Problems with cognitive flexibility have been associated with multiple psychiatric disorders, but there has been little understanding of how cognitive flexibility compares across these disorders. This study examined problems of cognitive flexibility in young adults across a range of psychiatric disorders using a validated computerized trans-diagnostic flexibility paradigm. We hypothesized that obsessive-compulsive spectrum disorders (eg, obsessive-compulsive disorder, trichotillomania, and skin-picking disorder) would be associated with pronounced flexibility problems as they are most often associated with irrational or purposeless repetitive behaviors.

A total of 576 nontreatment seeking participants (aged 18-29 years) were enrolled from general community settings, provided demographic information, and underwent structured clinical assessments. Each participant undertook the intra-extra-dimensional task, a validated computerized test measuring set-shifting ability. The specific measures of interest were total errors on the task and performance on the extra-dimensional (ED) shift, which reflects the ability to inhibit and shift attention away from one stimulus dimension to another.

Participants with depression and PTSD had elevated total errors on the task with moderate effect sizes; and those with the following had deficits of small effect size: generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), antisocial personality disorder, and binge-eating disorder. For ED errors, participants with PTSD, GAD, and binge-eating disorder exhibited deficits with medium effect sizes; those with the following had small effect size deficits: depression, social anxiety disorder, OCD, substance dependence, antisocial personality disorder, and gambling disorder.

These data indicate cognitive flexibility deficits occur across a range of mental disorders. Future work should explore whether these deficits can be ameliorated with novel treatment interventions.

Insomnia was associated with cerebral structural changes and Alzheimer’s disease. However, associations among cerebral perfusion, insomnia with cerebral small vessel disease (CSVD), and cognitive performance were little investigated.

This cross-sectional study included 89 patients with CSVDs and white matter hyperintensities (WMHs). They were dichotomized into the normal sleep and poor sleep group, according to Pittsburgh sleep quality index (PSQI). Baseline characteristics, cognitive performance, and cerebral blood flow (CBF) were measured and compared between the two groups. The association or correlation between cerebral perfusion, cognition, and insomnia was analyzed using binary logistic regression.

Our study found that declined MoCA score (P = .0317) was more prevalent in those with poor sleep. There was a statistical difference in the recall (P = .0342) of MMSE, the delayed recall (P = .0289) of MoCA between the two groups. Logistic regression analysis showed educational background (P < .001) and insomnia severity index (ISI) score (P = .039) were independently correlated with MoCA scores. Arterial spin labeling demonstrated that left hippocampal gray matter perfusion was significantly reduced (P = .0384) in the group with poor sleep. And, negative correlation was found between left hippocampal perfusion and PSQI scores.

In the patients with CSVDs, insomnia severity was associated with cognitive decline. Left hippocampal gray matter perfusion was correlated with PSQI scores in CSVDs.

Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day.

Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery–Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day).

After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day.

Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

The elevated prevalence of metabolic syndrome (MetS) in patients with depression has been associated with increased mortality. This post hoc analysis assessed the effect of treatment with lurasidone on risk of MetS in patients with bipolar depression.

Data used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (N = 1192), consisting of 1 monotherapy, and 2 adjunctive trials (lithium or valproate). Also analyzed was a 6-month open-label (OL) extension study (monotherapy, N = 316; adjunctive therapy, N = 497); and a 5-month, OL, stabilization phase followed by randomization to a 28-week DB, placebo-controlled, adjunctive therapy study with lurasidone (N = 490). MetS was defined based on NCEP ATP III criteria (2005 revision).

The proportion of patients with new-onset MetS was similar for lurasidone vs placebo in the short-term studies (monotherapy, 13.9% vs 15.3%; adjunctive therapy, 13.6% vs 11.0%); and remained stable during both the 6-month extension phase study (monotherapy, 15.2%; adjunctive therapy, 16.9%), and the 5-month stabilization study (adjunctive therapy, 12.2%). After 28 weeks of DB treatment (following 5-month treatment in the stabilization study), new onset MetS was observed at endpoint (OC) in 26.2% of the lurasidone group, and 30.8% of the placebo group.

