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Background and Hypothesis: Brain development/aging is not uniform across individuals, spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or aging map onto specific symptom facets., Study Design: Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms., Study Results: ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity., Conclusions: Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia., (Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center 2024.)

Background: Sensory prediction allows the brain to anticipate and parse incoming self-generated sensory information from externally generated signals. Sensory prediction breakdowns may contribute to perceptual and agency abnormalities in psychosis (hallucinations, delusions). The pons, a central node in a cortico-ponto-cerebellar-thalamo-cortical circuit, is thought to support sensory prediction. Examination of pons connectivity in schizophrenia and its role in sensory prediction abnormalities is lacking., Methods: We examined these relationships using resting-state functional magnetic resonance imaging and the electroencephalography-based auditory N1 event-related potential in 143 participants with psychotic spectrum disorders (PSPs) (with schizophrenia, schizoaffective disorder, or bipolar disorder); 63 first-degree relatives of individuals with psychosis; 45 people at clinical high risk for psychosis; and 124 unaffected comparison participants. This unique sample allowed examination across the psychosis spectrum and illness trajectory. Seeding from the pons, we extracted average connectivity values from thalamic and cerebellar clusters showing differences between PSPs and unaffected comparison participants. We predicted N1 amplitude attenuation during a vocalization task from pons connectivity and group membership. We correlated participant-level connectivity in PSPs and people at clinical high risk for psychosis with hallucination and delusion severity., Results: Compared to unaffected comparison participants, PSPs showed pons hypoconnectivity to 2 cerebellar clusters, and first-degree relatives of individuals with psychosis showed hypoconnectivity to 1 of these clusters. Pons-to-cerebellum connectivity was positively correlated with N1 attenuation; only PSPs with heightened pons-to-postcentral gyrus connectivity showed this pattern, suggesting a possible compensatory mechanism. Pons-to-cerebellum hypoconnectivity was correlated with greater hallucination severity specifically among PSPs with schizophrenia., Conclusions: Deficient pons-to-cerebellum connectivity linked sensory prediction network breakdowns with perceptual abnormalities in schizophrenia. Findings highlight shared features and clinical heterogeneity across the psychosis spectrum., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Recent neuroimaging studies and publicly disseminated analytic tools suggest that regional morphometric analyses covary for global thickness. We empirically demonstrated that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy control participants, 51 participants at clinical high risk for psychosis, and 78 participants with early-illness schizophrenia. Study 2 included 56 healthy control participants, 83 participants with nonaffective psychosis, and 30 participants with affective psychosis. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with and without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in the schizophrenia spectrum groups than the other groups. Regional thickness deficits in schizophrenia spectrum groups were attenuated or eliminated with global thickness covariation. Eliminating the variation that regional thickness shares with global thickness eliminated disease-related effects. This statistical approach results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high risk syndrome., (Published by Elsevier Inc.)

Background: Amplitude reduction of mismatch negativity (MMN), an event-related potential component indexing NMDA receptor-dependent auditory echoic memory and predictive coding, is widely replicated in schizophrenia. Time-frequency analyses of single-trial electroencephalography epochs suggest that theta oscillation abnormalities underlie MMN deficits in schizophrenia. However, this has received less attention in early schizophrenia (ESZ)., Methods: Patients with ESZ (n = 89), within 5 years of illness onset, and healthy control subjects (n = 105) completed an electroencephalography MMN paradigm (duration-deviant, pitch-deviant, duration + pitch double-deviant). Repeated measures analyses of variance assessed group differences in MMN, theta intertrial phase coherence (ITC), and theta total power from frontocentral electrodes, after normal age adjustment. Group differences were retested after covarying MMN and theta measures., Results: Relative to healthy control subjects, patients with ESZ showed auditory deviance deficits. Patients with ESZ had MMN deficits for duration-deviants (p = .041), pitch-deviants (ps = .007), and double-deviants (ps < .047). Patients with ESZ had reduced theta ITC for standards (ps < .040) and duration-deviants (ps < .030). Furthermore, patients with ESZ had reduced theta power across deviants at central electrodes (p = .013). MMN group deficits were not fully accounted for by theta ITC and power, and neither were theta ITC group deficits fully accounted for by MMN. Group differences in theta total power were no longer significant after covarying for MMN., Conclusions: Patients with ESZ showed reduced MMN and theta total power for all deviant types. Theta ITC showed a relatively specific reduction for duration-deviants. Although MMN and theta ITC were correlated in ESZ, covarying for one did not fully account for deficits in the other, raising the possibility of their sensitivity to dissociable pathophysiological processes., (Published by Elsevier Inc.)

