Clozapine, relapse, and adverse events: a 10-year electronic cohort study in Canada.

BACKGROUND: Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings. AIMS: To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts. METHOD: Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics. RESULTS: In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83-0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49-0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18-1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively. CONCLUSIONS: Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.

Copy Number Variation Analysis of Aggressive Behaviour in Schizophrenia.

INTRODUCTION: An increased proclivity towards violence is often associated with those diagnosed with schizophrenia (SCZ), despite contradictory findings from prior studies exploring the association between violence and SCZ. Evidence has shown that certain comorbidities, specifically the presence of a substance use disorders, can result in increased aggression in those with SCZ. Copy number variation (CNV) load has also previously been implicated in the genetic vulnerability of individuals with SCZ. For this study, we aimed to determine whether CNV load correlates with increased violence in SCZ. METHODS: Community-dwelling patients diagnosed with SCZ spectrum disorders (n = 203) were recruited from a non-forensic population. The assessment for aggression was completed using a cross-sectional and retrospective design, and CNV analysis was conducted analysing genomic DNA using the Illumina Omni 2.5 array. RESULTS: No correlation between the number of CNV events (either deletion or duplication) and the severity of the physical violence episode index was found. However, there was a significant association between larger deletion events across the violent behaviours under investigation. DISCUSSION: These results need to be confirmed in more extensive studies using standardized tools developed for non-forensic populations, such as the Brown-Goodwin Scale of Aggression.

GWAS of biological aging to find longevity genes in schizophrenia.

Schizophrenia (SCZ) is a severe psychotic disorder associated with premature mortality and aging. Moreover, the symptoms and progression of psychiatric disorders in general are associated with decreased lifespan, biological aging, and poorer medical outcomes. In this study, we investigated the relationship between several epigenetic clocks and scanned the entire genome for association in a cohort of SCZ individuals (n = 107). Biological age was computed from blood DNA methylation (DNAm) and tested for association against  common  variants across the genome using general linear models. Genes affecting epigenetic age acceleration in our cohort were found mainly when using the telomeric length clock rather than the other biological clocks. These findings pair with existing evidence that there are some genes associated with longevity and suggest further investigations of  putative biological mechanisms for morbidity and premature mortality, not only in patients with SCZ but also in the general population.

Adverse Childhood Experiences and Offending as a Function of Acquired Brain Injury Among Men in a High Secure Forensic Psychiatric Hospital.

BACKGROUND: Acquired brain injury (ABI) is a serious problem that disproportionately affects individuals in correctional services, but relatively little is known about ABI risks and correlates in forensic psychiatric services. METHODS: We conducted a retrospective chart review of all admissions to a high secure forensic hospital in Ontario, Canada from January 2009 to December 2012 (n = 637) and collected data on ABI, psychiatric diagnoses, developmental disadvantage, criminal offending, and in-hospital aggression. A k-means cluster analysis was employed to assess risk factors by which men with ABI could be identified and multivariate general linear models were used to identify ABI-related differences in offending history and in-hospital aggression. RESULTS: One-fifth of the men had a documented ABI indicator. Based on our cluster analysis, ABI was more likely to be identified by greater adverse childhood experiences (ACEs), more health problems from pregnancy to childhood, and lower socioeconomic status, suggesting that ABI within the forensic context is associated with greater developmental disadvantage. Men with ABI had more serious pre-admission offences, but not more serious admission offences or in-hospital aggression. Men with ABI were more likely than those without to have higher scores on the Violence Risk Appraisal Guide or to be diagnosed with mood and personality disorders, and less likely to have a schizophrenia diagnosis, suggesting an association between ABI and general mental health pathologies but not with psychotic illness. CONCLUSIONS: The disadvantage of ABI among men in forensic psychiatric hospitals is most likely evinced in antisocial behaviour rather than serious mental illness. Given that ACEs are likely to precede or co-occur with ABI, strategies that mitigate ACEs hold promise for ABI prevention.

The endocannabinoid system in borderline personality disorder and antisocial personality disorder: A scoping review.