This post hoc analysis found that both short and long-term treatment with lurasidone was associated with a relatively low risk for the development of MetS in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.

Although the association between chronotype and mood disorders has been consistently reported, conversely, attempts to measure the association between chronotype and anxiety symptoms have generated inconsistent results. We aimed at evaluating whether chronotype (assessed through subjective and objective measures) is associated with lifetime mood and panic-agoraphobic spectrum symptoms in healthy controls (HCs) and in patients with bipolar disorder (BD).

Overall, 173 subjects, patients with BD in euthymic phase (n = 76) and HC (n = 97), were evaluated through the reduced Morningness–Eveningness Questionnaire (rMEQ), actigraphy monitoring and mood and panic-agoraphobic spectrum self-report (MOODS-SR and PAS-SR). The discrepancy between objective (actigraphic-based) versus subjective (rMEQ-based) circadian typology was estimated through the Circadian Classification Discrepancy Index (CCDI).

rMEQ-based evening chronotype (ET) was associated with higher scores in MOODS-SR depressive and rhythmicity and vegetative functions domains in HC and BD.Both ET and morning chronotypes (MT) were associated with higher PAS-SR scores in BD only. Actigraphic-based MT was associated with higher MOODS-SR depressive scores in HC. Likewise, the discrepancy between actigraphic-based and rMEQ-based circadian typology was associated with depressive symptoms in HC only.

Self-reported ET was consistently associated with mood symptoms, while associations with panic-agoraphobic symptoms only emerged in BD and involved both extreme chronotypes. The discrepancy between the preferred circadian typology (rMEQ-based) and the actual one (actigraphic-based) could contribute to depressive symptoms in HC. These results pave the way for interventional studies targeting circadian typology in an attempt to prevent or treat mental health disorders.

Borderline personality disorder (BPD) is a common and disabling mental health disorder and has detrimental effects on affected individuals across multiple domains. We aimed to investigate whether individuals with BPD differ from control subjects in terms of cognitive functions, and to see if there is a relationship between cognitive functions, impulsivity, and BPD symptom severity.

BPD individuals (n = 26; mean age = 26.7; 69.2% female) and controls (n = 58; mean age = 25.3; 51.7% female) were enrolled. Intra/Extra-Dimensional Set Shift (IED) and One Touch Stockings of Cambridge (OTS) tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive functions. Barratt Impulsivity Scale-version 11 (BIS−11) was administered to measure impulsivity and both the Zanarini Scale for Borderline Personality Disorder self-report and the clinician-administered versions were used to assess BPD symptom severity.

BPD group showed significantly impaired cognitive performance on the IED task versus controls, but there was not a significant difference in the OTS task. BPD symptom severity was positively correlated with trait (BIS-11) impulsivity and no correlation was found between BPD symptom severity and cognitive functions.

This study suggests people with BPD experience impaired cognitive flexibility and heightened impulsivity. Only impulsivity appeared to be directly related to symptom severity, perhaps indicating that cognitive inflexibility could be a vulnerability marker. Future research should focus on a longitudinal approach to extend clinical and theoretical knowledge in this area.

Evidence has suggested that emotional dysregulation is a transdiagnostic feature in schizophrenia and major affective disorders. However, the relationship between emotional dysregulation and appetite hormone disturbance remains unknown in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder.

In total, 22 adolescents with schizophrenia; 31 with bipolar disorder; 33 with major depressive disorder; and 41 healthy age-, sex-, and body mass index (BMI)/BMI percentile-matched controls were enrolled for assessing levels of appetite hormones, namely leptin, ghrelin, insulin, and adiponectin. Emotional regulation symptoms were measured using the parent-reported Child Behavior Checklist―Dysregulation Profile.

Adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder exhibited greater emotional dysregulation symptoms than the control group (P = .037). Adolescents with bipolar disorder demonstrated higher log-transformed levels of insulin (P = .029) and lower log-transformed levels of leptin (P = .018) compared with the control group. BMI (P < .05) and log-transformed ghrelin levels (P = .028) were positively correlated with emotional dysregulation symptoms.

Emotional dysregulation and appetite hormone disturbance may occur in the early stage of severe mental disorders. Further studies are required to clarify the unidirectional or bidirectional association of emotional dysregulation with BMI/BMI percentile and appetite hormones among patients with severe mental disorder.

The importance of recognizing different kinds of autism spectrum presentations among adults, including subthreshold forms and the broad autism phenotype (BAP), has been increasingly highlighted in recent studies. Meanwhile, the possible involvement of immune system deregulation and altered methylation/trans-sulfuration processes in autism spectrum disorder (ASD) is gaining growing attention, but studies in this field are mainly focused on children. In this framework, the aim of this study was to compare plasmatic concentrations of IL-6 and homocysteine (HCY) among adults with ASD, their first-degree relatives, and healthy controls (CTLs), investigating also possible correlations with specific autism symptoms.

Plasma concentrations of IL-6 and HCY were measured in a group of adult subjects with ASD, their first-degree relatives (BAP group), and healthy controls (CTL). All participants were also evaluated with psychometric instruments.

IL-6 and HCY concentrations were significantly higher in the ASD group than in CTLs, while BAP subjects reported intermediate results. Significant correlations were reported between biochemical parameters and psychometric scales, particularly for the dimension of ruminative thinking.

These findings support the hypothesis of a key involvement of HCY-related metabolism and immune system alteration in autism spectrum pathophysiology. HCY and IL-6 seem to show different associations with specific autism dimensions.

The genetic load for major depressive disorder (MDD) may be higher in people who develop MDD earlier in life. This study aimed to investigate whether the parents of adolescents with MDD were more likely to have MDD, bipolar disorder (BD), schizophrenic disorder (SZ), alcohol use disorder, or substance use disorder than the parents of adolescents without MDD. We also examined whether the response to antidepressant treatment predicted the likelihood of parental psychiatric disorders.

In all, 1,758 adolescents aged 12–19 years with antidepressant-resistant depression, 7,032 (1:4) age-/sex-matched adolescents with antidepressant-responsive depression and 7,032 (1:4) age-/sex-matched controls were included. Parental psychiatric disorders of individuals enrolled were assessed.

The parents of the adolescents with MDD were more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than the parents of the control group. The parents of adolescents who were antidepressant resistant and the mothers of adolescents who were either treatment resistant or treatment responsive were more likely to be diagnosed with a psychiatric disorder.

Our study demonstrated that parents of adolescents with MDD may be more likely to be diagnosed with MDD, BD, SZ, alcohol use disorder, or substance use disorder than parents of adolescents without MDD, suggesting the within-disorder transmission and cross-disorder transmission of these psychiatric disorders. Furthermore, the parent’s sex and the response to antidepressant treatment may affect the within-disorder transmission of MDD.

Recently, a novel approach to obsessive-compulsive disorder has emerged, implicating altered reward functioning in the disorder. Yet, no study to date has directly examined the attentional aspect of reward functioning in participants with obsessive-compulsive (OC) symptoms, with past research mostly relying on reaction-time-based tasks.

A reward-based value-modulated attentional capture task was completed by a sample of nonclinical student participants—44 with high (HOC) and 48 with low (LOC) levels of OC symptoms. We measured the extent to which high and low reward-signaling distractors captured attention and impaired performance on the task, resulting in a lower possibility of obtaining a monetary reward. Attentional capture was indexed via fixation data, and further explored using saccade data.

