Luz Ospina

Introduction Cognitive dysfunction in individuals with schizophrenia (SZ) represents a major determinant of poor functioning and may arise in part due to deficits in sleep quality that have been reported in in this population. In the current project, we investigate the effect of acute sleep restriction on a sleep-dependent emotional memory task. Methods Six individuals with medication-controlled SZ encoded consensus-rated emotionally valent and neutral pictures from the International Affective Picture System in the evening before 2 counterbalanced, polysomnographically-recorded nights containing either ad libitum sleep (~11pm to 7am) or sleep restriction (SR) to 4 hours between 3 and 7 am. Image recall occurred within 1 hour of wake time. We compared memory performance for negative emotional/neutral memory and PSG measures across the two sleep conditions with paired signed-rank tests. Results Mean age was 38 years and 50% were women. Acute sleep restriction resulted in reduced total...

Decreased expression of oligodendrocyte/myelin-related (OMR) genes, including quaking (QKI), is a con-sistent finding in gene expression studies of post-mor-tem brain from subjects with schizophrenia, and these changes are most prominent in the hippocampus vs. the prefrontal cortex (PFC). Although expression of QKI and other OMR genes has been examined in rodents, little is known about their developmental trajectory in the human brain. Therefore, we examined expression of QKI and several putative mRNA targets of QKI in human PFC and hippocampus at different ages. The pattern of QKI expression in the PFC resembled that reported in rodents, with high QKI-5 in the fetal brain and an increase in QKI-6 and QKI-7 during the period of active myelination, although QKI-5 expression did

Exercise is a promising intervention for individuals at clinical high-risk for psychosis (CHR). However, these youth may not be reliable reporters on fitness. There have been no investigations that utilized objective fitness assessment in this population. The present study objectively characterizes the level of fitness in CHR youth, compares the accuracy of self-report measures to objective fitness indices, and explores clinical factors that may influence the accuracy of self-reported measures of fitness. Forty CHR individuals completed an exercise survey and objective indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed objective indices of fitness and a structured clinical interview ruling out the presence of psychiatric illness. CHR youth showed greater BMI and lowered VO2max compared to healthy volunteers. In the CHR group, self-report items (perceived fitness) did not reflect objective indices of fitness, whereas specific exercise behaviors (intensity o...

Background Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5–10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk. Methods Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will in...

IntroductionExercise is a promising intervention for clinical high-risk for psychosis (CHR) populations, who have attenuated positive symptoms, but evidence suggests that these youth may require tailored exercise interventions. Presently, the scope of the problem is unknown, as these youth may not be reliable reporters on fitness. This issue is compounded by the fact that there have been no investigations that utilized a formal fitness assessment in this critical population. The present study aims to determine the level of fitness in CHR youth with lab-based measures, test how effectively self-report measures characterize objective fitness indices, and explore clinical factors that may be interrupting reliable self-report-an important tool if these interventions are to be taken to scale.MethodsForty CHR individuals completed an exercise survey and lab-based indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed lab indices of fitness and a structured clinical ...

Emotion regulation (ER) difficulties are ubiquitous among individuals with schizophrenia and have been hypothesized to contribute to stress sensitivity and exacerbation of psychotic symptoms in this population. However, the evidence supporting this link is equivocal, potentially due to previous studies’ reliance on retrospective assessments of ER and psychosis, as well as lack of consideration of putative moderators such as emotion awareness. To address these limitations, we employed experience sampling method using mobile electronic devices to investigate the links between momentary in vivo use of ER strategies (mER), emotion awareness, and psychotic symptoms during daily functioning. Fifty-four individuals with schizophrenia completed assessment of mER and psychotic symptoms, along with traditional retrospective measures of ER and symptoms. Use of mER suppression predicted significant increases in momentary experiences of thought insertion, mind reading, auditory and visual halluc...

Neurocognitive difficulties are highly prevalent among people with schizophrenia and have been linked to increased inflammation, as well as dysfunction and disability. Poor neurocognitive functioning has also been documented in individuals at clinical high risk for psychosis (CHR) and a burgeoning literature point to alterations in inflammation markers in this population. However, there is limited information regarding the putative link between inflammation and neurocognition in CHR individuals, and the potential role of inflammation in the development of cognitive difficulties and psychosis. As previous reports indicate that early treatment in schizophrenia is associated with better outcomes, there is an urgent need to identify neurobiological mechanisms underlying cognitive deterioration and psychosis in CHR individuals to provide them with care prior to significant cognitive and functional declines. To address this gap in the literature, we review and summarize the relevant literatures on inflammation and neurocognitive dysfunction in schizophrenia and CHR individuals, point to remaining gaps, and suggest directions for future research.

Bipolar disorder (BPD) is a severe mood disorder that often has psychotic features. Its most severe forms are more common and significantly more likely to cause disability than originally thought. Studies of high-risk children have found them to be at increased risk for a variety of symptoms and neurobiological abnormalities. In contrast to schizophrenia, there is no formal prodromal syndrome that has been identified, and cognitive abnormalities do not precede the onset of the disorder. Abnormal sleep and circadian rhythms are prominent and have led to intriguing biological models. Neurobiological experiments have primarily focused on candidate pathways and include circadian abnormalities, epigenetic processes including histone modification, WNT/GSK3 signaling, other modulators of neuroplasticity, and mitochondrial dysfunction. Recent data suggest that BPD is a highly polygenic disease and that integration of prior modeling and data with the wide variety of new genetic risk loci wil...

