Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.

BACKGROUND: Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms. OBJECTIVE: The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report. METHODS: Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023. RESULTS: We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine. CONCLUSIONS: Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.

Elevated levels of serotonin 5-HT2A receptors in the orbitofrontal cortex of antisocial individuals.

Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the implication of this neurotransmitter in ASB is unclear. Here, we performed the first-ever postmortem analysis of serotonergic markers in the orbitofrontal cortex (OFC) of male subjects with ASB (n = 9). We focused on this brain region, given its well-recognized role in social response and ASB pathophysiology. Given that all individuals also had a substance use disorder (SUD) diagnosis, two age-matched control groups were used: SUD only and unaffected controls. Tissues were processed for immunoblotting analyses on eight key serotonergic targets: tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of brain serotonin synthesis; serotonin transporter (SERT), the primary carrier for serotonin uptake; monoamine oxidase A (MAOA), the primary enzyme for serotonin catabolism; and five serotonin receptors previously shown to influence social behavior: 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, and 5-HT4. Our analyses documented a significant increase in 5-HT2A receptor levels in the ASB + SUD group compared to SUD-only controls. Furthermore, TPH2 levels were significantly reduced in the SUD group (including SUD only and ASB + SUD) compared to unaffected controls. No difference was detected in the expression of any other serotonergic target. These results are in keeping with previous evidence showing high 5-HT2A receptor binding in the OFC of pathologically aggressive individuals and point to this molecule as a potential target for ASB treatment.

Substance Use Disorders and Antisocial Personality Disorder among a Sample of Incarcerated Individuals with Inadequate Health Care: Implications for Correctional Mental-Behavioural Health and Addiction Services.

Epidemiological estimates of substance use disorders (SUD) are critical for the planning of evidence-informed intervention and services. In this study, 250 incarcerated individuals in Nigeria were interviewed with the Mini International Neuropsychiatric Inventory (MINI) to diagnose SUD and antisocial personality disorder (ASPD). Most of the participants were males (97.6%), and the mean age was 35.4 (SD=13.5) years. Substance use disorder and ASPD were prevalent in 57.6% and 11.2% of the participants, respectively. Of those diagnosed with SUD, 35.2% and 22.4% had poly-SUD and mono-SUD respectively. Psychotic and dependence syndromes involving cannabis misuse were the most prevalent poly-SUD, and mono-SUD was characterized by alcohol, nicotine, and opioid dependence syndromes. Substance use disorder was more likely in participants charged with robbery and convicted, while ASPD was associated with prior and long-term imprisonment. There is a need for effective integration of treatment for ASPD/SUD into correctional mental health services in settings with inadequate health care using an appropriate model and a viable strategy.

Impulsive Lifestyle Counselling versus treatment as usual to reduce offending in people with co-occurring antisocial personality disorder and substance use disorder: a post hoc analysis.

OBJECTIVES: To assess the impact of a short psychoeducation intervention for antisocial personality disorder on offending after randomization to treatment. DESIGN: Multicentre, superiority, non-blinded randomized controlled trial. Random assignment was conducted in blocks of varying sizes at a central randomization centre. Participants were followed using national register data until 365 days after randomization, migration, or death, whichever occurred first. SETTING: Thirteen outpatient uptake areas in Denmark. PARTICIPANTS: Patients with antisocial personality disorder in treatment for substance use disorders were randomized to treatment as usual (TAU, n = 80) or Impulsive Lifestyle Counselling (ILC, n = 96). A total of 165 patients could be linked to criminal records (TAU, n = 74; ILC, n = 91). INTERVENTION: ILC is a brief psychoeducational program targeting antisocial behavior. The trial was conducted between January 2012 and June 2014. OUTCOMES: Number of criminal offences leading to convictions based on national registers. RESULTS: The mean number of offences was 2.76 in the TAU group (95% Poisson confidence interval [CI] = 2.39, 3.16) and 1.87 in the ILC group (95% CI = 0.97, 1.43). Negative binomial regression was used to assess total number of convictions, as well as convictions for violent, property, driving under the influence, and drug-related crimes. In both adjusted and unadjusted analyses, random assignment to ILC was associated with a lower number of total offences (incidence rate risk ratio [IRR] = 0.43, p = .013; adjusted IRR = 0.45, p < .001) and convictions related to violence (IRR = 0.19, p = .001 adjusted IRR = 0.19, p = .007) and property offences (unadjusted IRR = 0.30, p = 0.003, adjusted IRR = 0.42, p = 0.010). Differences between conditions were not significant for driving under the influence (unadjusted IRR = 0.49, p = .370; adjusted IRR = 0.53, p = .417) or drug offences (unadjusted IRR = 1.06, p = .907; adjusted IRR = 0.55, p = .223). CONCLUSIONS: The ILC program shows promise in reducing offending behavior in people with comorbid substance use and antisocial personality disorder. TRIAL REGISTRATION: ISRCTN registry, ISRCTN67266318 , 15/10/2012.

