Impaired Neuropsychological Functioning Research Articles

Deviant sexual interests but not antisocial behaviors are associated with deficits in executive functioning in individuals convicted of sexual offenses against children.

Objective: Impaired neuropsychological functioning is one possible factor contributing to sexual offending against children. Previous research showed that neuropsychological and especially executive functioning deficits could be related to the two most important risk factors for sexual (re-)offending, namely an antisocial lifestyle and deviant sexual interests. Method: By using a quasi-experimental research design, the present study compared the performance of a sample of men convicted of child sexual abuse (CSA) offenses (n = 70) with men convicted of sexual offenses against adults (n = 49), men convicted of nonsexual offenses (n = 54), and nonoffending men (n = 70) in a set of neuropsychological tests assessing different aspects of executive functioning. Results: All three offending groups had a higher prevalence of brain injury and performed worse compared to nonoffending men on almost all neuropsychological tests. Individuals convicted of CSA offenses showed no differences compared to the other two offending groups. Latent class analyses revealed that a small subset of CSA-offending participants showed most pronounced neuropsychological deficits. These persons also exhibited more intense pedosexual interests but not more indicators of antisociality. Conclusions: The results of the present study indicate that only a certain subset of CSA-offending individuals demonstrates considerable neuropsychological deficits, which seem to correlate with a particularly strong sexual interest in children. This subgroup could also be described as having a particularly high risk concerning sexual reoffending with a sexual abuse offense. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Impaired neuropsychological functioning in patients with hypopituitarism.

BackgroundTreatment of pituitary pathology mostly does not result in complete recovery of impairment in cognitive functioning. The primary aim of the current study was to assess cognitive impairment in patients with stable replacement therapy for hypopituitarism during the last 6 months prior to inclusion. It was expected that patients showed subjective and objective subnormal scores on neuropsychological functioning.MethodsForty‐two patients (40% men, 49 ± 15 years) treated for hypopituitarism conducted a neuropsychological test battery, including the Cognitive Failures Questionnaire (CFQ), 15‐Word test (15‐WT), Cambridge Neuropsychological Test Automated Battery (CANTAB) Motor Screening Task (MOT), Spatial Working Memory (SWM) and Affective Go/No‐go (AGN). Results were compared to reference values of healthy norm groups.ResultsMale and female participants scored significantly worse on the CFQ (P < .01, d = 0.91‐4.09) and AGN mean correct latency (P < .01, d = 1.66 and 1.29, respectively). Female participants scored significantly worse on 15‐WT direct recall (P = .01, d = 0.66), 15‐WT delayed recall (P = .01, d = 0.79), SWM total errors (P = .05, d = 0.41), SWM strategy (P = .04, d = 0.43), AGN errors of commission (P = .02, d = 0.56) and omission (P = .04, d = 0.41).ConclusionThis study shows that subjective cognitive functioning is worse in patients treated for hypopituitarism compared to reference data. Also, female participants treated for hypopituitarism score worse on objective aspects of memory and executive functioning compared to reference data. Besides worse focus attention, this objective cognitive impairment was not found in male participants. It is recommended to conduct additional research, which focuses on the design and evaluation of a cognitive remediation therapy, aimed at compensation of impairments in different aspects of memory and executive functioning.

Neurocognitive functions in patients with hepatitis C infection.

