Evaluating the impact of cannabis use on thalamic connectivity in youth at clinical high risk of psychosis.

BACKGROUND: Disruptions in thalamic functional connectivity have been observed in people with schizophrenia and in youth at clinical high risk (CHR) of psychosis. However, the impact of environmental risk factors for psychosis on thalamic dysconnectivity is poorly understood. We tested whether thalamic dysconnectivity is related to patterns of cannabis use in a CHR sample. METHODS: 162 CHR and 105 control participants were assessed on cannabis use severity, frequency, and age at onset of first use as part of the North American Prodrome Longitudinal Study and completed resting-state fMRI scans. Whole-brain thalamic functional connectivity maps were generated using individual subjects' anatomically defined thalamic seeds. RESULTS: Thalamic connectivity did not significantly correlate with current cannabis use severity or frequency in either CHR or controls. In CHR cannabis users, a significant correlation emerged between attenuated thalamic connectivity with left sensory/motor cortex and a younger age at onset of cannabis use. CHR who used cannabis before age 15 did not differ on thalamic connectivity as compared to CHR who used after age 15 or CHR who were cannabis naïve. No group differences in thalamic connectivity emerged when comparing CHR separated by moderate/high use frequency, low-frequency or cannabis naïve. CONCLUSIONS: Although a younger age at onset of cannabis use may be associated with disrupted thalamo-cortical coupling, cannabis use does not appear to be an identifying characteristic for thalamic connectivity in CHR with moderate/high use frequency compared to low-frequency users or CHR who are cannabis naïve.

North American Prodrome Longitudinal Study (NAPLS 2): The Prodromal Symptoms.

In studies describing the long-term follow-up up of youth at clinical high risk (CHR) of psychosis, little attention has been given to details of specific prodromal symptoms. In this paper, we describe the prodromal symptoms of 764 CHR participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6-, 12-, 18-, and 24-month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. Most of the CHR sample (92%) met criteria for the attenuated positive symptoms syndrome (APSS). Significant improvements in SOPS symptoms were observed over time. Unusual thought content, disorganized communication, and overall ratings on disorganized symptoms differentiated those who transitioned to psychosis from the other clinical outcome groups. Suspiciousness and total positive symptoms differentiated those in remission from the other clinical outcome groups.

Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis.

BACKGROUND: The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first-episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation. METHODS: We genotyped 2 single nucleotide polymorphisms (SNPs; rs1938526 and rs10994336) in ANK3 in patients with FEP. Multivariate analysis of variance compared risk allele carriers and noncarriers on 6 domains of cognition consistent with MATRICS consensus. A subsample of 82 patients was assessed using magnetic resonance imaging. We compared brain structure between carriers and noncarriers using cortical thickness analysis and voxel-based morphometry on white matter. RESULTS: In the 173 patients with FEP included in our study, rs1938526 and rs10994336 were in very high linkage disequilibrium (d' = 0.95), and analyses were therefore only carried out on the SNP (rs1938526) with the highest minor allele frequency (G). Allele G of rs1938526, was associated with lower cognitive performance across domains (F6,164 = 2.38, p = 0.030) and significantly lower scores on the domains of verbal memory (p = 0.015), working memory (p = 0.006) and attention (p = 0.019). The significant effects of this SNP on cognition were not maintained when controlling for IQ. Cortical thinning was observed in risk allele carriers at diverse sites across cortical lobes bilaterally at a threshold of p < 0.01, false discovery rate-corrected. Risk-allele carriers did not show any regions of reduced white matter volume. LIMITATIONS: The sample size is modest given that a low-frequency variant was being examined. CONCLUSION: The ANK3 risk allele rs1938526 appears to be associated with general cognitive impairment and widespread cortical thinning in patients with FEP.

Functional magnetic resonance imaging study of external source memory and its relation to cognitive insight in non-clinical subjects.

