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1.
Am J Hum Genet ; 105(2): 334-350, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374203

RESUMO

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness.

2.
Neuropsychopharmacology ; 44(11): 1948-1954, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31315130

RESUMO

Second-generation antipsychotic drugs (SGAs) are essential in the treatment of psychotic disorders, but are well-known for inducing substantial weight gain and obesity. Critically, weight gain may reduce life expectancy for up to 20-30 years in patients with psychotic disorders, and prognostic biomarkers are generally lacking. Even though other receptors are also implicated, the dorsal striatum, rich in dopamine D2 receptors, which are antagonized by antipsychotic medications, plays a key role in the human reward system and in appetite regulation, suggesting that altered dopamine activity in the striatal reward circuitry may be responsible for increased food craving and weight gain. Here, we measured striatal volume and striatal resting-state functional connectivity at baseline, and weight gain over the course of 12 weeks of antipsychotic treatment in 81 patients with early-phase psychosis. We also included a sample of 58 healthy controls. Weight measurements were completed at baseline, and then weekly for 4 weeks, and every 2 weeks until week 12. We used linear mixed models to compute individual weight gain trajectories. Striatal volume and whole-brain striatal connectivity were then calculated for each subject, and used to assess the relationship between striatal structure and function and individual weight gain in multiple regression models. Patients had similar baseline weights and body mass indices (BMI) compared with healthy controls. There was no evidence that prior drug exposure or duration of untreated psychosis correlated with baseline BMI. Higher left putamen volume and lower sensory motor connectivity correlated with the magnitude of weight gain in patients, and these effects multiplied when the structure-function interaction was considered in an additional exploratory analysis. In conclusion, these results provide evidence for a correlation of striatal structure and function with antipsychotic-induced weight gain. Lower striatal connectivity was associated with more weight gain, and this relationship was stronger for higher compared with lower left putamen volumes.

3.
Psychiatry Res ; 273: 647-652, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31207847

RESUMO

Avolition, a decrease in the initiation and persistence of goal-directed behavior, is a critical determinant of disability in patients with schizophrenia. Recent studies have demonstrated that avolition can be modeled using reward-based, behavioral paradigms. These studies suggest that avolition represents a motivational deficit, accounted for by a diminished ability to anticipate pleasurable experiences. Notably, although data suggest that "initiation" and "persistence" of goal-directed behavior may depend on different processes, few studies have sought to distinguish between these two components of avolitional symptoms. Such distinctions could have real consequences for the development and evaluation of interventions designed to ameliorate avolitional symptoms. Thus, the present study examined the relationship between anticipatory pleasure, a key driver of avolition, and both the initiation and persistence of reward-directed, effortful responding during the Effort Expenditures for Rewards Task in 103 healthy participants. We found that anticipatory pleasure was not significantly predictive of the initiation of effortful responding but was significantly predictive of the persistence of effortful responding; most notably when the probabilities of reward and non-reward were equivalent. These data suggest that although deficits in reward processes contribute to the likelihood of persisting in reward-driven behavior, they contribute little to the initiation of such behavior.

5.
Neuropsychopharmacology ; 44(5): 915-922, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30679724

RESUMO

Despite recent advances, there is still a major need for prediction of treatment success in schizophrenia, a condition long considered a disorder of dysconnectivity in the brain. Graph theory provides a means to characterize the connectivity in both healthy and abnormal brains. We calculated structural similarity networks in each participant and hypothesized that the "hubness", i.e., the number of edges connecting a node to the rest of the network, would be associated with clinical outcome. This prospective controlled study took place at an academic research center and included 82 early-phase psychosis patients (23 females; mean age [SD] = 21.6 [5.5] years) and 58 healthy controls. Medications were administered in a double-blind randomized manner, and patients were scanned at baseline prior to treatment with second-generation antipsychotics. Symptoms were assessed with the Brief Psychiatric Rating Scale at baseline and over the course of 12 weeks. Nodal degree of structural similarity networks was computed for each subject and entered as a predictor of individual treatment response into a partial least squares (PLS) regression. The model fit was significant in a permutation test with 1000 permutations (P = 0.006), and the first two PLS regression components explained 29% (95% CI: 27; 30) of the variance in treatment response after cross-validation. Nodes loading strongly on the first PLS component were primarily located in the orbito- and prefrontal cortex, whereas nodes loading strongly on the second PLS component were primarily located in the superior temporal, precentral, and middle cingulate cortex. These data suggest a link between brain network morphology and clinical outcome in early-phase psychosis.

