Birgitte Fagerlund

Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other psychotic disorders

Cognitive deficits have been found to be prevalent in early onset schizophrenia. Whether these deficits also characterise other early onset psychotic disorders to a similar degree is unclear, as very few comparative studies have been done. The primary purpose of this study was to compare the profile and severity of cognitive impairments in first-episode early onset psychotic patients who received the schizophrenia diagnosis to those diagnosed with other non-organic, non-affective psychotic disorders. The secondary purpose was to examine whether the profile of cognitive deficits, in terms of intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10 criteria. A healthy control group (N = 40) was included, matched on gender and age. Cognitive functions were assessed using WISC-III/R, the CANTAB battery, WCST, Trail Making B, fluency tasks, and Buschkes selective reminding task. A similar profile and level of impairment was found on measures of attention, executive functions, reaction time, and memory in the schizophrenic and psychotic adolescent groups. However, analyses of WISC-III factor profiles suggested that early onset schizophrenia patients may have more global IQ deficits than non-organic, non-affective psychoses when examined recently after illness onset. Compared to the deficits of adult schizophrenia described in the literature, the results suggest relatively spared simple reaction times in early onset patients.

Effects of donepezil adjunctive treatment to ziprasidone on cognitive deficits in schizophrenia : A double-blind, placebo-controlled study

The objective of this study was to examine the effects of adjunctive treatment with the acetylcholinesterase inhibitor, donepezil, on cognitive deficits and psychopathology in schizophrenic patients treated with the antipsychotic, ziprasidone. The design of the study was double blind, placebo controlled, and longitudinal. Patients were treated with ziprasidone for 8 weeks, thereafter randomized to 4 months of double-blind adjunctive treatment with either donepezil (dose, 5-10 mg) or placebo. The severity of psychopathology (PANSS) and the cognitive deficits were examined at baseline and after 4 months. A total of 21 schizophrenic patients were enrolled, of whom 11 patients completed the trial (donepezil, n = 7; placebo, n = 4). There were no within- or between-group differences in changes on the Positive and Negative Syndrome Scale scores or a global cognitive score. Within-group improvements (all at trend level P = 0.07) were seen in the placebo group on Trail-Making Test B, immediate verbal recall, and set-shifting errors. The donepezil group showed a significant deterioration on planning efficiency (P = 0.04). Between-group differences were found between the lack of improvement in immediate verbal recall in the donepezil group and the improvement in the placebo group (P = 0.02), and between the deterioration of planning efficiency in the donepezil group and the stability in the placebo group (trend level, P = 0.07). Linear regression analyses showed that neither baseline psychopathology scores, baseline levels of cognitive deficits, nor psychopathology changes over time accounted for these changes in cognitive scores. The study found no evidence of improved cognition after treatment with donepezil, although the conclusions that can be drawn are limited by the small sample size.

Effects of low-dose risperidone and low-dose zuclopenthixol on cognitive functions in first-episode drug-naive schizophrenic patients.

BACKGROUND Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogeneous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal. OBJECTIVE The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogeneous group of drug-naive first-episode schizophrenic patients in a longitudinal setting. METHODS First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N=25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naive, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time. RESULTS The patients showed considerable cognitive deficits when drug-naive. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls. CONCLUSION The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naive schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.

Social cognition and neurocognitive deficits in first-episode schizophrenia

BACKGROUND Recent research has shown a significant impact of social cognitive domains on real world functioning and prognosis in schizophrenia. However, the correlations between specific aspects of social cognition, neurocognition, IQ and clinical symptoms remain unclear in first-episode schizophrenia. Researchers have speculated about social cognitive subgroups since patients with schizophrenia appear to be a very heterogeneous group. METHODS Patients with a recent diagnosis of first-episode schizophrenia were tested regarding theory of mind, social perception, neurocognition, IQ, and clinical symptoms. RESULTS Data from 36 first-episode schizophrenia patients and 36 one to one matched healthy controls were analysed. Principal component analysis in the patient group was used to examine the variance contributed by different aspects of social cognition, neurocognition, and clinical symptoms. CONCLUSIONS Complex aspects of social cognition explained 24% of the variance in the patient group. The other principal components consisted mainly of aspects of simple perception of theory of mind. Neurocognition and clinical symptoms only explained a minor proportion of the variance in the patient group. The results imply that social cognitive deficits in first-episode schizophrenia come in two distinct versions where one is a complex, cognitive demanding form linked with IQ. The other version is related to simpler forms of social cognition and independent of IQ. These two forms are comparable to the implicit and explicit mentalising discussed in the developmental literature. The two forms of social cognitive deficits are likely to require quite different social cognitive interventions.

