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Negative symptoms in youths with psychosis spectrum features: complementary scales in relation to neurocognitive performance and function.

ABSTRACT: Negative symptoms in schizophrenia are related to impaired functioning. The presence of negative symptoms in early phases of psychosis in individuals at clinical risk is receiving increased attention.We evaluated comprehensively a sample of 92 young people (age range 15-25) applying the Clinical Assessment Interview for Negative Symptoms (CAINS), adapted for youth. Individuals at clinical high risk (CHR, n=29) were compared to individuals with schizophrenia (SZ, n=31) and normal controls (NC, n=32). In addition to the CAINS, participants were assessed with the Structured Interview for Prodromal Syndromes (SIPS), enabling examination of the relations among scales, as well as the Penn Computerized Neurocognitive Battery (CNB), to examine association with cognitive performance, and the Global Assessment of Function (GAF) to assess overall functioning.The CHR group was intermediate to SZ and NC on nearly all clinical measures. Negative symptoms on the CAINS correlated better with negative than with other symptoms on the SIPS and were associated with neurocognitive deficits and poorer functioning.This study illustrates the feasibility of in-depth evaluation of negative symptoms in youth and indicates that these symptoms are present already in the at-risk state and relate to impaired cognition and functioning.

SUBMITTER: Gur RE

PROVIDER: S-EPMC4512843 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Negative symptoms in youths with psychosis spectrum features: complementary scales in relation to neurocognitive performance and function.

Gur Raquel E RE March Mary M Calkins Monica E ME Weittenhiller Lauren L Wolf Daniel H DH Turetsky Bruce I BI Gur Ruben C RC

Schizophrenia research 20150617 1-3

<h4>Background</h4>Negative symptoms in schizophrenia are related to impaired functioning. The presence of negative symptoms in early phases of psychosis in individuals at clinical risk is receiving increased attention.<h4>Methods</h4>We evaluated comprehensively a sample of 92 young people (age range 15-25) applying the Clinical Assessment Interview for Negative Symptoms (CAINS), adapted for youth. Individuals at clinical high risk (CHR, n=29) were compared to individuals with schizophrenia (SZ ...[more]

PMID: 26093946

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Project description:ObjectiveThe authors created normative growth charts of amygdala functional connectivity in typically developing youths, assessed age-associated deviations of these trajectories in youths with psychosis spectrum disorders, and explored how these disruptions are related to clinical symptomatology.MethodsResting-state functional neuroimaging data from four samples (three cross-sectional, one longitudinal) were collected for 1,062 participants 10-25 years of age (622 typically developing control youths, 194 youths with psychosis spectrum disorders, and 246 youths with other psychopathology). The authors assessed deviations in the psychosis spectrum and other psychopathology groups in age-related changes in resting-state functional MRI amygdala-to-whole brain connectivity from a normative range derived from the control youths. The authors explored relationships between age-associated deviations in amygdala connectivity and positive symptoms in the psychosis spectrum group.ResultsNormative trajectories demonstrated significant age-related decreases in centromedial amygdala connectivity with distinct regions of the brain. In contrast, the psychosis spectrum group failed to exhibit any significant age-associated changes between the centromedial amygdala and the prefrontal cortices, striatum, occipital cortex, and thalamus (all q values <0.1). Age-associated deviations in centromedial amygdala-striatum and centromedial amygdala-occipital connectivity were unique to the psychosis spectrum group and were not observed in the other psychopathology group. Exploratory analyses revealed that greater age-related deviation in centromedial amygdala-thalamus connectivity was significantly associated with increased severity of positive symptoms (r=0.19; q=0.05) in the psychosis spectrum group.ConclusionsUsing neurodevelopmental growth charts to identify a lack of normative development of amygdala connectivity in youths with psychosis spectrum disorders may help us better understand the neural basis of affective impairments in psychosis, informing prediction models and interventions.