AIM: Previous research has linked cognitive insight (a measure of self-reflectiveness and self-certainty) in psychosis with neurocognitive and neuroanatomical disturbances in the fronto-hippocampal neural network. The authors' goal was to use functional magnetic resonance imaging (fMRI) to investigate the neural correlates of cognitive insight during an external source memory paradigm in non-clinical subjects. METHODS: At encoding, 24 non-clinical subjects travelled through a virtual city where they came across 20 separate people, each paired with a unique object in a distinct location. fMRI data were then acquired while participants viewed images of the city, and completed source recognition memory judgments of where and with whom objects were seen, which is known to involve prefrontal cortex. Cognitive insight was assessed with the Beck Cognitive Insight Scale. RESULTS: External source memory was associated with neural activity in a widespread network consisting of frontal cortex, including ventrolateral prefrontal cortex (VLPFC), temporal and occipital cortices. Activation in VLPFC correlated with higher self-reflectiveness and activation in midbrain correlated with lower self-certainty during source memory attributions. Neither self-reflectiveness nor self-certainty significantly correlated with source memory accuracy. CONCLUSION: By means of virtual reality and in the context of an external source memory paradigm, the study identified a preliminary functional neural basis for cognitive insight in the VLPFC in healthy people that accords with our fronto-hippocampal theoretical model as well as recent neuroimaging data in people with psychosis. The results may facilitate the understanding of the role of neural mechanisms in psychotic disorders associated with cognitive insight distortions.

The influence of contour fragmentation on recognition memory: an event-related potential study.

The present study was carried out to examine how the event-related potentials to fragmentation predict recognition success. Stimuli were abstract meaningless figures that were either complete or fragmented to various extents but still recoverable. Stimuli were first encoded as part of a symmetry discrimination task. In a subsequent recognition phase, encoded stimuli were presented complete along with never presented stimuli and participants performed an old/new discrimination task. Fragmentation stimuli elicited more negative ERPs than complete figures over the frontal, central and parietal areas between 180 and 260 ms, and over the occipito-temporal areas between 220 and 340 ms. Only this latter effect was modulated as a function of whether stimuli were recognized or not during the recognition phase of the memory test. More specifically, the effect occurred for stimuli that were later forgotten and was absent for stimuli that were later recognized. This ERP to fragmentation, the occipito-temporal N(frag), possibly reflects the brain response to encoding difficulty, and is thus predictive of recognition performance.

The effect of viewpoint on visual stimuli: a study of episodic memory in schizophrenia.

In everyday life, objects are rarely perceived in the exact same position as they were the first time. This change of position alters the perceptual viewpoint influencing the likelihood of recognizing the object - the similarity effect. Moreover, this effect may be a contributing factor to the overall episodic memory deficits that are apparent in people with schizophrenia. The present study investigated the influence of viewpoint on memory recognition in 43 schizophrenia and 23 healthy comparison participants. Photos of target objects were presented during the encoding phase alone and then during the recognition phase (as an old object) along with never-before presented objects. The old objects, however, now appeared either from the same viewpoint (unaltered condition) or from a different viewpoint (altered condition). Participants performed an old/new discrimination task during the recognition phase. Results, for both groups, revealed better recognition performance when the viewpoint was unaltered; that is, memory recognition was sensitive to viewpoint manipulation. There was no significant interaction however, between this similarity effect and group. Thus, visual functions solicited by changing the viewpoint, as well as the influence on the encoding and the subsequent memory retrieval, are likely intact in people with schizophrenia.

Examining the effects of two factors on working memory maintenance of bound information in schizophrenia.

Integrating information in space and time is a central feature of episodic memory. Although disturbance of the binding processes in episodic memory is well established in patients with schizophrenia, data on working memory (WM) remain discrepant. In a change detection procedure, two target displays of pairs of letters located in cells of grid were successively presented. Participants attempted to detect changes in binding information (i.e., recombination of studied features) or feature information (i.e., a novel letter and/or a novel spatial location). Recombinations consisted of features belonging to the same display (intradisplay) or different displays (interdisplays). Results showed that patients demonstrated overall lower performance, with no specific deficit for recognizing bound information or feature information. In addition, patients did not demonstrate deficits for interdisplay recombinations or intradisplay recombinations. Patients' ability to remember temporal occurrence of stimuli was not affected. Together, these results suggest that in patients with schizophrenia, binding processes in WM are not specifically disturbed.

Symptomatic determinants of insight in schizophrenia spectrum disorders.