Cognitive function in idiopathic intracranial hypertension: a prospective case–control study

Objective To explore the extent and nature of cognitive deficits in patients with idiopathic intracranial hypertension (IIH) at the time of diagnosis and after 3 months of treatment. Design Prospective case–control study. Setting Neurological department, ophthalmological department and a tertiary headache referral clinic at a Danish university hospital. Participants 31 patients with definite IIH referred from June 2011 to February 2013 and included within 1 week of diagnostic intracranial pressure (ICP) measurement. 29 patients completed re-examination at the 3-month follow-up. At the time of testing, none of the patients took medication potentially affecting cognitive function. Controls were 31 healthy age-matched and sex-matched volunteers from the local community. Outcome measures Executive function, working memory, visuospatial memory, processing speed, attention and reaction time assessed by a comprehensive neuropsychological test battery consisting of validated computerised (Cambridge neuropsychological test automated battery) and paper-and-pencil tests. Results Patients with IIH performed significantly worse than controls in four of six cognitive domains (p≤0.02). Deficits were most pronounced in reaction time (1.45 SD below controls 95% CI 2.10 to 0.85) and processing speed (1.48 SD below controls 95% CI 2.08 to 0.81). Despite marked improvement in ICP and headache, re-examination showed persistent cognitive dysfunction 3 months after diagnosis and start of treatment. Conclusions We demonstrate for the first time in a well-defined cohort of patients that IIH may be associated with cognitive dysfunction. This could explain the functional disability of patients with IIH. A focused multidisciplinary approach including neuropsychological rehabilitation, therefore, might be relevant in the treatment of patients with IIH.

Cognitive Profile of Children and Adolescents with Anorexia Nervosa

Objective Few studies of cognitive functioning in children and adolescents with anorexia nervosa (AN) have been conducted. The aim of this study was to examine the neurocognitive and intelligence profile of this clinical group. Method The study was a matched case–control (N = 188), multi-centre study including children and adolescents with AN (N = 94) and healthy control participants (N = 94). Results The results suggest that Full Scale Intelligence Quotient (Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III) in this patient group is close to the normal population mean of 100. Individuals with AN exhibited significantly worse performance in nonverbal intelligence functions (i.e. Wechsler Intelligence Scale for Children-III/Wechsler Adult Intelligence Scale-III, Perceptual Organization Index) and in verbal memory (Test of Memory and Learning—Second Edition, Memory for Stories) and motor speed (Cambridge Neuropsychological Test Automated Battery, Simple and Choice Reaction Time) compared with healthy control participants. No significant difference in set-shifting ability (Cambridge Neuropsychological Test Automated Battery, Intra-Extra Dimensional Set Shift and Trail Making Test B) was found. Conclusions Inefficiency in nonverbal intelligence functions and in specific cognitive functions was found in this study of children and adolescents with AN.

The relationship between cognitive ability and demographic factors in late midlife

Objective: The aim of the article is to analyze associations between sex, age, education, and social class and cognitive ability in late midlife and to evaluate differences in cognitive ability among the three Copenhagen Aging and Midlife Biobank (CAMB) cohorts. Method: The sample comprised 5,417 CAMB participants from three cohorts with scores on the Intelligenz-Struktur-Test 2000 R (I-S-T 2000 R). Results: Independent associations of cognitive ability with age, sex, education, and occupational social class were observed. Particularly, strong associations with cognitive ability were obtained for school education, and consistent sex differences were observed with higher cognitive ability in men. Differences in cognitive ability among the three cohorts were small and primarily reflected demographic differences. Discussion: Late-midlife cognitive ability is associated with a number of demographic factors, and demographic differences may contribute to individual differences in health and early aging. In analyses of cognitive ability, the three CAMB cohorts can be combined provided the relevant demographic variables are included as covariates.

