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1.
Schizophr Bull ; 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32648913

RESUMO

Research suggests that early identification and intervention with individuals at clinical high risk (CHR) for psychosis may be able to improve the course of illness. The first generation of studies suggested that the identification of CHR through the use of specialized interviews evaluating attenuated psychosis symptoms is a promising strategy for exploring mechanisms associated with illness progression, etiology, and identifying new treatment targets. The next generation of research on psychosis risk must address two major limitations: (1) interview methods have limited specificity, as recent estimates indicate that only 15%-30% of individuals identified as CHR convert to psychosis and (2) the expertise needed to make CHR diagnosis is only accessible in a handful of academic centers. Here, we introduce a new approach to CHR assessment that has the potential to increase accessibility and positive predictive value. Recent advances in clinical and computational cognitive neuroscience have generated new behavioral measures that assay the cognitive mechanisms and neural systems that underlie the positive, negative, and disorganization symptoms that are characteristic of psychotic disorders. We hypothesize that measures tied to symptom generation will lead to enhanced sensitivity and specificity relative to interview methods and the cognitive intermediate phenotype measures that have been studied to date that are typically indicators of trait vulnerability and, therefore, have a high false positive rate for conversion to psychosis. These new behavioral measures have the potential to be implemented on the internet and at minimal expense, thereby increasing accessibility of assessments.

2.
Schizophr Res ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32593735

RESUMO

Early intervention in psychotic spectrum disorders is critical for maximizing key clinical outcomes. While there is some evidence for the utility of intervention during the prodromal phase of the illness, efficacy of interventions is difficult to assess without appropriate risk stratification. This will require biomarkers that robustly help to identify risk level and are also relatively easy to obtain. Recent work highlights the utility of computer-based behavioral tasks for understanding the pathophysiology of psychotic symptoms. Computational modeling of performance on such tasks may be particularly useful because they explicitly and formally link performance and symptom expression. Several recent studies have successfully applied principles of Bayesian inference to understanding the computational underpinnings of hallucinations. Within this framework, hallucinations are seen as arising from an over-weighting of prior beliefs relative to sensory evidence. This view is supported by recently-published data from two tasks: the Conditioned Hallucinations (CH) task, which determines the degree to which participants use expectations in detecting a target tone; and a Sine-Vocoded Speech (SVS) task, in which participants can use prior exposure to speech samples to inform their understanding of degraded speech stimuli. We administered both of these tasks to two samples of participants at clinical high risk for psychosis (CHR; N = 19) and healthy controls (HC; N = 17). CHR participants reported both more conditioned hallucinations and more pre-training SVS detection. In addition, relationships were found between participants' performance on both tasks. On computational modeling of behavior on the CH task, CHR participants demonstrate significantly poorer recognition of task volatility as well as a trend toward higher weighting of priors. A relationship was found between this latter effect and performance on both tasks. Taken together, these results support the assertion that these two tasks may be driven by similar latent factors in perceptual inference, and highlight the potential utility of computationally-based tasks in identifying risk.

3.
Schizophr Res ; 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32402605

RESUMO

BACKGROUND: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. METHOD: Response to points of critique. RESULTS: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma. DISCUSSION: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.

5.
Schizophr Bull ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32432706

RESUMO

Hallucinations-while often considered an indication of mental illness-are commonly experienced by those without a need for clinical care. These nonclinical voice-hearers offer an opportunity to investigate hallucinations in the absence of confounds inherent to the clinical state. Recent work demonstrates an association between auditory verbal hallucinations (AVH) and structural variability in paracingulate sulcus (PCS) of medial prefrontal cortex in a clinical population. However, before PCS length may be considered a biomarker for clinical hallucination risk, it is necessary to investigate PCS structure in a nonclinical population of voice-hearers with AVH phenomenology similar to those of their clinical counterparts. In the current study, PCS length was measured from T1-weighted structural MRI scans of four groups of participants: (1) voice-hearers with a psychotic disorder (n = 15); (2) voice-hearers without a psychotic disorder (n = 15); (3) nonvoice-hearers with a psychotic disorder (n = 14); and (4) nonvoice-hearers without a psychotic disorder (n = 15). There was a main effect of AVH status-but not psychosis-on right PCS length, with no interaction of AVH and psychosis. Participants with AVH exhibited reduced right PCS length compared to participants without AVH (mean reduction = 8.8 mm, P < 0.05). While past studies have demonstrated decreased PCS length in clinical voice-hearers, ours is the first demonstration that shorter right PCS extends to nonclinical voice-hearers. Our findings support the hypothesis that differences in PCS length are related to the propensity to hear voices and not to illness, consistent with a continuum model of voice-hearing.