Individuals with borderline personality disorder (BPD) or antisocial personality disorder (ASPD) are overrepresented in forensic settings. Yet, despite the burden these disorders place on healthcare and criminal justice systems, there remains a lack of evidence-based pharmacological treatments. Epidemiological data have shown that comorbid cannabis use disorders are common in BPD and ASPD. ∆9 -Tetrahydrocannabinol, the primary psychoactive constituent of cannabis, is an exogenous cannabinoid that stimulates the endocannabinoid system (ECS). Hence, an investigation of the ECS in these conditions is warranted. This scoping review screened 105 records and summarized the extant research on the ECS in ASPD (n = 69) and BPD (n = 61) participants. Preliminary results suggest that alterations of the ECS may be present in these disorders. Although research examining the ECS in personality disorders is still in its infancy, more research is warranted given initial positive findings.

The Gut Microbiome in Depression and Potential Benefit of Prebiotics, Probiotics and Synbiotics: A Systematic Review of Clinical Trials and Observational Studies.

An emerging body of literature demonstrates differences in the gut microbiome (GMB) of patients with major depressive disorder (MDD) compared to healthy controls (HC), as well as the potential benefits of prebiotic, probiotic, and synbiotic treatment. We conducted a systematic review of 24 observational studies (n = 2817), and 19 interventional trials (n = 1119). We assessed alpha diversity, beta diversity, and taxa abundance changes in patients with MDD relative to HC, as well as the effect of prebiotics, probiotics, and synbiotics on depressive symptoms in individuals with clinical or subclinical depression. We observed no significant differences in alpha diversity but a significant difference in beta diversity between patients with MDD and HC. There were fluctuations in the abundance of specific taxa in patients with MDD relative to HC. Probiotic and synbiotic, but not prebiotic, treatment showed a modest benefit in reducing depressive symptoms in patients with MDD over four to nine weeks. The GMB profiles of patients with MDD differ significantly from HC, but further studies are needed to elucidate the benefits of prebiotic, probiotic and synbiotic treatments relative to antidepressants and over longer follow-up before these therapies are implemented into clinical practice.

Psychopathy in women: insights from neuroscience and ways forward for research.

Psychopathy is a severe form of personality disturbance, resulting in a detrimental impact on individuals, healthcare systems, and society as a whole. Until relatively recently, most research in psychopathy has focused on male samples, not least because of its link with criminal behavior and the large proportion of violent crime committed by men. However, psychopathy in women also leads to considerable problems at an individual and societal level, including substance misuse, poor treatment outcomes, and contribution to ever-increasing numbers of female prisoners. Despite this, due to relative neglect, most research into adult female psychopathy is underpowered and outdated. We argue that the field needs revitalizing, with a focus on the developmental nature of the condition and neurocognitive research. Recent work international consortia into conduct disorder in female youth-a precursor of psychopathy in female adults-gives cause for optimism. Here, we outline key strategies for enriching research in this important field with contemporary approaches to other psychiatric conditions.

Nutritional supplementation in the treatment of violent and aggressive behavior: A systematic review.

Aggression in correctional and psychiatric settings is relatively common and has a negative effect on physical and mental health both among inmates/clients and staff, as well as organizational-level functioning. The aim of the present study was to critically review the evidence on the effectiveness of nutritional supplements in reducing aggression and violence to contribute to a better understanding of options available for managing aggressive behaviors in adults. The EMBASE, MEDLINE, PsycINFO, Cochrane Library, and PubMed databases were searched for effectiveness studies published in English anytime up until March 2020. Study quality was assessed using the Mixed Methods Appraisal Tool. Altogether, 14 studies met inclusion criteria; 2 investigated micronutrients, 10 examined macronutrients, while further 2 examined a combination of micro and macronutrients. Out of the 14 studies, 5 reported a beneficial effect of nutritional supplementation (omega-3 fatty acids, vitamins/minerals, S-adenosyl-l-methionine, or tryptophan). Five studies did not report a significant beneficial effect of nutritional supplementation (omega-3 fatty acids, folic acid, tryptophan, broad range supplement containing vitamins and fatty acids, and fatty acids in augmentation with valproic acid), while four studies reported mixed effects (on l-tryptophan, broad-range micronutrient formula, folic acid, and omega-3 fatty acids). The results overall indicated that research in this area is in its infancy: very few studies examined the same composition of nutritional supplementation and when they did so the results were contradictory. The methodological shortcoming of existing studies and directions for future research are discussed to facilitate high-quality research in this evolving area of nutritional psychiatry.