6.
Am J Psychiatry ; 176(7): 521-530, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30606045

RESUMO

OBJECTIVE: Case-control study design and disease heterogeneity may impede biomarker discovery in brain disorders, including serious mental illnesses. To identify biologically and/or behaviorally driven as opposed to diagnostically driven subgroups of individuals, the authors used hierarchical clustering to identify individuals with similar patterns of brain activity during a facial imitate/observe functional MRI task. METHODS: Participants in the Social Processes Initiative in Neurobiology of the Schizophrenia(s) study (N=179; 109 with a schizophrenia spectrum disorder and 70 healthy control participants) underwent MRI scanning at three sites. Hierarchical clustering was used to identify new data-driven groups of participants; differences on social and neurocognitive tests completed outside the scanner were compared among the new groups. RESULTS: Three clusters with distinct patterns of neural activity were found. Cluster membership was not related to diagnosis or scan site. The largest cluster consisted of "typical activators," with activity in the canonical "simulation" circuit. The other clusters represented a "hyperactivating" group and a "deactivating" group. Between-participants Euclidean distances were smaller within clusters than within site or diagnostics groups. The deactivating group had the highest social cognitive and neurocognitive test scores. The hierarchical clustering analysis was repeated on a replication sample (N=108; 32 schizophrenia spectrum disorder, 37 euthymic bipolar disorder, and 39 healthy control participants), which exhibited the same three cluster patterns. CONCLUSIONS: The study findings demonstrate replicable differing patterns of neural activity among individuals during a socio-emotional task, independent of DSM diagnosis or scan site. The findings may provide objective neuroimaging endpoints (biomarkers) for subgroups of individuals in target engagement research aimed at enhancing cognitive performance independent of diagnostic category.

7.
Schizophr Bull ; 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30239900

RESUMO

Objective: The aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores and percentile ranks. Methods: A total of 502 healthy participants (aged 11-19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were included in this multisite study. Regression-predicted means for the MCCB tests, except the social cognition subtest, were calculated using the MCCB test scores as outcome variables and age, age2, sex, age × sex as predictors. The regression-predicted means for each combination of age and sex were added with the residuals from the entire cohort to yield the expected distribution of that group. Age effects were examined using regression models with age and age2 as predictors. Sex differences were examined using Student's t-tests. Results: Significant positive age effects were found for all tests, except for the Brief Visuospatial Memory Test, revised (BVMT-R; measure of visual learning). Females performed significantly better than males on BACS Symbol coding (measure of speed of processing) and BVMT-R, while males performed significantly better than females on NAB Mazes (measure of reasoning and problem solving). Based on the regression-predicted distributions of scores, 19 standardized scoring tables for each test and domain were created. Conclusions: With the results from this study, we have developed an accessible standardized data set of healthy adolescent test performance for the MCCB.

8.
Schizophr Bull ; 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-30107517

RESUMO

Background: Schizophrenia spectrum disorders (SSDs) often feature social cognitive deficits. However, little work has focused on the factor structure of social cognition, and results have been inconsistent in schizophrenia. This study aimed to elucidate the factor structure of social cognition across people with SSDs and healthy controls. It was hypothesized that a 2-factor model, including lower-level "simulation" and higher-level "mentalizing" factors, would demonstrate the best fit across participants. Methods: Participants with SSDs (N = 164) and healthy controls (N = 102) completed social cognitive tasks ranging from emotion recognition to complex mental state inference, as well as clinical and functional outcome, and neurocognitive measures. Structural equation modeling was used to test social cognitive models, models of social cognition and neurocognition, measurement invariance between cases and controls, and relationships with outcome measures. Results: A 2-factor (simulation and mentalizing) model fit the social cognitive data best across participants and showed adequate measurement invariance in both SSD and control groups. Patients showed lower simulation and mentalizing scores than controls, but only mentalizing was significantly associated with negative symptoms and functional outcome. Social cognition also mediated the relationship between neurocognition and both negative symptoms and functional outcome. Conclusions: These results uniquely indicate that distinct lower- and higher-level aspects of social cognition exist across SSDs and healthy controls. Further, mentalizing may be particularly linked to negative symptoms and functional outcome. This informs future studies of the neural circuitry underlying social cognition and the development of targeted treatment options for improving functional outcome.

