Torill Ueland

The validity of d prime as a working memory index: Results from the “Bergen n -back task”

The n-back task is frequently used as an experimental paradigm in imaging studies of working memory. This study aimed to investigate whether the Bergen 2-back task is suitable for use in desktop assessment of patients with schizophrenia. Looking at the psychometric properties of the task, including the newly added measure of discriminability, d prime (d ′), our analyses confirmed that the 2-back d ′ is the preferred measure of working memory dysfunction in desktop assessment compared to the Digit Span Backward and the Letter–Number Sequencing subtests from the Wechsler Adult Intelligence Scale–Third Edition (WAIS–III). d ′ has the advantage of capturing executive skills needed to perform mental operations in patients with schizophrenia, without being influenced by demographic variables or IQ.

Cognitive functioning in adolescents with schizophrenia spectrum disorders

In contrast to studies of cognitive functioning in adults with schizophrenia, there has been a relative paucity of studies assessing adolescents with schizophrenia. We investigated cognitive functioning in 22 adolescents with schizophrenia spectrum disorders compared with 30 healthy adolescents. The patient group demonstrated impaired performance on all of the functions investigated except sustained attention. Against the background of this broad impairment, executive function and psychomotor speed were the most impaired, sustained attention was spared, while preattentional processing, early visual information processing, visual long-term memory, auditory short-term memory and working memory emerged as relative deficits. The study shows that adolescents with schizophrenia spectrum disorders demonstrate a similar pattern of cognitive functioning to adults in all areas, except sustained attention.

Psychosocial function in schizophrenia and bipolar disorder: Relationship to neurocognition and clinical symptoms

In line with a dimensional approach to psychopathology, we examined whether psychosocial function and its relationship to neurocognition and clinical symptoms differ across schizophrenia and bipolar disorder subgroups with and without a history of affective or psychotic episodes. From the TOP study, a heterogeneous sample of individuals with schizophrenia spectrum disorders without (n = 60) and with a history of affective episodes (n = 54); individuals with bipolar spectrum disorders with (n = 64) and without a history of psychosis (n = 56) and healthy controls (n = 268) participated. Psychosocial functioning was measured with the Social Functioning Scale (self-rated) and the Global Assessment of Functioning Scale (clinician-rated), neurocognition with a comprehensive neuropsychological test battery, and symptoms with Inventory of Depressive Symptomatology, Young Mania Rating Scale, and Positive and Negative Syndrome Scale. Clinician-rated functioning was poorer in schizophrenia groups than in bipolar groups, but self-rated functioning was similar across all clinical groups and poorer than in controls. Neurocognition and current clinical symptoms were associated with psychosocial function in bivariate analyses, but current symptoms had a greater independent contribution to functioning than neurocognition across clinical groups in multivariate analyses. Despite differences in neurocognition and psychosocial function, groups showed the same pattern in prediction of functioning irrespective of DSM-IV or clinical definition.

Disintegration of Sensorimotor Brain Networks in Schizophrenia

BACKGROUND Schizophrenia is a severe mental disorder associated with derogated function across various domains, including perception, language, motor, emotional, and social behavior. Due to its complex symptomatology, schizophrenia is often regarded a disorder of cognitive processes. Yet due to the frequent involvement of sensory and perceptual symptoms, it has been hypothesized that functional disintegration between sensory and cognitive processes mediates the heterogeneous and comprehensive schizophrenia symptomatology. METHODS Here, using resting-state functional magnetic resonance imaging in 71 patients and 196 healthy controls, we characterized the standard deviation in BOLD (blood-oxygen-level-dependent) signal amplitude and the functional connectivity across a range of functional brain networks. We investigated connectivity on the edge and node level using network modeling based on independent component analysis and utilized the brain network features in cross-validated classification procedures. RESULTS Both amplitude and connectivity were significantly altered in patients, largely involving sensory networks. Reduced standard deviation in amplitude was observed in a range of visual, sensorimotor, and auditory nodes in patients. The strongest differences in connectivity implicated within-sensorimotor and sensorimotor-thalamic connections. Furthermore, sensory nodes displayed widespread alterations in the connectivity with higher-order nodes. We demonstrated robustness of effects across subjects by significantly classifying diagnostic group on the individual level based on cross-validated multivariate connectivity features. CONCLUSION Taken together, the findings support the hypothesis of disintegrated sensory and cognitive processes in schizophrenia, and the foci of effects emphasize that targeting the sensory and perceptual domains may be key to enhance our understanding of schizophrenia pathophysiology.

