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1.
Brain ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637303

RESUMO

The prediction error account of delusions has had success. However, its explanation of delusions with different contents has been lacking. Persecutory delusions and paranoia are the common unfounded beliefs that others have harmful intentions towards us. Other delusions include believing that one's thoughts or actions are under external control, or that events in the world have specific personal meaning. We compare learning on two different cognitive tasks, probabilistic reversal learning (PRL) and Kamin blocking, that have relationships to paranoid and non-paranoid delusion-like beliefs, respectively. We find that Clinical High-Risk status alone does not result in different behavioral results on the PRL task but that an individual's level of paranoia is associated with excessive switching behavior. During the Kamin blocking task, paranoid individuals learned inappropriately about the blocked cue. However, they also had decreased learning about the control cue, suggesting more general learning impairments. Non-paranoid delusion-like belief conviction (but not paranoia) was associated with aberrant learning about the blocked cue but intact learning about the control cue, suggesting specific impairments in learning related to cue combination. We fit task-specific computational models separately to behavioral data to explore how latent parameters vary within individuals between tasks, and how they can explain symptom-specific effects. We find that paranoia is associated with low learning rates on the PRL task as well as the blocking task. Non-paranoid delusion-like belief conviction was instead related to parameters controlling the degree and direction of similarity between cue updating during simultaneous cue presentation. These results suggest that paranoia and other delusion-like beliefs involve dissociable deficits in learning and belief updating, which - given the transdiagnostic status of paranoia - may have differential utility in predicting psychosis.

2.
Mol Psychiatry ; 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38081943

RESUMO

INTRODUCTION: Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension. METHODS: Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020. RESULTS: We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs. DISCUSSION: Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.

3.
Eur Arch Psychiatry Clin Neurosci ; 274(5): 1237-1240, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38244078

RESUMO

There is growing evidence of disproportionate retinal thinning in schizophrenia, but doubts are still raised regarding its significance in the context of the neurobiology of the disease. Therefore, we examined whether these abnormalities are significantly associated with neurological soft signs (NSS) which are closely related to the risk of schizophrenia. This cross-sectional study analyzing linear correlations between variables involved 56 schizophrenia inpatients and 60 controls. The results confirmed such relationships, and only in the patient sample. In addition, retinal abnormalities and NSS were significantly correlated with duration of illness. These findings provide further evidence for linked neurodevelopmental and neurodegenerative aspects of schizophrenia.


Assuntos
Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/patologia , Esquizofrenia/complicações , Masculino , Feminino , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Retina/patologia , Retina/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto Jovem
4.
J Ment Health ; : 1-10, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804258

RESUMO

BACKGROUND: Trauma and posttraumatic stress disorder (PTSD) are common among individuals with serious mental illness (SMI; e.g., schizophrenia, schizoaffective disorder, bipolar disorder, treatment refractory major depressive disorder), with resultant functional impairment. Previous studies have not evaluated the factor structure of the PTSD Checklist (PCL) among persons with SMI. AIMS: This study evaluated the factor structure of the PCL in two large SMI samples from public mental health treatment sectors screened for PTSD using the PCL. METHODS: Four different models of PTSD were tested using confirmatory factor analyses. RESULTS: Results indicated that the DSM-5 4-factor model (intrusion, avoidance, numbing, and hyperarousal) had the best fit. Further, the DSM-5 4-factor model demonstrated measurement invariance. CONCLUSIONS: Results supported the suitability of the DSM-5 4-factor model of PTSD among people with SMI.

5.
Eur J Neurosci ; 57(3): 458-478, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36504464

RESUMO

Visual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes, but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether brain network differences in schizophrenia occur in related illnesses or vary with illness features transdiagnostically. To address these topics, we scanned (functional magnetic resonance imaging, fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting-state connections for shape completion. Illusory/fragmented task activation differences ('modulations') in the dorsal attention network (DAN) could distinguish people with schizophrenia from the other groups (AUCs > .85) and could transdiagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except in schizophrenia. The secondary visual network was strongly and similarly modulated in each group. Task modulations were dispersed over more networks in patients compared to controls. In summary, DAN activity during visual perceptual organization is distinct in schizophrenia, symptomatically relevant, and potentially related to improper attention-related feedback into secondary visual areas.


Assuntos
Transtorno Bipolar , Ilusões , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico , Transtorno Bipolar/diagnóstico por imagem , Cognição , Imageamento por Ressonância Magnética
6.
Cogn Affect Behav Neurosci ; 23(1): 203-215, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36418846

RESUMO

Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.


