Kjetil Sundet

Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta‐analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view.

Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group

OBJECTIVES Neurocognitive dysfunction is milder in bipolar disorders than in schizophrenia spectrum disorders, supporting a dimensional approach to severe mental disorders. The aim of this study was to investigate the role of lifetime history of psychosis for neurocognitive functioning across these disorders. We asked whether neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends more on history of psychosis than diagnostic category or subtype. METHODS A sample of individuals with schizophrenia (n=102), schizoaffective disorder (n=27), and bipolar disorder (I or II) with history of psychosis (n=75) and without history of psychosis (n=61) and healthy controls (n=280), from a large ongoing study on severe mental disorder, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. RESULTS Compared with controls, all 3 groups with a history of psychosis performed poorer across neurocognitive measures, while the bipolar group without a history of psychosis was only impaired on a measure of processing speed. The groups with a history of psychosis did not differ from each other but performed poorer than the group without a history of psychosis on a number of neurocognitive measures. These neurocognitive group differences were of a magnitude expected to have clinical significance. In the bipolar sample, history of psychosis explained more of the neurocognitive variance than bipolar diagnostic subtype. CONCLUSIONS Our findings suggest that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders is determined more by history of psychosis than by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic category or subtype, supporting a more dimensional approach in future diagnostic systems.

Long-Term Follow-Up of the TIPS Early Detection in Psychosis Study: Effects on 10-Year Outcome

OBJECTIVE Early detection in first-episode psychosis confers advantages for negative, cognitive, and depressive symptoms after 1, 2, and 5 years, but longitudinal effects are unknown. The authors investigated the differences in symptoms and recovery after 10 years between regional health care sectors with and without a comprehensive program for the early detection of psychosis. METHOD The authors evaluated 281 patients (early detection, N=141) 18 to 65 years old with a first episode of nonaffective psychosis between 1997 and 2001. Of these, 101 patients in the early-detection area and 73 patients in the usual-detection area were followed up at 10 years, and the authors compared their symptoms and recovery. RESULTS A significantly higher percentage of early-detection patients had recovered at the 10-year follow-up relative to usual-detection patients. This held true despite more severely ill patients dropping out of the study in the usual-detection area. Except for higher levels of excitative symptoms in the early-detection area, there were no symptom differences between the groups. Early-detection recovery rates were higher largely because of higher employment rates for patients in this group. CONCLUSIONS Early detection of first-episode psychosis appears to increase the chances of milder deficits and superior functioning. The mechanisms by which this strategy improves the long-term prognosis of psychosis remain speculative. Nevertheless, our findings over 10 years may indicate that a prognostic link exists between the timing of intervention and outcome that deserves additional study.

Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction.

OBJECTIVES Studies on neurocognitive functioning in bipolar disorder, reporting deficits in memory, attention, and executive functioning, have primarily focused on bipolar I disorder. The aim of this study was to examine whether patients with bipolar I and bipolar II disorder have different neurocognitive profiles. METHODS Forty-two patients with bipolar I disorder, 31 patients with bipolar II and 124 healthy controls, from a large ongoing study on psychotic disorders, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. RESULTS The bipolar I group performed significantly poorer than the healthy control group and the bipolar II group on all measures of memory. Compared with the control group, the bipolar I group also had significantly reduced performance on most measures of attention and executive functioning, while the bipolar II group only had a significantly reduced performance on a subset of these measures. On average, 24% of the bipolar I group had clinically significant cognitive impairment (< or =1.5 SD below the control group mean) across measures, compared with 13% of the bipolar II group. CONCLUSIONS Patients with bipolar I and bipolar II disorder in this study have different neurocognitive profiles. Bipolar I patients have more widespread cognitive dysfunction both in pattern and magnitude, and a higher proportion has clinically significant cognitive impairments compared with patients with bipolar II. This may suggest neurobiological differences between the two bipolar subgroups.

Impairment across executive functions in recurrent major depression.

Depression is associated with impairment of cognitive functions, and especially executive functions (EFs). Despite the fact that most depressed patients experience recurrence of episodes, the pattern and the severity of executive impairment have not been well characterized in this group of depressed patients. We asked if and to what extent these patients were impaired on a range of neuropsychological tests measuring EFs, and also when confounding factors were adjusted for. Forty-five patients (aged 19–51 years) with moderate to severe (Hamilton score >18) recurrent major depressive disorder (DSM-IV) were compared to 50 healthy controls matched on age, education, gender and intellectual abilities. The subjects were administered a set of neuropsychological tests that assesses sub-components of EFs. The depressed patients were impaired compared to the control group on all selected tests, with a severity of impairment within −1 standard deviation from the control group mean. The group difference was statistically significant for eight of the 10 EFs that were assessed. These were measures of verbal fluency, inhibition, working memory, set-maintenance and set-shifting. The group difference was still significant for all sub-components except for set-shifting (Wisconsin Card Sorting Test) and planning (Tower of London), when additional medication and retarded psychomotor speed was adjusted for. In conclusion, the depressed subjects were mildly impaired across a wide range of EFs. This may have a negative impact on everyday functioning for this group of patients.