With improving treatment options, more attention is being paid to the neurocognitive symptoms related to hepatitis C infection (HCI). While HCI-related neurocognitive impairments are frequently subclinical, they can influence patients' quality of life and fitness to work. Objective - The aim of this study was to assess HCI patients' neurocognitive functions and explore the correlations between disease variables and neurocognitive symptoms. The study was conducted between January 1, 2013 and December 31, 2015. All patients with HCI were included in the study who were registered at the Hepatology Outpatient Clinic of Szent István and Szent László Hospitals, met inclusion criteria and volunteered to participate. Patients' sociodemographic data and medical history were recorded in a questionnaire designed for the study. The 21-item Beck Depression Inventory was used to detect depressive symptoms. Six computerized tests were used to evaluate patients' neuropsychological functions. Sixty patients participated in the study. In comparison with general population standards, patients demonstrated poorer performance in several neurocognitive tests. Neuropsychological performance was correlated with age, sex, length of time since HCI diagnosis, Fibroscan score and the number of previous antiviral treatments. The study's main finding is that compared to general population standards, patients with hepatitis C virus-related disease exhibit impaired neuropsychological functioning in visuomotor and visuospatial functions, working memory, executive functions, and reaction time. Executive functions and reaction time were the most sensitive indicators for the length and severity of the disease. Deterioration in these functions has a major negative effect on work performance particularly in certain occupations.

Brain microstructural alterations in type 2 diabetes: diffusion kurtosis imaging provides added value to diffusion tensor imaging.

To investigate brain microstructural changes in white matter and gray matter of type 2 diabetes mellitus (T2DM) patients using diffusion kurtosis imaging. Diffusion kurtosis imaging (b values = 0, 1250, and 2500s/mm2) was performed for 30 T2DM patients and 28 controls. FMRIB Software Library with tract-based spatial statistics was used to analyze intergroup differences in fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), axial kurtosis (K∥), and radial kurtosis (K⊥) of multiple white matter regions. Atlas-based ROI analysis was conducted in gray matter structures and some fiber tracts. Correlations between MK changes and clinical measurements were determined. In whole-brain tract-based spatial statistics analysis, T2DM patients exhibited abnormalities in 29.6%, 30.4%, 35.4%, 10.5%, and 26.0% of white matter regions as measured by FA, MD, MK, K∥, and K⊥, respectively, when compared to the controls. MK reduction was contributed more by the decreased K⊥. In atlas-based analysis, MK detected more ROIs (27/48) with white matter microstructural changes than FA (13/48) and MD (17/48). MK decreased in bilateral thalamus and caudate, while FA showed statistically significant difference only in the left caudate. MK values negatively correlated with disease duration in the genu of corpus callosum and anterior corona radiata (R = -0.512 and -0.459) and positively correlated with neuropsychological scores in the cingulum (hippocampus) (R = 0.466 and 0.440). Diffusion kurtosis imaging detects more brain regions with white matter and gray matter microstructural alterations of T2DM patients than DTI metrics. It provides valuable information for studying the pathology of diabetic encephalopathy and may lead to better imaging biomarkers for monitoring disease progression. • Diffusion kurtosis imaging detects more brain regions with microstructural alterations in white matter and gray matter of T2DM patients than DTI. • Mean kurtosis changes are associated with disease severity and impaired neuropsychological function in T2DM. • Diffusion kurtosis imaging demonstrates potential to assess cognitive impairment in T2DM patients and predict disease progression.

Neuropsychological Consequences for Survivors of Childhood Brain Tumor in Malaysia.

Objective: This study aimed to evaluate neuropsychological consequences in survivors of childhood brain tumor.Method: A case-control study was conducted over a period of 4 months in a tertiary referral center in Kuala Lumpur, Malaysia. Fourteen survivors of childhood brain tumor aged 7–18 years, who were off-treatment for at least 1 year and were in remission, and 31 unrelated healthy controls were recruited. The median age at diagnosis was 8.20 years (range: 0.92–12.96 years). The diagnoses of brain tumors were medulloblastoma, germ cell tumor, pineocytoma, pilocystic astrocytoma, suprasellar germinoma, and ependymoma. Eleven survivors received central nervous system irradiation. Seven tasks were selected from the Amsterdam Neuropsychological Tasks program to evaluate alertness (processing speed), and major aspects of executive functioning, such as working memory capacity, inhibition, cognitive flexibility, and sustained attention. Speed, stability and accuracy of responses were the main outcome measures.Results: Survivors of childhood brain tumor showed statistically significant poorer performance on all tasks compared to healthy controls. Both processing speed and accuracy were impaired in the survivors, in particular under more complex task conditions. The survivors demonstrated deficits in alertness, sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Longer duration off treatment appeared to be correlated with poorer alertness, memory capacity, and inhibition.Conclusion: Survivors of childhood brain tumor in our center showed impaired neuropsychological functioning. Development of less toxic treatment protocols is important to prevent late effects of cognitive deficits in survivors of childhood brain tumor.