Assuntos
Neuroanatomia , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagem , Lobo Frontal , Córtex Pré-Frontal/diagnóstico por imagem , Lobo Temporal , Imageamento por Ressonância Magnética
7.
Acta Psychiatr Scand ; 147(6): 623-633, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36905387

RESUMO

INTRODUCTION: Paranoia is a common and impairing psychosis symptom, which exists along a severity continuum that extends into the general population. Individuals at clinical high-risk for psychosis (CHR) frequently experience paranoia and this may elevate their risk for developing full psychosis. Nonetheless, limited work has examined the efficient measurement of paranoia in CHR individuals. The present study aimed to validate an often-used self-report measure, the revised green paranoid thoughts scale (RGPTS), in this critical population. METHOD: Participants were CHR individuals (n = 103), mixed clinical controls (n = 80), and healthy controls (n = 71) who completed self-report and interview measures. Confirmatory factor analysis (CFA), psychometric indices, group differences, and relations to external measures were used to evaluate the reliability and validity of the RGPTS. RESULTS: CFA replicated a two-factor structure for the RGPTS and the associated reference and persecution scales were reliable. CHR individuals scored significantly higher on both reference and persecution, relative to both healthy (ds = 1.03, 0.86) and clinical controls (ds = 0.64, 0.73). In CHR participants, correlations between reference and persecution and external measures were smaller than expected, though showed evidence of discriminant validity (e.g., interviewer-rated paranoia, r = 0.24). When examined in the full sample, correlation magnitude was larger and follow-up analyses indicated that reference related most specifically to paranoia (ß = 0.32), whereas persecution uniquely related to poor social functioning (ß = -0.29). CONCLUSION: These results demonstrate the reliability and validity of the RGPTS, though its scales related more weakly to severity in CHR individuals. The RGPTS may be useful in future work aiming to develop symptom-specific models of emerging paranoia in CHR individuals.


Assuntos
Transtornos Psicóticos , Humanos , Reprodutibilidade dos Testes , Transtornos Psicóticos/diagnóstico , Transtornos Paranoides/diagnóstico , Autorrelato , Relações Interpessoais
8.
Behav Cogn Psychother ; 51(5): 459-474, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37212149

RESUMO

BACKGROUND: People with post-traumatic stress disorder (PTSD) exhibit negative cognitions, predictive of PTSD severity. The Post-Traumatic Cognitions Inventory (PTCI) is a widely used instrument measuring trauma-related cognitions and beliefs with three subscales: negative thoughts of self (SELF), negative cognitions about the world (WORLD), and self-blame (BLAME). AIMS: The current study attempted to validate the use of the PTCI in people with serious mental illness (SMI), who have greater exposure to trauma and elevated rates of PTSD, using confirmatory factor analysis (CFA) and examining convergent and divergent correlations with relevant constructs. METHOD: Participants were 432 individuals with SMI and co-occurring PTSD diagnosis based on the Clinician Administered PTSD Scale, who completed PTCI and other clinical ratings. RESULTS: CFAs provided adequate support for Foa's three-factor model (SELF, WORLD, BLAME), and adequate support for Sexton's four-factor model that also included a COPE subscale. Both models achieved measurement invariance at configural, metric and scalar levels for three diagnostic groups: schizophrenia, bipolar and major depression, as well as for ethnicity (White vs Black), and gender (male vs female). Validity of both models was supported by significant correlations between PTCI subscales, and self-reported and clinician assessed PTSD symptoms and associated symptoms. CONCLUSIONS: Findings provide support for the psychometric properties of the PTCI and the conceptualization of Sexton's four-factor and Foa's three-factor models of PTCI among individuals diagnosed with SMI (Foa et al., ).


Assuntos
Transtorno Depressivo , Transtornos de Estresse Pós-Traumáticos , Humanos , Masculino , Feminino , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Psicometria , Reprodutibilidade dos Testes , Cognição
9.
Psychol Med ; 52(6): 1115-1125, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-32799938

RESUMO

BACKGROUND: Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function. METHODS: The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning. RESULTS: Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks. CONCLUSIONS: These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.


Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapêutico , Dopamina , Cognição , Memória de Curto Prazo , Testes Neuropsicológicos
10.
Neuroimage ; 236: 118069, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33878383

RESUMO

Visual shape completion recovers object shape, size, and number from spatially segregated edges. Despite being extensively investigated, the process's underlying brain regions, networks, and functional connections are still not well understood. To shed light on the topic, we scanned (fMRI) healthy adults during rest and during a task in which they discriminated pac-man configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Task activation differences (illusory-fragmented), resting-state functional connectivity, and multivariate patterns were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping (ActFlow) was used to evaluate the likely involvement of resting-state connections for shape completion. We identified 36 differentially-active parcels including a posterior temporal region, PH, whose activity was consistent across 95% of observers. Significant task regions primarily occupied the secondary visual network but also incorporated the frontoparietal, dorsal attention, default mode, and cingulo-opercular networks. Each parcel's task activation difference could be modeled via its resting-state connections with the remaining parcels (r=.62, p<10-9), suggesting that such connections undergird shape completion. Functional connections from the dorsal attention network were key in modelling task activation differences in the secondary visual network. Dorsal attention and frontoparietal connections could also model activations in the remaining networks. Taken together, these results suggest that shape completion relies upon a sparsely distributed but densely interconnected network coalition that is centered in the secondary visual network, coordinated by the dorsal attention network, and inclusive of at least three other networks.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/fisiologia , Conectoma/métodos , Percepção de Forma/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Cogn Affect Behav Neurosci ; 21(4): 679-697, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34050524

RESUMO

A considerable number of studies have attempted to account for the psychotic aspects of schizophrenia in terms of the influential predictive coding (PC) hypothesis. We argue that the prediction-oriented perspective on schizophrenia-related psychosis may benefit from a mechanistic model that: 1) gives due weight to the extent to which alterations in short- and long-term synaptic plasticity determine the degree and the direction of the functional disruption that occurs in psychosis; and 2) addresses the distinction between the two central syndromes of psychosis in schizophrenia: disorganization and reality-distortion. To accomplish these goals, we propose the Imbalanced Plasticity Hypothesis - IPH, and demonstrate that it: 1) accounts for commonalities and differences between disorganization and reality distortion in terms of excessive (hyper) or insufficient (hypo) neuroplasticity, respectively; 2) provides distinct predictions in the cognitive and electrophysiological domains; and 3) is able to reconcile conflicting PC-oriented accounts of psychosis.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Humanos , Plasticidade Neuronal
12.
J Nerv Ment Dis ; 209(3): 203-207, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315800

RESUMO

ABSTRACT: People with schizophrenia often experience attentional impairments that hinder learning during psychological interventions. Attention shaping is a behavioral technique that improves attentiveness in this population. Because reinforcement learning (RL) is thought to be the mechanism by which attention shaping operates, we investigated if preshaping RL performance predicted level of response to attention shaping in people with schizophrenia. Contrary to hypotheses, a steeper attentiveness growth curve was predicted by less intact pretreatment RL ability and lower baseline attentiveness, accounting for 59% of the variance. Moreover, baseline attentiveness accounted for over 13 times more variance in response to attention shaping than did RL ability. Results suggest attention shaping is most effective for lower-functioning patients, and those high in RL ability may already be close to ceiling in terms of their response to reinforcers. Attention shaping may not be a primarily RL-driven intervention, and other mechanisms of its effects should be considered.


Assuntos
Atenção , Psicologia do Esquizofrênico , Adulto , Cognição , Feminino , Humanos , Inteligência , Masculino , Reforço Psicológico , Esquizofrenia/diagnóstico
13.
Ophthalmic Physiol Opt ; 41(5): 985-995, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34382220

RESUMO

PURPOSE: People with vision loss are at increased risk for major depressive disorder (MDD) and subclinical depression. However, screening for depression is rarely done in eye care settings or among groups in the general population known to have vision disorders. METHODS: We examined the prevalence of depression, using the Patient Health Questionnaire - 2 (PHQ-2), among a group of older adults (N = 204; mean age = 82.15) at two senior living facilities (SLFs) and determined the relationships between severity of depression and objective visual findings, visual function, beliefs about taking an active role in one's own eye care (i.e., patient activation) and level of social support. RESULTS: Approximately 50% of the sample had impaired vision in at least one eye, and close to 30% of the sample obtained a score on the PHQ-2 indicating the likely presence of major depressive disorder. Visual testing findings were related to visual function (e.g., ability to read), but not to depression. Patient activation was also not significantly related to the level of depression. However, impaired visual functioning and less social support were both strong predictors of depression. These two variables and their interaction accounted for 17% of the total PHQ-2 score variance. CONCLUSIONS: These data indicate the potential utility of screening for depression as part of vision care in populations likely to have significant vision loss. The findings also suggest that a comprehensive approach to depression prevention and/or reduction in SLF and similar populations may require interventions to address reduced visual functioning and methods to strengthen social networks.


