Cognitive impairment in depression could present as subjective and objective, but the intensity of subjective impairment is higher and is not correlated with the deficits measured by neuropsychological tests. Subjective cognitive impairment lowers quality of life and is associated with the severity of depression. Among depressive patients, negative emotional bias is present. It is better memory for negative or positive information than for neutral information. We hypothesized that rumination is associated with subjective cognitive impairment.

The study was performed through the online PsyToolkit platform. The study sample consisted of 168 healthy controls and 93 patients with depression were enrolled in the study. Participants completed questionnaires and performed a memory task that contained emotional words. The forty words were chosen from the Nencki Affective Word List. The list for memory test consists of 5 words from each Category: Happiness, Anger, Fear, Sad, Disgusting, and Neutral, and 10 words from category ‘Unclassified’ to balance the valence and arousal of the set. After 15 minutes, they recognized old words from the list of 80 words. Half of them were the same as in the first part, and other words were new, chosen with the same criteria. Depression symptoms were measured using the Beck Depression Inventory-II, subjective cognitive impairment with the Perceived Deficits Questionnaire-20, and intensity of rumination with the Polish Questionnaire of Rumination.

Subjective cognitive impairment and rumination were higher in patients with depression. They also had a higher error rate than healthy controls U = 6462.5; p = .021, especially in words from the neutral (U = 6292; p = .008) and happiness category (U = 6585; p = .031). However, there was no association between subjective cognitive impairment and performance in memory tasks. The regression analysis showed that depressive symptoms and intensity of rumination are better predictors of subjective cognitive deficits than objective performance on a memory task. The results of PDQ-20 were correlated with the error rate of words from categories: Happiness (r = -.162**), Sad (r = -.116*) and Neutral (r = -.145**). Words from categories Happiness, Disgust and Neutral were significantly better recognized than Unclassified, Fear or Sad group of words χ 2 F (6) = 132.685; p < .001. In MDD group recognition of Disgust words were statistically highest than Anger and Fear words χ 2 F (6) = 36.795; p < .001. The recognition of Happiness and Neutral word were not significantly different to other words.

Cognitive problems are common in depression and affect quality of life. Subjective cognitive impairment is more closely related to rumination than objective cognitive impairment among healthy participants and patients with major depressive disorder. Emotional bias among depressive patients has been partially confirmed. Emotional impact is important for memory of words and subjective perception of cognition.

Severe OCD is often nonresponsive to pharmacological and behavioral therapies and thus surgical interventions are emerging. Surgical interventions have proven to be efficacious for treating refractory OCD, however limited publications suggest 22–40% of patients experience transient apathy and disinhibition post-surgery (McLaughlin et al., 2021). Apathy is highly associated with the same brain regions, the prefrontal cortex, striatum, and thalamus, which have also been implicated in OCD symptoms (Le Heron et al., 2018). Prior research noting post-surgical changes in apathy in OCD either used physician observations or less precise surgical methods (i.e., gamma knife or radiofrequency ablation). Apathy has also been highly associated with depression and executive dysfunction (Raffard et al, 2020) and often not co-assessed in prior studies. The newest intervention, cutting-edge MR-guided laser interstitial thermal therapy (LITT), limits damage outside the region of interest by precise control of thermal application in real-time. Thus, the current case series aims to investigate objective patient-reported change in apathy, disinhibition, depression, and executive dysfunction following anterior capsulotomy via this newest surgical approach for OCD.

In this retrospective study, the responses of ten consecutive patients pre- and post-LITT on the following measures were examined: Frontal Systems Behavior Scale (FrSBe), Beck Depression Inventory-II (BDI-II), and Yale Brown Obsessive-Compulsive Scale (Y-BOCS). Reliable Change Index (RCI) was used to evaluate meaningful change in pre- and post-LITT self-reported levels of apathy, disinhibition, executive dysfunction, along with depressive symptoms. Per prior published guidelines, patient-reported Y-BOCS (range 0–40) scores were used to measure OCD symptoms with 24–34 % score reduction representing partial and 35% or greater score reduction representing full response (Pepper et al., 2019).

Seven patients (70%) were male, with a sample mean age of 38.4 (SD=13.6) and a mean of 14.6 (SD =2.27) years of education. Mean Y-BOCS score decreased from 32 (SD=5.3) before surgery to 18.8 (SD=11.1) after. Over 65% had partial or full response in OCD symptoms post-surgery. Six patients endorsed increased apathy, with others endorsing no change. Half of the non-responders reported this increase in apathy. The cohort remained relatively stable in disinhibition and executive dysfunction. Over half the cohort demonstrated a significant decrease in depressive symptoms. Interestingly, two of the non-responders and one responder endorsed increased apathy despite stable or improving depressive symptoms, disinhibition, and executive dysfunction.

Surgical interventions for psychiatric disorders are emerging quickly and being refined daily. In this cohort, anterior capsulotomy via LITT provided full or partial OCD recovery for most patients. However, most patients reported significant increases in apathy, despite experiencing a decrease in depressive symptoms, with stable disinhibition and executive dysfunction. Despite these promising improvements in OCD symptomatology via LITT, impact of surgery on apathy levels is clearly warranted using objective, quantifiable methods. As apathy has consistently been related to functional impairment and poorer quality of life, understanding this outcome is imperative in larger trials. Better understanding of this finding and underlying circuity will allow patients to be fully informed regarding this promising surgical intervention.

Although some animal research suggests possible sex differences in response to THC exposure (e.g., Cooper & Craft, 2018), there are limited human studies. One study found that among individuals rarely using cannabis, when given similar amounts of oral and vaporized THC females report greater subjective intoxication compared to males (Sholler et al., 2020). However, in a study of daily users, females reported indistinguishable levels of intoxication compared to males after smoking similar amounts (Cooper & Haney, 2014), while males and females using 1–4x/week showed similar levels of intoxication, despite females having lower blood THC and metabolite concentrations (Matheson et al., 2020). It is important to elucidate sex differences in biological indicators of cannabis intoxication given potential driving/workplace implications as states increasingly legalize use. The current study examined if when closely matching males and females on cannabis use variables there are predictable sex differences in residual whole blood THC and metabolite concentrations, and THC/metabolites, subjective appraisals of intoxication, and driving performance following acute cannabis consumption.