Comparison of Cerebral Embolization During Off-Pump and On-Pump Coronary Artery Bypass Surgery

BACKGROUND Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury. At least 1% to 5% will suffer a stroke, and at 3-months postoperatively approximately 30% are reported to have cognitive impairment assessed by neuropsychologic testing. In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced. The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization. METHODS This was a prospective and randomized study of two comparable groups with regard to age, sex, years of education, preoperative cognitive functioning, and surgical characteristics. Fifty-two patients (29 off-pump) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery. Preoperative and postoperative clinical, cerebral magnetic resonance imaging, and neuropsychologic examinations were also carried out. RESULTS There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery (16.3 [range 0 to 131] versus 90.0 [range 15 to 274], p < 0.0001). No significant difference with regard to the incidence of neuropsychologic performance (decline in 29% off-pump, 35% on-pump) or neuroradiologic findings at 3 months was found, and there was no association between the number of cerebral microemboli and cognitive outcome. CONCLUSIONS This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization. A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population.

Attention profile in schizophrenia compared with depression: differential effects of processing speed, selective attention and vigilance

Objective: The aim of the study is to investigate whether subjects with schizophrenia and major depression display attention deficits for different reasons.

Comprehensive Driving Assessment: Neuropsychological Testing and On‐road Evaluation of Brain Injured Patients

The study investigates the correspondence between neuropsychological test results and on-road driving performance among 55 patients with a CT-verified brain damage or documented neurological disorder (cerebrovascular accident: 43, traumatic brain injury: 5, multiple sclerosis: 4, other: 3). 5 patients showed unimpaired test profiles and passed the on-road evaluation. 18 patients showed severe neuropsychological deficits contrary to driving and were not recommended for on-road evaluation. Of the remaining 32 patients with some neuropsychological deficits, all 100% in the minor impaired group (n = 8) passed the driving evaluation, compared to 69% in the mildly impaired (n = 16) and 38% in the moderately impaired group (n = 8). Measures of reduced visuoconstructive ability, reaction time, visual attention, and awareness of cognitive impairments, were found to discriminate between groups. It is concluded that neuropsychological assessment of targeted functions provide an ecological valid prediction of driving skill after brain damage, but that on-road evaluation is needed as supplement in cases with ambiguous test findings.

Persistent Cognitive Dysfunction Secondary to Cerebellar Injury in Patients Treated for Posterior Fossa Tumors in Childhood

Traditionally, the cerebral hemispheres have been regarded as the region of the brain responsible for cognitive functions, while the cerebellum has been considered to be primarily involved in motor functions. Recent studies focus also on the possible involvement of the cerebellum in neurocognitive functions. The aim of this study was to determine the neuropsychological profile of young adults treated for a posterior fossa tumor in childhood and look for possible support for the presence of the so-called ‘cerebellar cognitive affective syndrome’ in these patients. Two groups of young adults were studied. The astrocytoma group (n = 12) had been treated for a low-grade cerebellar astrocytoma with surgery alone (mean age at surgery was 8.6 years and mean age at neuropsychological testing was 23.5 years). The medulloblastoma group (n = 11) had been treated with surgery followed by radiotherapy and chemotherapy (mean age at surgery was 6.1 years and mean age at neuropsychological testing was 23.1 years). The neuropsychological test battery comprised measures of intelligence, motor function, attention, psychomotor speed, verbal memory and visual memory. The medulloblastoma group performed poorer than the astocytoma group on all neuropsychological measures except one. Nonetheless, the astrocytoma group also had impaired scores compared with standard norms on measures of motor speed, attention and executive function. No significant correlation between age at time of treatment and grade of neuropsychological impairment was found in the astrocytoma group, though there was a tendency that young age at time of treatment correlated with better outcome on IQ measures. In the medulloblastoma group, age was significantly correlated with outcome, for both IQ and degree of neuropsychological impairment. For this group, young age at time of treatment indicated a worse outcome. Conclusions: Persistent cognitive dysfunction was detected in patients treated for posterior fossa medulloblastoma and cerebellar astrocytoma. The astrocytoma group was treated with surgery alone, indicating that a cerebellar lesion can result in cognitive dysfunction. Thus, this study gives support to the existence of the cerebellar cognitive affective syndrome. Follow-up of all patients treated for posterior fossa tumor in childhood should include an extensive neuropsychological testing at regular intervals. This may be of benefit for school planning and later work planning.

Sex-dependent association of common variants of microcephaly genes with brain structure

Loss-of-function mutations in the genes associated with primary microcephaly (MCPH) reduce human brain size by about two-thirds, without producing gross abnormalities in brain organization or physiology and leaving other organs largely unaffected [Woods CG, et al. (2005) Am J Hum Genet 76:717–728]. There is also evidence suggesting that MCPH genes have evolved rapidly in primates and humans and have been subjected to selection in recent human evolution [Vallender EJ, et al. (2008) Trends Neurosci 31:637–644]. Here, we show that common variants of MCPH genes account for some of the common variation in brain structure in humans, independently of disease status. We investigated the correlations of SNPs from four MCPH genes with brain morphometry phenotypes obtained with MRI. We found significant, sex-specific associations between common, nonexonic, SNPs of the genes CDK5RAP2, MCPH1, and ASPM, with brain volume or cortical surface area in an ethnically homogenous Norwegian discovery sample (n = 287), including patients with mental illness. The most strongly associated SNP findings were replicated in an independent North American sample (n = 656), which included patients with dementia. These results are consistent with the view that common variation in brain structure is associated with genetic variants located in nonexonic, presumably regulatory, regions.