Assuntos
Transtorno Depressivo Maior , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Humanos , Inquéritos e Questionários , Transtornos da Visão/diagnóstico , Transtornos da Visão/epidemiologia , Visão Ocular , Acuidade Visual
14.
Cogn Affect Behav Neurosci ; 20(1): 76-90, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31811557

RESUMO

Higher cognitive functioning is supported by adaptive reconfiguration of large-scale functional brain networks. Cognitive control (CC), which plays a vital role in flexibly guiding cognition and behavior in accordance with our goals, supports a range of executive functions via distributed brain networks. These networks process information dynamically and can be represented as functional connectivity changes between network elements. Using graph theory, we explored context-dependent network reorganization in 56 healthy adults performing fMRI tasks from two cognitive domains that varied in CC and episodic-memory demands. We examined whole-brain modular structure during the DPX task, which engages proactive CC in the frontal-parietal cognitive-control network (FPN), and the RiSE task, which manipulates CC demands at encoding and retrieval during episodic-memory processing, and engages FPN, the medial-temporal lobe and other memory-related networks in a context dependent manner. Analyses revealed different levels of network integration and segregation. Modularity analyses revealed greater brain-wide integration across tasks in high CC conditions compared to low CC conditions. Greater network reorganization occurred in the RiSE memory task, which is thought to require coordination across multiple brain networks, than in the DPX cognitive-control task. Finally, FPN, ventral attention, and visual systems showed within network connectivity effects of cognitive control; however, these cognitive systems displayed varying levels of network reorganization. These findings provide insight into how brain networks reorganize to support differing task contexts, suggesting that the FPN flexibly segregates during focused proactive control and integrates to support control in other domains such as episodic memory.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Função Executiva/fisiologia , Memória Episódica , Rede Nervosa/fisiologia , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico , Humanos , Masculino , Memória de Curto Prazo , Rede Nervosa/fisiopatologia , Vias Neurais/fisiologia , Vias Neurais/fisiopatologia
15.
Soc Psychiatry Psychiatr Epidemiol ; 54(11): 1363-1378, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30937510

RESUMO

PURPOSE: A substantial body of research indicates that self-stigma is associated with poorer outcomes related to recovery among people with severe mental illnesses. Narrative Enhancement and Cognitive Therapy (NECT) is a structured, group-based approach which targets the effects of self-stigma. A randomized-controlled trial was conducted to examine the efficacy of NECT. METHODS: One hundred and seventy persons, recruited from both outpatient and comprehensive treatment settings, meeting criteria for schizophrenia-spectrum disorders and moderate-to-elevated self-stigma, were randomly assigned to NECT or supportive group therapy and assessed at four time points over the course of nearly a year. Participants completed measures of self-stigma, hope, self-esteem, functioning, psychiatric symptoms, coping with symptoms, and narrative insight. RESULTS: Analyses indicated that NECT participants in outpatient sites improved significantly more over time in self-stigma compared to supportive group therapy participants in outpatient sites, while NECT participants in comprehensive (including day treatment and psychiatric rehabilitation program) sites improved significantly more in hopelessness and narrative insight than other participants. NECT participants as a group showed decreases in the social withdrawal component of self-stigma, decreased in their use of avoidant coping strategies, and were more engaged in treatment than supportive group therapy participants. There was no evidence for effects of NECT on social functioning or psychiatric symptoms. CONCLUSIONS: Findings suggest that NECT primarily impacts self-stigma and related outcomes, and that the degree of its effects is partially dependent on the treatment context in which it is offered.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Terapia Narrativa/métodos , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Estigma Social , Adaptação Psicológica , Adulto , Feminino , Esperança , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Autoimagem , Ajustamento Social , Resultado do Tratamento , Adulto Jovem
16.
Mol Cell Neurosci ; 89: 20-32, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29601869