The current study was part of a randomized clinical trial (Marcotte et al., 2022). Participants smoked ad libitum THC cigarettes and then completed driving simulations, blood draws, and subjective measures of intoxication. The main outcomes were the change in Composite Drive Score (CDS; global measure of driving performance) from baseline, whole blood THC, 11-OH-THC, and THC-COOH levels (ng/mL), and subjective ratings of how “high” participants felt (0 = not at all, 100 = extremely). For this analysis of participants receiving active THC, males were matched to females on 1) estimated THC exposure (g) in the last 6 months (24M, 24F) or 2) whole blood THC concentrations immediately post-smoking (23M, 23F).

When matched on THC exposure in the past 6 months (overall mean of 46 grams; p = .99), there were no sex differences in any cannabinoid/metabolite concentrations at baseline (all p > .83) or after cannabis administration (all p > .72). Nor were there differences in the change in CDS from pre-to-post-smoking (p = .26) or subjective “highness” ratings (p = .53). When matched on whole blood THC concentrations immediately after smoking (mean of 34 ng/mL for both sexes, p = .99), no differences were found in CDS change from pre-to-post smoking (p = .81), THC metabolite concentrations (all p > .25), or subjective “highness” ratings (p = .56). For both analyses, males and females did not differ in BMI (both p > .7).

When male/female cannabis users are well-matched on use history, we find no significant differences in cannabinoid concentrations following a mean of 5 days of abstinence, suggesting that there are no clear biological differences in carryover residual effects. We also find no significant sex differences following ad libitum smoking in driving performance, subjective ratings of “highness,” nor whole blood THC and metabolite concentrations, indicating that there are no biological differences in acute response to THC. This improves upon previous research by closely matching participants over a wider range of use intensity variables, although the small sample size precludes definitive conclusions.

Determining neurobiological mechanisms underlying risk-taking behavior is paramount toward developing targeted therapeutics for psychiatric conditions with such behavioral deficits. Therapies are urgently needed given risk-taking is strongly linked to suicidal behavior. Risk-taking is often assessed in tasks of varied rewards and losses, complicating the interpretation of chasing rewards vs. avoiding punishments. A novel task in rats was designed which utilizes varying rewards only, so as to determine mechanisms contributing to ‘chasing’ higher rewards. This task was used to determine that the high reward (risk) preference of male rats was increased by pramipexole treatment [a dopamine D2 receptor-(D2R) family agonist] and decreased by optogenetic inhibition of D2R expressing neurons. The impact of D2R antagonists and sex-dependent differences were not examined however and remains unclear. Here, we trained female and male rats in the task to determine sex-differences in risk preference at baseline and in response to pharmacological challenges of pramipexole, the D2R antagonist sulpiride, and the dopamine transporter inhibitor GBR-12909.

In operant boxes animals could choose from one of two nose-pokes, one that delivered a 50 μl strawberry milkshake reward (safe-option), and the other a 10 μl reward with 75% probability and 170 μl reward with 25% probability (risky-option). Once trained to a stable baseline of risk preference, rats were treated with pramipexole (0.15- or 0.3-mg/kg; Experiment 1) or sulpiride (30-mg/kg; Experiment 2) for 3 days, each separated by a saline washout. Animals were once again trained to a stable baseline, then injected with GBR-12909 (5- or 16-mg/kg; Experiment 3).

Baseline: females were less risk-adverse/more risk-prone than males. Experiment 1: there was a main effect of drug on percent risk choice (%RC) change from baseline [F(1,18)=10.5, p<0.01], with pramipexole increasing %RC. When analyzed across each testing day, a main effect of session [F(6,108)=3.6, p<0.005] was observed, as was a session*sex*drug interaction [F(6,108)=2.2, p<0.05]. Post hoc analyses revealed females differed from males in the timing of their response to pramipexole based on dose. Experiment 2: there was a main effect of drug on %RC change from baseline [F(1,6)=20, p<0.01], with sulpiride decreasing %RC. There was also evidence for a drug*sex interaction [F(1,6)=3.6, p=0.11], with more pronounced attenuation by sulpiride in females. A similar pattern was observed when analyzed across testing days. Experiment 3: there was a main effect of drug on %RC change from baseline [F(2,26)=4.0, p<0.05], with the high dose of GBR-12909 (16-mg/kg) increasing %RC compared to VEH (p<0.05) and low dose (5-mg/kg).

Together these data indicate a sex-specific modulation of baseline risk preferences as measured explicitly via reward seeking behaviors. Additionally, female rats may be more sensitive to D2R manipulations on such risky decision-making behavior, highlighting the necessity of tracking sex-based differences in such tasks. Ongoing studies will determine whether D2R activity reveal a similar sex-specific change during such reward-seeking risk-preference. Furthermore, ongoing studies will determine the link of such behavior to effortful decision making and more traditional measures of risk-taking behavior, such as the Iowa Gambling Task used both in rodents and humans.

When asked to imagine future events, individuals with PTSD provide narratives with limited event-specific details, suggesting an impairment in event elaboration. Here we examined whether future thinking in PTSD is also associated with an impairment in the initial stage of event construction, by using a future-event fluency task that makes no demands on event elaboration (MacLeod, A. K., & Salaminiou, E. (2001). Reduced positive future-thinking in depression: Cognitive and affective factors. Cognition & Emotion, 15(1), 99–107).

Thirty-five veterans (6 female, 29 male; aged 27–51), assigned on the basis of structured diagnostic interviews to PTSD-only (n = 15), PTSD + depression (n = 9), or psychopathology-free control groups (n = 11), were asked to generate, in one minute, as many events as possible that they expected to happen in the future, across four conditions that varied in valence (positive, negative) and temporal framework (1 month, 10 years). Two independent raters classified each event generated as being specific (i.e., a unique, time-limited event), generic (i.e., ongoing or recurring events), or a repetition.

Results of linear mixed modeling carried out on the number of specific events generated showed that diagnostic group and event valence contributed significantly to the overall model fit. All participants generated more positive than negative events (β = 1.014, SE = 0.330, t(105) = 3.07 p = 0.003), and both PTSD groups generated fewer specific events than controls (PTSD-only (β = -2.203, SE = 0.744, t(35) = -2.96, p = 0.005); PTSD + depression (β = -1.859, SE = 0.842, t(35) = -2.21, p = 0.034). Adding the interaction between group and valence did not improve the model fit, suggesting that the PTSD groups were not differentially impaired in the generation of positive and negative events. When including scores on an emotionally neutral phonemic fluency task (FAS) as a covariate to account for verbal fluency, the PTSD-only group still generated significantly fewer events than the controls (β = -1.667, SE = 0.733, t(34) = -2.27, p = 0.030). After adjusting for FAS, the group effect was marginal for the PTSD + depression group (β = -1.600, SE = 0.801, t(34) = -2.00, p = 0.054).