DAT1 polymorphism associated with poor decision-making in males with antisocial personality disorder and high psychopathic traits.

Studies suggest that abnormalities of the dopaminergic system underlie decision-making deficits, a hallmark of antisocial personality disorder (ASPD) and psychopathy. The dopamine transporter gene (DAT1) is of particular interest due to a polymorphism that controls dopamine transporter (DAT) activity. However, the association between DAT1 genotypes and decision-making in ASPD has never been studied. The current study investigated the effect of DAT1 genotype on decision-making, as measured by the Iowa Gambling Task (IGT), in ASPD and healthy controls. A total of 17 participants with ASPD and 16 healthy control participants without ASPD were sampled. The Hare Psychopathy Checklist-Revised and the IGT were administered to all participants. All participants provided blood samples for genotyping. Data revealed a novel interaction effect between DAT1 genotype and diagnosis, whereby ASPD participants with low DAT activity genotypes performed significantly worse on the IGT and selected from disadvantageous decks more often, whereas the low DAT activity genotype in the healthy control group was associated with better performance on the IGT, and they selected from disadvantageous decks less often. We demonstrate, for the first time, that low DAT activity genotypes in ASPD with high psychopathic traits contribute to poor decision-making.

Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review.

Altered activity of fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system, has been implicated in several neuropsychiatric disorders, including major depressive disorder (MDD). It is speculated that increased brain FAAH expression is correlated with increased depressive symptoms. The aim of this scoping review was to establish the role of FAAH expression in animal models of depression to determine the translational potential of targeting FAAH in clinical studies. A literature search employing multiple databases was performed; all original articles that assessed FAAH expression in animal models of depression were considered. Of the 216 articles that were screened for eligibility, 24 articles met inclusion criteria and were included in this review. Three key findings emerged: (1) FAAH expression is significantly increased in depressive-like phenotypes; (2) genetic knockout or pharmacological inhibition of FAAH effectively reduces depressive-like behavior, with a dose-dependent effect; and (3) differences in FAAH expression in depressive-like phenotypes were largely localized to animal prefrontal cortex, hippocampus and striatum. We conclude, based on the animal literature, that a positive relationship can be established between brain FAAH level and expression of depressive symptoms. In summary, we suggest that FAAH is a tractable target for developing novel pharmacotherapies for MDD.

Sex differences in youth with mental health problems in inpatient, outpatient and youth justice settings.

BACKGROUND: Approximately 40-70% of justice-involved youth have untreated mental health problems. There is no current research that directly compares the mental health profiles of youth involved in the justice system to that of inpatients and outpatients. The research reported is significant because it directly compares the needs of these population by use of the same suite of standardized assessment tools. METHODS: The sample consisted of 755 youth aged 16-19 years recruited from youth justice and mental health facilities in Ontario, Canada. Participants completed semi-structured assessment interviews using the interRAI child and youth suite of instruments to assess for internalizing and externalizing concerns as well as exposure to traumatic life events. RESULTS: Findings indicated that justice-involved youth experienced higher levels of certain types of trauma. Analyses examining sex differences indicated that, controlling for age, males in the youth justice group reported higher cumulative trauma compared to male outpatients but not inpatients. Females in the youth justice group reported experiencing higher cumulative trauma compared to female outpatients and inpatients. In addition, controlling for sex and age, the youth justice group reported lower internalizing symptoms scores than inpatients and outpatients. Finally, males in the youth justice group scored lower than inpatients in externalizing symptoms, whereas females within the youth justice group scored higher in externalizing symptoms compared to inpatients and outpatients. CONCLUSIONS: Results indicated that youth who are involved with the justice system exhibit significant psychosocial issues that represent complex service needs which require unique interventions in order to be addressed appropriately.