Impaired insight in schizophrenia spectrum disorders has been linked to several psychopathologic features including positive symptoms, although not all dimensions of psychopathology have been studied and confounds from other symptoms have not been ruled out. In addition, the nature of the association between insight and specific positive symptoms, in particular delusions, remains unclear. The present investigation examined whether, in patients with schizophrenia spectrum disorders insight is associated with specific symptom dimensions including delusional severity. The factor structure was determined from scores of 151 patients rated on the Signs and Symptoms of Psychotic Illness scale. Associations of the Signs and Symptoms of Psychotic Illness insight item with the resulting components and delusions were assessed using regression-based methodology. Principal component analysis revealed 4 orthogonal symptom clusters. Correlational analyses demonstrated that only depression/anxiety and psychomotor excitation were significantly related to insight. Hierarchical regression indicated that delusions explained unique variance in insight over and above depression/anxiety and psychomotor excitation. These results suggest that depression/anxiety is associated with better insight and that psychomotor excitation and delusions are associated with poorer insight.

Clarifying associations between cortical thickness, subcortical structures, and a comprehensive assessment of clinical insight in enduring schizophrenia.

BACKGROUND: The relationship between poor insight and less favorable outcomes in schizophrenia has promoted research efforts to understand its neurobiological basis. Thus far, research on neural correlates of insight has been constrained by small samples, incomplete insight assessments, and a focus on frontal lobes. The purpose of this study was to examine associations of cortical thickness and subcortical volumes, with a comprehensive assessment of clinical insight, in a large sample of enduring schizophrenia patients. METHODS: Two dimensions of clinical insight previously identified by a factor analysis of 4 insight assessments were used: Awareness of Illness and Need for Treatment (AINT) and Awareness of Symptoms and Consequences (ASC). T1-weighted structural images were acquired on a 3 T MRI scanner for 110 schizophrenia patients and 69 healthy controls. MR images were processed using CIVET (version 2.0) and MAGeT and quality controlled pre and post-processing. Whole-brain and region-of-interest, vertex-wise linear models were applied between cortical thickness, and levels of AINT and ASC. Partial correlations were conducted between volumes of the amygdala, thalamus, striatum, and hippocampus and insight levels. RESULTS: No significant associations between both insight factors and cortical thickness were observed. Moreover, no significant associations emerged between subcortical volumes and both insight factors. CONCLUSIONS: These results do not replicate previous findings obtained with smaller samples using single-item measures of insight into illness, suggesting a limited role of neurobiological factors and a greater role of psychological processes in explaining levels of clinical insight.

Cognitive insight and verbal memory in first episode of psychosis.

Beck and collaborators have proposed a distinction between clinical insight and cognitive insight and have developed a tool for the assessment of the latter, namely the Beck Cognitive Insight Scale (BCIS). The present study explored in 51 patients with a first episode of psychosis the neurocognitive correlates of cognitive insight as assessed with the BCIS. Global measures for seven domains of cognition including verbal learning and memory, visual learning and memory, working memory, speed of processing, reasoning and problem solving, attention, and social cognition were examined. Secondly, we examined whether two clinical insight measures, the Scale to assess Unawareness of Mental Disorder (SUMD) and the insight item from the Positive and Negative Symptoms Scale (PANSS), could produce similar or different patterns of association with neurocognitive functions as those identified with the BCIS. Correlational analyses revealed significant associations between the BCIS Composite Index and the verbal learning and memory. No significant associations were observed between any of the neurocognitive domains and the PANSS or SUMD clinical insight measures, despite high inter-correlations among the three insight measures. These results suggest that cognitive insight, but not clinical insight, may rely on memory processes whereby current experiences are appraised based on previous ones.

A longitudinal study of cognitive insight and cortical thickness in first-episode psychosis.