These results suggest that the impairment in future thinking in PTSD concerns not only the elaboration of future events but also the processes involved in initial event specification, such as those involved in the search and selection of a specific event. Moreover, these findings highlight a distinction between the future thinking abnormalities in PTSD, characterized by reduced generation of both positive and negative future events, compared to depression, which has been associated with reduced generation of positive future events only (MacLeod & Salaminiou, 2001).

Functional connectivity of the default mode network (DMN) during rest has been shown to be different among adults with Mild Cognitive Impairment (MCI) relative to aged-matched individuals without MCI and is predictive of transition to dementia. Post-traumatic stress disorder (PTSD) is also associated with aberrant connectivity of the DMN. Prior work from this group has demonstrated a higher rate of MCI and PTSD among World Trade Center (WTC) responders relative to the general population. The current study sought to investigate the main and interactive effects of MCI and PTSD on DMN functioning. Based on prior work, we hypothesized that MCI, but not PTSD, would predict aberrant connectivity in the DMN.

99 WTC responders aged 44–65 stratified by MCI status (yes/no) and PTSD status (yes/no) and matched for age in years, sex (male vs. female), race (white, black, and other), and educational attainment (high school or less, some college / technical school, and university degree), and occupation on September 11, 2001 (law enforcement vs. other) underwent fMRI using a 3T Siemens Biograph MR scanner. A single 10-minute continuous functional MR sequence was acquired while participants were at rest with their eyes open. Group-level analyses were conducted using SPM-12, with correction for multiple comparisons using AFNI's 3dClustSim. Based on this threshold, the number of comparisons in our imaging volume, and the smoothness of our imaging data as measured by 3dFWHMx-acf, a minimum cluster size of 1134 voxels was required to have a corrected p . .05 with 2-sided thresholding. Spherical 3 mm seeds were placed in the dorsal (4, -50, 26) and ventral (4, -60, 46) posterior cingulate cortex (PCC).

Individuals with PTSD demonstrated significantly less connectivity of the dorsal posterior cingulate cortex (PCC) with medial insula (T = 5.21), subthalamic nucleus (T = 4.66), and postcentral gyrus (T = 3.81). There was no difference found in this study for connectivity between groups stratified by MCI status. There were no significant results for the ventral PCC seed.

Contrary to hypotheses that were driven by a study of cortical thickness in WTC responders, the impact of PTSD appears to outweigh the impact of MCI on dorsal DMN connectivity among WTC responders stratified by PTSD and MCI status. This study is limited by several issues, including low number of female and minority participants, relatively small group cell sizes (n = 23–27 per cell), a brief resting state sequence (10 minutes), and lack of a non-WTC control group. Importantly, responders are a unique population so generalizability to other populations may be limited. Individuals in the current study are now being followed longitudinally to relate baseline resting state functional connectivity with cognitive changes and changes in connectivity over a four-year period.

Schizophrenia (SCZ) is a neuropsychiatric disorder with strong genetic heritability and predicted genetic heterogeneity, but limited knowledge regarding the underlying genetic risk variants. Classification into phenotype-driven subgroups or endophenotypes is expected to facilitate genetic analysis. Here, we report a teen boy with chronic psychosis and cerebellar hypoplasia (CBLH) and analyze data on 16 reported individuals with SCZ or chronic psychosis not otherwise specified associated with cerebellar hypoplasia to look for shared features.

We evaluated an 18-year-old boy with neurodevelopmental deficits from early childhood and onset of hallucinations and other features of SCZ at 10 years who had mild vermis-predominant CBLH on brain imaging. This prompted us to review prior reports of chronic psychosis or SCZ with cerebellar malformations using paired search terms including (1) cerebellar hypoplasia, Dandy-Walker malformation, Dandy-Walker variant, or mega-cisterna magna with (2) psychosis or SCZ. We found reports of 16 affected individuals from 13 reports. We reviewed clinical features focusing on demographic information, prenatal-perinatal history and neuropsychiatric and neurodevelopmental phenotypes, and independently reviewed brain imaging features.

All 17 individuals had classic psychiatric features of SCZ or chronic psychosis as well as shared neurodevelopmental features not previously highlighted including a downward shift in IQ of about 20 points, memory impairment, speech-language deficits, attention deficits and sleep disturbances. The brain imaging findings among these individuals consistently showed posterior vermis predominant CBLH with variable cerebellar hemisphere hypoplasia and enlarged posterior fossa (a.k.a. mega-cisterna magna). None had features of classic DWM.

In 17 individuals with chronic psychosis or SCZ and cerebellar malformation, we found a high frequency of neurodevelopmental disorders, a consistent brain malformation consisting of posterior vermis-predominant (and usually symmetric) CBLH, and no evidence of prenatal risk factors. The consistent phenotype and lack of prenatal risk factors for CBLH leads us to hypothesize that psychosis or schizophrenia associated with vermis predominant CBLH comprises a homogeneous subgroup of individuals with chronic psychosis/schizophrenia that is likely to have an underlying genetic basis. No comprehensive targeted gene panel for CBLH has yet been defined, leading us to recommend trio-based exome sequencing for individuals who present with this combination of features.

Suicide risk among individuals with psychosis is elevated compared to the general population (e.g., higher rates of suicide attempts [SA] and completions, more severe lethality of means). Importantly, suicidal ideation (SI) seems to be more predictive of near-term and lifetime SAs in people with psychosis than in the general population. Yet, many randomized controlled trials in psychosis have excluded individuals with suicidality. Additionally, research suggests better cognitive and functional abilities are associated with greater suicide risk in psychotic disorders, which is dissimilar to the general population, but studies examining the link between cognition and suicidality are scarce. Because neuropsychological abilities can affect how individuals are able to attend to their environment, solve problems, and inhibit behaviors, further work is needed to consider how they may contribute to suicide risk in people with psychotic disorders. We sought to examine associations between neuropsychological performance and current SI and SA history in a large sample of individuals with psychosis.