Introduction: Alcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD., Materials and Methods: U.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition., Results: Smoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers., Conclusions: Overall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Neuroimaging studies have documented morphometric brain abnormalities in schizophrenia, but less is known about them in individuals at clinical high-risk for psychosis (CHR-P), including how they compare with those observed in early schizophrenia (ESZ). Accordingly, we implemented multivariate profile analysis of regional morphometric profiles in CHR-P (n = 89), ESZ (n = 93) and healthy controls (HC; n = 122). ESZ profiles differed from HC and CHR-P profiles, including 1) cortical thickness: significant level reduction and regional non-parallelism reflecting widespread thinning, except for entorhinal and pericalcarine cortex, 2) basal ganglia volume: significant level increase and regional non-parallelism reflecting larger caudate and pallidum, and 3) ventricular volume: significant level increase with parallel regional profiles. CHR-P and ESZ cerebellar profiles showed significant non-parallelism with HC profiles. Regional profiles did not significantly differ between groups for cortical surface area or subcortical volume. Compared to CHR-P followed for ≥18 months without psychosis conversion (n = 31), CHR-P converters (n = 17) showed significant non-parallel ventricular volume expansion reflecting specific enlargement of lateral and inferolateral regions. Antipsychotic dosage in ESZ was significantly correlated with frontal cortical thinning. Results suggest that morphometric abnormalities in ESZ are not present in CHR-P, except for ventricular enlargement, which was evident in CHR-P who developed psychosis., Competing Interests: Declaration of Competing Interest This work was supported by the National Institute of Mental Health (MH076989 [DHM]) and University of Missouri dissertation funds (JPYH). Manuscript writing by JPYH was supported by the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center (MIRECC). The aforementioned funding sources had no role in the study design, data collection, analysis and interpretation of data, writing of the report, and in the decision to submit the article for publication., (Published by Elsevier B.V.)

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to psychosis., Competing Interests: Declaration of competing interest DHM received compensation as a consultant for Boehringer-Ingelheim, Cadent Therapeutics, Neurocrine Biosciences, Gilgamesh Pharma, Recognify Life Sciences, and Syndesi Therapeutics. The other authors report no conflict of interest. The other authors report no conflict of interest. JPYH, SLF, JMF, and DHM are United States Government employees. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government., (Published by Elsevier B.V.)

Background: Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate > chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown., Methods: We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups., Results: HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age < chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables., Conclusions: These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

A shared mechanism across species heralds the arrival of self-generated sensations, helping the brain to anticipate, and therefore distinguish, self-generated from externally generated sensations. In mammals, this sensory prediction mechanism is supported by communication within a cortico-ponto-cerebellar-thalamo-cortical loop. Schizophrenia is associated with impaired sensory prediction as well as abnormal structural and functional connections between nodes in this circuit. Despite the pons' principal role in relaying and processing sensory information passed from the cortex to cerebellum, few studies have examined pons connectivity in schizophrenia. Here, we first briefly describe how the pons contributes to sensory prediction. We then summarize schizophrenia-related abnormalities in the cortico-ponto-cerebellar-thalamo-cortical loop, emphasizing the dearth of research on the pons relative to thalamic and cerebellar connections. We conclude with recommendations for advancing our understanding of how the pons relates to sensory prediction failures in schizophrenia., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Ltd.)

Introduction: Social anhedonia (SocAnh) predicts increased risk of schizophrenia-spectrum disorders, with evidence that these disorders are associated with increased creativity. However, it is still largely unknown whether SocAnh is associated with one central aspect of creative thinking, convergent thinking. Methods: In two studies, college students with either extreme levels of SocAnh ( n  = 44 and n  = 70) or controls with an average level of SocAnh ( n  = 111 and n  = 100) completed a convergent thinking task, the Remote Associates Test, and also completed measures of current affect. In the second study, participants also completed a divergent thinking task. Results: In both studies, the SocAnh group had better performance than controls on the convergent thinking task. Further, this group difference remained after removing shared variance with current affect. In Study 2, groups did not differ on divergent thinking. Conclusions: Overall, consistent with research linking schizophrenia-spectrum disorders and creativity, the current research suggests that SocAnh is associated with increases in some aspects of creativity.

