The endogenous opioid system affects metabolism, including weight regulation. Evidence from preclinical and clinical studies provides a rationale for targeting this system to mitigate weight-related side effects of antipsychotics. This review describes the role of the opioid system in regulating weight and metabolism, examines the effects of opioid receptor antagonism on those functions, and explores the use of opioid antagonists to mitigate antipsychotic-associated weight gain and/or metabolic effects.

A PubMed literature search was conducted to identify representative opioid antagonists and associated preclinical and clinical studies examining their potential for the regulation of weight and metabolism.

The mu opioid receptor (MOR), delta opioid receptor (DOR), and kappa opioid receptor (KOR) types have overlapping but distinct patterns of central and peripheral expression, and each contributes to the regulation of body weight and metabolism. Three representative opioid antagonists (eg, naltrexone, samidorphan, and LY255582) were identified for illustration. These opioid antagonists differed in their receptor binding and pharmacokinetic profiles, including oral bioavailability, systemic clearance, and half-life, and were associated with varying effects on food intake, energy utilization, and metabolic dysregulation.

Preclinical and clinical data suggest that antagonism of the endogenous opioid system is a mechanism to address antipsychotic-associated weight gain and metabolic dysregulation. However, evidence suggests that the differing roles of MOR, DOR, and KOR in metabolism, together with the differences in receptor binding, pharmacokinetic, and functional activity profiles of the opioid receptor antagonists discussed in this review, likely contribute to their differential pharmacodynamic effects and clinical outcomes observed regarding antipsychotic-associated weight gain.

In the present study, we aimed to perform a systematic review evaluating the cognitive performance of patients with hoarding disorder (HD) compared with controls. We hypothesized that HD patients would present greater cognitive impairment than controls.

A systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit. The search terms were “hoarding disorder,” “cognition,” “neuropsychology,” “cognitive impairment,” and “cognitive deficit.” We included original studies assessing cognitive functioning in patients with HD.

We retrieved 197 studies initially. Of those, 22 studies were included in the present study. We evaluated 1757 patients who were 41 to 72 years old. All selected studies comprised case–control studies and presented fair quality. Contrary to our hypothesis, HD patients showed impairment only in categorization skills in comparison with controls, particularly at confidence to complete categorization tasks. Regarding attention, episodic memory, working memory, information-processing speed, planning, decision-making, inhibitory control, mental flexibility, language, and visuospatial ability, HD patients did not show impairment when compared with controls. There is a paucity of studies on social cognition in HD patients, although they may show deficits. The impact of emotion in cognition is also understudied in HD patients.

Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls. Further work is needed to explore social cognition and the impact of emotion in cognitive performance in HD patients.

To investigate the effect of cariprazine on cognitive symptom change across bipolar I disorder and schizophrenia.

Post hoc analyses of 3- to 8-week pivotal studies in bipolar I depression and mania were conducted; one schizophrenia trial including the Cognitive Drug Research System attention battery was also analyzed. Outcomes of interest: Montgomery-Åsberg Depression Rating Scale [MADRS], Functioning Assessment Short Test [FAST], Positive and Negative Syndrome Scale [PANSS]). LSMDs in change from baseline to end of study were reported in the overall intent-to-treat population and in patient subsets with specified levels of baseline cognitive symptoms or performance.

In patients with bipolar depression and at least mild cognitive symptoms, LSMDs were statistically significant for cariprazine vs placebo on MADRS item 6 (3 studies; 1.5 mg=−0.5 [P<.001]; 3 mg/d=−0.2 [P<.05]) and on the FAST Cognitive subscale (1 study; 1.5 mg/d=−1.4; P=.0039). In patients with bipolar mania and at least mild cognitive symptoms, the LSMD in PANSS Cognitive subscale score was statistically significant for cariprazine vs placebo (3 studies; −2.1; P=.001). In patients with schizophrenia and high cognitive impairment, improvement in power of attention was observed for cariprazine 3 mg/d vs placebo (P=.0080), but not for cariprazine 6 mg/d; improvement in continuity of attention was observed for cariprazine 3 mg/d (P=.0012) and 6 mg/d (P=.0073).

These post hoc analyses provide preliminary evidence of greater improvements for cariprazine vs placebo across cognitive measures in patients with bipolar I depression and mania, and schizophrenia, suggesting potential benefits for cariprazine in treating cognitive symptoms.

