Trichotillomania (TTM) is a mental health disorder characterized by repetitive urges to pull out one’s hair. Cognitive deficits have been reported in people with TTM compared to controls; however, the current literature is sparse and inconclusive about affected domains. We aimed to synthesize research on cognitive functioning in TTM and investigate which cognitive domains are impaired.

After preregistration on the International Prospective Register of Systematic Reviews (PROSPERO), we conducted a comprehensive literature search for papers examining cognition in people with TTM versus controls using validated tests. A total of 793 papers were screened using preestablished inclusion/exclusion criteria, yielding 15 eligible studies. Random-effects meta-analysis was conducted for 12 cognitive domains.

Meta-analysis demonstrated significant deficits in motor inhibition and extradimensional (ED) shifting in people with TTM versus controls as measured by the stop-signal task (SST) (Hedge’s g = 0.45, [CI: 0.14, 0.75], p = .004) and ED set-shift task (g = 0.38, [CI: 0.13, 0.62], p = .003), respectively. There were no significant between-group differences in the other cognitive domains tested: verbal learning, intradimensional (ID) shifting, road map spatial ability, pattern recognition, nonverbal memory, executive planning, spatial span length, Stroop inhibition, Wisconsin card sorting, and visuospatial functioning. Findings were not significantly moderated by study quality scores.

Motor inhibition and ED set-shifting appear impaired in TTM. However, a cautious interpretation of results is necessary as samples were relatively small and frequently included comorbidities. Treatment interventions seeking to improve inhibitory control and cognitive flexibility merit exploration for TTM.

The catechol-o-methyltransferase (COMT) inhibitor tolcapone constitutes a potentially useful probe of frontal cortical dopaminergic function. The aim of this systematic review was to examine what is known of effects of tolcapone on human cognition in randomized controlled studies.

The study protocol was preregistered on the Open Science Framework. A systematic review was conducted using PubMed to identify relevant randomized controlled trials examining the effects of tolcapone on human cognition. Identified articles were then screened against inclusion and exclusion criteria.

Of the 22 full-text papers identified, 13 randomized control trials were found to fit the pre-specified criteria. The most consistent finding was that tolcapone modulated working memory; however, the direction of effect appeared to be contingent on the COMT polymorphism (more consistent evidence of improvement in Val–Val participants). There were insufficient nature and number of studies for meta-analysis.

The cognitive improvements identified upon tolcapone administration, in some studies, are likely to be due to the level of dopamine in the prefrontal cortex being shifted closer to its optimum, per an inverted U model of prefrontal function. However, the results should be interpreted cautiously due to the small numbers of studies. Given the centrality of cortical dopamine to understanding human cognition, studies using tolcapone in larger samples and across a broader set of cognitive domains would be valuable. It would also be useful to explore the effects of different dosing regimens (different doses; and single versus repeated administration).

To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery–Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD).

Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models.

In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (−12.8 [0.46] vs −10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044).

In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS.

ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown.

We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models.

Across 122 trials (N=15,760), SSRIs, SNRIs, and benzodiazepines produced significant improvement in anxiety compared to placebo. Benzodiazepines produced faster improvement by the first week of treatment (p < 0.001). By week 8, the response for benzodiazepines and SSRIs (p = 0.103) and SNRIs (p = 0.911) did not differ nor did SSRIs and SNRIs differ (p = 0.057), although for patients with generalized anxiety disorder (GAD), the benzodiazepines produced greater improvement than SNRIs at week 8 (difference − 12.42, CrI: −25.05 to −0.78, p = 0.037). Medication response was similar across anxiety disorders except for benzodiazepines, which produced greater improvement over the first 4 weeks compared to SSRIs and SNRIs in panic disorder. For SSRIs and SNRIs, women improved more than men, and for benzodiazepines, older patients improved more compared to younger patients. Finally, placebo response plateaued by week 4 of treatment, and, at week 8, social anxiety disorder trials had lower placebo response compared to other anxiety disorders.

Benzodiazepines show early improvement compared to SSRIs and SNRIs. However, by week 8, all treatments yield similar results. Patient characteristics influence the improvement trajectory and magnitude, suggesting potential for personalized medication selection.

To examine whether objective sleep parameters are associated with cognitive function (CF) in patients with major depressive disorder (MDD) with chronic insomnia (CI) and whether the severity of these disorders is related to CF.

Thirty patients with MDD with CI attending a tertiary care institution underwent two consecutive nights of polysomnographic (PSG) recording and a battery of neuropsychological tests, which included episodic memory, sustained attention, working memory, and executive function. The severity of MDD and CI was assessed by clinical scales. We examined the relationship between PSG parameters and CF, as well as whether the severity of the disorders is related to CF.

Linear regression analysis revealed that total sleep time (TST) was positively associated with higher learning and recall of episodic memory, as well as better attention. Slow-wave sleep (SWS) showed a positive association with better working memory. Furthermore, wake after sleep onset (WASO) was negatively associated with episodic memory and lower attention. No significant relationships were found between the severity of MDD or CI with CF.

Both sleep duration and depth are positively associated with several aspects of CF in patients with MDD with CI. Conversely, a lack of sleep maintenance is negatively related to CF in these patients. These findings could help identify modifiable therapeutic targets to reduce CF impairment.

Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD).

Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data.

At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: −2.73 [−3.63, −1.82], p < 0.0001) and amotivation scores (mean, 95% CI: −0.78 [−1.04, −0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time.

This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.

Difficulties with emotion regulation have been associated with multiple psychiatric conditions. In this study, we aimed to investigate emotional regulation difficulties in young adults who gamble at least occasionally (ie, an enriched sample), and diagnosed with a range of psychiatric disorders using the validated Difficulties in Emotion Regulation Scale (DERS).

A total of 543 non-treatment-seeking individuals who had engaged in gambling activities on at least 5 occasions within the previous year, aged 18–29 were recruited from general community settings. Diagnostic assessments included the Mini International Neuropsychiatric Inventory, Minnesota Impulsive Disorders Interview, attention-deficit/hyperactivity disorder World Health Organization Screening Tool Part A, and the Structured Clinical Interview for Gambling Disorder. Emotional dysregulation was evaluated using DERS. The profile of emotional dysregulation across disorders was characterized using Z-scores (those with the index disorder vs. those without the index disorder).

Individuals with probable ADHD displayed the highest level of difficulties in emotional regulation, followed by intermittent explosive disorder, social phobia, and generalized anxiety disorder. In contrast, participants diagnosed with obsessive-compulsive disorder showed relatively lower levels of difficulties with emotional regulation.

This study highlights the importance of recognizing emotional dysregulation as a trans-diagnostic phenomenon across psychiatric disorders. The results also reveal differing levels of emotional dysregulation across diagnoses, with potential implications for tailored treatment approaches. Despite limitations such as small sample sizes for certain disorders and limited age range, this study contributes to a broader understanding of emotional regulation’s role in psychiatric conditions.