Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: ...The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology.
•7 T fMRI & MRS data from controls, biological relatives, and people with psychosis.•FMRI tasks focused on visual perception.•MRS data collected from occipital and prefrontal regions.•88% of data ...sets passed all quality checks.•Data and code are publicly available to promote future research.
Visual perception is abnormal in psychotic disorders such as schizophrenia. In addition to hallucinations, laboratory tests show differences in fundamental visual processes including contrast sensitivity, center-surround interactions, and perceptual organization. A number of hypotheses have been proposed to explain visual dysfunction in psychotic disorders, including an imbalance between excitation and inhibition. However, the precise neural basis of abnormal visual perception in people with psychotic psychopathology (PwPP) remains unknown. Here, we describe the behavioral and 7 tesla MRI methods we used to interrogate visual neurophysiology in PwPP as part of the Psychosis Human Connectome Project (HCP). In addition to PwPP (n = 66) and healthy controls (n = 43), we also recruited first-degree biological relatives (n = 44) in order to examine the role of genetic liability for psychosis in visual perception. Our visual tasks were designed to assess fundamental visual processes in PwPP, whereas MR spectroscopy enabled us to examine neurochemistry, including excitatory and inhibitory markers. We show that it is feasible to collect high-quality data across multiple psychophysical, functional MRI, and MR spectroscopy experiments with a sizable number of participants at a single research site. These data, in addition to those from our previously described 3 tesla experiments, will be made publicly available in order to facilitate further investigations by other research groups. By combining visual neuroscience techniques and HCP brain imaging methods, our experiments offer new opportunities to investigate the neural basis of abnormal visual perception in PwPP.
Schizophrenia is characterized by abnormal brain structure such as global reductions in gray matter volume. Machine learning models trained to estimate the age of brains from structural neuroimaging ...data consistently show advanced brain-age to be associated with schizophrenia. Yet, it is unclear whether advanced brain-age is specific to schizophrenia compared to other psychotic disorders, and whether evidence that brain structure is "older" than chronological age actually reflects neurodevelopmental rather than atrophic processes. It is also unknown whether advanced brain-age is associated with genetic liability for psychosis carried by biological relatives of people with schizophrenia. We used the Brain-Age Regression Analysis and Computation Utility Software (BARACUS) prediction model and calculated the residualized brain-age gap of 332 adults (163 individuals with psychotic disorders: 105 schizophrenia, 17 schizoaffective disorder, 41 bipolar I disorder with psychotic features; 103 first-degree biological relatives; 66 controls). The model estimated advanced brain-ages for people with psychosis in comparison to controls and relatives, with no differences among psychotic disorders or between relatives and controls. Specifically, the model revealed an enlarged brain-age gap for schizophrenia and bipolar disorder with psychotic features. Advanced brain-age was associated with lower cognitive and general functioning in the full sample. Among relatives, cognitive performance and schizotypal symptoms were related to brain-age gap, suggesting that advanced brain-age is associated with the subtle expressions associated with psychosis. Exploratory longitudinal analyses suggested that brain aging was not accelerated in individuals with a psychotic disorder. In sum, we found that people with psychotic disorders, irrespective of specific diagnosis or illness severity, show indications of non-progressive, advanced brain-age. These findings support a transdiagnostic, neurodevelopmental formulation of structural brain abnormalities in psychotic psychopathology.
Proton-Magnetic Resonance Spectroscopy (1H-MRS) may serve as an important tool for identifying biomarkers that aid the understanding of early psychosis, as development of this condition may be ...associated with metabolite concentration changes that reflect an alteration in glutamatergic mechanisms. The current study explored 1H-MRS metabolite concentrations in the striatum and anterior cingulate cortex (ACC) as potential biomarkers of psychosis-risk symptom severity. In a sample of 12 adolescents at clinical high-risk for psychosis, the subclinical symptom of grandiosity significantly correlated with glutamate in the ACC. Striatal glutathione, a marker of oxidative stress linked to the glutamatergic system, significantly correlated with grandiosity. Anterior cingulate glutathione significantly correlated with grandiosity and disorganized communication. These findings suggest that within a small sample of young people at clinical high-risk, glutamatergic metabolites are correlated with symptomatology generally predictive of conversion to psychosis. These mechanisms may serve as relevant biomarkers for facilitating prediction of symptom severity and providing insight into the etiology of early psychosis.
•A sample of 12 adolescents at clinical high risk for psychosis were scanned.•Grandiosity correlated with glutamate in the anterior cingulate cortex (ACC).•Grandiosity correlated with striatal and anterior cingulate glutathione.•Disorganized communication correlated with glutathione in the ACC.•Glutamatergic metabolites may be biomarkers for early illness symptom severity.