6.
Schizophr Res ; 216: 443-449, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31806523

RESUMO

The recognition of a prodromal period preceding the onset of frank psychosis dates back to its first descriptions. Despite insights gained from a prospective approach to the study of the Clinical High Risk syndrome for psychosis (CHR-P), a prospectively-based understanding of the duration of the psychosis prodrome and the factors that may influence is not well-established. Here we analyze data from the second North American Prodrome Longitudinal Study (NAPLS-2) to characterize prodrome duration in those who converted to psychosis. Of the 764 participants identified as being at CHR-P, 94 converted to psychosis and 92 of these had recorded estimates of prodrome onset. Estimates of prodrome duration were derived from CHR-P syndrome onset and conversion dates from the Structured Interview for Psychosis-risk Syndromes. Results identified a mean prodrome duration of 21.6 months. Neither CHR-P sub-syndrome nor medication exposure was found to significantly influence prodrome duration in this sample. These results provide the most precise estimate of prodrome duration to date, although results are limited to prodromes identified by ascertainment as being at CHR-P. Our findings also suggest a rule of thirds with regard to prodrome duration in those followed for two years: one third of CHR-P patients who convert will do so by 1 year after CHR-P syndrome onset, another third 1-2 years after onset, and the final third more than 2 years after onset.

7.
Schizophr Res ; 216: 184-191, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31864837

RESUMO

Although the clinical high risk for psychosis (CHR) paradigm has become well-established over the past two decades, one key component has received surprisingly little investigative attention: the predictive validity of the criteria for conversion or transition to frank psychosis. The current study evaluates the predictive validity of the transition to psychosis as measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR individuals. Participants included 33 SIPS converters and 399 CHR non-converters both from the North American Prodromal Longitudinal Study (NAPLS-2), as well as a sample of 67 separately ascertained first-episode psychosis (FEP) patients from the STEP program. Comparisons were made at baseline and one-year follow-up on demographic, diagnostic stability (SCID), and available measurement domains relating to severity of illness (psychotropic medication, psychosocial treatment, and resource utilization). Principal findings are: 1) a large majority of cases in both SIPS converters (n = 27/33, 81.8%) and FEP (n = 57/67, 85.1%) samples met criteria for continued psychosis at one-year follow-up; 2) follow-up prescription rates for current antipsychotic medication were higher in SIPS converters (n = 17/32, 53.1%) compared to SIPS non-converters (n = 81/397, 20.4%), and similar as compared to FEP cases (n = 39/65, 60%); and 3) at follow-up, SIPS converters had higher rates of resource utilization (psychiatric hospitalizations, day hospital admissions, and ER visits) than SIPS non-converters and were similar to FEP in most categories. The results suggest that the SIPS definition of psychosis onset carries substantial predictive validity. Limitations and future directions are discussed.

9.
Schizophr Bull ; 45(45 Suppl 1): S56-S66, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715542

RESUMO

Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches. We begin with an overview of phenomenological observations on the interrelationships between auditory-verbal hallucinations (AVH) and delusional thoughts in general, before moving on to review several theoretical frameworks and empirical findings in the computational modeling of AVH. We then relate the computational models to the phenomenological accounts, with a special focus on AVH and delusions that involve the senses of agency and ownership of thought (delusions of thought interference). Finally, we offer some tentative directions for future research, emphasizing the importance of a mutual understanding between separate lines of inquiry.