Among individuals with psychosis, those with poor cognitive insight (lower Self-Reflectiveness, higher Self-Certainty) show volumetric reductions in cortical structure. We evaluated whether changes in cognitive insight are associated with progressive changes in cortical structure in first-episode psychosis (FEP) and control subjects. Beck Cognitive Insight Scale ratings and magnetic resonance imaging scans were acquired at baseline for 130 FEP and 52 controls, 59 FEP and 28 controls at 1-year, and 53 FEP and 20 controls at 2-years. Cortical thickness was computed across scans and analyzed with linear mixed models. At baseline, groups did not differ on Self-Reflectiveness or Self-Certainty. At baseline, higher Self-Reflectiveness significantly correlated with thinner right occipital cortex in FEP, and higher Self-Certainty was significantly negatively correlated with cortical thickness in left posterior cingulate in controls. Longitudinal analysis showed that Self-Reflectiveness and Self-Certainty did not change over time in either group. Interestingly, the lack of change in cognitive insight aligned with longitudinal cortical thickness results, where no interaction effects were seen with cortical thickness between time and either Self-Reflectiveness or Self-Certainty. Exploratory analyses with a reduced threshold found that in FEP, across all time-points, higher Self-Certainty associated with thinner cortex in left posterior cingulate/precuneus. Results suggest that the posterior cingulate may be a common neural correlate for Self-Certainty in FEP and non-clinical subjects.

A cognitive bias against disconfirmatory evidence (BADE) is associated with schizotypy.

A bias against disconfirmatory evidence (BADE) has been observed in schizophrenia, and in the present study we evaluated whether this extends to a nonclinical sample scoring high on a schizotypy scale. Thirty-seven high and 32 low schizotypy healthy participants were sequentially presented with three sentences that increasingly disambiguated the true content of a delusion-neutral scenario and were asked to rate the plausibility of four interpretations for this scenario. Relative to low schizotypy participants, high schizotypy participants continued to endorse their initial beliefs, even in the face of evidence that disconfirmed these beliefs. This result provides support for the "schizophrenia spectrum" account of psychosis.

A bias against disconfirmatory evidence is associated with delusion proneness in a nonclinical sample.

Previous work has suggested that a bias against disconfirmatory evidence (BADE) may be associated with the schizophrenia spectrum. The current investigation focused on whether a BADE (1) overlaps with traditional measures of memory and executive functions or selectively taps into a unique aspect of cognition and (2) is correlated with delusional ideation but not with other aspects of schizotypy. Sixty-eight undergraduate students were administered the Schizotypal Personality Questionnaire (SPQ), the BADE test, the Rey Auditory Verbal Learning Test (RAVLT), the Wisconsin Card Sorting Test (WCST), the Trail Making Tests A and B (TMT), and tests used to estimate IQ. Factor analysis of all cognition measures resulted in a 6-factor solution, 4 of which reflected the 4 domains of neuropsychological tests (WCST, RAVLT, TMT, and IQ), and 2 of which reflected different aspects of the BADE test: Initial Belief and Integration of Disconfirmatory Evidence. This solution suggests that BADE measures were independent from the other cognitive domains measured. Integration of Disconfirmatory Evidence was the only factor that correlated with delusion-content subscales of the SPQ, providing support for the contribution of a BADE to delusional ideation.

Longitudinal trajectory of clinical insight and covariation with cortical thickness in first-episode psychosis.

Among people with a first-episode of psychosis, those with poorer clinical insight show neuroanatomical abnormalities in frontal, temporal and parietal cortices compared to those with better clinical insight. Whether changes in clinical insight are associated with progressive structural brain changes is unknown. We aimed to evaluate 1) associations between clinical insight and cortical thickness at a baseline assessment, 2) covariation between clinical insight and cortical thickness across baseline, one-year and two-year follow-up assessments, and 3) the predictive value of clinical insight for cortical thickness at one-year and two-year follow-ups. Scale for the assessment of Unawareness of Mental Disorder ratings and magnetic resonance imaging scans were acquired at baseline, one-year, and two-year follow-ups in 128, 74, and 44 individuals with a first-episode psychosis, respectively. Cortical thickness metrics were then computed at baseline, one-year and two-year follow-ups and analyzed with linear mixed models. At baseline, clinical insight was not significantly associated with cortical thickness in any region. Longitudinal mixed effects models showed that a worsening in clinical insight between the one-year and two-year assessments was significantly associated with cortical thinning in dorsal pre-central and post-central gyri. Cortical thinning in left fusiform gyrus at two-years was predicted by poorer clinical insight at baseline. Results suggest that poor clinical insight soon after the onset of a first-episode psychosis may lead to progressive cortical changes in temporal lobe, while changes in clinical insight during the second year covary with cortical thinning in circumscribed dorsal frontal and parietal cortices.