Polygenic Risk for Schizophrenia Associated With Working Memory-related Prefrontal Brain Activation in Patients With Schizophrenia and Healthy Controls

Schizophrenia is a highly heritable and polygenic disease, and identified common genetic variants have shown weak individual effects. Many studies have reported altered working memory (WM)-related brain activation in schizophrenia, preferentially in the frontal lobe. Such differences in brain activations could reflect inherited alterations possibly involved in the disease etiology, or rather secondary disease-related mechanisms. The use of polygenic risk scores (PGRS) based on a large number of risk polymorphisms with small effects is a valuable approach to examine the effect of cumulative genetic risk on brain functioning. This study examined the impact of cumulative genetic risk for schizophrenia on WM-related brain activations, assessed with functional magnetic resonance imaging. For each participant (63 schizophrenia patients and 118 healthy controls), we calculated a PGRS for schizophrenia based on 18 862 single-nucleotide polymorphism in a large multicenter genome-wide association study including 9146 schizophrenia patients and 12 111 controls, performed by the Psychiatric Genomics Consortium. As expected, the PGRS was significantly higher in patients compared with healthy controls. Further, the PGRS was related to differences in frontal lobe brain activation between high and low WM demand. Specifically, even in absence of main effects of diagnosis, increased PGRS was associated with decreased activation difference in the right middle-superior prefrontal cortex (BA 10/11) and the right inferior frontal gyrus (BA 45). This effect was seen in both cases and controls, and was not influenced by sex, age, or task performance. The findings support the notion of dysregulation of frontal lobe functioning as an inherited vulnerability factor in schizophrenia.

Neurocognition and functional outcome in early-onset schizophrenia and attention-deficit/hyperactivity disorder: a 13-year follow-up.

OBJECTIVE The relation between neurocognitive impairments and functional outcome has been documented in both early onset schizophrenia (EOS) and attention-deficit/hyperactivity disorder (ADHD), but less is known about the long-term relation between these factors. The present study investigates how neurocognition at baseline is related to measures of functional outcome at 13-year follow-up in subjects with EOS and ADHD. METHOD Subjects with EOS (n = 15), ADHD (n = 19), and healthy controls (n = 30) were followed up 13 years after initial assessment. All subjects were between 12 and 18 years of age at baseline and between 24 and 30 at follow-up. They were retested at T2 with the same comprehensive neurocognitive test battery as used at T1, and reassessed with various symptom and behavior ratings and functional outcome measures. RESULTS Both groups were characterized by reduced functional outcome at follow-up, although of different magnitude and type, compared with healthy controls. In the EOS group, neurocognitive baseline measures were associated with social functioning at follow-up (η2 between .26 and .41), while for the ADHD group, no significant predictions were found. CONCLUSIONS Adolescents with EOS and ADHD are characterized by poor functional outcome compared with healthy controls when reassessed as young adults. Executive function, memory and attention were related to social and community functioning in EOS. For ADHD no significant predictions were found although functional outcome was poor. For both groups treatment should focus on training of social skills and activities of daily living to enhance the long-term functional outcome. For EOS cognitive remediation should also be considered.

Neurocognition and occupational functioning in patients with first-episode psychosis: a 2-year follow-up study.

Neurocognitive deficits are a core feature of schizophrenia that is associated with poor occupational functioning. Few studies have investigated this relationship in patients with first-episode psychosis. The current study examined the characteristics of employed and unemployed patients with first-episode psychosis at baseline and 2-year follow-up, and the predictive value of neurocognition on employment status. One-hundred and twenty-two first-episode psychosis patients were assessed with clinical and neurocognitive measures at baseline. Occupational status was assessed at baseline and 2-year follow-up. Those unemployed at baseline were rated lower on global functioning and were more likely to have a schizophrenia spectrum disorder. Total employment rates were 41% at baseline and 38% at 2-year follow-up. Four employment paths emerged at follow-up, defined as persistently employed, becoming unemployed, entering employment and persistently unemployed. The persistently employed group had the highest global functioning score. For the total sample, baseline employment status and sustained attention predicted employment status at follow-up. For those employed at baseline, better sustained attention, higher global functioning, more positive symptoms and less alcohol use predicted persistent employment at follow-up. For those unemployed at baseline, none of the variables predicted change in employment status. Implications of these results are discussed.

