Memantine augmentation of sertraline in the treatment of symptoms and executive function among patients with obsessive-compulsive disorder: A double-blind placebo-controlled, randomized clinical trial

Background Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually decrease the severity of the symptoms by 20–30%; however, 40–60% of OCD patients do not achieve a satisfactory response. Our main objective was to investigate the effectiveness of memantine, a non-competitive N-Methyl-D-aspartate (NMDA) receptor antagonist, as an adjunct therapy to sertraline, a selective serotonin reuptake inhibitor (SSRI), to improve severity of symptoms and executive function among patients with obsessive-compulsive disorder. Methods Seventy patients with OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) criteria, and a Yale-Brown obsessive compulsive scale (Y-BOCS) score of more than 21 were recruited to the study. They received sertraline (100 mg daily initially followed by 200 mg daily after week 4) and either memantine (10 mg twice daily) or placebo in a placebo controlled, double-blinded, parallel-group, clinical trial of 12 weeks. The primary outcome was OCD symptoms measured by the Y-BOCS. Moreover, executive function of participants was measured by the Wisconsin Card Sorting Test (WCST). Results The total score, and obsession and compulsion subscales of Y-BOCS significantly dropped in both groups with no significant difference between the two groups. However, memantine group showed a greater response in the number of completed categories subscale of the WCST (p value<0.001). We did not observe any major adverse effects in any of the groups. Conclusion Memantine has an acceptable safety and tolerability in patients with OCD and might have a positive effect on their executive function. Nevertheless, the current results don`t support the efficacy of memantine as an adjunctive agent to sertraline for symptoms in patients with OCD. Trial registration The trial was registered at the Iranian Registry of Clinical Trials on 04/10/2019 (www.irct.ir; IRCT ID: IRCT20170123032145N4).

Self-Reported Sleep and Executive Function in Early Primary School Children

The study investigated the associations between children’s self-reported habitual sleep disturbance and multidimensional executive function (EF). Two hundred and four 7–9-year-old typically developing children completed the Sleep Self-Report and finished the Red-Blue Test, Wisconsin Card Sorting Test, and Backward Digit Span Test, indexing different EF components including inhibitory control, cognitive flexibility, and working memory. Results revealed that all the three EF components were significantly correlated with sleep. However, cognitive flexibility was no longer significantly related to sleep when the other EF components – inhibitory control and working memory – were controlled for. Meanwhile, inhibitory control, as well as working memory, was still significantly related to sleep after controlling for the other EF components. Results suggest that children’s self-reported sleep might be associated directly with inhibitory control and working memory, but indirectly with cognitive flexibility.

Discrete Roles for Impulsivity and Compulsivity in Gambling Disorder

Background and Objective: Complex associations between gambling disorder (GD) and impulsivity have been identified. However, little is known regarding how compulsivity associates with different impulsivity domains in GD. In this study, we examined associations between self-reported and behavioral measures of impulsivity–assessed through the Barratt Impulsiveness Scale (BIS-11) and the Experiential Discounting Task (EDT), respectively- and compulsivity-measured using the Padua Inventory and the Wisconsin Card Sorting Test (WCST), respectively-, in an adult sample with GD (N = 132, 94 men and 38 women, ages ranging from 18 to 69 years). GD severity was assessed using the South Oaks Gambling Screen.Methods: Structural Equation Modeling was used to examine relationships between impulsivity and compulsivity measures, age, and GD severity.Results: BIS-11 non-planning and BIS-11 total scores positively correlated with GD severity. The standardized coefficients for the SEM showed direct positive contributions of BIS-11 non-planning, Padua and EDT scores to GD severity. Only participants' ages directly contributed to WCST perseverative errors, and no direct or indirect effects were found with respect to GD severity.Conclusion: The findings suggest that specific aspects of impulsivity and compulsivity contribute to GD severity. Interventions specifically targeting domains that are most relevant to GD severity may improve treatment outcomes.

Adverse childhood experiences (ACEs) associated with reduced cognitive flexibility in both college and community samples

The prefrontal cortex is sensitive to stress experiences and significantly impacted by early life adversity. Cognitive flexibility is an executive function that is associated with positive outcomes in adulthood and implicated in activity in the prefrontal cortex. The relationship between early life adversity and cognitive flexibility is underreported. Using the cumulative risk model, we conducted two studies to examine the association between early life adversity and cognitive flexibility in college students and adults (cumulative N = 510). Exposure to early life adversity was assessed using the adverse childhood experiences scale (ACEs). Cognitive flexibility was assessed using the Wisconsin Card Sorting Test (WCST). Additionally, as perceived chronic stress is associated with impaired prefrontal cortex function, we measured that as well. Higher number of ACEs was correlated with lower number of completed categories on the WCST in both college students and adults. Perceived chronic stress was not associated with cognitive flexibility, but did correlate positively with ACEs. Individuals with a higher number of ACEs were also more likely to report higher levels of perceived chronic stress. Hierarchical regression analyses indicated that exposure to adverse childhood experiences predicted lower scores on completed categories. Our findings provide further evidence that individuals with early life adversity exhibit reduced cognitive flexibility in adulthood.