Neighborhood Disadvantage and Neuropsychological Functioning as Part Mediators of the Race–Antisocial Relationship: A Serial Mediation Model

We test a serial multiple mediation model in which the relationship between ethnicity and antisocial behavior is sequentially mediated by disadvantaged neighborhoods and impaired neuropsychological functioning. Parental and self-report measures of antisocial behavior were assessed in a community sample of 341 adolescent males and females. Neighborhood disadvantage was assessed from census data. Neuropsychological functioning was evaluated using a computerized battery. Separate serial multiple mediation models were tested using non-executive functioning and executive functioning. The serial mediation model for executive functioning was supported, with the pathway from race to antisocial behavior through neighborhood disadvantage and executive functioning in serial accounting for 10.8% of the total effect of race on antisocial behavior. Findings support social neurocriminology theory by integrating neighborhood disadvantage and executive functioning as sequential mediators of the race–antisocial relationship. To our knowledge, these are the first findings to explain the race–antisocial relationship in terms of connected social and neuropsychological processes. While this pathway is significant, the effect is still relatively small and thus should be understood as one of many mechanisms through which race may affect antisocial behavior. From a translational science standpoint, the identification of neurocognitive mechanisms by which neighborhood disadvantage predisposes to antisocial behavior suggests the potential benefits of cognitive enhancement techniques to remediate the negative effects of adverse neighborhoods on brain functioning in at-risk minority groups.

Effects of early life stress and adolescent ethanol exposure on adult cognitive performance in the 5-choice serial reaction time task in Wistar male rats.

Early life stress combined with heavy adolescent alcohol use predicts impaired neuropsychological functioning in adulthood. We investigated whether adolescent intermittent ethanol (AIE) exposure combined with neonatal maternal separation in rats altered attentional processes and impulsivity in adulthood. Male Wistar rat pups were exposed to maternal separation (postnatal days (PNDs) 1-14) and moderate AIE exposure (PNDs 28-57). Adult rats were tested in the five-choice serial reaction time task, which provides separate measures of attention, motor impulsivity, and compulsivity. Rats were tested under baseline conditions and in response to task manipulations that increased attentional load and impulsive behaviors, and after acute ethanol administration. Short stimulus and short intertrial interval (ITI) durations disrupted attention while long ITI durations impaired impulsivity in all rats. Moderate- and high-dose ethanol challenges impaired attention in all rats. Rats exposed to maternal separation and/or AIE exposure had significantly decreased omissions than non-handled water-exposed rats at baseline and tended to retain this effect in response to task challenges (i.e., the shorter stimulus and ITI durations, longer test session) and ethanol challenges, indicating moderate improvement of attentional performance. Maternal separation significantly increased perseverative responses at baseline and in response to decreased stimulus duration challenge, suggesting increased compulsivity. Separate or combined exposure to early life stress and AIE exposure moderately disrupts some aspects of adult executive control functions (e.g., increased compulsivity) but improves others (e.g., increased attention). The relative intensity of either manipulation during neonatal and adolescent periods may influence the direction in which cognitive behaviors are affected in adulthood.

Longitudinal Growth and Neuropsychological Functioning at Age 7 in Moderate and Late Preterms.