176 participants with diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features completed clinical interviews, a neuropsychological assessment (MATRICS Consensus Cognitive Battery subtests), and psychiatric symptom measures (Positive and Negative Syndrome Scale [PANSS]; Montgomery-Asberg Depression Rating Scale [MADRS]. First, participants were divided into groups based on their current endorsement of SI in the past month on the Colombia Suicide Severity Rating scale (C-SSRS): those with current SI (SI+; n=86) and without current SI (SI-; n=90). We also examined lifetime history of SA (n=114) vs. absence of lifetime SA (n=62). Separate t-tests, chi-square tests, and logistic regressions were used to examine associations between neuropsychological performance and the two dichotomous outcome variables (current SI; history of SA).

The SI groups did not differ on diagnosis, demographics (e.g., age, gender, race, ethnicity, years of education, premorbid functioning), or on positive and negative symptoms. The SI+ group reported more severe depressive symptoms (t(169)= -5.90, p<.001) and had significantly worse performance on working memory tests than the SI- group (t(173)=2.28, p=.024). Logistic regression revealed that working memory performance uniquely predicted current SI+ group membership above and beyond depressive symptoms (B= -.040; OR= .96; 95% CI [.93, .99]; p= .034). The SA groups did not significantly differ on demographic variables or on positive/negative symptoms, but those with a history of SA had more severe depressive symptoms (t(169)= -2.80, p=.006) and worse performance on tests of working memory (t(173)=2.16, p=.033) and processing speed (t(166)=2.28, p=.024) than did those without a history of SA. Logistic regression demonstrated that after controlling for depressive symptom severity, working memory and processing speed did not predict unique variance in SA history (p=.25).

Worse working memory performance was associated with SI in the past month in individuals with psychotic disorders. Although our finding is consistent with literature in other psychiatric populations, it conflicts with existing psychosis literature. Thus, a more nuanced examination of how cognition relates to SI/SA in psychosis is warranted to identify and/or develop optimal interventions.

In persons with severe psychiatric disorders, distinct neurocognitive profiles hold differential associations to positive, negative and disorganized symptom dimensions of psychosis. These patterns portend specific functional outcomes, treatment efficacy, and prognoses. Similar associations have not been established in multimorbid samples in which persons present with a complex array of psychiatric symptoms. The objective of this study was to (1) establish neurocognitive profiles in a multimorbid, marginalized sample and (2) investigate their pattern(s) of association with psychiatric symptom dimensions and psychosocial outcomes.

Participants (n=370; Mage = 45 years; 74% male) were precariously housed, substance-using adults with multimorbidity, recruited from Single-Room Occupancy hotels and a community court within the Downtown Eastside of Vancouver, BC, Canada. Data were collected as part of a longitudinal examination consisting of annual, bi-annual, and monthly neurocognitive, psychosocial, and psychiatric assessments. Neurocognitive scores were combined into five cognitive domains (Attentional Control [AC]; Processing Speed [PS]; Fluid Reasoning [Problem Solving and Reversal Learning; Gf]; Encoding and Retrieval [ER]; and Decision Making [DM]) and submitted to a latent profile analysis. The resulting profiles capturing neurocognition were validated on sociodemographic and clinical variables. Finally, the profiles were compared across previously validated, population-distinct factors derived from the Positive and Negative Syndrome Scale (PANSS), as well as on measures of psychosocial functioning.

An optimal goodness-of-fit was reached for a three-profile model (BLRT=127.86, p=.01). Profile 1 (n=207, 55.9%) showed stronger neurocognition (all p<.05), with a within-profile strength in Gf (p<.001). With the exception of ER, Profile 2 (n=109, 29.5%) exhibited inferior neurocognition across all indicators compared to Profile 1 (all p <.05); yet showed a relative, within-profile strength in Gf (p < .01). Profile 3 (n=54, 14.6%) generally displayed comparable impairments to Profile 2. Additionally, their performance on Gf was remarkably low compared to Profiles 1 and 2 (p<.001). Psychiatrically, compared to Profile 1, Profile 2 exhibited more positive/disorganized symptoms and general psychopathology, as well as higher total PANSS (all p <.05), whereas Profile 3 showed the poorest insight/awareness (p<.01). Profiles 2 and 3 had lower levels of adaptive functioning and work productivity compared to Profile 1 (all p<.01).

Three neurocognitive profiles were detected in a sample of precariously housed adults with multimorbidity: one profile of comparatively higher neurocognitive capacity, with less symptoms of psychosis and better psychosocial functioning; a second profile of comparatively poorer neurocognition and psychosocial functioning, with more symptoms of psychosis; and a third profile with a severe deficit in fluid reasoning and poor insight and awareness. Given their poor insight, the third profile may be comprised of particularly vulnerable persons at greater risk of unmet healthcare needs. Interventions to improve these individuals' understanding of their personal health risks might facilitate their capacity to access services. Conversely, individuals from Profile 2 may benefit from outreach programs focusing on medication access and adherence to address their symptoms of psychosis. In sum, our findings suggest that the confluence of neurocognition and psychiatric symptoms may implicate unique treatment approaches and outcomes in precariously-housed persons with multimorbid conditions.

Social impairment is observed across psychotic-spectrum disorders (PSDs). Prior work demonstrates that neurocognition may account for social impairment in chronic PSDs. Concerning specific neurocognitive facets, there is support for a relationship between language/verbal performance and social outcomes in chronic PSDs. However, few studies have investigated this relationship in at-risk and early intervention samples, despite the clinical importance in these populations. The present study aimed to identify whether language is related to social functioning across the psychosis-spectrum, utilizing a sample comprised of individuals low in schizotypal personality traits, at-risk for psychosis (high in schizotypal traits), and those who recently experienced a first episode of psychosis (FEP). As an exploratory analysis and guided by findings from general studies of neurocognition and functional outcomes in the chronic PSD literature, we also investigated potential mediating mechanisms (i.e, negative traits; social cognition). We hypothesized that language is related to social functioning, and language is indirectly related to social functioning through negative traits and social cognition.