Research has found strong evidence for common and distinct morphometric brain abnormality profiles in nonaffective psychosis (NAff-P) and affective psychosis (Aff-P). Due to chronicity and prolonged medication exposure confounds, it is crucial to examine structural morphometry early in the course of psychosis. Using Human Connectome Project-Early Psychosis data, multivariate profile analyses were implemented to examine regional profiles for cortical thickness, cortical surface area, subcortical volume, and ventricular volume in healthy control (HC; n  = 56), early illness NAff-P ( n  = 83), and Aff-P ( n  = 30) groups after accounting for normal aging. Associations with symptom severity, functioning, and cognition were also examined. Group regional profiles were significantly nonparallel and differed in level for cortical thickness ( P  < .001), with NAff-P having widespread cortical thinning relative to HC and Aff-P and some regions showing greater deficits than others. Significant nonparallelism of group regional profiles was also evident for cortical surface area ( P  < .006), with Aff-P and N-Aff-P differing from HC and from each other ( P  < .001). For subcortical volume, there was significant profile nonparallelism with NAff-P having an enlarged left pallidum and smaller accumbens and hippocampus ( P  < .028), and Aff-P having a smaller accumbens and amygdala ( P  < .006), relative to HC. NAff-P also had larger basal ganglia compared to Aff-P. Furthermore, NAff-P had enlarged ventricles ( P  < .055) compared to HC and Aff-P. Additionally, greater ventricular volume was associated with increased manic symptoms in NAff-P and Aff-P. Overall, this study found common and distinct regional morphometric profile abnormalities in early illness NAff-P and Aff-P, providing evidence for both shared and disease-specific pathophysiological processes., (Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center 2022.)

Neuroimaging studies have consistently found structural cortical abnormalities in individuals with schizophrenia, especially in structural hubs. However, it is unclear what abnormalities predate psychosis onset and whether abnormalities are related to behavioral performance and symptoms associated with psychosis risk. Using surface-based morphometry, we examined cortical volume, gyrification, and thickness in a psychosis risk group at long-term risk for developing a psychotic disorder (n = 18; i.e., extreme positive schizotypy plus interview-rated attenuated psychotic symptoms [APS]) and control group (n = 19). Overall, the psychosis risk group exhibited cortical abnormalities in multiple structural hub regions, with abnormalities associated with poorer probabilistic category learning, a behavioral measure strongly associated with psychosis risk. For instance, the psychosis risk group had hypogyria in a right posterior midcingulate cortical hub and left superior parietal cortical hub, as well as decreased volume in a right pericalcarine hub. Morphometric measures in all of these regions were also associated with poorer probabilistic category learning. In addition to decreased right pericalcarine volume, the psychosis risk group exhibited a number of other structural abnormalities in visual network structural hub regions, consistent with previous evidence of visual perception deficits in psychosis risk. Further, severity of APS hallucinations, delusional ideation, and suspiciousness/persecutory ideas were associated with gyrification abnormalities, with all domains associated with hypogyria of the right lateral orbitofrontal cortex. Thus, current results suggest that structural abnormalities, especially in structural hubs, are present in psychosis risk and are associated both with poor learning on a psychosis risk-related task and with APS severity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: We investigated the extent to which physiological/biological measures of emotion dysregulation collected in the lab, resting respiratory sinus arrhythmia (RSA) in Study 1 and amygdala activation in response to negative stimuli in Study 2, combined with daily measures of interpersonal stressors predicted negative emotional states in outpatients better than the stressors alone., Methods: Participants were adult outpatients with emotional distress disorders (N=30 individuals in Study 1, and N=26 women in Study 2). After completing a laboratory session that collected physiological/biological measures of emotion dysregulation, participants then completed 1-3 weeks of ambulatory assessment during which they reported on interpersonal stressors and negative affective states several times per day., Results: Laboratory measures of emotion dysregulation were largely unrelated to either momentary or mean levels of daily-life hostility, sadness, and fear in both studies. However, resting RSA significantly moderated the association between day-level interpersonal stressors and momentary fear such that low resting RSA strengthened this association. Similarly, amygdala activation tended to moderate this relationship in the predicted direction., Limitations: Both samples were relatively small and focused on only a limited set of diagnoses associated with emotion dysregulation. Only two possible physiological/biological markers of emotion dysregulation were examined., Conclusions: The current studies support the collection of physiological/biological data on emotion dysregulation when indexing daily-life emotion dysregulation as the degree of emotional reactivity to stressors in daily life among outpatients with emotional distress disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Emerging adulthood is a critical neurodevelopmental stage, with alcohol use during this period consistently associated with brain abnormalities and damage in anatomical structure and white matter integrity. However, it is less clear how alcohol use is associated with the brain's structural organization (i.e., white matter connections between anatomical regions). Recent connectome research has focused on rich-club regions, a collection of highly-interconnected hubs that are critical in brain communication and global network organization and disproportionately vulnerable to insults., Methods: For the first time, we examined alcohol use associations with structural rich-club and connectome organization in emerging adults (N = 66)., Results: Greater lifetime drinks and current monthly drinks were significantly associated with lower rich-club organization (r s =-0.38, ps < 0.003) and lower rich-club connectivity (r s <-0.34, ps < 0.007). Additionally, rich-club connectivity was significantly more negatively correlated with alcohol use than connectivity among non-rich-club regions (ps < 0.035). Examining overall structural organization, greater lifetime drinks and current monthly drinks were significantly associated with lower network density (i.e., lower network resilience; r s <-0.36, ps = 0.004). Additionally, greater lifetime drinks and current monthly drinks were significantly associated with higher network segregation (i.e., network's tendency to divide into subnetworks; r s >0.33, ps<0.008). Alcohol use was not significantly associated with network integration (i.e., network's efficiency in combining information across the brain; ps > 0.064)., Conclusions: Results provide novel evidence that alcohol use is associated with decreased rich-club connectivity and structural network disorganization. Given that both are critical in global brain communication, these results highlight the importance of examining alcohol use and brain relationships in emerging adulthood., (Published by Elsevier B.V.)

