Emotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown.

In total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores.

Compared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginal gyrus (SMG), especially between vermis VI and the SMG in the attention networks, and lower RSFC between the right supplementary motor area and right lateral parietal area. Lower gray matter (GM) volume in the SMG was also found. RSFC was significantly correlated with clinical rating scale scores for all patients with ED due to ADHD or MDD. GM change was correlated with ED and MDD rating scale scores.

The cerebellum and attention networks might play major roles in ED pathophysiology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.

Ocular abnormalities and visual dysfunction have been associated with autism spectrum disorder (ASD). Our study assessed the risks of developing retinal diseases in individuals with ASD.

In all, 18 874 patients with ASD and 188 740 controls were selected from the Taiwan National Health Insurance Research Database between 2001 and 2009. The control group was matched based on demographic characteristics and medical and ophthalmological comorbidities. The hazard ratios (HRs) with 95% confidence intervals were calculated with Cox-regression analyses adjusted for selected confounders.

Individuals with ASD had a higher incidence of developing retinal diseases (1.48‰ vs 0.73‰, P < .001), and the diagnosis of retinal diseases occurred earlier than the controls (3.73 vs 6.28 years, P < .001). When compared to the control group, the HR of developing retinal diseases in the ASD group was 1.75 (95%: 1.04-2.94) and 7.84 (95%: 3.51-17.47) for retinal detachment. There was no association between the cumulative daily dose of atypical antipsychotics and the incidence of retinal diseases in the ASD group.

Individuals with ASD have a higher risk of developing retinal detachment and are diagnosed with retinal diseases earlier than controls. Future research is needed to elucidate the mechanisms mediating the progression of retinal diseases in the ASD population.

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.

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.

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.

“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.

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.

Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.

A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.

There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).

The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

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.

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.

The concurrent incidence of autoimmune comorbidities in obsessive–compulsive disorder (OCD) is known. However, the association between OCD and related autoimmune skin diseases (ASDs) has not been well studied.

This study aimed to investigate the association between OCD and the risk of ASDs.

To assess the risk of developing ASDs, we recruited 44 324 patients with OCD and 177 296 matched controls from the National Health Insurance Research Database in Taiwan. A Cox regression model was used for the analyses.

After adjusting for confounders, an increased risk of ASDs among the patients with OCD (adjusted hazard ratio [aHR]: 6.36; 95% confidence interval [CI]: 5.43-7.45) was found when compared to the controls. Statistically significant associations were found between OCD and seven individual ASDs, including psoriasis (aHR: 12.52; 95% CI: 8.78-17.85), lichen planus (aHR: 27.22; 95% CI: 13.09-56.60), alopecia areata (aHR: 13.69; 95% CI: 9.38-19.98), autoimmune bullous diseases (aHR: 4.30; 95% CI: 2.03-9.11), hidradenitis suppurativa (aHR: 29.95; 95% CI: 3.35-267.62), vitiligo (aHR: 9.35; 95% CI: 5.35-16.32), and lupus erythematosus (aHR: 2.10; 95% CI: 1.52-2.91).

Patients with OCD had an increased risk of developing ASDs compared to matched controls. Further studies are required to clarify the underlying mechanisms.

Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug reactions, including nocturnal enuresis and urinary incontinence. This side effect can be burdensome and lead to medication nonadherence and psychotic relapse. Evidence to guide treatment of clozapine-induced nocturnal enuresis and urinary incontinence is sparse. We therefore aimed to synthesize the evidence base to guide management for clinicians, patients, and their carers.

We systematically searched PubMed, Embase, PsycInfo, CINAHL, and the Cochrane Trial Registry databases from inception to May 2021 for publications on management of clozapine-induced nocturnal enuresis and urinary incontinence using a PROSPERO preregistered search strategy.

We identified 22 case reports and case series describing 74 patients. Interventions included clozapine dose reduction, nonpharmacological treatment, and pharmacological treatments. Among pharmacological treatments, desmopressin, oxybutynin, trihexyphenidyl, tolterodine, imipramine, amitriptyline, ephedrine, pseudoephedrine, aripiprazole, and verapamil were associated with complete resolution of nocturnal enuresis and urinary incontinence. Balancing evidence for effectiveness against risk of adverse effects, we developed a management framework for clozapine-induced nocturnal enuresis and urinary incontinence.

Following assessment of urological, psychiatric, pharmacological, and common comorbid medical issues, first-line treatments should be nonpharmacological, including bathroom alarms, voiding before bedtime, and nocturnal fluid restriction. If these interventions do not provide adequate relief, aripiprazole should be trialed. Desmopressin may be considered for severe refractory cases, but monitoring for hyponatremia is essential.

The aim of the post hoc analysis was to better understand the efficacy and safety of cariprazine in patients with schizophrenia for less than 5 years (early stage) and for more than 15 years (late stage).

Data from three phase II/III randomized, double-blind, placebo-controlled trials with similar design in patients with acute exacerbation of schizophrenia were pooled and patients with early and late stage of schizophrenia were determined. A mixed-effects model for repeated measures approach was applied and least square (LS) mean changes from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) total and factor scores were reported. Descriptive statistics were used for safety analyses including treatment emergent adverse events (TEAEs) and discontinuation rates.

Overall, 460 patients were identified as being in the early and 414 in the late stage of schizophrenia. The pooled analysis evaluating mean change from baseline to week 6 in the PANSS total score indicated statistically significant difference between cariprazine and placebo in favor of cariprazine in both the early (LS mean difference [LSMD] −7.5 P < .001) and late stage (LSMD −6.7, P < .01) subpopulation. Early stage patients experienced similar amount of TEAEs (CAR 67.3%, PBO 54.1%) as patients in the late stage (CAR 69.6%, PBO 65.6%).