We recruited 42 participants low in schizotypal traits and 44 high in schizotypal traits from undergraduate courses, and 15 FEP individuals were recruited from an early psychosis intervention center. On average, participants were 21.55 (4.39) years old and completed 14 (1.57) years of education. A majority were female (62%) and White (82%). Participants completed the Schizotypal Personality Questionnaire – Brief Revised Updated, which was used to categorize the schizotypy groups and sum negative traits; and measures of language/verbal ability (Similarities, Proverbs Test, semantic fluency, Digit Span), social cognition (Hinting Task, Affect Naming), and examiner-rated (Global functioning [GF]: Social) and performance-based social functioning (Social Skills Performance Assessment; SSPA). We also measured verbal processing speed and COVID-19 distress as covariates. Standardized scores were used for neurocognitive variables, and we used raw scores for most other variables. We utilized hierarchical linear regression models to examine whether specific language/verbal skills accounted for unique variance in examiner-rated and performance-based social functioning. For our exploratory analyses, we created averaged z-scores for language, social cognition, and social functioning and then, employed PROCESS Macro Model 4 to examine whether negative traits or social cognition were significant mediators in two separate mediation models.

Controlling for verbal processing speed and COVID-19 distress, language accounted for a significant portion of variance in SSPA performance, p = .008, ΔR2 = .12. Specifically, better Proverbs Test performance was uniquely associated with better SSPA performance, β = .33, p = .002. Controlling for study covariates, language was unrelated to GF: Social ratings, p = .31, ΔR2 = .038. In exploratory analyses, language was significantly indirectly related to social functioning through social cognition, β = .15, SE = .04, 95% CI [.04, .27], but not through negative traits, β = .08, SE = .06, 95% CI [-.001, .17].

Our findings suggest that executively-mediated language tasks (e.g., Proverbs Test) and social cognition may be beneficial treatment targets for social impairment. Limitations include generalizability of the present findings, small FEP sample, and cross-sectional design. Future work should replicate these findings in longitudinal models.

Deficits in cognitive ability are common among patients with schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB) was designed to assess cognitive ability in studies of patients diagnosed with schizophrenia and has demonstrated high test-retest reliability with minimal practice effects, even in multi-site trials. However, given the motivational challenges associated with schizophrenia, it is unknown whether performance on MCCB tasks affects performance at later stages of testing. The goal of this study was to determine whether there are differences between people with and without schizophrenia in how their performance on individual MCCB tasks influences their performance throughout the battery.

The sample comprised 92 total participants including 49 cognitively healthy comparison participants and 43 outpatients diagnosed with schizophrenia. The mean age of participants was 44.2 years (SD = 12.0, range 21–69) and 61% identified as male. The Trail Making Test, Brief Assessment of Cognition in Schizophrenia, Hopkins Verbal Learning Test – Revised, Letter-Number Span, and Category Fluency from the MCCB were administered in the same order at 2 different sites and studies from 2016–2022. The autocorrelation between t-scores for task scores within each participant was computed and then compared between control and outpatient participants to determine if there are differences between groups. Group mean t-scores for each task were also compared between groups.

We found no significant difference in autocorrelations across MCCB tasks between healthy comparison participants and outpatients. However, mean performance in all tasks was lower for the outpatient group than for the healthy comparison group. None of the tasks used stood out as having significantly lower mean scores than other tasks for either group.

Our findings suggest that performance on individual MCCB tasks do not affect performance throughout the battery differently between the healthy comparison group and outpatients. This suggests that participants with schizophrenia are not particularly reactive to past performance on MCCB tasks. Additionally, this finding further supports use of the MCCB in this population. Further research is needed to determine whether subgroups of patients and/or different batteries of measures show different patterns of reactivity.

People with psychotic disorders often experience neurocognitive deficits, such as neurocognitive impairment (NCI), which can negatively affect their daily activities (e.g., performing independent tasks) and recovery. Because of this, the American Psychology Association advocates integrating neurocognitive testing into routine care for people living with psychotic disorders, especially those in their first episode, to inform treatment and improve clinical outcomes. However, in low-and-middle income countries (LMICs), such as Uganda where the current study took place, administering neurocognitive tests in healthcare settings presents numerous challenges. In Uganda there are few resources (e.g., trained clinical staff, and culturally relevant and normed tests) to routinely offer testing in healthcare settings. NeuroScreen is a brief, highly automated, tablet-based neurocognitive testing tool that can be administered by all levels of healthcare staff and has been translated into indigenous Ugandan languages. To examine the psychometric properties of NeuroScreen, we measured convergent and criterion validity of the NeuroScreen tests by comparing performance on them to performance on a traditional battery of neurocognitive tests widely used to assess neurocognition in people with psychotic disorders, the Matric Consensus Cognitive Battery (MCCB).

Sixty-five patients admitted into Butabika Mental Referral Hospital in Uganda after experiencing a psychotic episode and forty-seven demographically similar control participants completed two neurocognitive test batteries: the MCCB and NeuroScreen. Both batteries include tests measuring the neurocognitive domains of executive functioning, working memory, verbal learning, and processing speed. Prior to completing each battery, patients were medically stabilized and could not exhibit any positive symptoms on the day of testing. On the day of testing, medication dosages were scheduled so that patients would not experience sedative effects while testing. To examine convergent validity, we examined correlations between overall performance on NeuroScreen and the MCCB, as well as tests that measured the same neurocognitive domains. To examine criterion validity, an ROC curve was computed to examine the sensitivity and specificity of NeuroScreen to detect NCI as defined by the MCCB.

There was a large correlation between overall performance on NeuroScreen and the MCCB battery of tests, r(110) = .65, p < .001. Correlations of various strengths were found among tests measuring the same neurocognitive domains in each battery: executive functioning [r(110) = .56 p <.001], processing speed [r(110) = .44, p <.001)], working memory [r(110) = .29, p<.01], and verbal learning [r(110) = .22, p < .01]. ROC analysis of the ability of NeuroScreen to detect MCCB defined NCI showed an area under curve of .798 and optimal sensitivity and specificity of 83% and 60%, respectively.

Overall test performance between the NeuroScreen and MCCB test batteries was similar in this sample of Ugandans with and without a psychotic disorder, with the strongest correlations in tests of executive functioning and processing speed. ROC analysis provided criterion validity evidence of NeuroScreen to detect MCCB defined NCI. These results provide support for use of NeuroScreen to assess neurocognitive functioning among patients with psychotic disorders in Uganda, however more work needs to be to determine how well it can be implemented in this setting. Future directions include assessing cultural acceptability of NeuroScreen and generating normative data from a larger population of Ugandan test-takers.