Background:
Current methods to identify people with psychosis risk involve administration of specialized tools such as the Structured Interview for Psychosis-Risk Syndromes (SIPS), but these methods ...have not been widely adopted. Validation of a more multipurpose assessment tool—such as the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS)—may increase the scope of identification efforts.
Methods:
We assessed the correspondence between SIPS-determined clinical high risk/early psychosis (CHR/early psychosis) status and K-SADS psychosis screen (child and parent reports and their combination) in a sample of 147 help-seeking individuals aged 12–25. Detailed classification results are reported.
Results:
Both the child and parent interviews on the K-SADS psychosis screen were strongly predictive of CHR/early psychosis status, although parent reports contributed no significant additional information beyond child reports. Across informants, the presence of either subthreshold hallucinations or subthreshold delusions was highly suggestive of CHR/early psychosis status as determined by SIPS interview (78% (child) and 74% (parent) accuracy).
Conclusions:
Subthreshold scores on the two-item K-SADS psychosis screen may be good indicators of the presence or absence of early signs of psychosis. The option of using a non-specialized assessment such as the K-SADS as a staged approach to assess for CHR/early psychosis status could increase rates of early psychosis screening and treatment.
Abstract
Background
Psychotic disorders, including schizophrenia and bipolar disorder with psychotic features, can be conceptualized in a dimensional rather than categorical way. Such disorders might ...share similarities in illness pathophysiology. Disruptions in certain neurotransmitter systems (aberrant dopamine; hypo-functioning glutamatergic NMDA receptors) are thought to be involved in the development of psychosis. Whether such neurotransmitters fluctuate in tandem with psychotic symptom severity remains unclear. We sought to examine dimensional symptom severity of psychosis in relation to neurochemical concentrations using magnetic resonance spectroscopy, which allows for the quantification of neurochemicals.
Methods
As part of the ongoing Psychosis Human Connectome Project, we acquired MR spectroscopy data at 7 Tesla, which has better spectral resolution in general than data acquired at lower field-strengths. Using a STEAM sequence, we measured both excitatory (glutamate) and inhibitory metabolites (Gamma-Aminobutyric Acid; GABA) in the prefrontal cortex among individuals with psychosis (n=18) and healthy control participants (n=12). In order to explore potential genetic liability, we also studied first-degree biological relatives of individuals with a psychotic disorder (n=8).
Results
Among individuals with psychosis, we found a significant inverse correlation between glutamate and disorientation as measured by the Brief Psychiatric Rating Scale (BPRS; r = -.61, p = .004). Among the full sample with good-quality imaging data (N=30), we found a significant positive correlation between GABA and cognitive-perceptual disturbances as measured by the Schizotypal Personality Questionnaire (SPQ; r = .40, p = .030).
Discussion
More severe psychotic-like symptoms corresponded with lower concentrations of the excitatory neurotransmitter glutamate and higher concentrations of inhibitory GABA. These findings suggest that an imbalance in excitatory and inhibitory neurotransmitters may underlie psychotic-like symptoms that are present in a range of clinical and non-clinical populations. As we continue to collect data, we will increase our sample size which will enable us to examine whether concentrations of these metabolites differ across individuals affected by psychotic illness, those carrying genetic liability for such disorders, and non-psychiatric control participants.
Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other ...disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation.
We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI.
PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation.
Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.
Abstract The development of widely used interview tools has helped to standardize the criteria for a “clinical high risk” syndrome, thus enabling advances in efforts to develop interventions for this ...phase of illness. These assessments, however, are burdensome to administer and not likely to be adopted for widespread use. Scalable early intervention depends on the availability of brief, low-cost assessment tools that can serve to screen populations of interest or triage treatment-seekers toward specialized care. The current study examines the sensitivity, specificity, and predictive strength of three self-report measures (Prime Screen—Revised, Prodromal Questionnaire—Brief, and Youth Psychosis at Risk Questionnaire—Brief) with regard to psychosis onset and symptom persistence over six months of follow-up within an indicated sample of 54 adolescents and young adults ages 12–22. Within this sample, all three measures demonstrated excellent sensitivity to emerging psychosis and strong agreement with clinician evaluations of attenuated psychosis symptoms. Additionally, all screeners obtained negative predictive values of 1.00 with regard to psychosis onset, indicating that an individual scoring below the recommended threshold score would be extremely unlikely to develop psychosis over the following six months. The longitudinal validation of psychosis risk screening tools constitutes an important step toward establishing a standard of care for early identification and monitoring in this vulnerable population.
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