Single-Photon Emission Computed Tomography and Positron Emission Tomography Studies of Antisocial Personality Disorder and Aggression: a Targeted Review.

PURPOSE OF REVIEW: This paper aims to provide a comprehensive discussion of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies of antisocial personality disorder (ASPD) and aggression. RECENT FINDINGS: Among ASPD males with high impulsivity, the density of brainstem serotonin (5-HT) transporters shows a relationship with impulsivity, aggression, and ratings of childhood trauma. 5-HT1B receptor (R) binding in the striatum, anterior cingulate cortex, and orbitofrontal cortex (OFC) correlated with anger, aggression, and psychopathic traits in another study of violent offenders, most of whom were diagnosed with ASPD. Finally, the density of monoamine oxidase-A (MAO-A), a mitochondrial enzyme that degrades 5-HT, norepinephrine, and dopamine (DA), was reported as lower in the OFC and ventral striatum of ASPD. Among non-clinical populations, 5-HT4R binding, as an index of low cerebral 5-HT levels, has been associated with high trait aggression, but only in males. Furthermore, evidence suggests that individuals with high-activity MAO-A genetic variants compared with low-activity MAO-A allelic variants release more DA in the ventral caudate and putamen when exposed to violent imagery. There are very few PET or SPECT studies that exclusively sample individuals with ASPD. However, among ASPD samples, there is evidence of regional serotonergic abnormalities in the brain and alteration of neural MAO-A levels. Future studies should consider employing additional molecular probes that could target alternative neurotransmitter systems to investigate ASPD. Furthermore, examining different typologies of aggression in clinical and non-clinical populations using SPECT/PET is another important area to pursue and could shed light on the neurochemical origins of these traits in ASPD.

Correlation Between Violence and Antipsychotic Dosage in Schizophrenia: A Secondary Analysis of The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) Dataset.

INTRODUCTION: Violent behavior is more common in individuals with schizophrenia, compared to the general population. Studies suggest higher psychotic symptoms are predictive of greater violent behavior. On the other hand, violent behaviors are reduced with antipsychotic treatment. However, the relationship between antipsychotic dosage and violence has not been studied to date. Thus, we aimed to determine if there exists an association between antipsychotic dosage and violence scores and whether the maximum violence would be predictive of the final antipsychotic dosage. We hypothesized that the violence scores at the final assessment in the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) would be correlated with the corresponding drug dosage and the maximum violence severity score would be predictive of the final dosage. METHODS: Antipsychotic dosage at the end of the trial was converted into defined daily dosage and chlorpromazine equivalents (CPZe). Final and maximum violence sum scores were analyzed from the final violence assessment interviews. Spearman's rank-order correlation and linear regression analyses were used to analyze the relationship between the violence scores and standardized antipsychotic dosages. RESULTS: The analysis was on 952 individuals with schizophrenia. There was a significant association between maximum violence severity score and the final CPZe dosage (p=0.049). Exploratory analysis of age and ethnicity revealed younger non-white individuals to be at a higher risk of engaging in violent activities. DISCUSSION: Violence in schizophrenia is associated with poor illness course. Further studies focusing on violence in younger non-white individuals are warranted.

Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.

BACKGROUND: The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region. METHODS: We utilized monoamine oxidase A genotyping and seed-to-voxel-based functional connectivity to investigate the relationship between genotype and corticostriatal connectivity in 21 male participants with severe antisocial personality disorder and 19 male healthy controls. RESULTS: Dorsal striatal connectivity to the frontal pole and anterior cingulate gyrus differentiated antisocial personality disorder subjects and healthy controls by monoamine oxidase A genotype. Furthermore, the linear relationship of proactive aggression to superior ventral striatal-angular gyrus functional connectivity differed by monoamine oxidase A genotype in the antisocial personality disorder groups. CONCLUSIONS: These results suggest that monoamine oxidase A genotype may affect corticostriatal connectivity in antisocial personality disorder and that these functional connections may also underlie use of proactive aggression in a genotype-specific manner.

Examining the effect of social bonds on the relationship between ADHD and past arrest in a representative sample of adults.