9.
Schizophr Res ; 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30126815

RESUMO

Emotional deficits are an integral feature of schizophrenia (SZ), but our understanding of these deficits is limited. In the present study, we examined whether the severity of emotional deficits reflects difficulty in the cognitive processing of affectively valenced stimuli. Healthy controls (HC; N = 170) and stable outpatients with SZ (N = 245), characterized as either deficit syndrome (DS; N = 62) or non-deficit syndrome (NDS; N = 183), completed an Affective Go/NoGo task requiring discrimination of positively, negatively or neutrally valenced words. Accuracy (d') and response bias (c) were calculated for each of the three conditions, and a series of ANOVAs were carried out to examine group differences. Examination of accuracy revealed significant main effects of group and valence and a significant valence × group interaction, indicating that while affective valence impacted accuracy for the HC and NDS groups, the DS group maintained the same low level of accuracy across all levels of affective valence. Examination of response bias also revealed significant main effects of group and valence and a significant valence × group interaction. Specifically, within the HC and NDS groups, response bias did not differ between negatively and positively valenced words while response bias in the DS group was lowest for neutral, higher for negatively valenced and higher still for positively valenced words. These results suggest that emotional deficits in DS may be directly related to deficits in processing affective information. Moreover, although this deficit is observed across both positively and negatively valenced stimuli, it is most pronounced for positively valenced material.

10.
Hum Brain Mapp ; 39(11): 4509-4518, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30160325

RESUMO

Resting state functional magnetic resonance imaging studies of psychosis have focused primarily on the amplitude of low-frequency fluctuations in the blood oxygen level dependent (BOLD) signal ranging from .01 to 0.1 Hz. Few studies, however, have investigated the amplitude of frequency fluctuations within discrete frequency bands and higher than 0.1 Hz in patients with psychosis at different illness stages. We investigated BOLD signal within three frequency ranges including slow-4 (.027-.073 Hz), slow-3 (.074-0.198 Hz) and slow-2 (0.199-0.25 Hz) in 89 patients with either first-episode or chronic psychosis and 119 healthy volunteers. We investigated the amplitude of frequency fluctuations within three frequency bands using 47 regions-of-interest placed within 14 known resting state networks derived using group independent component analysis. There were significant group x frequency interactions for the visual and motor cortex networks, with the largest significant group differences (patients < healthy volunteers) evident in slow-4 and slow-3, respectively. Also, healthy volunteers had an overall higher amplitude of frequency fluctuations compared to patients across the three frequency ranges in the visual cortex, dorsal attention and motor cortex networks with the opposite effect (patients > healthy volunteers) evident within the salience and frontal gyrus networks. Subsequent analyses indicated that these effects were evident in both first-episode and chronic patients. Our study provides new data regarding the importance of BOLD signal fluctuations within different frequency bands in the neurobiology of psychosis.

11.
Dev Neuropsychol ; 43(7): 566-580, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30160534

RESUMO

The present study examined the role of executive control functions (ECF) in adaptive risk-taking during adolescence. Healthy individuals aged 8-25 were administered ECF measures and the Balloon Analogue Risk Task (BART), a computerized measure of risk-taking propensity. Findings demonstrated that adolescents who executed a more consistent response strategy evidenced better performance on the BART. Greater working memory (WM) predicted lower response variability and WM capacity mediated the relationship between age and variability. Results suggest that intra-individual response variability may index adaptive risk-taking and that the development of ECF, specifically WM, may play an integral role in adaptive decision making during adolescence and young adulthood.