To determine the association between longitudinal growth measures (height, weight, head circumference, and extent of catch-up growth) and neuropsychological functioning at 7 years in moderately and late preterm children. This study was part of a prospective, community-based cohort study. Data on growth were obtained from records on routine assessments in well-child centers until age 4 years and in a research setting at 7 years. Neuropsychological functioning was assessed at age 7 years. We assessed associations of growth with neuropsychological functioning and determined odds ratios for impaired neuropsychological functioning. All analyses were corrected for maternal education. We included 234 children. Median gestational age was 34 weeks (P25-75: 33-35 weeks), and mean birth weight was 2.2 kg (± 0.5 kg). Short stature at all ages was associated with poorer motor, IQ, and attention scores and led to increased risks of impaired motor skills and low IQ. Lower weight at 1 and 4 years was associated with poorer IQ scores. Increased weight gain between age 4 and 7 years was, however, associated with poorer motor, IQ, and attention scores. Decreased head circumference gain in the first year of life was associated with poorer motor and attention scores and led to an increased risk of impaired motor and attention skills. In moderately and late preterm children, poorer growth in the first 7 years is associated with poorer neuropsychological functioning. Regarding height, short stature was also associated with a higher likelihood of clinically relevant impaired neuropsychological functioning.

Neurobehavioral Deficits Consistent Across Age and Sex in Youth with Prenatal Alcohol Exposure.

Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Subjects were 407 youth with prenatal alcohol exposure (n=192) and controls (n=215). Two age groups (child [5 to 7years] or adolescent [10 to 16years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history)×2 (sex)×2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains.

Altered behaviour and cognitive function following combined deletion of Toll-like receptors 2 and 4 in mice

Activation of the immune system due to infection or aging is increasingly linked to impaired neuropsychological function. Toll-like receptors 2 and 4 (TLR2, TLR4) are well-characterised for their role in inflammatory events, and their combined activation has been implicated in neurological diseases. We therefore determined whether TLR2 and TLR4 double gene knockout (GKO) mice showed modified behaviour and cognitive function during a 16-day test sequence that employed the automated IntelliCage test system. The IntelliCage features a home cage environment in which groups of mice live and where water reward is gained through performing various tasks centred on drinking stations in each corner of the apparatus. All mice were tested twice, one month apart (the first sequence termed “R1”and the second “R2”). There were fewer corner visits and nosepokes in TLR2/4 GKO compared to wild-type mice during early exploration in R1, suggesting elevated neophobia in GKO mice. Reduced exploration persisted over subsequent test modules during the dark phase. TLR2/4 GKO mice also displayed increased corner visits during drinking sessions compared to non-drinking sessions, but this was not associated with increased drinking. In subsequent, more complex test modules, TLR2/4 GKO mice had unimpaired spatial learning, but showed markedly poorer performance in a visual discrimination reversal task compared to wild-type mice. These results indicated subtle impairments in behaviour and cognitive functions due to double deficiency in TLR2 and TLR4. These finding are highly relevant to understanding the combined actions of TLR2 and TLR4 on neurological status in a range of different disease conditions.

Process for production of xylenes and light olefins

Activation of the immune system due to infection or aging is increasingly linked to impaired neuropsychological function. Toll-like receptors 2 and 4 (TLR2, TLR4) are well-characterised for their role in inflammatory events, and their combined activation has been implicated in neurological diseases. We therefore determined whether TLR2 and TLR4 double gene knockout (GKO) mice showed modified behaviour and cognitive function during a 16-day test sequence that employed the automated IntelliCage test system. The IntelliCage features a home cage environment in which groups of mice live and where water reward is gained through performing various tasks centred on drinking stations in each corner of the apparatus. All mice were tested twice, one month apart (the first sequence termed “R1”and the second “R2”). There were fewer corner visits and nosepokes in TLR2/4 GKO compared to wild-type mice during early exploration in R1, suggesting elevated neophobia in GKO mice. Reduced exploration persisted over subsequent test modules during the dark phase. TLR2/4 GKO mice also displayed increased corner visits during drinking sessions compared to non-drinking sessions, but this was not associated with increased drinking. In subsequent, more complex test modules, TLR2/4 GKO mice had unimpaired spatial learning, but showed markedly poorer performance in a visual discrimination reversal task compared to wild-type mice. These results indicated subtle impairments in behaviour and cognitive functions due to double deficiency in TLR2 and TLR4. These finding are highly relevant to understanding the combined actions of TLR2 and TLR4 on neurological status in a range of different disease conditions.

Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age

Prenatal exposure to pesticides may affect neurodevelopment, while the impact of modern pesticides is unclear. From 1997–2001, women working in greenhouse horticultures were recruited at the beginning of their pregnancy. Based on detailed interview of the women and their employers, those categorized as occupationally exposed to pesticides were moved to unexposed work functions or went on paid leave, while women without any exposure were considered unexposed controls. Of the resulting birth cohort of 203 children, 133 (65%) were examined at age 6 to 11years together with 44 newly recruited children of same age whose mothers were not occupationally exposed to pesticides in pregnancy. All children underwent a standardized examination including a battery of neurodevelopmental tests. Maternal occupational pesticide exposure in early pregnancy was associated with prolonged brainstem auditory evoked potential latencies in the children as a whole and with impaired neuropsychological function in girls, while no effect was apparent in boys. In girls, language and motor speed functions were significantly inversely associated with prenatal exposure, and a non-significant tendency toward decreased function was also seen for other neuropsychological outcomes. A structural equation model that combined all these test results showed an overall impaired neuropsychological function in girls prenatally exposed to pesticides. Thus, our findings suggest an adverse effect of maternal occupational pesticide exposure on their children's neurodevelopment, despite the fact that the exposures occurred solely during early pregnancy and under well regulated working conditions, where special measures to protect pregnant women were applied.

Cognitive Reserve Protects Against Apathy in Individuals with Human Immunodeficiency Virus

Apathy is associated with impaired neuropsychological functioning in individuals with HIV. While cognitive reserve (CR) delays neurocognitive decline, CR's relationship with apathy has never been studied. We examined CR's association with apathy in 116 HIV-positive individuals recruited from an urban AIDS center and assessed whether this relationship is moderated by age and/or disease severity. Participants completed the Wechsler Test of Adult Reading and Apathy Evaluation Scale. A CR-composite, combining years of education and word-reading ability, significantly predicted apathy (t = -2.37, p = .02). CR's relationship with apathy was not moderated by age, but participants with nadir CD4 levels ≤ 200 demonstrated a stronger association (t = -3.25, p = .002) than those with nadir CD4 levels > 200 (t = -0.61, p = .55). These findings suggest a protective effect of CR against apathy in HIV-infected individuals across the age span, particularly after a certain threshold of disease severity.

Abnormal Functional Network Connectivity among Resting-State Networks in Children with Frontal Lobe Epilepsy

Epilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function. Fifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups. The frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects. We found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.

Abnormal white matter correlates with neuropsychological impairment in children with localization‐related epilepsy

The white matter (WM) is considered critical for linking cortical processing networks necessary for cognition. The aim of this study was to assess diffusion tensor imaging (DTI) measures of regional WM in children with nonlesional localization-related epilepsy in comparison to controls, and to determine the relation between lobar WM and neuropsychological performance. Forty children with nonlesional localization-related epilepsy and 25 healthy controls with no neurological or psychiatric disorders and normal magnetic resonance imaging (MRI) were recruited. All patients and controls underwent neuropsychological testing that evaluated intelligence, language, memory, executive function, and motor function, as well as DTI to assess regional WM measures of fractional anisotropy (FA) and mean diffusivity (MD). The regional FA and MD were compared between patients and controls, and correlated with neuropsychological function. The relations between regional FA and MD with age at seizure onset and duration of epilepsy were assessed. Twenty-one patients had left-sided and 19 patients had right-sided epilepsy. There were no significant differences in seizure-related variables including age at seizure onset, duration of epilepsy, seizure frequency, and number of antiepileptic medications, as well as no significant differences in neuropsychological function and DTI measures of white matter in left-sided compared to right-sided epilepsy. Therefore, all the patients with epilepsy were treated as one group. Patients with epilepsy performed significantly worse on intelligence (p < 0.001), language (p < 0.001), and executive function (p = 0.001) evaluation than controls. Patients had significantly reduced FA in left frontal (p = 0.015), right frontal (p = 0.004), left temporal (p = 0.039), right temporal (p = 0.003), right parietal (p = 0.014), and right occipital (p = 0.025) WM relative to controls. There were no significant regional WM differences (all p > 0.05) in MD between patients and controls. There was a significant positive correlation between right temporal FA with language (r = 0.535, p < 0.001) and executive function (r = 0.617, p < 0.001), as well as between body of corpus callosum FA with intelligence (r = 0.536, p < 0.001) and language (r = 0.529, p < 0.001) in patients. Left parietal MD was significantly correlated with language (r = -0.545, p < 0.001) in patients. FA of right temporal WM was significantly associated with age at seizure onset (t = 4.97, p < 0.001). There was widespread regional WM abnormality in children with nonlesional localization-related epilepsy, which was associated with impaired neuropsychological function. The impairment in WM may reflect disruption in the connectivity for cortical processing networks, which is necessary for the development of cognition.