Both groups performed more poorly when a high-reward signaling distractor was present, compared to when a low-reward signaling distractor was present. Importantly, this difference was significantly greater in the HOC group, and was found to be driven by the specific effects of reward-signaling distractors. Similar results emerged when exploring saccade data, and remained significant after controlling for both addiction-related compulsivity and depressive symptoms.

Current findings suggest that attentional reward-related functioning may be associated with OC symptoms. Different aspects of reward functioning, including attention, should be further explored and incorporated into future research and clinical endeavors.

A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2.

The multicenter, randomized, double-blind ENLIGHTEN-2 study (NCT02694328) included outpatients aged 18–55 years with a diagnosis of schizophrenia based on DSM-5 criteria, a body mass index (BMI) of 18 to 30 kg/m2, and stable body weight (self-reported change ≤5% for ≥3 months before study entry). Patients were randomized 1:1 to receive OLZ/SAM or olanzapine for 24 weeks. Co-primary endpoints (previously reported) were percent change in body weight and proportion of patients with at least 10% weight gain from baseline at week 24. Prespecified exploratory subgroup analyses by sex, age, self-reported race, and baseline BMI were conducted.

At week 24, treatment with OLZ/SAM resulted in numerically less percent weight gain than with olanzapine across all subgroups evaluated. The proportion of patients with at least 10% weight gain was smaller in each subgroup treated with OLZ/SAM vs olanzapine.

In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population.

Limited studies have investigated cannabis use in patients with obsessive-compulsive disorder (OCD), despite its widespread use by patients with psychiatric illnesses. The aim of this study was to assess the frequency, correlates, and clinical impact of cannabis use in an Italian sample of patients with OCD.

Seventy consecutive outpatients with OCD were recruited from a tertiary specialized clinic. To assess cannabis-related variables, patients completed a questionnaire developed for the purpose of this study, investigating cannabis use-related habits and the influence of cannabis use on OCD symptoms and treatments. A set of clinician and self-reported questionnaires was administered to measure disease severity. The sample was then divided into three subgroups according to the pattern of cannabis use: “current users” (CUs), “past-users” (PUs), and “non-users” (NUs).

Approximately 42.8% of patients reported lifetime cannabis use and 14.3% reported current use. Approximately 10% of cannabis users reported an improvement in OCD symptoms secondary to cannabis use, while 23.3% reported an exacerbation of anxiety symptoms. CUs showed specific unfavorable clinical variables compared to PUs and NUs: a significant higher rate of lifetime use of tobacco, alcohol, and other substances, and a higher rate of pre-OCD onset comorbidities. Conversely, the three subgroups showed a similar severity of illness.

A considerable subgroup of patients with OCD showed a predisposition towards cannabis use and was associated with some specific clinical characteristics, suggesting the need for targeted consideration and interventions in this population.

To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response.

A post hoc analysis of pooled data from ASPIRE I and ASPIRE II evaluated ESK plus SoC vs PBO plus SoC in adults with MDSI without response (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at 24 hours after the first dose or at week 1 after the first two doses (ie, 24-hour and week 1 nonresponders). Response and remission (MADRS score ≤ 12) rates were assessed on day 25.

The analysis included 362 patients (n = 182, ESK plus SoC; n = 180, PBO plus SoC). Among 24-hour nonresponders, more patients receiving ESK plus SoC vs PBO plus SoC achieved response (63.9% vs 48.0%, P = .010) and remission (35.1% vs 24.4%, P = .074) at day 25. Odds of response/remission were higher with ESK plus SoC vs PBO plus SoC (response: 1.89, 95% CI, 1.17-3.05; remission: 1.48, 95% CI, 0.93-2.35). Similar findings were observed among week 1 nonresponders for response (48.4% vs 34.5%, P = .075), remission (25.0% vs 13.1%, P = .060), and odds of response/remission (response: 2.03, 95% CI, 1.22-3.40; remission: 1.63, 95% CI, 1.01-2.62).

Patients with MDSI not responding within the first week of treatment with ESK plus SoC may still benefit from a full 4-week treatment course.