12.
Twin Res Hum Genet ; 21(5): 394-397, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30001766

RESUMO

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

13.
Nat Genet ; 50(7): 912-919, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29942086

RESUMO

Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29735154

RESUMO

BACKGROUND: Psychotic-like experiences (PLEs) are associated with lower social and occupational functioning, and lower executive function. Emerging evidence also suggests that PLEs reflect neural dysfunction resembling that of psychotic disorders. METHODS: The present study examined dynamic connectivity related to a measure of PLEs derived from the Achenbach Adult Self-Report, in an otherwise-healthy sample of adults from the Human Connectome Project. A total of 76 PLE-endorsing and 153 control participants were included in the final sample. To characterize network dysfunction, dynamic connectivity states were examined across large-scale resting-state networks using dynamic conditional correlation and k-means clustering. RESULTS: Three dynamic states were identified. The PLE-endorsing group spent more time than the control group in state 1, a state reflecting hyperconnectivity within visual regions and hypoconnectivity within the default mode network, and less time in state 2, a state characterized by robust within-network connectivity for all networks and strong default mode network anticorrelations. Within the PLE-endorsing group, worse executive function was associated with more time spent in and more transitions into state 1 and less time spent in and fewer transitions into state 3. CONCLUSIONS: PLEs are associated with altered large-scale brain dynamics, which tip the system away from spending more time in states reflecting more "typical" connectivity patterns toward more time in states reflecting visual hyperconnectivity and default mode hypoconnectivity.

15.
Biol Psychiatry ; 84(9): 665-674, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29779671

RESUMO

BACKGROUND: Deficits in neurocognition and social cognition are drivers of reduced functioning in schizophrenia spectrum disorders, with potentially shared neurobiological underpinnings. Many studies have sought to identify brain-based biomarkers of these clinical variables using a priori dichotomies (e.g., good vs. poor cognition, deficit vs. nondeficit syndrome). METHODS: We evaluated a fully data-driven approach to do the same by building and validating a brain connectivity-based biomarker of social cognitive and neurocognitive performance in a sample using resting-state and task-based functional magnetic resonance imaging (n = 74 healthy control participants, n = 114 persons with schizophrenia spectrum disorder, 188 total). We used canonical correlation analysis followed by clustering to identify a functional connectivity signature of normal and poor social cognitive and neurocognitive performance. RESULTS: Persons with poor social cognitive and neurocognitive performance were differentiated from those with normal performance by greater resting-state connectivity in the mirror neuron and mentalizing systems. We validated our findings by showing that poor performers also scored lower on functional outcome measures not included in the original analysis and by demonstrating neuroanatomical differences between the normal and poorly performing groups. We used a support vector machine classifier to demonstrate that functional connectivity alone is enough to distinguish normal and poorly performing participants, and we replicated our findings in an independent sample (n = 75). CONCLUSIONS: A brief functional magnetic resonance imaging scan may ultimately be useful in future studies aimed at characterizing long-term illness trajectories and treatments that target specific brain circuitry in those with impaired cognition and function.

16.
Brain Imaging Behav ; 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29744804

RESUMO

Prior functional magnetic resonance imaging (fMRI) studies have investigated the neural mechanisms underlying cognitive control in patients with psychosis with findings of both hypo- and hyperfrontality. One factor that may contribute to inconsistent findings is the use of complex and polyfactorial tasks to investigate frontal lobe functioning. In the current study we employed a simple response conflict task during fMRI to examine differences in brain activation between patients experiencing their first-episode of psychosis (n = 33) and age- and sex-matched healthy volunteers (n = 33). We further investigated whether baseline brain activation among patients predicted changes in symptom severity and treatment response following 12 weeks of controlled antipsychotic treatment. During the task subjects were instructed to press a response button on the same side or opposite side of a circle that appeared on either side of a central fixation point. Imaging data revealed that for the contrast of opposite-side vs. same-side, patients showed significantly greater activation compared with healthy volunteers in the anterior cingulate cortex and intraparietal sulcus. Among patients, greater baseline anterior cingulate cortex, temporal-parietal junction, and superior temporal cortex activation predicted greater symptom reduction and therapeutic response following treatment. All findings remained significant after covarying for task performance. Intact performance on this relatively parsimonious task was associated with frontal hyperactivity suggesting the need for patients to utilize greater neural resources to achieve task performance comparable to healthy individuals. Moreover, frontal hyperactivity observed using a simple fMRI task may provide a biomarker for predicting treatment response in first-episode psychosis.