Emotional conflict adaptation involving ventral anterior cingulate cortex (ACC) suppression of the amygdala is thought to be important in emotion regulation, with evidence of impaired implicit emotion regulation in emotional distress disorders. However, it is unclear how this impairment is associated with daily-life emotion dysregulation in emotional distress disorders. In the current study, female participants with an emotional distress disorder (N = 27) were scanned with MRI while completing an implicit emotion conflict regulation task that involved identifying the facial expression of an image while ignoring an overlaid congruent or incongruent affect label. Participants then completed two weeks of ambulatory assessment of daily-life emotion dysregulation. Consistent with previous research on comorbid emotional distress disorders (Etkin and Schatzberg, 2011), there was no behavioral effect of emotional conflict adaptation (p = .701) but a significant effect of congruent adaptation (p = .006), suggesting impairment is specific to implicit emotional conflict regulation. Additionally, there was no neural evidence of emotional conflict adaptation in the ventral ACC and amygdala (ps > .766). Further, in our primary psychophysiological interactions analyses, we examined ventral ACC-amygdala functional connectivity. As hypothesized, increased ventral ACC-amygdala functional connectivity for emotional conflict adaptation was associated with increased daily-life affective instability (p = .022), but not mean daily-life negative affect (p = .372). Overall, results provide behavioral and neural evidence of impaired implicit emotional conflict adaptation in individuals with emotional distress disorders and suggests that this impairment is related to daily-life affective instability in these disorders., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Emerging adulthood is a critical neurodevelopment period in which extreme drinking has a potentially pronounced neurotoxic effect. Therefore, extreme drinking, even a single episode, could be particularly harmful to the developing brain's structure. Relatedly, heavy alcohol use in emerging adults has been associated with structural brain damage, especially in the corpus callosum. However, it is unclear whether and how much a single extreme drinking episode would affect brain morphometry., Methods: For the first time in the literature, the current study prospectively examined the impact of an extreme drinking episode (i.e., twenty-first birthday celebration) on the brain morphometry of emerging adults immediately following their birthday celebration (n = 50) and approximately 5 weeks post-birthday celebration (n = 29)., Results: We found evidence that a single extreme drinking episode was associated with structural changes immediately post-birthday celebration. Specifically, higher twenty-first birthday estimated blood-alcohol concentration was associated with decreased volume of the posterior and central corpus callosum immediately post-birthday celebration. This extreme drinking episode was not associated with further structural changes, or recovery, 5 weeks post-twenty-first birthday celebration., Conclusions: Overall, results suggest that a single episode of heavy drinking in emerging adulthood may be associated with immediate structural changes of the corpus callosum. Thus, emerging adulthood, which is characterized by high rates of extreme drinking, could be a critical period for targeted prevention and intervention., (© 2020 by the Research Society on Alcoholism.)