Our objective is to investigate whether handedness is associated with performance on verbal and visual neuropsychological tests in people with severe mental disorders. A recent study, applying a continuous scale of hand preference, reports that handedness is not associated with test performance in people with schizophrenia disorders. Conversely, in a recent large meta-analysis where handedness was applied as a dichotomous variable, right-handers had better performance in spatial ability (but not verbal ability) compared to left-handers, irrespective of gender or health status. We hypothesize that a dichotomous classification of handedness will reveal an advantage of right-handedness on tests of visuospatial functions—but not verbal functions—in people with severe mental disorders. We expect that gender will not be associated with the neuropsychological test results.

Data from a sample of 385 patients with severe mental disorders, mainly within the schizophrenia spectrum, were analyzed. All participants had Norwegian as their first language. Their mean age was 24.8 years (SD=6.2) and 153 (39.7%) were women. Handedness was evaluated by observation of preferred hand in writing and drawing during neuropsychological assessment. Chi-square tests were used to compare proportions of cases with reported frequencies of handedness in the general population and comparable clinical samples. Raw scores on Semantic Fluency and Line Orientation from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were analyzed using Mann-Whitney U tests, and possible effects of gender with two-way ANOVA. Frequencies of low scores were analyzed using frequency analyses.

Overall prevalence of left-handers was 10.4% compared to 10.6% in the general population (χ2=.018, p=.893). Observed prevalence for women was 9.2% compared to expected prevalence of 9.5% (χ2=.026, p=.873) and for men 10.7% and 11.6%, respectively (χ2=.039, p=.844). There was a significant difference in Line Orientation scores (Mdright-handers=18, Mdleft-handers=17; U=5268.0, p=.013) but not Semantic Fluency scores (Mdright-handers=17, Mdleft-handers=18.5; U=7568.5, p=.315). Right-handed men had higher scores on Line Orientation but there was no handedness by gender interaction (F(1)=1.69, p=.194). For Semantic Fluency, left-handed men had higher scores and a gender by handedness interaction was found (F(1)=7.21, p=.008). Using scores corresponding to <5th percentile, 15% of left-handers and 8% of right-handers had scores <5th percentile on Line Orientation, as opposed to 15% and 14% on Semantic Fluency.

Right-handers had significantly better performance on a test measuring visuospatial function, irrespective of gender. Left-handers had about twice the number of scores in the impaired range (i.e., <5th percentile) compared to right-handers. Left-handed men had better performance on a test of verbal functions, which was unexpected. A recent study reported no right-hand associated advantage on visuospatial tests in people with schizophrenia disorders when measuring handedness on a continuous scale. This suggests that the classification of handedness as either a dichotomous or as a continuous variable is important in studies of handedness and cognitive functions.

Cohort studies demonstrate that people who later develop schizophrenia, on average, present with mild cognitive deficits in childhood and endure a decline in adolescence and adulthood. Yet, tremendous heterogeneity exists during the course of psychotic disorders, including the prodromal period. Individuals identified to be in this period (known as CHR-P) are at heightened risk for developing psychosis (~35%) and begin to exhibit cognitive deficits. Cognitive impairments in CHR-P (as a singular group) appear to be relatively stable or ameliorate over time. A sizeable proportion has been described to decline on measures related to processing speed or verbal learning. The purpose of this analysis is to use data-driven approaches to identify latent subgroups among CHR-P based on cognitive trajectories. This will yield a clearer understanding of the timing and presentation of both general and domain-specific deficits.

Participants included 684 young people at CHR-P (ages 12–35) from the second cohort of the North American Prodromal Longitudinal Study. Performance on the MATRICS Consensus Cognitive Battery (MCCB) and the Wechsler Abbreviated Scale of Intelligence (WASI-I) was assessed at baseline, 12-, and 24-months. Tested MCCB domains include verbal learning, speed of processing, working memory, and reasoning & problem-solving. Sex- and age-based norms were utilized. The Oral Reading subtest on the Wide Range Achievement Test (WRAT4) indexed pre-morbid IQ at baseline. Latent class mixture models were used to identify distinct trajectories of cognitive performance across two years. One- to 5-class solutions were compared to decide the best solution. This determination depended on goodness-of-fit metrics, interpretability of latent trajectories, and proportion of subgroup membership (>5%).

A one-class solution was found for WASI-I Full-Scale IQ, as people at CHR-P predominantly demonstrated an average IQ that increased gradually over time. For individual domains, one-class solutions also best fit the trajectories for speed of processing, verbal learning, and working memory domains. Two distinct subgroups were identified on one of the executive functioning domains, reasoning and problem-solving (NAB Mazes). The sample divided into unimpaired performance with mild improvement over time (Class I, 74%) and persistent performance two standard deviations below average (Class II, 26%). Between these classes, no significant differences were found for biological sex, age, years of education, or likelihood of conversion to psychosis (OR = 1.68, 95% CI 0.86 to 3.14). Individuals assigned to Class II did demonstrate a lower WASI-I IQ at baseline (96.3 vs. 106.3) and a lower premorbid IQ (100.8 vs. 106.2).

Youth at CHR-P demonstrate relatively homogeneous trajectories across time in terms of general cognition and most individual domains. In contrast, two distinct subgroups were observed with higher cognitive skills involving planning and foresight, and they notably exist independent of conversion outcome. Overall, these findings replicate and extend results from a recently published latent class analysis that examined 12-month trajectories among CHR-P using a different cognitive battery (Allott et al., 2022). Findings inform which individuals at CHR-P may be most likely to benefit from cognitive remediation and can inform about the substrates of deficits by establishing meaningful subtypes.

Adequate effort by examinees during neurocognitive testing is a prerequisite to valid interpretation of test results. Utilizing performance validity tests (PVTs) is strongly recommended within pediatric mild Traumatic Brain Injury (mTBI) populations. PVTs have historically been created based on majority-white and monolingual groups; investigating their validity in additional patient populations remains essential. The Automatized Sequencing Task (AST) was developed as a brief validity measure within mTBI youth (Kirkwood, et.al., 2014). This study aimed to examine the clinical utility of the AST among youth identifying as Hispanic/Latino and/or bilingual within a mTBI clinical sample.