“Subsyndromal” obsessive-compulsive disorder symptoms (OCDSs) are common and cause impaired psychosocial functioning. OCDSs are better captured by dimensional models of psychopathology, as opposed to categorical diagnoses. However, such dimensional approaches require a deep understanding of the underlying neurocognitive drivers and impulsive and compulsive traits (ie, neurocognitive phenotypes) across symptoms. This study investigated inhibitory control and self-monitoring across impulsivity, compulsivity, and their interaction in individuals (n = 40) experiencing mild–moderate OCDSs.

EEG recording concurrent with the stop-signal task was used to elicit event-related potentials (ERPs) indexing inhibitory control (ie, N2 and P3) and self-monitoring (ie, error-related negativity and correct-related negativity (CRN): negativity following erroneous or correct responses, respectively).

During unsuccessful stopping, individuals high in both impulsivity and compulsivity displayed enhanced N2 amplitude, indicative of conflict between the urge to respond and need to stop (F(3, 33) = 1.48, P < .05, 95% Cl [−0.01, 0.001]). Individuals high in compulsivity and low in impulsivity showed reduced P3 amplitude, consistent with impairments in monitoring failed inhibitory control (F(3, 24) = 2.033, P < .05, 95% CI [−0.002, 0.045]). Following successful stopping, high compulsivity (independent of impulsivity) was associated with lower CRN amplitude, reflecting hypo-monitoring of correct responses (F(4, 32) = 4.76, P < .05, 95% CI [0.01, 0.02]), and with greater OCDS severity (F(3, 36) = 3.32, P < .05, 95% CI [0.03, 0.19]).

The current findings provide evidence for differential, ERP-indexed inhibitory control and self-monitoring profiles across impulsive and compulsive phenotypes in OCDSs.

To better understand current practices of U.S.-based physicians in the management of Tourette syndrome (TS) and identify gaps that may be addressed by future education.

Two survey instruments were developed to gather data on management of TS and perceptions from physicians and caregivers of children with TS. The clinician survey was developed in consultation with a TS physician expert and utilized clinical vignettes to assess and quantify practice patterns. The caregiver survey was adapted from the clinician survey and other published studies and gathered details on diagnosis, treatment, and perceptions regarding management.

Data included responses from 138 neurologists (including 57 pediatric neurologists), 162 psychiatrists (including 42 pediatric psychiatrists), and 67 caregivers. Most (65%) pediatric neurologists rely solely on clinical findings to make a diagnosis, whereas the majority of other specialists utilize additional testing (eg, neuroimaging, lab testing, and genetics). Most psychiatrists (96%) utilize standardized criteria to make a diagnosis, whereas 22% of neurologists do not. Many physicians (44% of psychiatrists and 20% of neurologists) use pharmacotherapy to treat a patient with “slightly bothersome” tics and no functional impairment, whereas caregivers favored behavioral therapy. Most (76%) caregivers preferred to make the final treatment decision, whereas 80% of physicians preferred equal or physician-directed decision-making.

This study provides insight into practice patterns and perceptions of U.S.-based neurologists and psychiatrists in managing TS. Results highlight the potential value of physician education, including diagnostic approach, tic management and monitoring, involvement of caregivers in decision-making, and updates on TS management.

Evidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones.

To compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs.

This cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected.

A total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P < .05) and had higher levels of ghrelin (P = .002), and lower levels of CRP (P = .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed.

Profiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.

Attentional problems are common and have been associated with multiple psychiatric disorders. This study examined problems of sustained attention across a range of psychiatric disorders using a validated computerized trans-diagnostic attentional paradigm (a continuous performance task). We hypothesized that multiple psychiatric disorders, particularly attention deficit hyperactivity disorder (ADHD), would be associated with pronounced attentional problems.

Totally, 576 non-treatment seeking participants (aged 18–29 years) were enrolled from general community settings, provided demographic variables, and underwent clinical assessments to detect mental health disorders. Each participant underwent the rapid visual information processing task, a validated computerized test measuring sustained attention. The two measures of sustained attention were the sensitivity index and target detection (proportion of targets detected). The profile of attentional deficits was examined across different disorders using z-scores relative to controls.

