitute one of the essential biological changes implementing substance abuse vulnerability. Moreover, genotype variables and its environment interactions have been associated with an increased risk for early onset substance abuse. In this paper we present several data that support the hypothesis of the involvement of hypothalamus-pituitary-adrenal (HPA) axis in mediating the combined effect of early adverse experiences and gene variants affecting neurotransmission. The presented data also confirm the relationship between basal plasma levels of cortisol and ACTH, on the one hand, and retrospective measures of neglect during childhood on the other hand: the higher the mother and father neglect (CECA-Q) scores are, the higher the plasma levels of the two HPA hormones are. Furthermore, such positive relationship has been proved to be particularly effective and important when associated with the "S" promoter polymorphism of the gene encoding the 5-HTT transporter, both in homozygote and heterozygote individuals., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Cocaine dependence is characterized by compulsive drug seeking and high vulnerability to relapse. Overall, cocaine remains one of the most used illicit drugs in the world. Given the difficulty of achieving sustained recovery, pharmacotherapy of cocaine addiction remains one of the most important clinical challenges. Recent advances in neurobiology, brain imaging and clinical trials suggest that certain medications show promise in the treatment of cocaine addiction. The pharmacotherapeutic approaches for cocaine dependence include medications able to target specific subtypes of dopamine receptors, affect different neurotransmitter systems (i.e. noradrenergic, serotonergic, cholinergic, glutamatergic, GABAergic and opioidergic pathways), and modulate neurological processes. The systematic reviews concerning the pharmacological treatment of cocaine dependence appear to indicate controversial findings and inconclusive results. The aim of future studies should be to identify the effective medications matching the specific needs of patients with specific characteristics, abandoning the strategies extended to the entire population of cocaine dependent patients. In the present review we summarize the current pharmacotherapeutic approaches to the treatment of cocaine dependence with a focus on the new patents.

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The hypotheses of (1) gene x environment interaction in the susceptibility to experiment with drugs and (2) hypothalamus-pituitary-adrenal (HPA) axis involvement in mediating the effects of early adverse experiences and gene variants affecting serotonin function on substance abuse vulnerability were tested by investigating in 187 healthy adolescents the possible relevance of 5-HTT "S" polymorphism, childhood parental neglect reported retrospectively and HPA axis function to the susceptibility to experiment with illicit drugs. Higher frequency of the 5-HTT SS genotype seems to be associated with an increased susceptibility to use illegal psychotropic drugs among the adolescents. At the same time, reduced maternal care perception was found to represent a key intermediate factor of the association between SS polymorphism and drug use, suggesting that genetic factors and parental behavior concur to drug use susceptibility. Our results also confirm the relationship between basal plasma levels of cortisol and adrenocorticotropic hormone (ACTH) on the one hand, and retrospective measures of neglect during childhood: the higher the mother and father neglect CECA-Q scores, the higher the plasma levels of the two HPA hormones. Such positive relationship has been proved to be particularly effective and important when associated to the S-allele, both in homozygote and heterozygote individuals. However, when tested together with genotype and parental neglect, the effect of HPA hormones such as cortisol and ACTH was not found to improve significantly the explanatory power of the risk model.

For centuries Cannabis sativa and cannabis extracts have been used in natural medicine. Delta(9)-tetrahydrocannabinol (THC) is the main active ingredient of Cannabis. THC seems to be responsible for most of the pharmacological and therapeutic actions of cannabis. In a few countries THC extracts (i.e. Sativex) or THC derivatives such as nabilone, and dronabinol are used in the clinic for the treatment of several pathological conditions like chemotherapy-induced nausea and vomiting, multiple sclerosis and glaucoma. On the other hand the severe side effects and the high abuse liability of these agents represent a serious limitation in their medical use. In addition, diversion in the use of these active ingredients for recreational purpose is a concern. Over recent years, alternative approaches using synthetic cannabinoid receptor agonists or agents acting as activators of the endocannabinoid systems are under scrutiny with the hope to develop more effective and safer clinical applications. Likely, in the near future few of these new molecules will be available for clinical use. The present article review recent study and patents with focus on the cannabinoid system as a target for the treatment of central nervous system disorders with emphasis on agonists.