Stability of prepulse inhibition and habituation of the startle reflex in schizophrenia: a 6-year follow-up study of initially antipsychotic-naive, first-episode schizophrenia patients

Deficits in information processing appear to be core features in the pathogenesis of schizophrenia. Prepulse inhibition (PPI) and habituation of the startle reflex are operational measures of early information processing. Impaired PPI in schizophrenia has been replicated in many studies and is regarded as an endophenotype for schizophrenia. However, reports on the stability of PPI over a longer period of time are lacking, both for patients with schizophrenia and for healthy subjects. The current study examined 25 initially drug-naive, first-episode schizophrenia patients and 23 healthy matched controls. Three PPI measures [stimulus onset asynchrony (SOA) 30, 60, 120 ms] and habituation were assessed at baseline, and again after 6 yr. Sixteen patients and 17 healthy controls completed the study, and 13 patients and 17 healthy controls were included in the final analysis. The schizophrenia patients had PPI deficits compared to controls at baseline. After 6 yr, no significant group differences were found. PPI had increased significantly in the patients and had decreased significantly in controls. In addition, patients showed significantly less habituation than controls while habituation did not change in patients or controls. The present results show that PPI in drug-naive, first-episode schizophrenia patients can improve significantly over time. As PPI increased in patients over the same period that it decreased in controls, it is likely that the increase was caused by disease-related factors such as disease process, clinical state, or medication.

Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II)

Objective To compare the effects of five years of specialised early intervention (SEI) treatment for first episode schizophrenia spectrum disorder with the standard two years of SEI plus three years of treatment as usual. Design Randomised, superiority, parallel group trial with blinded outcome assessment. Randomisation was centralised and computerised with concealed randomisation sequence carried out at an external site. Setting Participants were recruited from six OPUS teams in Denmark between 2009 and 2012. OPUS teams provide SEI treatment to all patients diagnosed with a schizophrenia spectrum disorder in Denmark. Participants 400 participants (51% women) with a mean age of 25.6 (standard deviation 4.3) were randomised to five years of SEI (experimental intervention; n=197) or to two years of SEI plus three years of treatment as usual (control; n=203). Interventions OPUS treatment consists of three core elements—modified assertive community treatment, family involvement, and social skill training—with a patient-case manager ratio of no more than 12:1. For participants randomised to five years of OPUS treatment, the treatment was largely unchanged. Participants randomised to the control group were mostly referred to community health centres after two years of SEI treatment. Main outcomes Follow-up assessments were conducted five years after start of OPUS treatment. Primary outcome was negative symptoms measured on the scale for assessment of negative symptoms (avolition-apathy, anhedonia, alogia, and affective blunting). Secondary outcomes were remission of both negative and psychotic symptoms, psychotic symptoms, suicidal ideation, substance abuse, compliance with medical treatment, adherence with treatment, client satisfaction, days in hospital care, and labour market affiliation. Results Levels of negative symptoms did not differ between the intervention group and control group (1.72 v 1.81 points; estimated mean difference −0.10 (95% confidence interval 0.33 to 0.13), P=0.39). Participants receiving five years of OPUS treatment were more likely to remain in contact with specialised mental health services (90.4% v 55.6%, P<0.001), had higher client satisfaction (estimated mean difference 2.57 points (95% confidence interval 1.36 to 3.79), P<0.001), and had a stronger working alliance (estimated mean difference 5.56 points (95% confidence interval 2.30 to 8.82), P=0.001) than the control group. Conclusions This trial tests SEI treatment for up to five years for patients with first episode schizophrenia spectrum disorder; previous trials have found treatment effects for programmes lasting from one to three years. The prolonged SEI treatment had few effects, which could be due to the high level of treatment provided to control participants and the late start of specialised treatment. Trial registration Clinicaltrial.gov NCT00914238.

Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits

BackgroundAntipsychotic-induced weight gain constitutes a major unresolved clinical problem which may ultimately be associated with reducing life expectancy by 25 years. Overweight is associated with brain deterioration, cognitive decline and poor quality of life, factors which are already compromised in normal weight patients with schizophrenia.Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes between schizophrenia and overweight patients.DiscussionCurrent interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogs used in the treatment of type 2 diabetes are associated with significant and sustained weight loss in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogs are discussed.ConclusionsWe propose that adjunctive treatment with GLP-1 analogs may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies in schizophrenia patients with antipsychotic-induced weight gain. Clinical research to support this idea is highly warranted.