The DAO Gene Is Associated with Schizophrenia and Interacts with Other Genes in the Taiwan Han Chinese Population

BackgroundSchizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment.MethodsWe analyzed 99 SNPs from 10 candidate genes in 1,512 subject samples. The permutation-based single-locus, multi-locus association tests, and a gene-based multifactorial dimension reduction procedure were used to examine genetic associations and interactions to schizophrenia.ResultsWe found that no single SNP was significantly associated with schizophrenia. However, a risk haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene, was strongly associated with schizophrenia. Interaction analyses identified multiple between-gene and within-gene interactions. Between-gene interactions including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for CACNG2 were found among schizophrenia subjects with severe sustained attention deficits, suggesting a modifying effect of impaired neuropsychological functioning. Other interactions such as the within-gene interaction of DAO and the between-gene interaction of DAO and PTK2B were consistently identified regardless of stratification by neuropsychological dysfunction. Importantly, except for the within-gene interaction of CACNG2, all of the identified risk haplotypes and interactions involved SNPs from DAO.ConclusionsThese results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. Besides, the interaction between DAO and RASD2 has provided an insight in integrating the glutamate and dopamine hypotheses of schizophrenia.

New Approaches to Understand Cognitive Changes Associated With Chemotherapy for Non-Central Nervous System Tumors

ContextResearchers have described a constellation of cognitive deficits (e.g., impairments in executive functions, working memory, attention, and information-processing speed) associated with cancer treatment, and specifically chemotherapy, for non-central nervous system tumors. However, findings have been inconsistent, largely because of measurement and study design issues. ObjectivesTo propose ways for researchers to more clearly delineate and characterize the mild cognitive deficits and related outcomes that appear to affect a subset of cancer patients and suggest methods to make more effective use of the existing data to understand risk factors for impaired neuropsychological functioning. MethodsWe examined the literature on the relationship between chemotherapy and cognitive impairment, as well as related literature on neuropsychological measurement, structural and functional neuroimaging, alternative measures of health outcomes, and integrative data analysis. ResultsA more comprehensive picture of cognitive functioning might be obtained by incorporating nontraditional ecological measures, self-reports, computational modeling, new neuroimaging methods, and markers of occupational functioning. Case-control and integrative data analytic techniques potentially could leverage existing data to identify risk factors for cognitive dysfunction and test hypotheses about the etiology of these effects. ConclusionThere is a need to apply new research approaches to understand the real-world functional implications of the cognitive side effects of chemotherapy to develop and implement strategies to minimize and remediate these effects before, during, and after cancer treatment.

Lower Health Related Quality of Life and Psychosocial Difficulties in Children with Monosymptomatic Nocturnal Enuresis—Is Snoring a Marker of Severity?

