White matter connectivity reductions in the pre-clinical continuum of psychosis: A connectome study.

Widespread white matter connectivity disruptions have commonly been reported in schizophrenia. However, it is questionable whether structural connectivity decline is specifically associated with schizophrenia or whether it extends along a continuum of psychosis into the healthy population. Elucidating brain structure changes associated with psychotic-like experiences in healthy individuals is insofar important as it is a necessary first step towards our understanding of brain pathology preceding florid psychosis. High resolution, multishell diffusion-weighted magnetic resonance images (MRI) were acquired from 89 healthy individuals. Whole-brain white matter fibre tracking was performed to quantify the strength of white matter connections. Network-based statistics were applied to white matter connections in a regression model in order to test for a linear relationship between streamline count and psychotic-like experiences. A significant subnetwork was identified whereby streamline count declined with increasing psychotic-like experiences. This network of structural connectivity reductions affected all cortical lobes, subcortical structures and the cerebellum and spanned along prominent association and commissural white matter pathways. A widespread network of linearly declining connectivity strength with increasing number of psychotic-like experiences was identified in healthy individuals. This finding is in line with white matter connectivity reductions reported from early to chronic stages of schizophrenia and might therefore aid the development of tools to identify individuals at risk of transitioning to psychosis.

Psychotic like experiences as part of a continuum of psychosis: Associations with effort-based decision-making and reward responsivity.

Research examining psychotic disorders typically involves comparison between individuals with a clinical disorder and healthy controls. However, research suggests that psychotic symptoms, such as delusions and hallucinations, may exist on a continuum ranging from variation in healthy individuals to diagnosable psychotic disorders. On this continuum, some individuals endorse occasional psychotic like experiences (PLEs) that do not cause sufficient impairment or distress to warrant a clinical diagnosis. Given this continuum model, one might expect to observe impairments in those with PLEs in the same behavioral domains impaired in schizophrenia. Thus, we examined two domains typically impaired in schizophrenia, effort allocation and reward responsivity, in a large university sample (n = 126). Participants completed tasks assessing effort-based decision-making, reward responsivity, and questionnaires assessing PLEs. Greater PLEs were associated with greater effort expenditure regardless of probability of receiving a reward or reward value. Higher PLEs were related to greater positive feelings when receiving rewards. Importantly, these relationships remained the same when controlling for other symptoms such as depression, anhedonia, and anxiety. These findings suggest that PLEs may be associated with hypersensitivity to reward at the less severe end of the psychotic continuum, with effort to attain a reward expended in a potentially inefficient manner. This pattern is consistent with models of hyperdopaminergic states in psychotic individuals not taking antipsychotic medications, given the role of dopamine in modulating effort allocation and reward anticipation.

Examining the continuum of psychosis: Frequency and characteristics of psychotic-like symptoms in relatives and non-relatives of patients with schizophrenia.

BACKGROUND: A key finding underlying the continuum of psychosis concept is the presence of psychotic-like experiences (PLEs) in healthy subjects. However, it remains uncertain to what extent these experiences are related to the genetic risk for schizophrenia and how far they actually resemble attenuated forms of psychotic symptoms. METHODS: Forty-nine adults with no history of mental illness in first-degree relatives and 59 siblings of patients with schizophrenia were rated on the psychosis section of the Computerized Diagnostic Interview Schedule IV (C DIS-IV) and the Rust Inventory of Schizotypal Cognitions (RISC). Those who rated positive on the CDIS-IV were re-interviewed using the lifetime version of the Present State Examination 9th edition (PSE-9) and the Structured interview for Schizotypy (SIS). RESULTS: Seventeen (34.69%) of the non-relatives and 22 (37.29%) of the relatives responded positively to one or more of the psychosis questions on the DIS. This difference was not significant. RISC scores were also similar between the groups. At follow-up interview with the PSE-9, 13/40 PLEs (32.50%) in the non-relatives were classified as possible or probable psychotic symptoms compared to 11/46 (23.91%) in the relatives. Using liberal symptom thresholds, 5 of those who attended the follow-up interview (2 non-relatives and 3 relatives) met SIS criteria for schizotypal personality disorder. CONCLUSIONS: Rates of PLEs, however considered, do not differ substantially between relatives and non-relatives of patients with schizophrenia. Only a minority of PLEs picked up by screening interviews resemble attenuated forms of psychotic symptoms.