Participants ages 8-17 (N=103, M age=14.08, SD=2.2, 51.5% male, 42.7% Hispanic/Latino, 23.6% bilingual) were drawn from an outpatient mTBI/concussion program within the past 2.6 years. Median time of evaluation since injury was 3.7 weeks. Eligibility criteria included: 1) evaluated for a mTBI (GCS . 13) and 2) 8 through 17 years of age. Language status included English only and English-Spanish bilingual youth. Of the bilingual youth, 95% were considered English dominant. Youth were timed while reciting four well-learned (i.e., automatized) sequences as rapidly as possible: 1) the alphabet, 2) counting from 1-20, 3) the days of the week, and 4) the months of the year. Pass rates for the AST were examined using chi-square tests to compare performance based on ethnic/cultural identity (Hispanic vs Non-Hispanic), language status, age (children 8-12; teens 13-17), and gender.

In the clinical sample, 11.7% (n=12) could not complete AST months; 75% of non-completers were Hispanic/Latino. Participants who identified as Hispanic/Latino compared to Non-Hispanic/Latino participants were significantly more likely to fail the 4-item AST, χ2(1) =4.3, p<.05. The odds of failing the 4-item AST was 2.3 times higher if patients identified as Hispanic/Latino. Further, patients identifying as bilingual were even more likely to fail the 4-item AST, χ2(1) =4.5, p<.05. The odds of failing the 4-item AST was 3.0 times higher if patients were bilingual. There were no ethnicity or bilingual group differences in AST failure when examining performance on the 3-item AST. Neither age nor gender were a significant predictor of failure on the 3-item or 4-item AST.

Results suggest that the month item on the AST does not function consistently across Hispanic/Latino and bilingual youth. It cannot be presumed to be ‘automatic’ as a significant number of Hispanic/Latino and/or bilingual patients were unable to complete the month item, but with otherwise intact performance on the first three items. Administering only the first three items on the AST appears to be a more culturally sensitive alternative given the increased odds of 4-item failure in Hispanic/Latino and bilingual youth. Additional research is needed to explore the predictive validity of the AST as a PVT in varying ethnic, culturally, linguistically, and socioeconomically diverse mTBI pediatric populations.

Process-based measures of verbal learning, such as the recently described learning ratio (LR; Hammers et al., 2022) may add valuable data to neuropsychological assessment. Women tend to have higher episodic verbal memory ability compared to men at all ages, including older adulthood (Golchert et al., 2019; Maitland et al., 2004). However, it is unclear whether gender is related to the process of learning, as quantified through measures of learning slope and ratio. To date only one study has examined this, with Hammers et al. (2021) finding no gender differences on LR in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS); therefore, further study is necessary. We examined whether men and women differed in LR, learning over time (LOT), and raw learning slope (RLS) in a healthy older adult sample, as well as whether these learning process variables predicted delayed memory equally for men and women.

203 cognitively healthy community-dwelling adults aged 50 and above (mean age 67.7; 133 women) were taken from a larger archival database; all were administered the RBANS in the context of other studies. LR, LOT, and RLS were calculated from the List Learning task. We examined whether men and women differed in these learning process measures. We then examined whether process measures differentially predicted performance on list recall and delayed memory index (DMI) of the RBANS for men and women.

Men and women did not differ in age or years of education. After accounting for age and education, there were no gender differences on LR (p=.455) or RLS (p=.502) but LOT was lower in women (p=.013).

LR was equally predictive of list recall across genders (p<.001 for LR; p=.21 for gender). Correlations between LR and list recall were r=.65 (p<.001) for men and r=.56 (p<.001) for women. Both LR (p<.001) and gender (p=.008) predicted DMI but the interaction was nonsignificant. Correlations between LR and DMI were r=.52 for men (p<.001) and r=.46 for women (p<.001).

RLS predicted list recall equally across genders (p<.001 for RLS; p=.07 for gender; p=.18 for interaction). Correlations between RLS and list recall were r=.43 for men (p<.001) and r=.23 for women (p=.008). RLS (p<.001) and gender (p=.002; p=.19 for interaction) predicted DMI scores. Correlations between RLS and DMI were r=.31 for men (p=.008) and r=.21 for women (p=.015).

LOT predicted list recall equally across genders (p<.001; p=.97 for gender; p=.80 for interaction). Correlations between LOT and list recall were r=-.50 for men (p<.001) and r=-.60 for women (p<.001). LOT also predicted DMI equally across genders (p<.001; p=.084 for gender; p=.159 for interaction). Correlations between LOT and DMI were r=-.46 for men (p<.001) and r=-.49 for women (p<.001).

Of the three process variables, LR was the only one that did not show gender differences and was related to delayed memory outcomes with medium to large effect across both genders. Results suggest that LR can be used consistently across genders. As this sample consisted of healthy, independently-living older adults, future study should examine LR by gender in MCI and dementia samples.

There are gender-related disparities in age of diagnosis of Mild Cognitive Impairment (MCI) or dementia, with women often receiving delayed diagnoses compared to men. These delays may be related to the general female advantage in episodic verbal memory across aging. Thus, it is important to identify methods of examining memory performance that can help to reduce disparities in diagnosis. The serial position effect, a pattern where individuals tend to remember more words at the beginning (primacy) and end (recency) of a list, is predictive of dementia and may provide an avenue for this endeavor. Whereas healthy adults tend to exhibit a prototypical U-shaped serial position profile, those with MCI or dementia tend to show reduced primacy relative to recency (i.e., a J-shaped profile). To date, few studies have examined gender differences in the serial position effect. There is some evidence to suggest that older, cognitively healthy women perform better than men on middle and recency, but more research is needed to clarify the relationship between gender and the serial position effect, which was the focus of this study.

We utilized data across three archival datasets, which included a total of 338 participants (67.5% female; Mage=66.9, SDage=9.4) divided into three age groups (50-64, 65-75, 76+). Scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) immediate and delayed memory indices (IMI and DMI, respectively) were used to assess verbal episodic memory abilities. Performances across learning trials of the List Learning task were utilized to examine the serial position effect. ANCOVA analyses were conducted and utilized regional scoring of list learning performance, which examined the percentage of correctly recalled words in each portion of the list (primacy, middle, and recency). We also calculated the relative strength of primacy to list learning to examine the relationship between J-curve performance and gender. Years of education was included as a covariate in all analyses.