BACKGROUND: Several studies have found a connection between attentional deficit hyperactivity disorder (ADHD) and criminal behaviour in clinical and prison samples of adults, but there is a lack of representative general population data on this. AIM: To test relationships between histories of ADHD and arrest. Our main research question was whether any such relationship is direct or best explained by co-occurring variables, especially indicators of social bonds. METHOD: Data were from a sample of 5,376 adults (18+) representative of the general population of Ontario, Canada. Logistic regression analysis was used to explore the relationship between self-reported arrest on criminal charges and ADHD as measured by the Adult Self Report Scale (ASRS-v1.1). Indicators of strong social bonds (post secondary education, household size) and weak bonds (drug use, antisocial behaviours, alcohol dependence) were also obtained at interview and included in the statistical models. RESULTS: In a main effects model, screening positive for ADHD was twice as likely (OR 2.05 CI 1.30, 3.14) and past use of medications for ADHD three times as likely (OR 3.94 CI 2.46, 6.22) to be associated with ever having been arrested. These associations were no longer significant after controls for weak and strong social bonds were added to the models. In the best fitting statistical model, ever having been arrested was not associated with ADHD, but it was significantly associated with indicators of strong and weak social bonds. CONCLUSIONS: The observed connection between ADHD and criminality may be better understood through their shared relationships with indicators of poor social bonds. These include antisocial behaviour more generally, but also drug use and failure to progress to any form of tertiary education, including vocational training. Copyright © 2017 John Wiley & Sons, Ltd.

From Clozapine to Cognitive Remediation.

OBJECTIVE: Although a minority of persons with schizophrenia (SCZ) commits violent acts, SCZ remains a risk factor for violence. Here, we present a broad overview of evidence-based treatments for violence in SCZ, including biological and psychosocial interventions. METHOD: We conducted MEDLINE and PsychINFO literature searches to retrieve articles relating to treatments for violent, hostile, or aggressive behaviours in SCZ. RESULTS: Clozapine shows the strongest evidence for treating the acute violence of SCZ. Other atypical antipsychotics also possess antiaggressive effects, although the evidence is not as robust as that for clozapine. Psychosocial treatments can be useful adjuncts to pharmacotherapy once patients' positive symptoms have stabilized. Cognitive behavioural therapy for psychosis and cognitive remediation are 2 psychosocial interventions that have demonstrated positive outcomes for violence in SCZ. Most psychosocial studies that examined violence as an outcome were conducted in forensic psychiatric settings. CONCLUSIONS: Effective treatments exist for persons with SCZ who pose a risk for violent and aggressive behaviour, although the overall evidence base remains relatively weak. More randomized controlled trials of programs showing evidence for reduction of violence in SCZ are required. Further research should delineate which patients could benefit from multimodal treatment and where and when such treatments are optimally delivered.

Adult attention deficit hyperactivity disorder symptom profiles and concurrent problems with alcohol and cannabis: sex differences in a representative, population survey.

BACKGROUND: Adult attention deficit hyperactivity disorder (ADHD) shows a robust association with alcohol and cannabis misuse, and these relationships are expressed differently in males and females. Manifestation of specific ADHD symptom profiles, even in the absence of the full disorder, may also be related to problems with alcohol and cannabis, although these relationships have not been investigated in epidemiological studies. To address this question, we studied the sex-specific associations of ADHD symptomatology with problematic alcohol and cannabis use in a representative sample of adults aged 18 years and older residing in Ontario, Canada. METHODS: Data were obtained from the Centre for Addiction and Mental Health Monitor, an ongoing cross-sectional telephone survey, between January 2011 and December 2013. Respondents (n = 5080) reported on current ADHD symptomatology, measured using the Adult ADHD Self-Report Version 1.1 Screener (ASRS-V1.1) and four additional items, and alcohol and cannabis use, which were measured using the Alcohol Use Disorders Identification Test (AUDIT) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), respectively. Logistic regression analyses were conducted in men and women to test the association of each ADHD symptom cluster (hyperactivity, inattentiveness, impulsivity) with problematic alcohol and cannabis use. RESULTS: After controlling for age, education, and comorbid internalizing and externalizing psychopathology, hyperactive symptoms were associated with problematic alcohol use in both men and women and with problematic cannabis use in men. Impulsive symptoms were independently associated with problematic cannabis use in men. By contrast, inattentive symptomatology predicted problems with alcohol and cannabis only in women. In all models, age was negatively associated with substance misuse and externalizing behavior was positively correlated and the strongest predictor of hazardous alcohol and cannabis use. CONCLUSIONS: ADHD symptom expression in adulthood is related to concurrent hazardous use of alcohol and cannabis. Distinctive ADHD symptom profiles may confer increased risk for substance misuse in a sex-specific manner.

Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the Development of Monoamine Oxidase Inhibitors.

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer's, and Parkinson's Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives were to determine the dose-occupancy relationship of moclobemide and the occupancy of phenelzine at typical clinical dosing. METHODS: Major depressive episode (MDE) subjects underwent [(11)C]harmine positron emission tomography scanning prior to and following 6 weeks of treatment with moclobemide or phenelzine. RESULTS: Mean brain MAO-A occupancies were 74.23±8.32% for moclobemide at 300-600 mg daily (n = 11), 83.75±5.52% for moclobemide at 900-1200 mg daily (n = 9), and 86.82±6.89% for phenelzine at 45-60 mg daily (n = 4). The regional dose-occupancy relationship of moclobemide fit a hyperbolic function [F(x) = a(x/[b + x]); F(1,18) = 5.57 to 13.32, p = 0.002 to 0.03, mean 'a': 88.62±2.38%, mean 'b': 69.88±4.36 mg]. Multivariate analyses of variance showed significantly greater occupancy of phenelzine (45-60mg) and higher-dose moclobemide (900-1200 mg) compared to lower-dose moclobemide [300-600 mg; F(7,16) = 3.94, p = 0.01]. CONCLUSIONS: These findings suggest that for first-line MDE treatment, daily moclobemide doses of 300-600mg correspond to a MAO-A occupancy of 74%, whereas for treatment-resistant MDE, either phenelzine or higher doses of moclobemide correspond to a MAO-A occupancy of at least 84%. Therefore, novel MAO inhibitor development should aim for similar thresholds. The findings provide a rationale in treatment algorithm design to raise moclobemide doses to inhibit more MAO-A sites, but suggest switching from high-dose moclobemide to phenelzine is best justified by binding to additional targets.

Patient Characteristics by Type of Hypersexuality Referral: A Quantitative Chart Review of 115 Consecutive Male Cases.

Hypersexuality remains an increasingly common but poorly understood patient complaint. Despite diversity in clinical presentations of patients referred for hypersexuality, the literature has maintained treatment approaches that are assumed to apply to the entire phenomenon. This approach has proven ineffective, despite its application over several decades. The present study used quantitative methods to examine demographic, mental health, and sexological correlates of common clinical subtypes of hypersexuality referrals. Findings support the existence of subtypes, each with distinct clusters of features. Paraphilic hypersexuals reported greater numbers of sexual partners, more substance abuse, initiation to sexual activity at an earlier age, and novelty as a driving force behind their sexual behavior. Avoidant masturbators reported greater levels of anxiety, delayed ejaculation, and use of sex as an avoidance strategy. Chronic adulterers reported premature ejaculation and later onset of puberty. Designated patients were less likely to report substance abuse, employment, or finance problems. Although quantitative, this article nonetheless presents a descriptive study in which the underlying typology emerged from features most salient in routine sexological assessment. Future studies might apply purely empirical statistical techniques, such as cluster analyses, to ascertain to what extent similar typologies emerge when examined prospectively.

A Primer for Increasing Competency in Forensic Psychiatry Research.

Empirical research is foundational to the discipline of forensic psychiatry. Candilis and Parker provide a cogent systematic review of the empirical literature on restoration of competence to stand trial using National Institutes of Health quality metrics. Components of the study methodology are highlighted, as they represent current best practices for conducting a systematic review. A discussion of strategies to increase empirical research uptake in forensic psychiatry is pursued alongside concrete examples of how the American Academy of Psychiatry and the Law Research Committee can help facilitate this goal.