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1.
Schizophr Bull Open ; 1(1): sgaa014, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32803161

RESUMO

Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD.

2.
Brain Imaging Behav ; 14(2): 353-361, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32125612

RESUMO

The deleterious outcomes associated with exposure to childhood maltreatment (CM) are well known and may be at least partially mediated by self-harm behaviors. It has been suggested that these self-harm behaviors serve as a means of decreasing negative mood states but the effects of CM on health outcomes may be much more sinister. A wealth of data suggest that CM may lead to experience-dependent changes in neural circuits underlying reward processes; processes associated with many harmful behaviors. The present study examined the relationship between a history of CM and the microstructure of a white matter tract that may be central to reward processes. Healthy adults (N = 122) were assessed with a diffusion tensor imaging (DTI) exam and the Childhood Trauma Questionnaire (CTQ). Probabilistic tractography was used to delineate the accumbofrontal "reward" tract, connecting the orbitofrontal cortex and nucleus accumbens, and measures of white matter microstructure were extracted. We then examined whether variation in CTQ scores were associated with variation in the microstructure of this tract as measured by fractional anisotropy (FA). After accounting for the effects of age and sex, the CTQ total score accounted for approximately 6% of the variance of FA in the accumbofrontal tract (F(3, 121) = 5.74; p = .001). Post hoc analyses indicated that the overall severity of CM, rather than a specific type of maltreatment, drove this result. These findings indicate that CM influences white matter microstructure in a fiber tract that is likely central to reward processes and adds to a growing literature implicating CM in long-term health-related outcomes.

3.
Neuroimage ; 208: 116469, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31846756

RESUMO

Parasympathetic arousal is associated with states of heightened attention and well-being. Arousal may affect widespread cortical and subcortical systems across the brain, however, little is known about its influence on cognitive task processing and performance. In the current study, healthy adult participants (n â€‹= â€‹20) underwent multi-band echo-planar imaging (TR â€‹= â€‹0.72 â€‹s) with simultaneous pulse oximetry recordings during performance of the Multi Source Interference Task (MSIT), the Oddball Task (OBT), and during rest. Processing speed on both tasks was robustly related to heart rate (HR). Participants with slower HR responded faster on both the MSIT (33% variance explained) and the OBT (25% variance explained). Within all participants, trial-to-trial fluctuations in processing speed were robustly related to the heartbeat-stimulus interval, a metric that is dependent both on the concurrent HR and the stimulus timing with respect to the heartbeat. Models examining the cardiac-BOLD response revealed that a distributed set of regions showed arousal-related activity that was distinct for different task conditions. Across these cortical regions, activity increased with slower HR. Arousal-related activity was distinct from task-evoked activity and it was robust to the inclusion of additional physiological nuisance regressors into the models. For the MSIT, such arousal-related activity occurred across visual and dorsal attention network regions. For the OBT, this activity occurred within fronto-parietal regions. For rest, arousal-related activity also occurred, but was confined to visual regions. The pulvinar nucleus of the thalamus showed arousal-related activity during all three task conditions. Widespread cortical activity, associated with increased parasympathetic arousal, may be propagated by thalamic circuits and contributes to improved attention. This activity is distinct from task-evoked activity, but affects cognitive performance and therefore should be incorporated into neurobiological models of cognition and clinical disorders.

4.
Hum Brain Mapp ; 36(12): 4954-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26366528

RESUMO

The presence of an anatomical connection between the orbitofrontal cortex and ventral striatum, forming a so-called reward network, is well established across species. This connection has important implications for reward processing and is relevant to a number of neuropsychiatric disorders. Moreover, white matter (WM) is known to continue to mature across adolescence and into early adulthood, and developmental change in the reward network is an important component of models of decision making and risk taking. Despite the importance of this connection, the underlying WM has only recently been characterized in humans histologically, and not yet in-vivo using brain imaging. Here, we implemented diffusion tensor imaging (DTI) in a large cross-sectional sample of 295 healthy individuals ages 8-68 to further characterize the WM of this connection and its development from childhood into adulthood. We demonstrate that the accumbofrontal tract, connecting the orbitofrontal cortex and nucleus accumbens, can be identified using standard DTI sequences. Using Poisson modeling, we show that the accumbofrontal tract undergoes significant change across the lifespan, with males showing a higher and earlier peak compared to females. Moreover, the change occurs in a pattern consistent with developmental models of decision-making. These findings support the hypothesis that developmental differences in WM integrity may be a contributing factor to the observed risk taking that occurs in adolescence. The accumbofrontal tract is not yet included in standard WM atlases, but may be important for inclusion in studies investigating fronto-striatal networks, as well as in investigations of substance abuse and decision making.