Personality disorder and mild traumatic brain injury.

Mild traumatic brain injury (mTBI) poses risk to the neurocognitive, emotional, and financial well-being of affected individuals. While aggression and impulsivity have been examined in relation to mTBI, little work has been done to evaluate the relationship between history of mTBI and personality disorder (PD). The authors examined the associations between history of mTBI and PD in a control group without history of mTBI (N = 1189) and individuals with history of mTBI (N = 267). Results demonstrated that any PD diagnosis is a significant risk factor for mTBI (p < 0.001). Cluster B diagnoses, particularly borderline and antisocial PD, were independently significant risk factors for mTBI. These data suggest a role for screening for a history of mTBI in patients with PDs and associated traits.

Risk-taking and fairness among cocaine-dependent patients in dual diagnoses: Schizophrenia and Anti-Social Personality Disorder.

This study reports experimental results from a clinical sample of patients with a cocaine-related disorder and dual diagnosis: Schizophrenia and Anti-Social Personality Disorder. Both types of patients as well as a non-clinical group of students performed two incentivized decision-making tasks. In the first part of the experiment, they performed a lottery-choice task in order to elicit their degree of risk aversion. In the second part, they decided in two modified dictator games aimed at eliciting their aversion to advantageous and disadvantageous inequality. It is found that the Anti-Social Personality Disorder group exhibits no significant differences from the non-clinical sample in either task. However, compared with the students' sample, subjects from the group with schizophrenia show more risk aversion and exhibit more aversion towards disadvantageous inequality.

Mental disorders in patients with epilepsy. / Zaburzenia psychiczne u chorych na padaczke.

Mental disorders occur in patients with epilepsy significantly more frequently than in the general population or in those with other chronic diseases. The specificity of epilepsy as a condition of the central nervous system with complex somatic, psychic and social consequences contributes to co-occurrence of these disorders. Moreover, common patomechanisms are suggested for epilepsy and mental disorders, associated with disturbances of bioelectrical activity and neurotransmission in certain areas of the brain.The authors present a review of main groups of mental disorders observed in epileptic patients: psychotic, affective, anxiety, personality, and conduct disorders. They discuss their epidemiology and clinical presentation, with a particular focus on their risk factors and temporal relation to epileptic seizures. They also highlight problems associated with differential diagnosis and optimal therapeutic strategy. Mental disorders have a significant impact on the quality of life and functioning of patients with epilepsy. Further exploration of interrelationships between these illnesses, as well as cooperation between neurologists and psychiatrists promote an early and precise diagnosis of mental disturbances in this group of patients and their effective treatment.

Youth with Co-occurring Delinquency and Depressive Symptoms: Do They Have Better or Worse Delinquent Outcomes?

Delinquent youth often experience depression, but depression's impact on their future deviance is unclear. Using survey and social network data on a panel of 9th graders (N = 8701; Mage at baseline = 15.6; 48% male; 85% white; 18% eligible for free or reduced-price school lunch) followed throughout high school, this study tested whether depressive symptoms predicted later deviance or deviant peer affiliations among already delinquent youth. A latent class analysis revealed that 4% of respondents showed above-average levels of delinquency but not depressive symptoms, and 3% were above average on both. Compared to the delinquent-only group, the delinquent-depressed group went on to have less deviant friends, and to engage in less deviance themselves. However, peer deviance was not a reliable explanation for the reductions in respondents' own future deviance. Depressive symptoms thus may play a protective role against continued delinquency and substance use among youth who are already delinquent, but it is not because they reduce deviant peer affiliations.

The "core" of the dark triad: A test of competing hypotheses.