Cascade process mediated by left hippocampus and left superior frontal gyrus affects relationship between aging and cognitive dysfunction

Background Cognitive function declines with age and has been shown to be associated with atrophy in some brain regions, including the prefrontal cortex. However, the details of the relationship between aging and cognitive dysfunction are not well understood. Methods Across a wide range of ages (24- to 85-years-old), this research measured the gray matter volume of structural magnetic resonance imaging data in 39 participants, while some brain regions were set as mediator variables to assess the cascade process between aging and cognitive dysfunction in a path analysis. Results Path analysis showed that age affected the left hippocampus, thereby directly affecting the left superior frontal gyrus. Furthermore, the gyrus directly affected higher order flexibility and maintenance abilities calculated as in the Wisconsin card sorting test, and the two abilities affected the assessment of general cognitive function. Conclusion Our finding suggests that a cascade process mediated by the left hippocampus and left superior frontal gyrus is involved in the relationship between aging and cognitive dysfunction.

How increased cognitive load affects the dual-task cost in healthy young adults? A randomized, double-blind sham-controlled study

Our ability to interact flexibly with the surrounding environment and achieve an adaptive goal-directed response is one of the necessities of balance control. This study aimed to examine the interaction between cognitive demand and the necessity for keeping balance in unstable conditions. We examined the effects of performing two cognitive tasks, namely the Stroop test and Wisconsin Card Sorting Test (WCST), on postural balance in healthy young adults. Stroop and the WCST test assess selective attention and cognitive flexibility in shifting between rules, respectively. Thirty-two healthy adults were included in two experimental conditions (control and treatment) in random order, separated by at least seven days. Standing balance was evaluated by the Sway Medical Mobile application in eyes open (EO) and eyes closed (EC) in different stance positions: feet apart, feet together, semi-tandem, tandem, and single-leg stance (SLS). Balance was evaluated before and after the cognitive test in each experimental condition. Our findings indicate that performing cognitively demanding tasks adversely affected the balance ability in more demanding balance tests such as the SLS with EC (P ˂ 0.05). However, no significant changes were seen in other balance tests (P ˃ 0.05). Additionally, no significant changes were seen in balance ability after the Stroop or Wisconsin card sorting test alone. These results confirm that performing cognitively demanding tasks significantly reduced the ability to keep balance in less stable conditions. These findings have significant implications in understanding and preventing falls and incidents resulting from an impaired balance in complex and cognitively demanding conditions.

Dopamine, Cognitive Flexibility, and IQ: Epistatic Catechol-O-MethylTransferase:DRD2 Gene–Gene Interactions Modulate Mental Rigidity

Cognitive flexibility has been hypothesized to be neurochemically rooted in dopamine neurotransmission. Nonetheless, underpowered sample sizes and contradictory meta-analytic findings have obscured the role of dopamine genes in cognitive flexibility and neglected potential gene–gene interactions. In this largest neurocognitive-genetic study to date (n = 1400), single nucleotide polymorphisms associated with elevated prefrontal dopamine levels (catechol-O-methyltransferase; rs4680) and diminished striatal dopamine (C957T; rs6277) were both implicated in Wisconsin Card Sorting Test performance. Crucially, however, these genetic effects were only evident in low-IQ participants, suggesting high intelligence compensates for, and eliminates, the effect of dispositional dopamine functioning on flexibility. This interaction between cognitive systems may explain and resolve previous empirical inconsistencies in highly educated participant samples. Moreover, compensatory gene–gene interactions were discovered between catechol-O-methyltransferase and DRD2, such that genotypes conferring either elevated prefrontal dopamine or diminished striatal dopamine—via heightened striatally concentrated D2 dopamine receptor availability—are sufficient for cognitive flexibility, but neither is necessary. The study has therefore revealed a form of epistatic redundancy or substitutability among dopamine systems in shaping adaptable thought and action, thus defining boundary conditions for dopaminergic effects on flexible behavior. These results inform theories of clinical disorders and psychopharmacological interventions and uncover complex fronto-striatal synergies in human flexible cognition.

Impact of citalopram combined with mindfulness-based stress reduction on symptoms, cognitive functions and self-confidence in patients with depression

Purpose: To investigate the impact of the combination of citalopram and mindfulness-based stress reduction (MBSR) on the symptoms, cognitive functions and self-confidence of patients with depression.Methods: A total of 98 patients with depression were selected as study subjects and divided into combination therapy group (CT, n = 51) and conventional group (C, n = 47. The conventional group was treated with citalopram, while the combined group was treated with a combination of citalopram and MBSR. Depressive symptoms and self-confidence were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and General Self-efficacy Scale (GSES). Cognitive functions were assessed by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Changes in depressive symptoms, cognitive functions, self-confidence and clinical efficacies between the two groups were compared.Results: At weeks 1, 4 and 8 after treatment, CT group had lower HAMD-17 scores but higher GSES scores when compared with the conventional group (p < 0.05). In addition, CT group was superior to the conventional group in efficacy and overall response rate (100.00 vs. 85.11 %, p < 0.05). Also, CT group showed a shorter time of perseverative and non-perseverative errors on WCST and a shorter time for TMT-A and TMT-B, compared with the conventional group (p < 0.05).Conclusion: The combination therapy of citalopram and MBSR is effective in ameliorating depressive symptoms, and enhancing cognitive functions and self-confidence in patients with depression. These findings will increase the understanding of this combination therapy, and provide a clinical reference for the treatment of depression.