RESUMO

Antipsychotic medications are inefficient at treating symptoms of schizophrenia (SCZ), and N-methyl d-aspartate receptor (NMDAR) agonists are potential therapeutic alternatives. As such, these agonists may act on different pathways and proteins altered in the brains of patients with SCZ than do antipsychotic medications. Here, we investigate the effects of administration of the antipsychotic haloperidol and NMDAR agonist d-serine on function and expression of three proteins that play significant roles in SCZ: nitric oxide synthase 1 adaptor protein (NOS1AP), dopamine D2 (D2) receptor, and disrupted in schizophrenia 1 (DISC1). We administered haloperidol or d-serine to male and female Sprague Dawley rats via intraperitoneal injection for 12 days and subsequently examined cortical expression of NOS1AP, D2 receptor, and DISC1. We found sex-specific effects of haloperidol and d-serine treatment on the expression of these proteins. Haloperidol significantly reduced expression of D2 receptor in male, but not female, rats. Conversely, d-serine reduced expression of NOS1AP in male rats and did not affect D2 receptor expression. d-serine treatment also reduced expression of DISC1 in male rats and increased DISC1 expression in female rats. As NOS1AP is overexpressed in the cortex of patients with SCZ and negatively regulates NMDAR signaling, we subsequently examined whether treatment with antipsychotics or NMDAR agonists can reverse the detrimental effects of NOS1AP overexpression in vitro as previously reported by our group. NOS1AP overexpression promotes reduced dendrite branching in vitro, and as such, we treated cortical neurons overexpressing NOS1AP with different antipsychotics (haloperidol, clozapine, fluphenazine) or d-serine for 24 h and determined the effects of these drugs on NOS1AP expression and dendrite branching. While antipsychotics did not affect NOS1AP protein expression or dendrite branching in vitro, d-serine reduced NOS1AP expression and rescued NOS1AP-mediated reductions in dendrite branching. Taken together, our data suggest that d-serine influences the function and expression of NOS1AP, D2 receptor, and DISC1 in a sex-specific manner and reverses the effects of NOS1AP overexpression on dendrite morphology.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Córtex Cerebral/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Serina/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antipsicóticos/farmacologia , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Feminino , Haloperidol/farmacologia , Isomerismo , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Serina/química , Fatores Sexuais
17.
Psychol Med ; 48(12): 2023-2033, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29233210

RESUMO

BACKGROUND: Prior optical coherence tomography (OCT) studies of schizophrenia have identified thinning of retinal layers. However, findings have varied across reports, and most studies have had serious methodological limitations. To address unresolved issues, we determined whether: (1) retinal thinning in schizophrenia occurs independently of comorbid medical conditions that affect the retina; (2) thinning is independent of antipsychotic medication dose; (3) optic nerve parameters are abnormal in schizophrenia; and (4) OCT indices are related to visual and cognitive impairments common in schizophrenia. METHODS: A total of 32 people with schizophrenia and 32 matched controls participated. Spectral domain OCT generated data on retinal nerve fiber layer (RNFL), macula, and ganglion cell-inner plexiform layer (GCL-IPL) thickness, in addition to cup volume and the cup-to-disc ratio at the optic nerve head. Subjects with schizophrenia also completed measures of symptoms, visual processing, and IQ. RESULTS: The groups did not differ on RNFL, macula, or GCL-IPL thickness. However, thinning of these layers was related to the presence of diabetes or hypertension across the sample as a whole. The schizophrenia group demonstrated enlarged cup volume and an enlarged cup-to-disc ratio in both eyes, which were unrelated to medical comorbidity, but were related to increased cognitive symptoms. CONCLUSIONS: Past reports of retinal thinning may be artifacts of medical comorbidity that is over-represented in schizophrenia, or other confounds. However, optic nerve head abnormalities may hold promise as biomarkers of central nervous system abnormality, including cognitive decline, in schizophrenia.


Assuntos
Disfunção Cognitiva/patologia , Macula Lutea/patologia , Disco Óptico/patologia , Neurônios Retinianos/patologia , Esquizofrenia/patologia , Adulto , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Feminino , Humanos , Macula Lutea/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Disco Óptico/diagnóstico por imagem , Células Ganglionares da Retina/patologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto Jovem
18.
Psychol Med ; 48(16): 2776-2785, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29501072