As research on the dark triad (DT; the interrelated constructs of Machiavellianism, narcissism, and psychopathy) has accumulated, a subset of this research has focused on explicating what traits may account for the overlap among the DT members. Various candidate traits have been investigated, with evidence supporting several of them, including antagonism (vs. agreeableness), honesty-humility, and callousness and interpersonal manipulation (the latter 2 as a set). The present study sought to test the leading candidates against one another in their ability to account for the shared variance among the DT members. Using a preregistered analytical plan, we found that agreeableness (as measured by the International Personality Item Pool-NEO-120), honesty-humility (H/H) from the HEXACO-Personality Inventory, and the Self-Report Psychopathy Scale subscales of Callous Affect and Interpersonal Manipulation accounted for all or nearly all of the shared variance among the DT members. Big Five Inventory (BFI)-based measures of Agreeableness (BFI and BFI-2) accounted for notably less variance in most cases. The results were consistent across 2 large samples (Ns of 627 and 628) and across various DT measurement approaches. We argue that the most parsimonious explanation for findings on the core of the DT is that such traits all fall under the umbrella of antagonism. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

An Exploratory Study of Female Psychopathy and Drug-Related Violent Crime.

There is a clear link between drugs and violence, and the extensive burden drug-related violence inflicts on society. However, drug-related violence is largely understudied, especially in female populations. The aim of the present study was to explore whether women convicted of drug-related violent crime differed on individual-level risk factors from women convicted of a nondrug-related violent crime and women convicted of nonviolent crimes. One hundred and twenty-five female inmates were classified using official criminal records. Multinomial logistic regression indicated inmates higher in antisocial psychopathic traits and low level of educational attainment were more likely to be in the drug-related violent crime group. In comparison, inmates higher in callous psychopathic traits were more likely to be in the nondrug-related violent crime group. Using official records of prison misconduct, a secondary aim tested whether prison violence increased the likelihood of being in either of the violent crime groups. Results show inmates who had committed violent misconducts over a 6-month period were more likely to be the nondrug-related violent crime group. Prison violence did not differentiate inmates in the nonviolent crime group from the drug-related violent crime group. These findings are the first to explore the relation between psychopathy and drug-related violent crime, and drug-related violent crime predicting future violent behavior in female criminals. This study demonstrates the heterogeneity in female violent behavior. Furthermore, psychopathy is not only shown to be an important risk factor for violence in women but also highlights that the dimensional construct is essential for understanding context-dependent violence.

[Conduct disorder and antisocial personality disorders: challenges for treatment in adolescence and young adulthood]. / Störung des Sozialverhaltens und Antisoziale Persönlichkeitsstörung - Herausforderungen in der Transition vom Jugend- zum Erwachsenenalter.

Aggressive behaviour is a typical phenomenon in childhood and adolescence. Aggression is one of the frequent reasons for parents to seek child and adolescent psychiatric and psychotherapeutic treatment. Disorders with increased aggressive behaviour, such as conduct or oppositional defiant disorder, carry an increased risk for long-lasting negative impact on well-being, especially when comorbid with substance abuse or affective symptoms. Barriers for treatment are frequently a lack of insight into consequences and non-compliance with intervention shown by adolescents. In addition, interdisciplinary intervention needs to combine psychiatric and psychotherapeutic interventions as well as complex interventions supported by the youth welfare system, and in particular including families. Further research is needed for the implementation of evidence-based treatments in routine care as well in special populations, such as girls with conduct disorders or youth with substance abuse.

Executive function, attention, and memory deficits in antisocial personality disorder and psychopathy.

Antisocial personality disorder (ASPD) and psychopathy attempt to represent individuals demonstrating callousness and disregard for others. ASPD has been criticized for capturing a heterogeneous population whilst missing the essence of the diagnosis by neglecting interpersonal/affective deficits which measures of psychopathy include. This heterogeneity in operationalizations has led to diverse findings without clear understanding of what characterizes this broader population. This study sought to clarify the neuropsychological profiles of ASPD and psychopathy. The Cambridge Neuropsychological Test Assessment Battery was administered to 85 adult male offenders in a personality disorder secure service and to 20 healthy controls. Of patients with ASPD, 46% met criteria for psychopathy. Of those with psychopathy, 89% met criteria for ASPD. There were two sets of comparisons: ASPD versus other personality disorders versus controls and psychopathy versus other personality disorders versus controls. ASPD showed deficits across executive functions, visual short-term and working memory, and attention (compared with controls). Psychopathy showed deficits limited to attention, complex planning, inhibitory control, and response reversal. Response reversal and visual search deficits appeared specific to ASPD and psychopathy versus other personality disorders and may underpin antisocial traits. Additional deficits in inhibitory control and working memory appeared to distinguish ASPD from other personality disorders.

Psychopathy and neurodynamic brain functioning: A review of EEG research.