Inflammatory markers are associated with general cognitive abilities in schizophrenia and bipolar disorder patients and healthy controls

BACKGROUND The mechanisms underlying cognitive impairment in schizophrenia and bipolar disorders are largely unknown. Immune abnormalities have been found in both disorders, and inflammatory mediators may play roles in cognitive function. We investigated if inflammatory markers are associated with general cognitive abilities. METHODS Participants with schizophrenia spectrum (N=121) and bipolar spectrum (N=111) disorders and healthy controls (N=241) were included. General intellectual abilities were assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serum concentrations of the following immune markers were measured: Soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin, von Willebrand factor, C-reactive protein, interleukin-6 and CD40 ligand. RESULTS After adjusting for age, sex and diagnostic group, significant negative associations with general cognitive function were found for sTNF-R1 (p=2×10(-5)), IL-1Ra (p=0.002) and sCD40 ligand (p=0.003). Among patients, the associations remained significant (p=0.006, p=0.005 and p=0.02) after adjusting for possible confounders including education, smoking, psychotic and affective symptoms, body mass index, cortisol, medication and time of blood sampling. Subgroup analysis, showed that general cognitive abilities were significantly associated with IL-1Ra and sTNF-R1 in schizophrenia patients, with sCD40L and IL-1Ra in bipolar disorder patients and with sTNF-R1 in healthy controls. CONCLUSION The study shows significant negative associations between inflammatory markers and general cognitive abilities after adjusting for possible confounders. The findings strongly support a role for inflammation in the neurophysiology of cognitive impairment.

Do Low-Effort Learning Strategies Mediate Impaired Memory in ADHD?

As a group, participants with attention-deficit/hyperactivity disorder (ADHD) are impaired in academic performance and learning. This may be due to a mild intellectual impairment, impaired attention, or inability to allocate sufficient effort. If the latter is the case, this should be evident in the learning strategies applied. Four indices of learning strategy, considered to measure degree of effort, were analyzed from 67 participants with ADHD and 67 age-matched normal controls between 9 and 16 years of age. The participants with ADHD were impaired with regard to semantic clustering, retroactive interference, and percentage items reported from the middle section of the list even when controlling for IQ and comorbid conduct or oppositional defiant disorders symptoms. In addition, participants with combined ADHD (ADHD-C) did not display the normal proactive interference effect. The four effort indices explained 39% and 35% of the variance in free recall among participants with inattentive ADHD (ADHD-I) and ADHD-C, respectively. IQ was still significant when the effect of strategy measures were accounted for, whereas diagnosis was no longer significant when entered into the regression analysis after the effort indices. The study shows that participants with ADHD employ less effortful learning strategies than healthy controls and that low effort to a large degree can account for diagnosis related variance in memory performance.

Prevalence, Employment Rate, and Cost of Schizophrenia in a High-Income Welfare Society: A Population-Based Study Using Comprehensive Health and Welfare Registers

Schizophrenia is associated with recurrent hospitalizations, need for long-term community support, poor social functioning, and low employment rates. Despite the wide- ranging financial and social burdens associated with the illness, there is great uncertainty regarding prevalence, employment rates, and the societal costs of schizophrenia. The current study investigates 12-month prevalence of patients treated for schizophrenia, employment rates, and cost of schizophrenia using a population-based top-down approach. Data were obtained from comprehensive and mandatory health and welfare registers in Norway. We identified a 12-month prevalence of 0.17% for the entire population. The employment rate among working-age individuals was 10.24%. The societal costs for the 12-month period were USD 890 million. The average cost per individual with schizophrenia was USD 106 thousand. Inpatient care and lost productivity due to high unemployment represented 33% and 29%, respectively, of the total costs. The use of mandatory health and welfare registers enabled a unique and informative analysis on true population-based datasets.