In conclusion, cariprazine, a potent D3-D2 partial agonist has been found to be safe and effective in the treatment of early and late stage schizophrenia.

Analysis of efficacy and tolerability of vortioxetine 20 mg/day, and optimal timing of dose adjustment, in patients with major depressive disorder (MDD).

Pooled analysis of six randomized, fixed-dose studies of vortioxetine 5 to 20 mg/day. Mean change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score was analyzed by vortioxetine dose using a mixed model for repeated measures. Tolerability was assessed over the 8-week treatment period and from day 8 (ie, following dose increase to 20 mg/day). Data from three randomized, flexible-dose studies were examined for frequency and timing of dose adjustment.

A clear dose–response relationship for vortioxetine was confirmed in terms of improvement in MADRS total score. Significant differences vs placebo were seen for vortioxetine 20 mg/day from week 2 onwards; vortioxetine 10 mg did not separate from placebo until week 4. At week 8, mean change in MADRS total score from baseline was significantly greater for vortioxetine 20 mg/day vs 10 mg/day (difference, −1.03 points; P < .05). Incidence of adverse events was not increased in patients who received vortioxetine 20 mg/day vs 10 mg/day. In flexible-dose studies, dosage was increased to 20 mg/day after 1 week in 48.0% of patients; final dosage was 20 mg/day in 64.3% of patients.

Vortioxetine 20 mg is significantly more effective than vortioxetine 10 mg in patients with MDD, with a similar tolerability profile. In flexible-dose studies, almost half of all patients received 20 mg/day after 1 week and two-thirds received 20 mg/day as their final dosage.

The clinical value of the identification of mood disorders in patients with acute coronary syndrome (ACS) is well established. However, assessment based on DSM criteria presents some limitations. This study aimed to provide an innovative strategy for evaluating the spectrum of mood disturbances in ACS.

A total of 288 patients with a first episode of ACS underwent interviews based on DSM-IV-TR criteria (major depressive disorder, minor depression, and dysthymia), Diagnostic Criteria for Psychosomatic Research-DCPR (demoralization and type A behavior), and the Clinical Interview for Depression-CID. Additional self-report inventories (psychological well-being and distress) were administered. A total of 100 consecutive patients who satisfied criteria for DSM-IV-TR depression or DCPR demoralization were enrolled in a randomized controlled trial on a sequential combination of cognitive-behavioral and well-being therapy (CBT/WBT) vs clinical management (CM) and reassessed up to 30-month post-intervention.

A total of 29.9% of patients showed a DSM-IV-TR depressive syndrome. Inclusion of demoralization and type A identified psychological distress in 58% of the sample. According to CID, reactivity to social environment, fatigue, depressed mood, and somatic anxiety were the most common symptoms. Somatic symptoms were significantly associated with DSM-IV-TR depression (fatigue and changes of appetite), whereas environmental reactivity with demoralization. Both depression and demoralization were associated with higher distress and lower well-being. Unlike CM, CBT/WBT was significantly associated with decrease of guilt, pessimism, fatigue, and early insomnia (CID).

The findings indicate that standard psychiatric approach identifies only a narrow part of mood disturbances affecting ACS patients. A more articulated assessment unravels specific clinical configurations that may entail prognostic and therapeutic implications.

Clinicians who recognize functional neurological disorders (FND) may not share that diagnosis with patients. Poor communication delays treatment and contributes to substantial disability in FND. Diagnostic (ICD-10) coding, one form of medical communication, offers an insight into clinicians’ face-to-face communication. Therefore, quantifying the phenomenon of noncoding, and identifying beliefs and practice habits that reduce coding, may suggest routes to improve medical communication in FND.

We reviewed all pediatric neurology consultations in our hospital from 2017 to 2020, selecting those in which neurologists explicitly stated an FND-related diagnosis (N = 57). We identified the neurological symptoms and ICD-10 codes assigned for each consultation. In parallel, we reviewed all encounters that utilized FND-related codes to determine whether insurers paid for this care. Finally, we assessed beliefs and practices that influence FND-related coding through a nationwide survey of pediatric neurologists (N = 460).

After diagnosing FND, neurologists selected FND-related ICD-10 codes in only 22.8% of consultations. 96.2% of neurologists estimated that they would code for non-epileptic seizure when substantiated by electroencephalography; in practice, they coded for 36.7% of such consultations. For other FND manifestations, neurologists coded in only 13.3% of cases. When presented with FND and non-FND scenarios with equal levels of information, neurologists coded for FND 41% less often. The strongest predictor of noncoding was the outdated belief that FND is a diagnosis of exclusion. Coding for FND never resulted in insurance nonpayment.

Noncoding for FND is common. Most factors that amplify noncoding also hinder face-to-face communication. Research based on ICD-10 coding (eg, prevalence and cost) may underestimate the impact of FND by >fourfold.

Increasing research is stressing the importance of identifying autistic traits (ATs) in clinical and general populations. University students may be a group at higher risk for the presence of ATs. Recently, specific attention has been paid to camouflaging strategies used by subjects in the autism spectrum in order to cope with the social environment. The aim of this work was to evaluate the prevalence of ATs and camouflaging behaviors in a population of University students.

Subjects were requested to anonymously fill out through an online form the Adult Autism Subthreshold Spectrum and the Camouflaging AT Questionnaire.

ATs were more represented among males and among students of specific fields of study. Camouflaging behaviors were significantly more frequent among subjects with more severe autism spectrum symptoms, without differences depending from sex.

Our study confirms the strong association between ATs and camouflaging behaviors and the relationship between ATs, sex, and specific fields of study.