Assuntos
Delusões/fisiopatologia , Alucinações/fisiopatologia , Modelos Teóricos , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Pensamento/fisiologia , Humanos
10.
Schizophr Bull ; 45(45 Suppl 1): S24-S31, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715545

RESUMO

That trauma can play a significant role in the onset and maintenance of voice-hearing is one of the most striking and important developments in the recent study of psychosis. Yet the finding that trauma increases the risk for hallucination and for psychosis is quite different from the claim that trauma is necessary for either to occur. Trauma is often but not always associated with voice-hearing in populations with psychosis; voice-hearing is sometimes associated with willful training and cultivation in nonclinical populations. This article uses ethnographic data among other data to explore the possibility of multiple pathways to voice-hearing for clinical and nonclinical individuals whose voices are not due to known etiological factors such as drugs, sensory deprivation, epilepsy, and so forth. We suggest that trauma sometimes plays a major role in hallucinations, sometimes a minor role, and sometimes no role at all. Our work also finds seemingly distinct phenomenological patterns for voice-hearing, which may reflect the different salience of trauma for those who hear voices.


Assuntos
Percepção Auditiva/fisiologia , Alucinações/etiologia , Alucinações/fisiopatologia , Trauma Psicológico/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Alucinações/classificação , Humanos , Trauma Psicológico/complicações , Transtornos Psicóticos/complicações
11.
Trends Cogn Sci ; 23(2): 114-127, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30583945

RESUMO

Hallucinations, perceptions in the absence of objectively identifiable stimuli, illustrate the constructive nature of perception. Here, we highlight the role of prior beliefs as a critical elicitor of hallucinations. Recent empirical work from independent laboratories shows strong, overly precise priors can engender hallucinations in healthy subjects and that individuals who hallucinate in the real world are more susceptible to these laboratory phenomena. We consider these observations in light of work demonstrating apparently weak, or imprecise, priors in psychosis. Appreciating the interactions within and between hierarchies of inference can reconcile this apparent disconnect. Data from neural networks, human behavior, and neuroimaging support this contention. This work underlines the continuum from normal to aberrant perception, encouraging a more empathic approach to clinical hallucinations.


Assuntos
Alucinações/fisiopatologia , Ilusões/fisiologia , Rede Nervosa/fisiopatologia , Percepção da Fala/fisiologia , Humanos
13.
15.
Behav Brain Sci ; 41: e83, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-31064450

RESUMO

Individual-specific predispositions may precede the cultural evolution of shamanism and may be linked to it via principles of predictive coding. We have used these principles to identify commonalities between clinical and shaman-like non-clinical voice-hearers. The author may find this approach helpful in relating the experiences of shamans to those of their clients.


Assuntos
Transtornos Psicóticos , Xamanismo , Evolução Cultural , Humanos
16.
Schizophr Bull ; 44(2): 254-263, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29036402

RESUMO

More than 20 years after the clinical high risk syndrome for psychosis (CHR) was first articulated, it remains controversial whether the CHR syndrome predicts onset of psychosis with diagnostic specificity or predicts pluripotential diagnostic outcomes. Recently, analyses of observational studies, however, have suggested that the CHR syndrome is not pluripotential for emergent diagnostic outcomes. The present report conducted additional analyses in previously reported samples to determine (1) whether comorbid disorders were more likely to persist in CHR patients compared to a comparison group of patients who responded to CHR recruitment efforts but did not meet criteria, termed help-seeking comparison subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups could be identified. All data were derived from 2 multisite studies in which DSM-IV structured diagnostic interviews were conducted at baseline and at 6-month intervals. Across samples we observed persistence of any nonpsychotic disorder in 80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with persistence of anxiety, depressive, and bipolar disorders considered separately were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful. These findings add additional support to the view that the CHR syndrome is not pluripotential for predicting various diagnostic outcomes but rather is specific for predicting emergent psychosis.


Assuntos
Transtornos de Ansiedade/diagnóstico , Transtorno Bipolar/diagnóstico , Transtornos do Humor/diagnóstico , Transtornos Psicóticos/diagnóstico , Adolescente , Adulto , Transtornos de Ansiedade/epidemiologia , Transtorno Bipolar/epidemiologia , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Transtornos do Humor/epidemiologia , Sintomas Prodrômicos , Prognóstico , Transtornos Psicóticos/epidemiologia , Risco , Síndrome , Adulto Jovem
17.
Schizophr Bull ; 43(1): 84-98, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28053132