RESUMO

BACKGROUND: Neurocognitive deficits are often seen as core features of schizophrenia, and as primary determinants of poor functioning. Yet, our clinical observations suggest that individuals who score within the impaired range on standardized tests can reliably perform better in complex real-world situations, especially when performance is embedded within a positive socio-affective context. METHODS: We analyzed literature on the influence of non-neurocognitive factors on test performance in order to clarify their contributions. RESULTS: We identified seven non-neurocognitive factors that significantly contribute to neurocognitive test performance: avolition, dysfunctional attitudes, effort, stress, negative emotions, asociality, and disorganized symptoms. We then proposed an alternative model based on dysfunctional (e.g. defeatist) attitudes and their consequences for motivation and sustained task engagement. We demonstrated that these factors account for substantial variance in negative symptoms, neurocognitive test performance, and functional outcomes. We then demonstrated that recovery-oriented cognitive therapy - which is derived from this alternative model and primarily targets dysfunctional beliefs - has been successful in the treatment of low functioning individuals with schizophrenia. CONCLUSION: The contributions of neurocognitive impairments to poor real-world functioning in people with schizophrenia may be overstated in the literature, and may even be limited relative to non-neurocognitive factors. We offer suggestions for further research to more precisely quantify the contributions of attitudinal/motivation v. neurocognitive factors in schizophrenia.


Assuntos
Atitude , Disfunção Cognitiva/fisiopatologia , Emoções/fisiologia , Função Executiva/fisiologia , Motivação/fisiologia , Esquizofrenia/fisiopatologia , Comportamento Social , Estresse Psicológico/fisiopatologia , Disfunção Cognitiva/etiologia , Humanos , Esquizofrenia/complicações
19.
Cogn Neuropsychiatry ; 23(5): 267-283, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30019984

RESUMO

Introduction Impaired perceptual organisation in schizophrenia has been repeatedly described in clinical and research literatures. It has also been associated with problems in more complex aspects of visual function, including visuospatial and visual cognitive test performance. Two therapeutic interventions were developed here that target perceptual organisation: (1) Computer-based training, which emphasized stimulus-driven processing (bottom-up approach), and (2) Instrumental Enrichment therapy, which is a therapist-guided interactive learning method (top-down approach). Methods Twenty-eight patients diagnosed with schizophrenia or schizoaffective disorder participated in a 12-week programme. For both forms of interventions, task difficulty increased progressively, based upon successful performance. The third group of patients, which served as controls, received a similar therapeutic intervention that did not include a perceptual organisation component. Before and after intervention, participants received tests of perceptual organisation, as well as a battery of neuropsychological tests. Results Results indicate that both forms of intervention improved perceptual organisation ability relative to the control condition. In addition, the improvement was found for select neuropsychological tests, although the pattern of improvement did not favour capacities more closely associated with visual organisational or visuospatial function. Conclusions Together, results demonstrate the effectiveness of new remediation protocols that target mid-level visual processing, which generalized to select visual cognitive functions.


Assuntos
Psicoterapia/métodos , Esquizofrenia/terapia , Psicologia do Esquizofrênico , Percepção Espacial , Percepção Visual , Adulto , Cognição , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Esquizofrenia/diagnóstico , Resultado do Tratamento
20.
Psychopathology ; 50(1): 60-67, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28073112

RESUMO

BACKGROUND/AIMS: Perception of space and objects is a traditional focus within phenomenology, and disturbances in these aspects of perception among people with schizophrenia have long been discussed within phenomenological psychiatry. Despite this, there has been little empirical work on the causes and effects of most of these perceptual alterations in people with schizophrenia. Progress towards this goal can be accelerated by the use of EAWE (Examination of Anomalous World Experience), an interview-based tool to elicit, categorize, and quantify abnormal perceptual and other experiential phenomena. METHODS: In this brief paper, we review the main types of disturbances in space and object perception in schizophrenia - as described by phenomenologists, clinicians from other theoretical orientations, and experimental psychopathologists - as a first step in a research agenda to achieve a better integration of the clinical and experimental literatures. RESULTS/CONCLUSION: This review indicates that in some cases the cognitive and neurobiological mechanisms of altered space and object perception in schizophrenia are relatively well understood, while in other cases there exist only plausible hypotheses. In still other cases, however, almost nothing is known. Moreover, a fundamental hypothesis of phenomenological psychiatry - that perceptual changes are related to disturbances in the sense of self - has yet to be investigated actively. From this context, we offer suggestions for future research and suggest general research designs that may be useful for advancing progress in this area.


Assuntos
Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Neurociência Cognitiva , Humanos , Entrevista Psicológica , Percepção
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