Project description:The continuum view of the psychosis spectrum (PS) implies that, in population-based samples, PS symptoms should be associated with neural abnormalities similar to those found in help-seeking clinical risk individuals and in schizophrenia. To our knowledge, functional neuroimaging has not previously been applied in large population-based PS samples and can help us understand the neural architecture of psychosis more broadly and identify brain phenotypes beyond symptoms that are associated with the extended psychosis phenotype.To examine the categorical and dimensional relationships of PS symptoms to prefrontal hypoactivation during working memory and to amygdala hyperactivation during threat emotion processing.The Philadelphia Neurodevelopmental Cohort is a genotyped, prospectively accrued, population-based sample of almost 10,000 youths who received a structured psychiatric evaluation and a computerized neurocognitive battery. The study was conducted at an academic and children's hospital health care network, between November 1, 2009 to November 30, 2011. A subsample of 1445 youths underwent neuroimaging, including functional magnetic resonance imaging tasks examined herein. Participants were youth aged 11 to 22 years old identified through structured interview as having PS features (PS group) (n = 260) and typically developing (TD) comparison youth without significant psychopathology (TD group) (n = 220).Two functional magnetic resonance imaging paradigms were used: a fractal n-back working memory task probing executive system function and an emotion identification task probing amygdala responses to threatening faces.In the n-back task, working memory evoked lower activation in the PS group than the TD group throughout the executive control circuitry, including dorsolateral prefrontal cortex (cluster-corrected P <?.05). Within the PS group, dorsolateral prefrontal cortex activation correlated with cognitive deficits (r =?.32, P <?.001), but no correlation was found with positive symptom severity. During emotion identification, PS demonstrated elevated responses to threatening facial expressions in amygdala, as well as left fusiform cortex and right middle frontal gyrus (cluster-corrected P <?.05). The response in the amygdala correlated with positive symptom severity (r =?.16, P =?.01) but not with cognitive deficits.The pattern of functional abnormalities observed in the PS group is similar to that previously found in schizophrenia and help-seeking risk samples. Specific circuit dysfunction during cognitive and emotion-processing tasks is present early in the development of psychopathology and herein could not be attributed to chronic illness or medication confounds. Hypoactivation in executive circuitry and limbic hyperactivation to threat could reflect partly independent risk factors for PS symptoms, with the former relating to cognitive deficits that increase the risk for developing psychotic symptoms and the latter contributing directly to positive psychotic symptoms.

Project description:ImportanceStructural brain abnormalities are prominent in psychotic disorders, including schizophrenia. However, it is unclear when aberrations emerge in the disease process and if such deficits are present in association with less severe psychosis spectrum (PS) symptoms in youth.ObjectiveTo investigate the presence of structural brain abnormalities in youth with PS symptoms.Design, setting, and participantsThe Philadelphia Neurodevelopmental Cohort is a prospectively accrued, community-based sample of 9498 youth who received a structured psychiatric evaluation. A subsample of 1601 individuals underwent neuroimaging, including structural magnetic resonance imaging, at an academic and children's hospital health care network between November 1, 2009, and November 30, 2011.Main outcomes and measuresMeasures of brain volume derived from T1-weighted structural neuroimaging at 3 T. Analyses were conducted at global, regional, and voxelwise levels. Regional volumes were estimated with an advanced multiatlas regional segmentation procedure, and voxelwise volumetric analyses were conducted as well. Nonlinear developmental patterns were examined using penalized splines within a general additive model. Psychosis spectrum (PS) symptom severity was summarized using factor analysis and evaluated dimensionally.ResultsFollowing exclusions due to comorbidity and image quality assurance, the final sample included 791 participants aged youth 8 to 22 years. Fifty percent (n = 393) were female. After structured interviews, 391 participants were identified as having PS features (PS group) and 400 participants were identified as typically developing comparison individuals without significant psychopathology (TD group). Compared with the TD group, the PS group had diminished whole-brain gray matter volume (P = 1.8 × 10-10) and expanded white matter volume (P = 2.8 × 10-11). Voxelwise analyses revealed significantly lower gray matter volume in the medial temporal lobe (maximum z score = 5.2 and cluster size of 1225 for the right and maximum z score = 4.5 and cluster size of 310 for the left) as well as in frontal, temporal, and parietal cortex. Volumetric reduction in the medial temporal lobe was correlated with PS symptom severity.Conclusions and relevanceStructural brain abnormalities that have been commonly reported in adults with psychosis are present early in life in youth with PS symptoms and are not due to medication effects. Future longitudinal studies could use the presence of such abnormalities in conjunction with clinical presentation, cognitive profile, and genomics to predict risk and aid in stratification to guide early interventions.

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Negative symptoms in youths with psychosis spectrum features: complementary scales in relation to neurocognitive performance and function.

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Negative symptoms in youths with psychosis spectrum features: complementary scales in relation to neurocognitive performance and function.

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