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

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

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

Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is a recurrent genetic mutation that is highly penetrant for psychosis. Behavioral research suggests that 22q11DS patients exhibit a characteristic neurocognitive phenotype that includes differential impairment in spatial working memory (WM). Notably, spatial WM has also been proposed as an endophenotype for idiopathic psychotic disorder, yet little is known about the neurobiological substrates of WM in 22q11DS. In order to investigate the neural systems engaged during spatial WM in 22q11DS patients, we collected functional magnetic resonance imaging (fMRI) data while 41 participants (16 22q11DS patients, 25 demographically matched controls) performed a spatial capacity WM task that included manipulations of delay length and load level. Relative to controls, 22q11DS patients showed reduced neural activation during task performance in the intraparietal sulcus (IPS) and superior frontal sulcus (SFS). In addition, the typical increases in neural activity within spatial WM-relevant regions with greater memory load were not observed in 22q11DS. We further investigated whether neural dysfunction during WM was associated with behavioral WM performance, assessed via the University of Maryland letter-number sequencing (LNS) task, and positive psychotic symptoms, assessed via the Structured Interview for Prodromal Syndromes (SIPS), in 22q11DS patients. WM load activity within IPS and SFS was positively correlated with LNS task performance; moreover, WM load activity within IPS was inversely correlated with the severity of unusual thought content and delusional ideas, indicating that decreased recruitment of working memory-associated neural circuitry is associated with more severe positive symptoms. These results suggest that 22q11DS patients show reduced neural recruitment of brain regions critical for spatial WM function, which may be related to characteristic behavioral manifestations of the disorder

Default mode network connectivity and reciprocal social behavior in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is a genetic mutation associated with disorders of cortical connectivity and social dysfunction. However, little is known about the functional connectivity (FC) of the resting brain in 22q11DS and its relationship with social behavior. A seed-based analysis of resting-state functional magnetic resonance imaging data was used to investigate FC associated with the posterior cingulate cortex (PCC), in (26) youth with 22qDS and (51) demographically matched controls. Subsequently, the relationship between PCC connectivity and Social Responsiveness Scale (SRS) scores was examined in 22q11DS participants. Relative to 22q11DS participants, controls showed significantly stronger FC between the PCC and other default mode network (DMN) nodes, including the precuneus, precentral gyrus and left frontal pole. 22q11DS patients did not show age-associated FC changes observed in typically developing controls. Increased connectivity between PCC, medial prefrontal regions and the anterior cingulate cortex, was associated with lower SRS scores (i.e. improved social competence) in 22q11DS. DMN integrity may play a key role in social information processing. We observed disrupted DMN connectivity in 22q11DS, paralleling reports from idiopathic autism and schizophrenia. Increased strength of long-range DMN connectivity was associated with improved social functioning in 22q11DS. These findings support a \u27developmental-disconnection\u27 hypothesis of symptom development in this disorder

Memory systems in schizophrenia: Modularity is preserved but deficits are generalized

OBJECTIVE: Schizophrenia patients exhibit impaired working and episodic memory, but this may represent generalized impairment across memory modalities or performance deficits restricted to particular memory systems in subgroups of patients. Furthermore, it is unclear whether deficits are unique from those associated with other disorders. METHOD: Healthy controls (n=1101) and patients with schizophrenia (n=58), bipolar disorder (n=49) and attention-deficit-hyperactivity-disorder (n=46) performed 18 tasks addressing primarily verbal and spatial episodic and working memory. Effect sizes for group contrasts were compared across tasks and the consistency of subjects\u27 distributional positions across memory domains was measured. RESULTS: Schizophrenia patients performed poorly relative to the other groups on every test. While low to moderate correlation was found between memory domains (r=.320), supporting modularity of these systems, there was limited agreement between measures regarding each individual\u27s task performance (ICC=.292) and in identifying those individuals falling into the lowest quintile (kappa=0.259). A general ability factor accounted for nearly all of the group differences in performance and agreement across measures in classifying low performers. CONCLUSIONS: Pathophysiological processes involved in schizophrenia appear to act primarily on general abilities required in all tasks rather than on specific abilities within different memory domains and modalities. These effects represent a general shift in the overall distribution of general ability (i.e., each case functioning at a lower level than they would have if not for the illness), rather than presence of a generally low-performing subgroup of patients. There is little evidence that memory impairments in schizophrenia are shared with bipolar disorder and ADHD

Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS Consensus Cognitive Battery: A Multisite Study.

The aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores and percentile ranks.A total of 502 healthy participants (aged 11-19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were included in this multisite study. Regression-predicted means for the MCCB tests, except the social cognition subtest, were calculated using the MCCB test scores as outcome variables and age, age2, sex, age × sex as predictors. The regression-predicted means for each combination of age and sex were added with the residuals from the entire cohort to yield the expected distribution of that group. Age effects were examined using regression models with age and age2 as predictors. Sex differences were examined using Student\u27s t-tests.Significant positive age effects were found for all tests, except for the Brief Visuospatial Memory Test, revised (BVMT-R; measure of visual learning). Females performed significantly better than males on BACS Symbol coding (measure of speed of processing) and BVMT-R, while males performed significantly better than females on NAB Mazes (measure of reasoning and problem solving). Based on the regression-predicted distributions of scores, 19 standardized scoring tables for each test and domain were created.With the results from this study, we have developed an accessible standardized data set of healthy adolescent test performance for the MCCB

Predicting risky choices from brain activity patterns

Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects performing a naturalistic risk-taking task and used a classification analysis approach to predict whether individuals would choose risky or safe options on upcoming trials. We were able to predict choice category successfully in 71.8% of cases. Searchlight analysis revealed a network of brain regions where activity patterns were reliably predictive of subsequent risk-taking behavior, including a number of regions known to play a role in control processes. Searchlights with significant predictive accuracy were primarily located in regions more active when preparing to avoid a risk than when preparing to engage in one, suggesting that risk taking may be due, in part, to a failure of the control systems necessary to initiate a safe choice. Additional analyses revealed that subject choice can be successfully predicted with minimal decrements in accuracy using highly condensed data, suggesting that information relevant for risky choice behavior is encoded in coarse global patterns of activation as well as within highly local activation within searchlights

Intracranial and subcortical volumes in adolescents with early‐onset psychosis: A multisite mega‐analysis from the ENIGMA consortium

Early‐onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early‐onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early‐onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early‐onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed‐effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = −0.39) and hippocampal (d = −0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early‐onset schizophrenia (d = −0.34) and affective psychosis (d = −0.42), and early‐onset schizophrenia showed lower hippocampal (d = −0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = −0.42). The findings demonstrate a similar pattern of brain alterations in early‐onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early‐onset psychosis