Assuntos
Imagem de Tensor de Difusão , Lobo Frontal/anatomia & histologia , Lobo Frontal/crescimento & desenvolvimento , Núcleo Accumbens/anatomia & histologia , Núcleo Accumbens/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Mapeamento Encefálico , Criança , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiologia , Caracteres Sexuais , Substância Branca/anatomia & histologia , Substância Branca/crescimento & desenvolvimento , Adulto Jovem
5.
Schizophr Res ; 152(1): 223-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24321710

RESUMO

BACKGROUND: Neurodevelopmental models of schizophrenia suggest that cognitive deficits may be observed during childhood and adolescence, long before the onset of psychotic symptoms. Elucidating the trajectory of normal cognitive development during childhood and adolescence may therefore provide a basis for identifying specific abnormalities related to the development of schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB), which was designed for use in clinical trials targeting cognitive deficits most common in schizophrenia, may provide a mechanism to understand this trajectory. To date, however, there is no performance data for the MCCB in healthy children and adolescents. The present study sought to establish performance data for the MCCB in healthy children, adolescents, and young adults. METHODS: The MCCB was administered to a community sample of 190 healthy subjects between the ages of 8 and 23years. All MCCB domain scores were converted to T-scores using sample means and standard deviations and were compared for significant performance differences between sex and age strata. RESULTS: Analyses revealed age effects following quadratic trends in all MCCB domains, which is consistent with research showing a leveling off of childhood cognitive improvement upon approaching late adolescence. Sex effects after controlling for age only presented for one MCCB domain, with males exhibiting well-known spatial reasoning advantages. CONCLUSIONS: Utilizing this performance data may aid future research seeking to elucidate specific deficits that may be predictive of later development of SZ.


Assuntos
Desenvolvimento Infantil , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Testes Neuropsicológicos , Esquizofrenia/diagnóstico , Adolescente , Fatores Etários , Criança , Transtornos Cognitivos/etiologia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Adulto Jovem
6.
J Psychiatr Res ; 47(9): 1174-9, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23726669

RESUMO

Recent data suggests that a history of childhood maltreatment is associated with reductions in hippocampal volume in healthy adults. Because this association is also evident in adults with psychiatric illness, it has been suggested that reductions in hippocampal volume associated with childhood maltreatment may be a risk factor for psychiatric illness. Such an interpretation suggests that healthy adults with a history of childhood maltreatment are more resilient to the effects of maltreatment. Current models of resilience suggest, however, that resiliency should be measured across multiple domains of functioning. The present study sought to investigate childhood maltreatment in relationship to hippocampal volumes in healthy adults and to address the question of whether the putative resiliency extends to other domains of functioning. Sixty-seven healthy Caucasian adults were assessed for a history of childhood emotional abuse, emotional neglect and physical abuse and received high resolution structural MR imaging scans. Participants with and without histories of abuse or neglect were compared on measures of total hippocampal volume, general cognitive ability and subclinical psychopathology. Our results suggest that childhood emotional abuse is associated with reduced hippocampus volume in males, but not in females. However, emotional abuse was associated with higher levels of subclinical psychopathology in both males and females. These data suggest that while females may be more resilient to the neurological effects of childhood maltreatment, they are not more resilient to the psychiatric symptoms associated with childhood maltreatment. Further research is needed to elucidate the mechanisms involved in these different levels of resilience.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Transtornos Cognitivos/patologia , Hipocampo/patologia , Transtornos Psicóticos/patologia , Caracteres Sexuais , Adulto , Transtornos Cognitivos/etiologia , Feminino , Humanos , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/etiologia , Inquéritos e Questionários , Adulto Jovem
7.
Psychiatry Res ; 200(2-3): 242-5, 2012 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-22818174

RESUMO

Studies investigating the impact of cannabis use on bipolar clinical characteristics and neurocognition are limited. The objective of the present study was to compare clinical and neurocognitive measures in individuals with bipolar disorder with a history of cannabis use disorder (CUD) versus those without a history of CUD. We conducted a retrospective analysis of a large cohort (N=200) of bipolar I subjects, either with (CUD+; N=50) or without (CUD-; N=150) a history of CUD. We compared the groups on clinical and demographic variables, as well as on performance on neurocognitive tests. Patient groups did not differ regarding age, age of onset or global assessment of functioning. Compared to the CUD- group, the CUD+ group had a higher proportion of men and a higher proportion of patients with a history of psychosis. CUD+ subjects demonstrated significantly better performance on measures of attention, processing speed, and working memory. The history of CUD is associated with history of psychosis, suggestive of poorer clinical prognosis. Interestingly, bipolar patients with history of CUD had better neurocognitive performance as compared to patients with no history of CUD.