Consistent with prior literature, men performed worse performance on both IMI F(1, 331)=17.20, p<.001, and DMI, F(1, 331)=6.87, p=.009, across aging. Repeated measured GLM showed that the serial position effect was seen across the full sample, F(1.93, 639.874)=5.66, p=.004, and interacted with gender, F(1.933, 639.874)=5.70, p=.004, and education, F(1.933, 639.874)=6.13, p = .003. Although men and women did not differ in primacy, p = .67, women performed better in middle, p < .001, and recency, p = .03, performance. Higher education was associated with better primacy, but not middle or recency, performance. Additionally, 23.1% of the sample exhibited a J-curve pattern, and there was a main effect of J-curve pattern for both IMI, F(1, 334)=12.33, p<.001, and DMI, F(1, 334)=15.62, p<.001, with those showing a J=curve having worse memory performance.

Our finding of no gender difference in primacy suggests that focusing on primacy performance in verbal list learning may help to address gender-related disparities in MCI or dementia diagnosis. Additionally, given evidence of education being associated with primacy, but not middle or recency, performance, future research should investigate the development of education-based normative data for primacy performance.

The serial position effect is the tendency to recall items at the beginning (primacy) and end (recency) of a word list best and middle items the worst, demonstrated by a 'U-shaped’ profile. Individuals with memory impairment often demonstrate a 'J-shaped’ profile, with a diminished primacy effect. An attenuated primacy effect could be one of the earliest indicators of cognitive decline in older adults. Chronic elevations in cortisol are related to hippocampal atrophy and decreased learning and recall. Given the rehearsal and encoding required to recall words at the beginning of a list, we hypothesized that reduced primacy would be related to higher cortisol levels, measured via hair cortisol concentration, in older adults, particularly caregivers of people with dementia (PWD), who are under increased stress.

Data were taken from a deidentified dataset of 60 community-dwelling older adults (> 50) with no evidence of dementia who participated in a larger study on memory and caregiving stress; 26 identified themselves as caregivers of PWD. The sample was 83% women and 98% White, with a mean age of 67.58 (SD=8.85) and 80% holding at least a college degree. Stress was measured with the Perceived Stress Scale. The List Learning and List Recall subtests from the Repeatable Battery for the Assessment of Neuropsychological Status were used to assess the serial position effect. Primacy and recency were determined by the first three and last three words on the list, respectively, and were measured for trials 1-4. Relative strength of primacy versus recency at delayed recall was also calculated such that positive scores indicate better primacy than recency and negative scores indicate worse primacy than recency (J-shaped profile). Hair samples were collected, and the first one cm of hair was used to assay hair cortisol concentration, reflecting the past month of cortisol.

Caregivers were younger than non-caregivers (p<.001), but groups did not differ in gender (p=.412). Age was controlled for in all subsequent analyses. Caregivers reported more stress (p<.001), but groups were not different in hair cortisol (p=.093). On memory tasks, caregivers showed lower list learning raw scores (p=.002) and lower list recall raw score (p=.046); groups were not different in primacy learning (p=.114), but caregivers showed worse recency over learning trials (p<.001). Caregivers were not more likely to show the J-shaped serial position profile at recall (p=.285). Collapsed across groups, perceived stress was not related to cortisol (p=.124) but was related to recency (p=.001) and list learning raw (p=.004), but not list recall raw (p=.485) or primacy (p=.109). Cortisol was not related to primacy (p=.277) or recency (p=.538).

Contrary to predictions, caregivers were not worse on primacy but were worse on recency. Caregivers also reported more stress; collapsed across groups, stress was associated with recency performance. This may suggest that stress is related more to poor attention and short-term memory (recency) than encoding and recall related memory problems (primacy).

Learning process variables such as the serial position effect and learning ratio (LR) are predictive of cognitive decline and dementia. Gender differences on memory measures are well documented, but there is inconsistent evidence for gender effects on learning process variables. In the present study, we examined the relationship of serial position and LR to memory performance and to cortisol levels, considering gender as a potential moderator.

Data were taken from a deidentified dataset of a study on stress and aging in which 123 healthy community-dwelling adults over age 50 completed various assessments. Our analyses included 100 participants (56% female, 93% white, Mage 60.65, Meducation 15.22 years) who completed all measures of interest. LR, primacy effect, and recency effect were calculated from the learning trials of the Auditory Verbal Learning Test (AVLT). Additional memory measures included recall measures from the AVLT and from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). AUC cortisol was calculated from salivary cortisol samples taken across 6 time points in the study.

Women performed better than men on LR, primacy, and traditional memory measures (ps=<.001 to .018) but not on recency (p=.40). LR was moderately correlated with primacy (r=.481, p<.001) and weakly correlated with recency (r=.271, p=.008), after controlling for age, gender, and education. After controlling for age, gender, and education, better LR was related to better memory performance across all measures (rs=.276-.693, ps= <.001-.007) and better recency was related to better performance on all memory measures (rs=.212-.396, ps=<.001-.038). Better primacy was related to better AVLT immediate and delayed recall and RBANS Immediate Memory Index (rs=.326-.532, p<.001) but not RBANS delayed (r=.115, p=.263).

Hierarchical linear regressions were conducted to examine gender as a moderator of relationships between learning process variables and memory performance, after accounting for age, gender, and education. There were no gender by LR (ps=.349-.830) or gender by primacy interactions (ps=.124-.671). There was an interaction between gender and recency on AVLT memory measures (ps=.006-.022), but not on RBANS measures (ps=.076-.745). For men, higher recency was related to higher AVLT immediate and delayed recall (rs=.501-.541, ps<.001), but not for women (rs=.-.029-.020, ps=.839-.888), after controlling for age and education. The relationship of AUC salivary cortisol to learning process measures was also moderated by gender (LR/gender interaction p=.055; primacy/gender interaction p=.047; but not recency/gender p=.79). Interestingly, for women, higher cortisol was related to higher LR (r=.16) and higher primacy (r=.36), while for men, it was related to lower LR (r=-.22) and not to primacy (r=-.05). Cortisol was not related to recency (rs=-.04 to -.07).

Women performed better on LR and primacy, as well as on other traditional memory variables, but gender did not appear to differentially impact the relationship of LR or primacy to memory outcomes. Findings suggest some differential relationships of recency to memory outcomes by gender. Results also suggested potential gender differences in the relationship of cortisol to learning process variables, but further study is necessary, especially with samples of individuals with memory impairment.