Mapping structural covariance networks of facial emotion recognition in early psychosis: A pilot study.

People with psychosis show deficits recognizing facial emotions and disrupted activation in the underlying neural circuitry. We evaluated associations between facial emotion recognition and cortical thickness using a correlation-based approach to map structural covariance networks across the brain. Fifteen people with an early psychosis provided magnetic resonance scans and completed the Penn Emotion Recognition and Differentiation tasks. Fifteen historical controls provided magnetic resonance scans. Cortical thickness was computed using CIVET and analyzed with linear models. Seed-based structural covariance analysis was done using the mapping anatomical correlations across the cerebral cortex methodology. To map structural covariance networks involved in facial emotion recognition, the right somatosensory cortex and bilateral fusiform face areas were selected as seeds. Statistics were run in SurfStat. Findings showed increased cortical covariance between the right fusiform face region seed and right orbitofrontal cortex in controls than early psychosis subjects. Facial emotion recognition scores were not significantly associated with thickness in any region. A negative effect of Penn Differentiation scores on cortical covariance was seen between the left fusiform face area seed and right superior parietal lobule in early psychosis subjects. Results suggest that facial emotion recognition ability is related to covariance in a temporal-parietal network in early psychosis.

A pilot study of cognitive insight and structural covariance in first-episode psychosis.

Cognitive insight is described as a balance between one's self-reflectiveness (recognition and correction of dysfunctional reasoning), and self-certainty (overconfidence). Neuroimaging studies have linked the ventrolateral prefrontal cortex (VLPFC) to cognitive insight in people with psychosis. However, the relationship between cognitive insight and structural connectivity between the VLPFC and other brain areas is unknown. Here, we investigated the modulation of cognitive insight on structural covariance networks involving the VLPFC in a first-episode psychosis sample. Fifteen patients with a first-episode psychosis provided magnetic resonance (MR) scans and completed the Beck Cognitive Insight Scale (BCIS). MR scans were also available for 15 historical controls. Seed-based analysis of structural covariance was conducted using the Mapping Anatomical Correlations Across the Cerebral Cortex (MACACC) methodology, whereby Pearson correlation coefficients were extracted between seed regions in left and right VLPFC and cortical thickness across the brain. Structural covariance maps between groups were compared at each vertex. In first-episode subjects, we evaluated the modulation of BCIS scores on cortical covariance between VLPFC and every other vertex. Findings showed no significant group difference between first-episode psychosis subjects and controls in thickness covariance seeded from left or right VLPFC. However, in first-episode psychosis subjects, a positive association with self-certainty was found in networks seeded from both left and right VLPFC with thickness in medial frontal cortex and right pars triangularis. No significant associations were found for self-reflectiveness. These results suggest that self-certainty, but not self-reflectiveness, positively modulated cortical covariance in a frontal network in patients with a first-episode psychosis.

Anxiety in youth at clinical high risk for psychosis.

AIM: High rates of anxiety have been observed in youth at clinical high risk (CHR) of developing psychosis. In CHR, anxiety often co-occurs with depression, and there is inconsistent evidence on anxiety in relation to transition to psychosis. The aim of this study was to examine: (i) the prevalence of anxiety disorders in individuals at CHR; (ii) clinical differences between those with and without anxiety; and (iii) the association of baseline anxiety with later transition to psychosis. METHODS: The sample consisted of 765 CHR individuals and 280 healthy controls. CHR status was determined with the Structured Interview of Prodromal Syndromes, mood and anxiety diagnoses with the Structured Clinical Interview for DSM-IV Disorders, and severity of anxiety with the Social Interaction Anxiety Scale and Self-Rating Anxiety Scale. RESULTS: In the CHR sample, 51% met criteria for an anxiety disorder. CHR participants had significantly more anxiety diagnoses and severity than healthy controls. Anxiety was correlated to attenuated psychotic and negative symptoms in CHR and those with an anxiety disorder demonstrated more suspiciousness. CHR participants with obsessive-compulsive disorder (OCD) exhibited more severe symptomatology than those without OCD. An initial presentation of anxiety did not differ between those who did or did not transition to psychosis. CONCLUSIONS: In this large sample of individuals at CHR, anxiety is common and associated with more severe attenuated psychotic symptoms. Treatment not only to prevent or delay transition to psychosis but also to address presenting concerns, such as anxiety, is warranted.

Cognitive insight is associated with cortical thickness in first-episode psychosis.

Compared to non-clinical subjects, people with psychosis show poor cognitive insight as reflected in low Self-Reflectiveness and high Self-Certainty. Neuroimaging studies have reported that 1) low Self-Reflectiveness is associated with volumetric reductions in ventrolateral prefrontal cortex (VLPFC), 2) higher Self-Certainty is associated with volumetric reductions in hippocampus, and 3) higher Self-Certainty is associated with fractional anisotropy in the fornix, in people with psychosis. The aims of the current study were to expand on this research by 1) performing an exploratory whole-brain cortical thickness analysis of the neural correlates of cognitive insight, to reveal whether regions outside the VLPFC are important for cognitive insight, and 2) to evaluate associations between cognitive insight and subfields of the hippocampus, which are distinct, interacting, and have different functions. We also aimed to replicate previous research documenting associations between cognitive insight and 3) total hippocampal volumes and 4) fornix fractional anisotropy. Fifteen people with a first-episode psychosis completed the Beck Cognitive Insight Scale and provided magnetic resonance and diffusion tensor imaging scans. Cortical thickness and hippocampal volumes were analyzed in FreeSurfer, and fornixfractional anisotropy was analyzed in Diffusion Toolkit/TrackVis. Higher Self-Reflectiveness and lower Self-Certainty significantly associated with thickness and thinness in VLPFC, respectively, as well as thickness and thinness in widespread frontal, parietal and temporal cortices. No associations emerged between Self-Reflectiveness or Self-Certainty and hippocampal total or sub-field volumes, or fornix fractional anisotropy. Results suggest that the neural correlates of cognitive insight involve a network of frontal, temporal and parietal brain regions.

Relation between cannabis use and subcortical volumes in people at clinical high risk of psychosis.

Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala were extracted with FreeSurfer, and compared across groups. Comparing all CHR participants with healthy control participants revealed no significant differences in volumes of any ROI. However, when comparing CHR users to CHR non-users, a significant ROI×Cannabis group effect emerged: CHR users showed significantly smaller amygdala compared to CHR non-users. However, when limiting analysis to CHR subjects who reported using alcohol at a 'use without impairment' severity level, the amygdala effect was non-significant; rather, smaller hippocampal volumes were seen in CHR cannabis users compared to non-users. Controlling statistically for effects of alcohol and tobacco use rendered all results non-significant. These results highlight the importance of controlling for residual confounding effects of other substance use when examining the relationship between cannabis use and neural structure.

Traumatic brain injury in individuals at clinical high risk for psychosis.

BACKGROUND: Recent research suggests that a traumatic brain injury (TBI) can significantly increase the risk of later development of psychosis. However, it is unknown whether people at clinical high risk (CHR) of psychosis have experienced TBI at higher rates, compared to otherwise healthy individuals. This study evaluated the prevalence of mild TBI, whether it was related to past trauma and the relationship of mild TBI to later transition to psychosis. METHODS: Seven-hundred forty-seven CHR and 278 healthy controls (HC) were assessed on past history of mild TBI, age at first and last injury, severity of worst injury and number of injuries using the Traumatic Brain Injury Interview. Attenuated psychotic symptoms were assessed with the Scale of Psychosis-risk Symptoms. IQ was estimated using the Wechsler Abbreviated Scale of Intelligence and past trauma and bullying were recorded using the Childhood Trauma and Abuse Scale. RESULTS: CHR participants experienced a mild TBI more often than the HC group. CHR participants who had experienced a mild TBI reported greater total trauma and bullying scores than those who had not, and those who experienced a mild TBI and later made the transition to psychosis were significantly younger at the age at first and most recent injury than those who did not. CONCLUSION: A history of mild TBI is more frequently observed in CHR individuals than in HC. Inclusion or study of CHR youth with more severe TBI may provide additional insights on the relationship between TBI and later transition to psychosis in CHR individuals.