Cortical Suppression to Delayed Self-Initiated Auditory Stimuli in Schizotypy: Neurophysiological Evidence for a Continuum of Psychosis.

Schizophrenia patients have been shown to exhibit subnormal levels of electrophysiological suppression to self-initiated, button press elicited sounds. These self-suppression deficits have been shown to improve following the imposition of a subsecond delay between the button press and the evoked sound. The current study aimed to investigate whether nonclinical individuals who scored highly on the personality dimension of schizotypy would exhibit similar patterns of self-suppression abnormalities to those exhibited in schizophrenia. Thirty-nine nonclinical individuals scoring above the median (High Schizotypy) and 41 individuals scoring below the median (Low Schizotypy) on the Schizotypal Personality Questionnaire (SPQ) underwent electroencephalographic recording. The amplitude of the N1-component was calculated while participants (1) listened to tones initiated by a willed button press and played back with varying delay periods between the button press and the tone (Active conditions) and (2) passively listened to a series of tones (Listen condition). N1-suppression was calculated by subtracting the amplitude of the N1-component of the auditory evoked potential in the Active condition from that of the Listen condition, while controlling for the activity evoked by the button press per se. The Low Schizotypy group exhibited significantly higher levels of N1-suppression to undelayed tones compared to the High Schizotypy group. Furthermore, while N1-suppression was found to decrease linearly with increasing delays between the button press and the tone in the Low Schizotypy group, this was not the case in the High Schizotypy group. The findings of this study suggest that nonclinical, highly schizotypal individuals exhibit subnormal levels of N1-suppression to undelayed self-initiated tones and an abnormal pattern of N1-suppression to delayed self-initiated tones. To the extent that these results are similar to those previously reported in patients with schizophrenia, these findings provide support for the existence of a neurophysiological "continuum of psychosis".

Subnormal sensory attenuation to self-generated speech in schizotypy: Electrophysiological evidence for a 'continuum of psychosis'.

BACKGROUND: A 'continuum of psychosis' refers to the concept that psychotic-like experiences occur to certain extents in the healthy population and to more severe extents in individuals with psychotic disorders. If this concept is valid, neurophysiological abnormalities exhibited by patients with schizophrenia should also be present, to some degree, in non-clinical individuals who score highly on the personality dimension of schizotypy. Patients with schizophrenia have consistently been shown to exhibit electrophysiological suppression abnormalities to self-generated speech. The present study aimed to investigate whether these electrophysiological suppression abnormalities were also present in non-clinical individuals who scored highly on schizotypy. METHODS: Thirty-seven non-clinical individuals scoring High (above median) and 37 individuals scoring Low (below median) on the Schizotypal Personality Questionnaire (SPQ; a commonly used schizotypy scale) underwent electroencephalographic (EEG) recording. The amplitude of the N1 component of the auditory-evoked potential was measured while participants (a) vocalized simple syllables (Talk condition), (b) passively listened to a recording of these vocalizations (Listen condition) and (c) listened to a recording of the vocalizations while simultaneously watching a video depicting the sound-wave of the forthcoming vocalizations, allowing them to be temporally predicted (Cued Listen condition). RESULTS: The Low Schizotypy group exhibited significantly reduced N1-amplitude in the Talk condition relative to both the Listen and Cued Listen conditions; that is, they exhibited significant N1-suppression. The High Schizotypy group exhibited significantly lower levels of N1-suppression compared to the Low Schizotypy group. Furthermore, while the Cued Listen condition induced significantly lower N1-amplitudes compared to the Listen condition in the Low Schizotypy group, this was not the case for the High Schizotypy group. CONCLUSIONS: The results suggest that non-clinical, highly schizotypal individuals exhibit subnormal levels of N1-suppression to self-generated speech, similar to the N1-suppression abnormalities which have previously been reported in patients with schizophrenia. This finding provides empirical support for the existence of a neurophysiological 'continuum of psychosis'.