It is thought that altered connectivity between the striatum and the cortex could contribute to psychosis. However, whether psychosis risk is associated with altered white matter connectivity between the striatum and any cortical region is still unclear. Further, no previous study has directly examined whether psychosis risk is associated with altered striatal connectivity with specific cortical networks. The current study examined the integrity of corticostriatal white matter tracts in psychosis risk (n=18) and in non-psychosis risk comparison participants (n=19). We used probabilistic tractography to identify white matter tracts connecting each of four different striatal subregions with their most functionally connected cortical network: limbic, default mode, frontoparietal, and motor networks. We then compared groups on fractional anisotropy in these four tracts. Psychosis risk was associated with decreased fractional anisotropy in white matter tracts connecting the limbic striatum with the limbic cortical network, especially in an anterior right external capsule segment and in tracts specifically connected to the right prefrontal cortex. In contrast, psychosis risk was not associated with decreased white matter integrity in other corticostriatal tracts. Hence, the current research suggests that psychosis risk is especially associated with decreased corticostriatal white matter integrity involved in processing emotional and personally relevant information., Competing Interests: Declaration of Competing Interest We wish to draw the attention of the editors to the role of our funding sources which could be considered a possible conflict of interest. This research was supported by National Institute of Mental Health [grant R21 MH100359, grant T32 MH014677] and University of Missouri research funds., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Young adulthood has the highest rates of alcohol use and high-risk drinking behavior. This period is also a critical neurodevelopmental stage, with neural insults having a profound neurotoxic effect on the brain. Cortical gyrification is thought, in part, to reflect early brain maturation (e.g., hypogyrification in fetal alcohol syndrome). There is also evidence that cortical gyrification is sensitive to later-life events (e.g., fluctuations in malnutrition in young adults). However, no study has examined how alcohol use in young adulthood is associated with cortical gyrification., Methods: We examined the associations between cortical gyrification with lifetime alcohol use and past year hangover symptoms in young adults (N = 78)., Results: Lifetime alcohol use was associated with hypogyria in multiple cortical regions (rs ≤ -.27, ps ≤ .0159; right orbitofrontal, right temporal pole, and left lateral occipital). Further, past year hangover symptoms were associated with hypogyria (rs ≤ -.27, ps ≤ .0034), overlapping with lifetime alcohol use (right orbitofrontal and left lateral occipital). Hangover symptoms were also uniquely associated with hypogyria of other cortical regions (rs ≤ -.30, ps ≤ .0002; right parahippocampal gyrus, left inferior temporal/parahippocampal gyrus and right anterior insula)., Conclusions: Thus, results suggest that young adulthood is a critical period for targeted prevention and intervention, especially for individuals exhibiting heavy alcohol consumption and high-risk drinking behavior., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Affective instability (i.e., large and frequent shifts in negative emotions) is a key emotion dysregulation symptom in emotional distress disorders and can be reliably and validly assessed using ambulatory assessment. However, no study has examined whether affective instability is associated with brain function and structure. Using multimodal neuroimaging and ambulatory assessment, we examined associations between functional activation and cortical structure with ambulatory-assessed affective instability in emotional distress disorders (n = 27). Increased daily life-affective instability was associated with decreased neural activation on an emotion regulation task in a left inferior parietal region consistently associated with emotion regulation. Daily-life affective instability was also associated with hypogyria in this same left inferior parietal region, with hypogyria extending into additional posterior parietal regions. This study found evidence that daily-life affective instability was associated with both functionstructure of the posterior parietal cortex, a key attentional control region involved in emotion regulation., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Jumping to conclusions is associated with delusions. It is unclear whether positive schizotypy, which refers to delusion-like and hallucination-like symptoms, is associated with jumping to conclusions. Relatedly, the relative validity of two jumping to conclusions scores, extreme responding and draws to decision, is unclear, particularly whether extreme responding (responding after one or two draws) reflects the same bias as decreased draws to decision on non-extreme responding trials. Methods: Extreme positive schizotypy individuals with increased psychosis risk ( n  = 69) and controls ( n  = 95) completed the Probabilistic Reasoning Task and reported on recent distress, which was previously associated with jumping to conclusions. We calculated extreme responding, draws to decision (number of draws), and draws to decision/non-extreme responding (number of draws on trials with three or more draws). Results: Positive schizotypy was associated with extreme responding, but not draws to decision/non-extreme responding. Furthermore, draws to decision and draws to decision/non-extreme responding were associated with recent distress, whereas extreme responding was not. Conclusion: Positive schizotypy was specifically associated with extreme responding and not draws to decision/non-extreme responding, which suggests that the nature of extreme responding and of draws to decision might be different. This could have relevance for assessing and treating jumping to conclusions.

Psychosis is strongly related to increased striatal dopamine. However, the neural consequences of increased striatal dopamine in psychosis risk are still not fully understood. Consistent with an increase in striatal dopamine, in previous research, psychosis risk has been associated with neural EEG evidence of a greater response to unexpected reward than unexpected punishment feedback on a reversal-learning task. However, previous research has not directly examined whether psychosis risk is associated with altered striatal activation when receiving unexpected feedback on this task. There were two groups of participants: an antipsychotic medication-naive psychosis risk group (n = 21) who had both (a) extreme levels of self-reported psychotic-like beliefs and experiences and (b) interview-rated current-attenuated psychotic symptoms; and a comparison group (n = 20) who had average levels of self-reported psychotic-like beliefs and experiences. Participants completed a reversal-leaning task during fMRI scanning. As expected, in both ROI and whole-brain analyses, the psychosis risk group exhibited greater striatal activation (for whole-brain analyses, the peak was located in the right caudate) to unexpected reward than unexpected punishment feedback relative to the comparison group. These results indicate that psychosis risk is associated with a relatively increased neural sensitivity to unexpected reward than unexpected punishment outcomes and appears consistent with increased striatal dopamine. The results may help us better understand and detect striatal dysfunction in psychosis risk.

Psychosis is linked to aberrant salience or to viewing neutral stimuli as self-relevant, suggesting a possible impairment in self-relevance processing. Psychosis is also associated with increased dopamine in the dorsal striatum, especially the anterior caudate (Kegeles et al., 2010). Critically, the anterior caudate is especially connected to (a) the cortical default mode network (DMN), centrally involved in self-relevance processing, and (b) to a lesser extent, the cortical frontoparietal network (FPN; Choi, Yeo, & Buckner, 2012). However, no previous study has directly examined striatal-cortical DMN connectivity in psychosis risk. In Study 1, we examined resting-state functional connectivity in psychosis risk (n = 18) and control (n = 19) groups between (a) striatal DMN and FPN subregions and (b) cortical DMN and FPN. The psychosis risk group exhibited decreased connectivity between the striatal subregions and the cortical DMN. In contrast, the psychosis risk group exhibited intact connectivity between the striatal subregions and the cortical FPN. Additionally, recent distress was also associated with decreased striatal-cortical DMN connectivity. In Study 2, to determine whether the decreased striatal-cortical DMN connectivity was specific to psychosis risk or was related to recent distress more generally, we examined the relationship between connectivity and distress in individuals diagnosed with nonpsychotic emotional distress disorders (N = 25). In contrast to Study 1, here we found that distress was associated with evidence of increased striatal-cortical DMN connectivity. Overall, the present results suggest that decreased striatal-cortical DMN connectivity is associated with psychosis risk and could contribute to aberrant salience.

Although emotion deficits in schizotypy have been reported, the exact nature of these deficits is now well understood. Specifically, for social anhedonia (SocAnh), there are questions about whether any decrease in positive affect only reflects an explicit bias not observed in other measures (e.g., implicit affect measure). At the same time, for individuals with elevated levels of perceptual aberrations or magical ideation (PerMag), there is some evidence of an increased influence of affect on judgment. It is also possible that the influence of implicit affect on judgment might be especially pronounced in PerMag; however, this has not been previously examined. The current study involved people with elevated levels of SocAnh ( n = 95), elevated levels of PerMag ( n = 62), and people with average or lower levels of both ( n = 246). We found that SocAnh was associated with decreases in both explicit and implicit positive affect. We also found that PerMag was related to stronger relationships between implicit affect, both positive and negative, and a judgment task. These results suggest that decreased positive affect is a core feature of SocAnh and that a heightened influence of affect could be related to the development of peculiar beliefs/experiences associated with PerMag.

Background: Psychosis risk is associated with striatal dysfunction, including a previous behavioral study that found that psychosis risk is associated with impaired performance on a probabilistic category learning task (PCLT; ie, the Weather Prediction Task), a task strongly associated with striatal activation. The current study examined whether psychosis risk based on symptom levels was associated with both poor behavioral performance and task-related physiological dysfunction in specific regions of the striatum while performing the PCLT., Methods: There were 2 groups of participants: psychosis risk (n = 21) who had both (a) extreme levels of self-reported psychotic-like beliefs and experiences and (b) interview-rated current attenuated psychotic symptoms (APS); and a comparison group (n = 20) who had average levels of self-reported psychotic-like beliefs and experiences. Participants completed the PCLT during fMRI scanning., Results: The current research replicated previous work finding behavioral PCLT deficits at the end of the task in psychosis risk. Furthermore, as expected, the psychosis risk group exhibited decreased striatal activation on the task, especially in the associative striatum. The psychosis risk group also displayed decreased activation in a range of cortical regions connected to the associative striatum. In contrast, the psychosis risk group exhibited greater activation predominantly in cortical regions not connected to the associative striatum., Conclusions: Psychosis risk was associated with both behavioral and striatal dysfunction during performance on the PCLT, suggesting that behavioral and imaging measures using this task could be a marker for psychosis risk., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

As a risk factor for psychosis, childhood trauma rates are elevated in the clinical-high-risk (CHR) syndrome compared to the general population. However, it is unknown whether trauma is typically experienced in childhood or adolescence/young adulthood, whether it occurred prior to CHR syndrome onset, and how severe trauma relates to presenting symptoms. In this study, we examined the relationship of trauma history to symptoms and functioning in individuals diagnosed with the CHR syndrome on the Structured Interview for Psychosis-Risk Syndromes (N = 103). Trauma, defined as meeting the DSM-IV A1 criterion of actual or threatened death or injury, was assessed by semi-structured interview. A large proportion of CHR participants (61%) reported trauma exposure, including interpersonal trauma, trauma prior to CHR onset, and childhood trauma prior to age 12. Those with a trauma history (versus those without trauma) were rated as having more severe perceptual disturbances, general/affective symptoms and more impairment on the Global Assessment of Functioning Scale. The number of traumatic events correlated with more severe ratings in those three domains. Additionally, the number of interpersonal traumas was correlated with ratings of suspiciousness. Trauma was unrelated to specific measures of social and role functioning. A small proportion of CHR participants were diagnosed with formal PTSD (14%), which was unrelated to symptom severity or functioning. Thus, we demonstrate that trauma exposure is often early in life (before age 12), occurs prior to the onset of the CHR syndrome, and is related to both positive and affective symptoms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Positive schizotypy and mania risk scales are strongly correlated, and both are linked to alterations in striatal dopamine. Previous research has not examined whether these risk scales form distinct factors or whether they are differentially related to other measures of psychopathology risk or striatal dopamine. In the current study (N = 596), undergraduate students completed both positive schizotypy and mania risk scales as well as scales assessing related psychopathology (i.e., negative and disorganized schizotypy; self-reported manic-like episodes). Additionally, we measured spontaneous eye blink rate, which has been consistently associated with striatal dopamine levels. Positive schizotypy and mania risk factors were strongly correlated (factor correlation = 0.73). However, a two-factor model with positive schizotypy and mania risk as separate factors fit significantly better than a one-factor risk model. After removing shared variance, only positive schizotypy was positively associated with both negative and disorganized schizotypy, and only mania risk was related to self-reported manic-like episodes. Furthermore, positive schizotypy was associated with decreased spontaneous eye blink rate, and mania risk was associated with increased spontaneous eye blink rate. Overall, these results suggest that positive schizotypy and mania risk can be distinguished as separate factors and that they might be differentially associated with striatal dopamine measures., (Copyright © 2018 Elsevier B.V. All rights reserved.)