Examining the Psychosis Continuum

The notion that psychosis may exist on a continuum with normal experience has been proposed in multiple forms throughout the history of psychiatry. However, in recent years there has been an exponential increase in efforts aimed at elucidating what has been termed the \u27psychosis continuum\u27. The present review seeks to summarize some of the more basic characteristics of this continuum and to present some of the recent findings that provide support for its validity. While there is still considerable work to be done, the emerging data holds considerable promise for advancing our understanding of both risk and resilience to psychiatric disorders characterized by psychosis

The relation between childhood maltreatment and psychosis in patients with schizophrenia and non-psychiatric controls

Several lines of evidence suggest that childhood maltreatment is associated with an increased risk for both psychotic disorders and subclinical psychotic-like experiences in the general population. Few studies, however, have sought to examine whether the strength of this relationship is comparable across patient and non-patient groups. The present study sought to compare the strength of the association between childhood maltreatment and self-reported psychotic symptoms in 447 healthy adult volunteers and 184 stable outpatients with schizophrenia or schizoaffective disorder. Strong positive correlations between childhood maltreatment and self-reported symptoms were observed in both groups. Although patients scored significantly higher than controls on both history of childhood maltreatment and self-reported symptoms, the strength of the relationship did not differ between groups. These data provide strong support for etiological continuity between subclinical psychotic symptoms and psychotic disorders. (C) 2014 Elsevier B.V. All rights reserved

Evidence from structural and diffusion tensor imaging for frontotemporal deficits in psychometric schizotypy

BACKGROUND: Previous studies of nonclinical samples exhibiting schizotypal traits have provided support for the existence of a continuous distribution of psychotic symptoms in the general population. Few studies, however, have examined the neural correlates of psychometric schizotypy using structural and diffusion tensor imaging (DTI). METHODS: Healthy volunteers between the ages of 18 and 68 were recruited from the community and assessed using the Schizotypal Personality Questionnaire and received structural and DTI exams. Participants with high (N = 67) and low (N = 71) psychometric schizotypy were compared on gray and white matter volume, and cortical thickness in frontal and temporal lobe regions and on fractional anisotropy (FA) within 5 association tracts traversing the frontal and temporal lobes. RESULTS: Higher levels of schizotypy were associated with lower overall volumes of gray matter in both the frontal and temporal lobes and lower gray matter thickness in the temporal lobe. Regionally specific effects were evident in both white matter and gray matter volume of the rostral middle frontal cortex and gray matter volume in the pars orbitalis. Moreover, relative to individuals who scored low, those who scored high in schizotypy had lower FA in the inferior fronto-occipital fasciculus as well as greater asymmetry (right \u3e left) in the uncinate fasciculus. CONCLUSIONS: These findings are broadly consistent with recent data on the neurobiological correlates of psychometric schizotypy as well as findings in schizotypal personality disorder and schizophrenia and suggest that frontotemporal lobe dysfunction may represent a core component of the psychosis phenotype

Subcortical modulation in auditory processing and auditory hallucinations

Hearing perception in individuals with auditory hallucinations has not been well studied. Auditory hallucinations have previously been shown to involve primary auditory cortex activation. This activation suggests that auditory hallucinations activate the terminal of the auditory pathway as if auditory signals are submitted from the cochlea, and that a hallucinatory event is therefore perceived as hearing. The primary auditory cortex is stimulated by some unknown source that is outside of the auditory pathway. The current study aimed to assess the outcomes of stimulating the primary auditory cortex through the auditory pathway in individuals who have experienced auditory hallucinations. Sixteen patients with schizophrenia underwent functional magnetic resonance imaging (fMRI) sessions, as well as hallucination assessments. During the fMRI session, auditory stimuli were presented in one-second intervals at times when scanner noise was absent. Participants listened to auditory stimuli of sine waves (SW) (4-5.5kHz), English words (EW), and acoustically reversed English words (arEW) in a block design fashion. The arEW were employed to deliver the sound of a human voice with minimal linguistic components. Patients\u27 auditory hallucination severity was assessed by the auditory hallucination item of the Brief Psychiatric Rating Scale (BPRS). During perception of arEW when compared with perception of SW, bilateral activation of the globus pallidus correlated with severity of auditory hallucinations. EW when compared with arEW did not correlate with auditory hallucination severity. Our findings suggest that the sensitivity of the globus pallidus to the human voice is associated with the severity of auditory hallucination

MATRICS cognitive consensus battery (MCCB) performance in children, adolescents, and young adults

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 23 years. 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. (C) 2013 Elsevier B.V. All rights reserved

Functional Activation During a Cognitive Control Task in Healthy Youth Specific to Externalizing or Internalizing Behaviors

© 2017 Society of Biological Psychiatry Background: Externalizing behaviors are negative behaviors expressed outwardly, including rule breaking, aggression, and risk taking; internalizing behaviors are expressed inwardly, including depression, withdrawal, and anxiety. Such behavior can cause problems in early life and predict difficulties across the lifespan. There is evidence for a relationship between executive function and both externalizing and internalizing. However, although these behaviors occur along a spectrum, there is little neuroimaging research on this relationship in typically developing youth. Methods: We assessed 41 youth (10–19 years of age) using the Multi-Source Interference Task during functional magnetic resonance imaging and related the findings to self-reported externalizing and internalizing scores as measured by the Youth Self-Report. We performed a general linear model using FSL software; externalizing, internalizing, age, and sex were included in the model. Results: Compared to the control condition, the more difficult Multi-Source Interference Task interference condition was associated with greater engagement of the frontoparietal cognitive control system and decreased engagement of regions in the default mode network, based on a cluster threshold of Z \u3e 3.1 (p =.01). When we examined regions uniquely associated with either internalizing or externalizing, we found that within the same group of subjects, higher externalizing behavior was associated with hyperactivity in the parietal lobe; in contrast, higher internalizing behavior was associated with increased activation in the medial prefrontal cortex. Conclusions: These findings suggest that externalizing and internalizing may be associated with altered, but different, patterns of activation during cognitive control. This has implications for our understanding of the relationship between cognitive control and behavioral problems in youth

Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value=2.57x10-4) and rs9960767 (p-value=6.23x10-4). Replication in an independent sample of 16-year-olds (N=3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed