Dataset Information

Hippocampal Shape Abnormalities Predict Symptom Progression in Neuroleptic-Free Youth at Ultrahigh Risk for Psychosis.

ABSTRACT:

Introduction

Hippocampal abnormalities have been widely studied in schizophrenia spectrum populations including those at ultrahigh risk (UHR) for psychosis. There have been inconsistent findings concerning hippocampal morphology prior to and during the transition to psychosis, and little is known about how specific subregions are related to the symptom progression.

Methods

A total of 80 participants (38 UHR and 42 healthy controls) underwent a 3T MRI scan, as well as structured clinical interviews. Shape analysis of hippocampi was conducted with FSL/FIRST vertex analysis to yield a localized measure of shape differences between groups. A subgroup of the sample (24 UHR and 24 controls) also returned for a 12-month clinical follow-up assessment.

Results

The UHR group exhibited smaller hippocampal volumes bilaterally, and shape analysis revealed significant inversion in the left ventral posterior hippocampus in the UHR group. Greater inversion in this subregion was related to elevated symptomatology at baseline and increased positive symptoms, negative symptoms, and impaired tolerance to normal stress 12 months later. These results did not hold when left hippocampal volume was used as a predictor instead.

Discussion

This represents the first study to use vertex analysis in a UHR sample and results suggest that abnormalities in hippocampal shape appear to reflect underlying pathogenic processes driving the progression of illness. These findings suggest that examining shape and volume may provide an important new perspective for our conception of brain alterations in the UHR period.

SUBMITTER: Dean DJ

PROVIDER: S-EPMC4681548 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Hippocampal Shape Abnormalities Predict Symptom Progression in Neuroleptic-Free Youth at Ultrahigh Risk for Psychosis.

Dean Derek J DJ Orr Joseph M JM Bernard Jessica A JA Gupta Tina T Pelletier-Baldelli Andrea A Carol Emily E EE Mittal Vijay A VA

Schizophrenia bulletin 20150625 1

<h4>Introduction</h4>Hippocampal abnormalities have been widely studied in schizophrenia spectrum populations including those at ultrahigh risk (UHR) for psychosis. There have been inconsistent findings concerning hippocampal morphology prior to and during the transition to psychosis, and little is known about how specific subregions are related to the symptom progression.<h4>Methods</h4>A total of 80 participants (38 UHR and 42 healthy controls) underwent a 3T MRI scan, as well as structured cl ...[more]

PMID: 26113620

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Project description:Spontaneous movement abnormalities, occurring independent of medication status, are thought to reflect basal ganglia pathology in patients at ultrahigh risk (UHR) for psychosis. To date, the research literature has primarily focused on movements associated with elevated striatal dopamine (i.e., hyperkinesia) while little is known about motor symptoms associated with low levels of subcortical dopamine (i.e., spontaneous parkinsonisms; SPs). As SPs (e.g., bradykinesia) may be governed by distinct neural mechanisms, this line of research can provide a clearer picture of the etiological processes in the prodrome. AIMS: To examine SPs and striatal structural correlates in youth at risk for psychosis. A total of 81 (35 UHR, 46 healthy controls) adolescents were administered a structured clinical interview, structural MRI scan, and handwriting kinematic analysis capable of assessing SPs that are not detectable by traditional observer-based inventories. The UHR group exhibited significant decreased velocity scaling (indicative of SPs), t(79) = -2.65, P ≤ 0.01, as well as decreased ipsilateral t(68) = -3.16, P ≤ 0.001 and contralateral t(68) = -3.32, P ≤ 0.001 putamen volume compared with the healthy control group. Further, decreased velocity scaling was significantly associated with smaller ipsilateral putamen r(68) = 0.23, P ≤ 0.05, 95% confidence interval (CI) (-0.005, 0.44), left r(68) = 0.23, P ≤ 0.05, 95% CI (-0.005, 0.44) and right r(68) = 0.21, P ≤ 0.05, 95% CI (-0.03, 0.42) caudate volume, as well as increased positive r(79) = - 0.20, P = 0.05, 95% CI (-0.40, - 0.02) and negative r(79) = - 0.27, P ≤ 0.05, 95% CI (-0.46, -0.06) symptoms across the sample. These findings represent the first evidence for hypokinetic movement abnormalities in the UHR period, indicating that pathophysiological processes in UHR patients may also involve hypodopaminergia. The results implicate a dopamine-induced imbalance contributing to frontal-subcortical circuit dysfunction in the psychosis prodrome.

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.

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Project description:In a recent machine learning study classifying "brain age" based on cross-sectional neuroanatomical data, clinical high-risk (CHR) individuals were observed to show deviation from the normal neuromaturational pattern, which in turn was predictive of greater risk of conversion to psychosis and a pattern of stably poor functional outcome. These effects were unique to cases who were between 12 and 17 years of age when their prodromal and psychotic symptoms began, suggesting that neuroanatomical deviance observable at the point of ascertainment of a CHR syndrome marks risk for an early onset form of psychosis. In the present study, we sought to clarify the pattern of neuroanatomical deviance linked to this "early onset" form of psychosis and whether this deviance is associated with poorer premorbid functioning. T1 MRI scans from 378 CHR individuals and 190 healthy controls (HC) from the North American Prodrome Longitudinal Study (NAPLS2) were analyzed. Widespread smaller cortical volume was observed among CHR individuals compared with HC at baseline evaluation, particularly among the younger group (i.e., those who were 12 to 17 years of age). Moreover, the younger CHR individuals who converted or presented worsened clinical symptoms at follow-up (within 2 years) exhibited smaller surface area in rostral anterior cingulate, lateral and medial prefrontal regions, and parahippocampal gyrus relative to the younger CHR individuals who remitted or presented a stable pattern of prodromal symptoms at follow-up. In turn, poorer premorbid functioning in childhood was associated with smaller surface area in medial orbitofrontal, lateral frontal, rostral anterior cingulate, precuneus, and temporal regions. Together with our prior report, these results are consistent with the view that neuroanatomical deviance manifesting in early adolescence marks vulnerability to a form of psychosis presenting with poor premorbid adjustment, an earlier age of onset (generally prior to the age of 18 years), and poor long-term outcome.

Project description:Cognitive behavioural therapy for psychosis (CBTp) involves helping patients to understand and reframe threatening appraisals of their psychotic experiences to reduce distress and increase functioning. Whilst CBTp is effective for many, it is not effective for all patients and the factors predicting a good outcome remain poorly understood. Machine learning is a powerful approach that allows new predictors to be identified in a data-driven way, which can inform understanding of the mechanisms underlying therapeutic interventions, and ultimately make predictions about symptom improvement at the individual patient level. Thirty-eight patients with a diagnosis of schizophrenia completed a social affect task during functional MRI. Multivariate pattern analysis assessed whether treatment response in those receiving CBTp (n = 22) could be predicted by pre-therapy neural responses to facial affect that was either threat-related (ambiguous 'neutral' faces perceived as threatening in psychosis, in addition to angry and fearful faces) or prosocial (happy faces). The models predicted improvement in psychotic (r = 0.63, p = 0.003) and affective (r = 0.31, p = 0.05) symptoms following CBTp, but not in the treatment-as-usual group (n = 16). Psychotic symptom improvement was predicted by neural responses to threat-related affect across sensorimotor and frontal-limbic regions, whereas affective symptom improvement was predicted by neural responses to fearful faces only as well as prosocial affect across sensorimotor and frontal regions. These findings suggest that CBTp most likely improves psychotic and affective symptoms in those endorsing more threatening appraisals and mood-congruent processing biases, respectively, which are explored and reframed as part of the therapy. This study improves our understanding of the neurobiology of treatment response and provides a foundation that will hopefully lead to greater precision and tailoring of the interventions offered to patients.

Dataset Information

Hippocampal Shape Abnormalities Predict Symptom Progression in Neuroleptic-Free Youth at Ultrahigh Risk for Psychosis.

Introduction

Methods

Results

Discussion

Publications

Hippocampal Shape Abnormalities Predict Symptom Progression in Neuroleptic-Free Youth at Ultrahigh Risk for Psychosis.

Similar Datasets

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