Studies related to psychopathy and EEG have increased over the past decade making it a good time to examine where the field is on this topic as well as to determine future directions. The current study reviewed 68 research reports that focused on psychopathy and various components of EEG. We examined early, mid, and late level ERP processing as well as spectra analyses. The results indicate that psychopathic individuals exhibit generally unencumbered performance categorizing cognitive stimuli and demonstrate the typical facilitation of physical responses commensurate with an intact orienting response. Moreover, the results suggest that individuals with elevated psychopathic traits are especially adept at screening out distracting threat-related and other irrelevant information allowing them to allocate attention to stimuli that are goal-relevant. Those with elevated psychopathic traits also do not appear to have significant impairments in associative learning or error processing. Where psychopathic individuals diverge most from those with low levels of these traits is in relation to processing affect-laden content. In some contexts, psychopathic individuals appear to quickly terminate the processing of emotional information and in other contexts (e.g., seeing others in pain) they elaborately process emotional information both of which may help explain their prototypical lack of conscience. Much of the aberrant functioning of those with elevated psychopathic traits depends on the psychopathy factor being examined with F1 traits showing less cognitive impairment than F2 traits. Recommendations for future research are provided.

Attention deficit hyperactivity disorder and future alcohol outcomes: Examining the roles of coping and enhancement drinking motives among young men.

OBJECTIVE: Although there is evidence that Attention Deficit Hyperactivity Disorder (ADHD) symptoms are positively related to alcohol use and related problems among young adults, little research has examined the mechanisms that might explain this association. In response, this study examined the mediating effects of coping and enhancement drinking motives on the prospective associations between ADHD symptoms and alcohol outcomes. METHOD: Participants (N = 4,536) were young men from the Cohort Study on Substance Use Risk Factors. Measures of ADHD symptoms and those of drinking motives, heavy episodic drinking (HED) and alcohol use disorder symptoms were used from the baseline and 15-month follow-up assessments. RESULTS: Findings indicated that the associations of ADHD-inattention symptoms with alcohol use disorder (AUD) symptoms and with HED were partially and completely mediated through drinking motives, respectively, whereas drinking motives did not mediate the ADHD-hyperactivity/impulsivity-symptoms-alcohol outcomes associations. CONCLUSION: Results indicated that coping and enhancement motives partially explained the ADHD-inattention symptoms-subsequent alcohol outcomes association. These findings suggest that interventions targeting enhancement and coping motives may help prevent problematic drinking among young men with elevated ADHD-inattention symptoms.

The etiology of antisocial personality disorder: The differential roles of adverse childhood experiences and childhood psychopathology.

Antisocial Personality Disorder (ASPD) is a severe personality disorder with robust associations with crime and violence, but its precise etiology is unknown. Drawing on near-population of federal correctional clients in the Midwestern United States, the current study examined antecedent background factors spanning adverse childhood experiences and childhood psychopathology. Greater adverse childhood experiences were associated with ASPD diagnosis with physical abuse showing associations with ASPD symptoms and sexual abuse with lifetime diagnosis for ASPD. Conduct Disorder was strongly linked to ASPD; however, Oppositional Defiant Disorder and ADHD had null associations. Given the role of environmental factors in the development of ASPD, greater criminological attention should be devoted to understanding how assorted forms of abuse and neglect coupled with childhood psychopathology contribute to ASPD especially given its linkages to severe criminal offending.

Evaluating dysfunction in cognition and reward among offenders with antisocial personality disorder.

Antisocial personality disorder (APD) is a costly clinical condition. Previous studies identify executive dysfunction and reward sensitivity as factors contributing to APD. However, empirical evidence supporting the role of these factors in APD is mixed. The present study aimed to identify and specify APD-related dysfunction in cognitive and reward factors. In a sample of incarcerated males (N = 116), we administered three tasks targeting distinct cognitive (perception, executive functioning, and probabilistic decision-making) and reward (magnitude and consciousness) factors. APD was associated with impaired perception when high magnitude rewards were at stake, regardless of reward consciousness. APD was associated with worse executive functioning during conscious high rewards, as well as worse inhibition during high rewards when working memory demands were high. There was no APD-related performance difference during probabilistic decision-making. These findings expose the multifaceted nature of cognitive-affective dysfunction in APD, highlighting the importance of systematic research and providing insight into treatment targets. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Childhood serotonergic function and early adult outcomes in youth with ADHD: A 15-year follow-up study.