Despite the overlap between schizophrenia and bipolar disorder, neurodevelopmental abnormalities are thought to be associated primarily with schizophrenia. Transdiagnostic and empirical identification of subgroups based on premorbid adjustment (PMA) may enhance understanding of illness trajectories. 160 patients with bipolar I or II disorder (BD; n = 104) or schizophrenia or schizoaffective disorder (SZ; n = 56) were assessed on PMA course from childhood to late adolescence and current symptoms and functioning. A hierarchical cluster analysis was performed using social and academic PMA scores, resulting in three optimal clusters. Cluster 1 (n = 28 SZ, 65 BD) had normal social and academic PMA, the most education, and mildest current symptoms. Cluster 2 (n = 15 SZ, 24 BD) had normal social PMA but an impaired-declining academic course and had a greater proportion of males than Cluster 1. Cluster 3 (n = 13 SZ, 15 BD) had an impaired-stable social PMA and an impaired-declining academic course and the most severe current negative symptoms and childhood trauma. The proportions of SZ and BD diagnoses, current neurocognition, and functioning did not differ between clusters. These findings suggest shared neurodevelopmental abnormalities between SZ and BD, with subgroups exhibiting distinct PMA trajectories that cut across disorders.

Individuals with schizophrenia display substantial deficits in neurocognition, resulting in poor daily functioning and disability. Recent reports have suggested that neurocognitive dysfunction in this population is linked to increased inflammation. However, there is paucity of evidence supporting this link, as well as lack of information about the putative link of inflammation to daily functioning. We examined neurocognition (MCCB) and daily functioning (SLOF), as well as inflammatory markers (TNF-α, IL-6, IL-1β, and IL-12p70) in 41 individuals with schizophrenia. Poor neurocognition was significantly associated with increased peripheral TNF-α and IL-12p70 (r = -0.44 and r = -0.38, respectively, controlling for BMI, depression and antipsychotic medication). Notably, difficulties with daily functioning were significantly associated with increased peripheral TNF-α (r = -0.51) and a trend with increased IL-12p70. Our findings support previous hypotheses linking neurocognitive impairment to increased inflammation in individuals with schizophrenia. Our results extend these associations in this population, linking inflammation to poor daily functioning in this population.

Background: Verbal memory (VM) impairment is prominent in bipolar disorder (BD) and is linked to functional outcomes. However, the intricacies of VM impairment have not yet been studied in a large sample of BD patients. Moreover, some have proposed VM deficits that may be mediated by organizational strategies, such as semantic or serial clustering. Thus, the exact nature of VM break-down in BD patients is not well understood, limiting remediation efforts. We investigated the intricacies of VM deficits in BD patients versus healthy controls (HCs) and examined whether verbal learning differences were mediated by use of clustering strategies. Methods: The California Verbal Learning Test (CVLT) was administered to 113 affectively stable BD patients and 106 HCs. We compared diagnostic groups on all CVLT indices and investigated whether group differences in verbal learning were mediated by clustering strategies. Results: Although BD patients showed significantly poorer attention, learning...

Several studies have documented the prevalence and effects of cigarette smoking on cognition in psychotic disorders; fewer have focused on bipolar disorder (BD). Cognitive and social dysfunction are common in BD, and the severity of these deficits may be related both to illness features (e.g., current symptoms, psychosis history) and health-related behaviors (e.g., smoking, alcohol use). The current study assessed the influence of cigarette smoking on general and social cognition in a BD cohort, accounting for illness features with a focus on psychosis history. We assessed smoking status in 105 euthymic patients with BD, who completed a comprehensive battery including social (facial affect recognition, emotional problem-solving, and theory of mind) and general (the MATRICS Consensus Cognitive Battery and executive functioning) cognitive measures. We compared smokers vs nonsmokers on cognitive performance and tested for the effects of psychosis history, premorbid intellectual functioning, substance use, and current affective symptoms. Within the nonpsychotic subgroup with BD (n=45), smokers generally outperformed nonsmokers; by contrast, for subjects with BD with a history of psychosis (n=41), nonsmokers outperformed smokers. This pattern was noted more globally using a general composite cognitive score and on social/affective measures assessing patients' ability to identify emotions of facial stimuli and solve emotional problems. Cigarette smoking differentially affects performance on both general and social cognition in patients with BD as a function of psychosis history. These results suggest that there may be at least partially divergent underlying neurobiological causes for cognitive dysfunction in patients with BD with and without psychosis.

Bipolar disorder (BD) patients encounter significant life adversity, which has contributed to bipolar disorder being a leading cause of disability worldwide. Studies suggest BD patients have more maladaptive coping strategies, some of which can impact their illness course. Yet research on which coping strategies most influence disability is lacking. Such research could inform cognitive-behavioral targets to improve functional outcomes. Thus, we sought to identify relations between coping strategies and real-world function in BD. In 92 affectively-stable BD outpatients, we measured coping strategies via the Brief COPE, real-world disability via the World Health Organization Disability Assessment Schedule, current symptoms, illness chronicity, and neurocognitive functioning via the MATRICS. Multiple regression analysis served to identify the neurocognitive domains predictive of disability for entry into subsequent analyses. Multiple regressions assessed how adaptive and maladaptive co...