17.
Nat Commun ; 9(1): 2098, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29844566

RESUMO

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

18.
Schizophr Res ; 2018 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-29510927

RESUMO

Psychotic like experiences (PLE's) are common in the general population, particularly during adolescence, which has generated interest in how PLE's emerge, and the extent to which they reflect either risk for, or resilience to, psychosis. The "attachment-developmental-cognitive" (ADC) model is one effort to model the effect of risk factors on PLEs. The ADC model proposes attachment insecurity as an early environmental insult that can contribute to altered neurodevelopment, increasing the likelihood of PLE's and psychosis. In particular, early-life attachment disruptions may negatively impact numerous aspects of executive function (EF), including behavioral inhibition and emotion regulation. Yet despite the relationship of disrupted attachment to EF impairments, no studies have examined how these factors may combine to contribute to PLE's in adolescents. Here, we examined the relative contributions of daily-life EF and attachment difficulties (avoidance and anxiety) to PLEs in typically developing youth (N=52; ages 10-21). We found that EF deficits and high attachment insecurity both accounted for a significant proportion of the variance in PLE's, and interacted to predict PLE manifestation. Specifically, positive PLEs were predicted by greater trouble monitoring behavioral impact, less difficulty completing tasks, greater difficulty regulating emotional reactions, greater difficulty controlling impulses and higher attachment anxiety. Negative PLEs were predicted by greater difficulty in alternating attention, transitioning across situations, and regulating emotional reactions as well as higher attachment anxiety. These results are consistent with the ADC model, providing evidence that early-life attachment disruptions may impact behavioral regulation and emotional control, which together may contribute to PLEs.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29529408

RESUMO

BACKGROUND: Externalizing behaviors are negative behaviors expressed outwardly, including rule breaking, aggression, and risk taking; internalizing behaviors are expressed inwardly, including depression, withdrawal, and anxiety. Such behavior can cause problems in early life and predict difficulties across the lifespan. There is evidence for a relationship between executive function and both externalizing and internalizing. However, although these behaviors occur along a spectrum, there is little neuroimaging research on this relationship in typically developing youth. METHODS: We assessed 41 youth (10-19 years of age) using the Multi-Source Interference Task during functional magnetic resonance imaging and related the findings to self-reported externalizing and internalizing scores as measured by the Youth Self-Report. We performed a general linear model using FSL software; externalizing, internalizing, age, and sex were included in the model. RESULTS: Compared to the control condition, the more difficult Multi-Source Interference Task interference condition was associated with greater engagement of the frontoparietal cognitive control system and decreased engagement of regions in the default mode network, based on a cluster threshold of Z > 3.1 (p = .01). When we examined regions uniquely associated with either internalizing or externalizing, we found that within the same group of subjects, higher externalizing behavior was associated with hyperactivity in the parietal lobe; in contrast, higher internalizing behavior was associated with increased activation in the medial prefrontal cortex. CONCLUSIONS: These findings suggest that externalizing and internalizing may be associated with altered, but different, patterns of activation during cognitive control. This has implications for our understanding of the relationship between cognitive control and behavioral problems in youth.

20.
Schizophr Res ; 195: 385-390, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29056491

RESUMO

Over the last several decades Quality of Life (QoL) has become increasingly important as an indicator of treatment outcomes; particularly in schizophrenia spectrum disorders because of its close association with functional disability. Numerous studies seeking to elucidate the factors that contribute to QoL in this population have implicated both symptom severity and cognition in determining QoL but the findings have been mixed. The critical factors that appear to impede the lack of consensus in the extant literature examining determinants of QoL include the heterogeneity of the samples and measures examined as well as medication effects across different studies. Thus, the present study sought to address some of these issues by examining the relationship between subjective QoL and both symptom severity and cognitive function in a relatively homogeneous patient sample of patients and a community control sample assessed for dimensional symptom severity. Our results suggest that both global cognitive function and psychiatric symptoms have a significant impact on the subjective QoL of both people with schizophrenia spectrum disorders and psychiatrically healthy adults. Specifically, we found that a global index of cognition as well as self-reported avolitional and depressive symptoms were significantly predictive of QoL in both samples. These findings highlight the importance of addressing cognitive, depressive and avolitional symptoms in the treatment of patients with schizophrenia spectrum disorders and suggest that improvements in these domains may have a meaningful impact on their overall QoL.

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