Assuntos
Transtorno Bipolar/psicologia , Cognição , Abuso de Maconha/psicologia , Fumar Maconha/psicologia , Adulto , Atenção , Transtorno Bipolar/complicações , Função Executiva , Feminino , Humanos , Masculino , Abuso de Maconha/complicações , Memória de Curto Prazo , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prognóstico , Estudos Retrospectivos
8.
Neuropsychopharmacology ; 36(8): 1587-92, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21451499

RESUMO

The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was devised to identify a neurocognitive battery to be used in clinical trials targeting cognition in schizophrenia, a process, which resulted in the MATRICS Consensus Cognitive Battery (MCCB). The MCCB has been selected by the United States Food and Drug Administration to be used as the primary outcome measure in registry trials for cognitive agents in schizophrenia. Given the clinical and cognitive overlap between schizophrenia and bipolar disorder (BPD), it is likely that any compound shown to have cognitive benefits in schizophrenia will subsequently be tested in BPD. Unlike the MCCB for schizophrenia, there remains no consensus regarding outcome measures if cognitive trials were to be undertaken in BPD. The utility of the MCCB in BPD has not yet been systematically investigated. We administered the MCCB to 80 bipolar I patients; 37 were strictly euthymic and 43 were symptomatic. We compared their performance with a demographically matched healthy sample (n=148) on seven MCCB domains, and the composite. BPD patients were statistically significantly impaired on five of seven MCCB domains at levels consistent with meta-analytic studies of cognition in BPD. In contrast, patients' performance was less impaired on the Reasoning and Problem-solving and Social Cognition domains, differences that did not survive statistical correction for multiple testing. Symptomatic status only modestly influenced performance. These data suggest that the MCCB, devised for use in schizophrenia, may also represent a useful outcome measure in cognitive trials for BPD. Additional studies should address important psychometric features such as repeatability and potential practice and/or ceiling effects.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Testes Neuropsicológicos/normas , Cognição/fisiologia , Humanos , Resultado do Tratamento
9.
Bipolar Disord ; 13(2): 164-72, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21443570

RESUMO

OBJECTIVES: Bipolar disorder (BD) has been associated with impairment in affective processing during depressive and manic states; however, there are limited data as to whether this population exhibits such difficulty during stable periods. We examined the pattern of affective processing in stable BD patients and compared their profile to that of healthy controls (HC) and patients diagnosed with schizophrenia (SZ). METHODS: A total of 336 subjects were administered an Affective Go/No-go test to evaluate target detection of negatively valenced, positively valenced, and neutral stimuli. Accuracy and response bias served as dependent variables in a series of multivariate analyses of covariance to test for group differences. RESULTS: The BD group relative to the HC group exhibited response biases toward negatively valenced information (p<0.01). Deficits were also evident in discrimination of and accurate responses to positively valenced information in the BD group versus the HC group (p<0.05). In contrast to the controls, the SZ group performed poorly on all task components and was less accurate across all conditions regardless of affective valence (p<0.01). Patients with SZ evidenced reverse biases for positive information, as they were less likely to respond to positive words (p<0.05) despite comparable response bias on neutral and negative conditions. CONCLUSIONS: Affective processing impairment evident in BD is a feature of the disorder that is present even during stable periods. Prior studies comparing BD with SZ have highlighted clear quantitative but inconsistent qualitative differences in cognitive functioning. Our data suggest that a response bias toward negative stimuli may be a critical and relatively specific feature of BD.


Assuntos
Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Emoções/fisiologia , Inibição Psicológica , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adolescente , Adulto , Idoso , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação , Análise de Regressão , Adulto Jovem
10.
Nat Genet ; 41(11): 1223-7, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19855392

RESUMO

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).


Assuntos
Cromossomos Humanos Par 16 , Duplicação Gênica , Predisposição Genética para Doença , Esquizofrenia/genética , Humanos , Fatores de Risco
11.
Biol Psychol ; 79(1): 103-10, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18078707

RESUMO

BACKGROUND: DISC1 is considered a susceptibility gene for schizophrenia and schizoaffective disorder, but little is known regarding the potential mechanisms through which it may confer increased risk. Given that DISC1 plays a role in cerebral cortex development, polymorphisms in this gene may have relevance for neurobiological models of schizophrenia that have implicated cortical deficits in its pathophysiology. METHODS: We investigated whether the DISC1 leu607phe polymorphism was associated with prefrontal gray matter volumes using magnetic resonance imaging in a cohort of patients with schizophrenia (N=19) and healthy volunteers (N=25) and positive and negative symptoms in 200 patients with schizophrenia. RESULTS: Among patients and healthy volunteers, phe carriers (N=11) had significantly less gray matter in the superior frontal gyrus and anterior cingulate gyrus compared to leu/leu homozygotes (N=33). Further, among patients left superior frontal gyrus gray matter volume was significantly negatively correlated with severity of hallucinations. In addition, patients who were phe carriers (N=144) had significantly greater severity of positive symptoms (hallucinations) compared to patients who were leu/leu homozygotes (N=56). DISCUSSION: These findings implicate DISC1 in variation of prefrontal cortical volume and positive symptoms, thus providing a potential mechanism through which DISC1 may confer increased risk for schizophrenia or schizoaffective disorder.


Assuntos
Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Córtex Pré-Frontal/patologia , Esquizofrenia/patologia , Psicologia do Esquizofrênico , Adulto , Estudos de Coortes , Feminino , Lobo Frontal/patologia , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Polimorfismo Genético/genética , Escalas de Graduação Psiquiátrica
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