RESUMO

Hearing voices that are not present is a prominent symptom of serious mental illness. However, these experiences may be common in the non-help-seeking population, leading some to propose the existence of a continuum of psychosis from health to disease. Thus far, research on this continuum has focused on what is impaired in help-seeking groups. Here we focus on protective factors in non-help-seeking voice-hearers. We introduce a new study population: clairaudient psychics who receive daily auditory messages. We conducted phenomenological interviews with these subjects, as well as with patients diagnosed with a psychotic disorder who hear voices, people with a diagnosis of a psychotic disorder who do not hear voices, and matched control subjects (without voices or a diagnosis). We found the hallucinatory experiences of psychic voice-hearers to be very similar to those of patients who were diagnosed. We employed techniques from forensic psychiatry to conclude that the psychics were not malingering. Critically, we found that this sample of non-help-seeking voice hearers were able to control the onset and offset of their voices, that they were less distressed by their voice-hearing experiences and that, the first time they admitted to voice-hearing, the reception by others was much more likely to be positive. Patients had much more negative voice-hearing experiences, were more likely to receive a negative reaction when sharing their voices with others for the first time, and this was subsequently more disruptive to their social relationships. We predict that this sub-population of healthy voice-hearers may have much to teach us about the neurobiology, cognitive psychology and ultimately the treatment of voices that are distressing.


Assuntos
Percepção Auditiva/fisiologia , Alucinações/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Adulto , Transtorno da Personalidade Borderline/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno da Personalidade Esquizotípica/fisiopatologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-28626813

RESUMO

The problem of whether and how information is integrated across hierarchical brain networks embodies a fundamental tension in contemporary cognitive neuroscience, and by extension, cognitive neuropsychiatry. Indeed, the penetrability of perceptual processes in a 'top-down' manner by higher-level cognition-a natural extension of hierarchical models of perception-may contradict a strictly modular view of mental organization. Furthermore, some in the cognitive science community have challenged cognitive penetration as an unlikely, if not impossible, process. We review the evidence for and against top-down influences in perception, informed by a predictive coding model of perception and drawing heavily upon the literature of computational neuroimaging. We extend these findings to propose a way in which these processes may be altered in mental illness. We propose that hallucinations - perceptions without stimulus - can be understood as top-down effects on perception, mediated by inappropriate perceptual priors.

19.
Psychopathology ; 48(6): 376-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26361209

RESUMO

BACKGROUND: Ketamine, the NMDA glutamate receptor antagonist drug, is increasingly employed as an experimental model of psychosis in healthy volunteers. At subanesthetic doses, it safely and reversibly causes delusion-like ideas, amotivation and perceptual disruptions reminiscent of the aberrant salience experiences that characterize first-episode psychosis. However, auditory verbal hallucinations, a hallmark symptom of schizophrenia, have not been reported consistently in healthy volunteers even at high doses of ketamine. SAMPLING AND METHODS: Here we present data from a set of healthy participants who received moderately dosed, placebo-controlled ketamine infusions in the reduced stimulation environment of the magnetic resonance imaging (MRI) scanner. We highlight the phenomenological experiences of 3 participants who experienced particularly vivid hallucinations. RESULTS: Participants in this series reported auditory verbal and musical hallucinations at a ketamine dose that does not induce auditory hallucination outside of the scanner. CONCLUSIONS: We interpret the observation of ketamine-induced auditory verbal hallucinations in the context of the reduced perceptual environment of the MRI scanner and offer an explanation grounded in predictive coding models of perception and psychosis - the brain fills in expected perceptual inputs, and it does so more in situations of altered perceptual input. The altered perceptual input of the MRI scanner creates a mismatch between top-down perceptual expectations and the heightened bottom-up signals induced by ketamine. Such circumstances induce aberrant percepts, including musical and auditory verbal hallucinations. We suggest that these circumstances might represent a useful experimental model of auditory verbal hallucinations and highlight the impact of ambient sensory stimuli on psychopathology.


Assuntos
Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiopatologia , Alucinações/induzido quimicamente , Ketamina/efeitos adversos , Transtornos Psicóticos/tratamento farmacológico , Adulto , Delusões/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Alucinações/diagnóstico , Humanos , Ketamina/administração & dosagem , Imagem por Ressonância Magnética , Masculino , Percepção , Transtornos Psicóticos/patologia , Adulto Jovem
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