Participants with social phobia, obsessive-compulsive disorder (OCD), bulimia nervosa, and intermittent explosive disorder showed the greater impairment in target sensitivity, all with effect sizes of at least 0.8. Target detection was impaired across multiple disorders, with OCD and binge eating disorder exhibiting the most pronounced impairment. Post-traumatic stress disorder (PTSD) and compulsive sexual behavior were associated with particularly spared performance on both measures.

These data indicate that impaired attention is non-specific for ADHD and in fact several other disorders are associated with markedly larger deficits. Instead of clinicians assuming sustained attention problems are due to ADHD, a variety of disorders should be screened for when people report attentional problems. Future work should examine the contribution of comorbidities and psychoactive substances (prescribed or illicit) to the profiles identified.

Obsessive-compulsive disorder (OCD) is one of the most common neuropsychiatric disorders with lifetime prevalence higher than that of schizophrenia and bipolar disorders. Inadequate response to available pharmacological and psychotherapeutic interventions is common in OCD. Adjunctive brain stimulation methods to address the inadequate treatment response in OCD have found a special interest in research. This study aimed to examine the efficacy of adjunctive deep transcranial magnetic stimulation (dTMS) in ameliorating the symptoms of OCD and the effect of dTMS on activation of brain regions while performing the Stroop task using functional magnetic resonance imaging (fMRI).

A total of 41 patients were assessed for the study out of which 15 OCD patients received 10 sessions of high-frequency dTMS using the H7 coil to target the anterior cingulate cortex and the medial prefrontal cortex over a period of 2 weeks. The Yale-Brown Obsessive-Compulsive Scale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale were used for the pre- and post-stimulation clinical assessment. fMRI was used to measure the activation of brain regions while performing the Stroop task.

There was a significant improvement in the obsessive-compulsive, anxiety, and depressive symptoms after the 2 weeks of the dTMS treatment. A significant decrease in the activation of left caudate nucleus and adjacent white matter was noted while performing the Stroop task after the dTMS treatment.

The study provides preliminary evidence for functional correlates of effectiveness of dTMS as an adjunctive treatment modality for OCD.

Prior research suggests that religiosity may be associated with healthier levels of mental health in certain domains (eg, higher self-esteem and lower rates of substance use problems). However, very little is known about religiosity and impulsive plus compulsive tendencies. This study examined associations between religiosity and impulsive and compulsive behaviors and traits among university students.

Nine thousand, four hundred and forty-nine students received a 156-item anonymous online survey which assessed religiosity, alcohol and drug use, mental health issues, and impulsive and compulsive traits. Two groups of interest were defined: those with high religiosity, and those with low religiosity, based on z-scores. The two groups were compared on the measures of interest.

Three thousand, five hundred and seventy-two university students (57.1% female) responded to the survey. Those with high levels of organizational religious activity, as well as those with high levels of intrinsic or subjective religiosity, differed from their fellow students in having better self-esteem, being less likely to have alcohol or drug problems, and generally being less impulsive in terms of attention and planning. Compulsivity did not differ between groups. Associations were of small effect size except for the link between religiosity and lower impulsivity, which was of medium effect size.

This study shows a link between higher religiosity and lower impulsivity, as well as higher levels of mental health across several domains. Whether these associations are causal—and if so, the direction of such causality—requires rigorous longitudinal research.

Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological correlates of adult forms of ASD and of those subthreshold ASD manifestations frequently found in relatives of ASD probands, known as broad autism phenotype (BAP). This work aimed to evaluate circulating levels of TRP and metabolites of KYN pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables’ levels and ASD symptoms.

A sample of ASD adults, together with a group of first-degree relatives (BAP group) and unrelated CTLs were assessed by means of psychometric scales. Circulating levels of TRP, KYN, quinolinic acid (QA), and kynurenic acid (KYNA) were assessed in all subjects.

ASD patients reported significantly higher total scores than the other groups on all psychometric scales. BAP subjects scored significantly higher than CTLs. ASD patients reported significantly lower TRP levels than BAP and CTL groups. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP groups than in CTLs. Specific patterns of associations were found between autism symptoms and biochemical variables.

Our findings confirm in adult samples the presence of altered TRP metabolism through KYN pathway. The intermediate alterations reported among relatives of ASD patients further stress the presence of a continuum between subthreshold and full-threshold ASD phenotypes also from a biochemical perspective.