Longitudinal studies have shown that clinical precursors of antisocial personality disorder (ASPD) include attention-deficit/hyperactivity disorder (ADHD) and more notably comorbid ADHD and conduct disorder (CD). Despite existing evidence for the purported role of abnormal serotonergic function in aggressive youth and adults, little evidence exists on the role of serotonin in the progression from childhood disruptive behavior disorders to adult psychopathology, including ASPD. This study examined the relation between serotonergic function in children diagnosed with ADHD and the development of ASPD in early adulthood. We hypothesized that low serotonin response to a pharmacological probe in childhood would predict the development of adult ASPD. Towards this goal we divided 40 adults (M = 37, F = 3), ages 23-26 (m-24.57, sd-2.33) diagnosed with childhood ADHD into 2 groups: participants with (n = 21) and without (n = 19) ASPD. We used logistic regression to assess whether serotonergic measures in childhood assessed via prolactin and cortisol responses to a fenfluramine challenge, would selectively predict the development of ASPD in early adulthood. Logistic regression models showed that low central serotonergic response in childhood indexed by cortisol response significantly predicted adult ASPD (Wald = 4.427, p = .035) but not ADHD diagnosis in adulthood. Adults without ASPD had the highest serotonergic response whereas adults with adolescent ASPD (i.e. early onset ASPD) had the lowest response. Thus we provide new evidence of the link between low serotonergic function in childhood and the development of ASPD in adulthood, particularly for boys with adolescent onset of ASPD. These findings are relevant for understanding the contribution of childhood neurobiology to risk for later ASPD.

Predictors of adult outcomes in clinically- and legally-ascertained youth with externalizing problems.

Externalizing problems (EP), including rule-breaking, aggression, and criminal involvement, are highly prevalent during adolescence, but the adult outcomes of adolescents exhibiting EP are characterized by heterogeneity. Although many youths' EP subside after adolescence, others' persists into adulthood. Characterizing the development of severe EP is essential to prevention and intervention efforts. Multiple predictors of adult antisocial personality disorder (ASPD) and legal outcomes of a large sample (N = 1205) of clinically- or legally-ascertained adolescents (ages 12-19 years) with severe EP were examined. Many psychosocial predictors hypothesized to predict persistence of EP demonstrated zero-order associations with adult outcomes, but accounted for little unique variation after accounting for baseline conduct disorder symptoms (CD) and demographic factors. Baseline measures of intelligence, which explained independent variation in legal outcomes, provided the only consistent exception to this pattern, though future work is needed to parse these effects from those of socioeconomic factors. CD severity during adolescence is a parsimonious index of liability for persistence of EP into adulthood that explains outcome variance above and beyond all other demographic and psychosocial predictors in this sample.

Sex Differences in Personality Disorders.

PURPOSE OF REVIEW: This review aims to give an overview on the current literature on sex differences in personality disorders and to highlight the potential of dimensional approaches. RECENT FINDINGS: Empirical findings on sex differences in personality disorders are inconsistent and appear to be highly dependent on study settings. Current studies have mainly focused on borderline and antisocial personality disorder and the question whether these are sex-specific representations of a common substrate. In general, sexes differ in the manifestation of personality disorders as well as in comorbidities. Criticism of the established categorical model led to an additional dimensional model of personality disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Investigations on sex differences in personality disorders are sparse and mainly limited to antisocial and borderline personality disorder. The introduction of a dimensional model offers the chance to re-think the construct of "personality disorder" and thereby also opens the possibility for a better understanding of sex differences.

A review of factors associated with severe violence in schizophrenia.

BACKGROUND: There is a modest but consistent association between violence and schizophrenia. The consequences of serious violence could be catastrophic for the victims, as well as the patients themselves and the community. Any knowledge that would help to prevent acts of serious violence would be of considerable value for the individual and the society. AIM: To identify external and clinical risk factors for serious violence in schizophrenia, in addition to considering the strength of the association between the factors assessed and severe violence. METHODS: This was accomplished by a literature survey. One-hundred and two relevant papers were identified that were published during the past 20 years. Forty-four papers were assessed for eligibility. In all, 27 studies including clinical or cognitive variables were reviewed systematically. An effect size was reported where an odds ratio (OR) could be identified or calculated from available data. Five external factors and six clinical domains were evaluated. RESULTS: Substance abuse is robustly linking schizophrenia and violence. Among the clinical factors, insight, impulsivity, psychopathy, motor speed and a global measure of cognition are the factors with the strongest empirical evidence for an association with severe violence. CONCLUSION: This is the first systematic review of risk factors for severe violence in schizophrenia, in which a great number of clinical and external factors have been evaluated. Most of the clinical factors have been compared on effect size. The identified factors that represent an increased risk of violence in patients with schizophrenia should be included in risk assessments.