Rationale The N-methyl-d-aspartate (NMDA) glutamate receptor antagonist ketamine has demonstrated rapid antidepressant effects in patients with treatment-resistant depression (TRD). Despite the promise of a novel and urgently needed treatment for refractory depression, concerns regarding potential adverse neurocognitive effects of ketamine remain. Objectives Although extensive research has been conducted in healthy volunteers, there is a paucity of studies examining the neurocognitive effects of ketamine in depressed patients. Therefore, the aims of the current study were to characterize the relationship between baseline neurocognition and antidepressant response to ketamine, measure the acute impact of ketamine on neurocognition, and investigate the relationship between acute neurocognitive effects of ketamine and antidepressant response. Methods Neurocognitive functioning was assessed in 25 patients with TRD using a comprehensive battery: estimated premorbid IQ, current IQ, and tests from the MATRICS battery (MCCB). A subset of the MCCB was repeated immediately following a 40-min intravenous infusion of ketamine (0.5 mg/kg). Results Patients who responded to ketamine 24 hours following treatment had poorer baseline neurocognitive performance relative to non-responders, and in particular slower processing speed (F=8.42, df=23, p=0.008). Ketamine was associated with selective impairments in memory recall and the degree of cognitive change carried negative prognostic significance (e.g. negative cognitive effects immediately after ketamine predicted lower response rate at 24 hours; Fisher’s Exact Test 2-sided p=0.027). Conclusions Taken together, our findings suggest a potential baseline neurocognitive predictor of ketamine response and an inverse relationship between the cognitive effects of ketamine and antidepressant efficacy.

Many patients with bipolar disorder (BD) have difficulties in facial emotion recognition, which may also be impaired in maltreated children and in subjects who have a positive history of childhood traumatic experiences. Childhood trauma is reported with a high prevalence in BD and it is considered a risk factor for the disorder. As the relationship between facial emotion recognition and childhood trauma in BD has not yet been directly investigated, in this study we examined whether the presence of a childhood trauma in affectively stable BD patients was associated with poorer performance in emotion recognition. Seventy-five BD I and II participants completed the Childhood Trauma Questionnaire retrospectively assessing five types of childhood trauma (emotional, physical and sexual abuse, and emotional and physical neglect) and the Emotion Recognition Task evaluating the ability to correctly identify six basic facial emotions (happiness, sadness, anger, disgust, fear and surprise). Our results suggest that the presence of childhood trauma in participants with BD is associated with a more severe clinical presentation (earlier onset, longer duration of illness, and higher depressive symptom ratings) and that BD patients with a positive childhood history of emotional neglect perform worse than those without such a history in recognizing anger.

Background There is evidence that patients with bipolar disorder (BD) score higher on affective temperament ratings compared to healthy controls (HCs). Moreover, unaffected relatives demonstrate similar patterns as BD patients suggesting that such temperaments are related to the genetic risk for BD and may serve as endophenotypes for the disorder. It is unknown whether affective temperaments are associated with other core features of BD, such as impairments in neurocognition. This study examined the relationship between affective temperaments and neurocognition in patients with BD and in HCs. Methods Temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) in 64 patients with BD and 109 HCs. Neurocognitive functioning was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Correlational analyses between temperaments and cognition were conducted in BD and HC subjects. Results Data suggest that affective temperaments and neurocognition are correlated. In BD higher ratings of cyclothymia and irritability were associated with better processing speed, working memory, reasoning and problem-solving. In the HC group, increased irritability was related to worse performance on measures of attention and social cognition. Limitations Lack of functional outcome measures to evaluate the impact of temperaments and cognition on psychosocial functioning. It would be useful to test these findings on unaffected relatives of BD patients. Conclusions Cyclothymic and irritable temperaments are correlated with specific aspects of neurocognition in BD. This study is among the few exploring the dimensional relationship of temperaments and cognition in BD, and provides preliminary evidence for future studies investigating the neural and genetic mechanisms underlying the association between these variables.

Backgrounds Sleep and circadian rhythm disruptions are prominent, trait-like features of bipolar disorder (BD) which precede the onset of mood episodes. Neurocognitive impairments also characterize BD not only during acute phases of the illness but also during remission. Although the relationship between these two debilitating aspects of the illness might seem intuitive, very little is known about their relationship. We examined the association between sleep dysfunction and neurocognition in BD. Methods In a sample of 117 BD patients(mean age = 45.0±10.7; 59.0% (n=69) male), neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Sleep quality data were collected using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). Partial Pearson correlations tested for a relationship between sleep and neurocognition. Path analyses were conducted to examine the hypothesized direct influence of sleep disruption on neurocognition. Results Higher levels of sleep disruptions were associated with a more severe clinical presentation and poorer performance in social cognition, visual learning and working memory. Social cognition and working memory were directly (negatively) predicted by sleep disruptions. Limitations The study was limited by a relatively small sample size and the lack of behavioral and biological objectives measure of activity/rest cycles. Conclusions Our study suggests that in patients with BD, sleep disruptions have a detrimental effect on general level of psychopathology and contribute directly to impaired cognitive functioning in the domains of social cognition and working memory. More research using objective measurement of sleep should be pursued to support these data and to further investigate the causal relationship between these disabling aspects of the illness.

Objective Anticholinergic/sedative drug use, measured by the Drug Burden Index (DBI), is linked to cognitive impairment in older adults. Yet, studies on the DBI's association with neuropsychological functioning are lacking, especially in underserved groups at increased risk of cognitive impairment. We examined cross‐sectional relationships between total DBI (DBIT) and an age‐adjusted analogue (Adj DBIT) with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in diverse adults with type 2 diabetes mellitus (T2DM). Based on results of a prior study, we anticipated higher DBIs would be associated with worse memory at older ages. Methods One hundred five adults with T2DM (age = 57 ± 9 years, 65% female, 62% Black, 27% Hispanic/Latino, HbA1c = 7.8 ± 1.8) participated. Although memory outcomes were normally distributed, DBIT values were positively skewed. Spearman correlations assessed their bivariate relationships with RBANS. Adjusting for comorbidities, polypharmacy, HbA1c, and education, we tested the moderating effect of age on DBI‐RBANS associations at mean ±1 standard deviations of age. Results One third of the participants endorsed current sedative/anticholinergic use. Mean DBIT was 0.385, and mean Adj DBIT was 0.393 (ranges = 0.00‐4.22). Drug burden negatively correlated with RBANS Immediate Memory (DBIT rs = −0.237, P = .013; Adj DBIT rs = −0.239, P = .014) but no other indices. There was a significant DBI*Age interaction; the negative effect of drug burden on Immediate Memory was significant for ages greater than or equal to 55 years old. Conclusions Sedative/anticholinergic drug exposure was prevalent in these diverse T2DM patients. Adjusting for covariates, greater drug burden was associated with worse memory acquisition among older adults only. Prospective studies should examine these relationships over time and assess whether dementia biomarkers affect the interaction.