Sleep disordered breathing in children is linked to numerous negative psychosocial consequences, including lower health related quality of life, increased behavioral problems and impaired neuropsychological functioning. We examined whether snoring, which is the least severe form of sleep disordered breathing, or health related quality of life could account for the increased rate of psychosocial difficulty in children with monosymptomatic nocturnal enuresis. Patients diagnosed with monosymptomatic nocturnal enuresis seen at an outpatient pediatric urology clinic completed measures of health related quality of life (Obstructive Sleep Apnea Syndrome-18-Item Questionnaire), sleep disordered breathing (Pediatric Sleep Questionnaire) and psychosocial difficulty (Pediatric Symptom Checklist). Patients were categorized into 2 groups (snoring vs no snoring) based on the Pediatric Symptom Checklist snoring subscale score. Included in the study were 62 males and 45 females with a mean ± SD age of 9.09 ± 2.58 years and a mean body mass index of 21.00 ± 6.93 kg/m(2) (range 13 to 49). The sample was evenly split between 56 snorers (52.3%) and 51 nonsnorers (47.7%). Compared to children with monosymptomatic nocturnal enuresis who did not snore, MANCOVA results revealed that patients with monosymptomatic nocturnal enuresis who snored had significantly more externalizing problems and total psychosocial problems, in addition to significantly more impairment in all areas of health related quality of life. Snoring in children with monosymptomatic nocturnal enuresis puts them at increased risk for behavioral and psychosocial problems, in addition to impaired health related quality of life. These findings support the need for future studies of the neurological links between sleep disordered breathing and monosymptomatic nocturnal enuresis.

Clinical and biological correlates of adolescent anorexia nervosa with impaired cognitive profile

Some neuropsychological studies of anorexia nervosa (AN) have yielded conflicting results, and it has been established that not all adult patients with AN are cognitively impaired. The objective of this study is to determine the percentage of adolescents with AN who present worse cognitive functioning according to neuropsychological criteria of cognitive impairment, and to study their clinical characteristics. Thirty-seven adolescents (11-18years) with a diagnosis of AN in an acute state of the illness and with low body mass index (BMI) were compared with 41 healthy subjects of the same sex and similar age and intelligence using a comprehensive neuropsychological battery. Overall, AN patients took longer to copy Rey's Figure than the control group (p=0.001). Thirty per cent of patients showed impaired neuropsychological functioning (defined as scoring two standard deviations lower than the average or lower than their intelligence level in two tasks) with worse performance on visuo-spatial tasks. This subgroup of patients presented lower BMI (p=0.023) and higher trait anxiety (p=0.028). The performance of adolescents in an acute state of AN was similar to that of the healthy control group, with the exception of lower time to completion in copying a complex figure. However, cognitive performance varied in these patients, being clearly impaired in one-third of the sample. The cognitive impairment subgroup showed lower BMI and higher anxiety. Longitudinal follow-up studies are necessary to assess the stability of this profile after longer treatment periods.

Cholinergic system function and cognition in mild cognitive impairment

Evidence for cholinergic dysfunction in very early stages of neurodegeneration like mild cognitive impairment (MCI) is inconclusive. Previous positron emission tomography (PET) studies based on small samples investigated if it is related to memory impairment. We examined whether cortical acetylcholine esterase (AChE) activity is reduced at this stage and correlated with cognitive function. N-[11C]-methyl-4-piperidyl acetate ([11C]MP4A), a positron emission tomography tracer for measuring cerebral AChE activity in vivo, was applied in 21 controls and 17 MCI patients. Parametric images of AChE activity were analyzed using standard atlas regions. Principal components analysis (PCA) of regional values of AChE activity and correlation analysis with neuropsychological test results was performed. Cortical AChE activity showed a significant decline in MCI patients compared with controls which was most pronounced in temporal regions. They formed the main part of a principal component that was related significantly to verbal and nonverbal memory, language comprehension and executive function. Cholinergic dysfunction is an early hallmark even before onset of dementia at the clinical stage of MCI. Its impact especially on temporal neocortex is associated with impaired neuropsychological function.