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IntroductionPersistent negative symptoms (PNS) are described as continuing moderate negative symptoms. More severe negative symptoms have been associated with poor premorbid functioning in both chronic schizophrenia and first episode psychosis patients. Furthermore, youth at clinical high risk (CHR) for developing psychosis may also present with negative symptoms and poor premorbid functioning. The aim of this current study was to: (1) define the relationship between PNS and premorbid functioning, life events, trauma and bullying, previous cannabis use, and resource utilization, and (2) to examine what explanatory variables best predicted PNS.MethodCHR participants (N = 709) were recruited from the North American Prodrome Longitudinal Study (NAPLS 2). Participants were divided into two groups: those with PNS (n = 67) versus those without PNS (n = 673). A K-means cluster analysis was conducted to distinguish patterns of premorbid functioning across the different developmental stages. The relationships between premorbid adjustment and other variables were examined using independent samples t-tests or chi square for categorical variables.ResultsThere was significantly more males in the PNS group. Participants with PNS had significantly lower levels of premorbid adjustment in childhood, early adolescence, and late adolescence, compared to CHR participants without PNS. There were no differences between the groups in terms of trauma, bullying, and resource utilization. The non-PNS group had more cannabis use and more desirable and non-desirable life events.ConclusionIn terms of better understanding relationships between early factors and PNS, a prominent factor associated with PNS was premorbid functioning, in particular poor premorbid functioning in later adolescence.

Supplemental material, sj-docx-1-cpx-10.1177_21677026221138819 for Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals by Katrina Aberizk, Esra Sefik, Jean Addington, Alan Anticevic, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Ming T. Tsuang, Scott W. Woods and Elaine F. Walker in Clinical Psychological Science

Supplemental material, sj-pdf-3-cpx-10.1177_21677026221138819 for Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals by Katrina Aberizk, Esra Sefik, Jean Addington, Alan Anticevic, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Ming T. Tsuang, Scott W. Woods and Elaine F. Walker in Clinical Psychological Science

Supplemental material, sj-pdf-2-cpx-10.1177_21677026221138819 for Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals by Katrina Aberizk, Esra Sefik, Jean Addington, Alan Anticevic, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Ming T. Tsuang, Scott W. Woods and Elaine F. Walker in Clinical Psychological Science

Supplemental material, sj-pdf-3-cpx-10.1177_21677026221138819 for Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals by Katrina Aberizk, Esra Sefik, Jean Addington, Alan Anticevic, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Ming T. Tsuang, Scott W. Woods and Elaine F. Walker in Clinical Psychological Science

Supplemental material, sj-pdf-2-cpx-10.1177_21677026221138819 for Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals by Katrina Aberizk, Esra Sefik, Jean Addington, Alan Anticevic, Carrie E. Bearden, Kristin S. Cadenhead, Tyrone D. Cannon, Barbara A. Cornblatt, Matcheri Keshavan, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Ming T. Tsuang, Scott W. Woods and Elaine F. Walker in Clinical Psychological Science

Background and hypothesisNegative symptom trajectory in clinical high risk (CHR) for psychosis is ill defined. This study aimed to better characterize longitudinal patterns of change in negative symptoms, moderators of change, and differences in trajectories according to clinical subgroups. We hypothesized that negative symptom course will be nonlinear in CHR. Clinical subgroups known to be more severe variants of psychotic illness-deficit syndrome (DS), persistent negative syndrome (PNS), and acute psychosis onset-were expected to show more severe baseline symptoms, slower rates of change, and less stable rates of symptom resolution.Study designLinear, curvilinear, and stepwise growth curve models, with and without moderators, were fitted to negative symptom ratings from the NAPLS-3 CHR dataset (N = 699) and within clinical subgroups.Study resultsNegative symptoms followed a downward curvilinear trend, with marked improvement 0-6 months that subsequently stabilized (6-24 months), particularly among those with lower IQ and functioning. Clinical subgroups had higher baseline ratings, but distinct symptom courses; DS vs non-DS: more rapid initial improvement, similar stability of improvements; PNS vs non-PNS: similar rates of initial improvement and stability; transition vs no transition: slower rate of initial improvement, with greater stability of this rate.ConclusionsContinuous, frequent monitoring of negative symptoms in CHR is justified by 2 important study implications: (1) The initial 6 months of CHR program enrollment may be a key window for improving negative symptoms as less improvement is likely afterwards, (2) Early identification of clinical subgroups may inform distinct negative symptom trajectories and treatment needs.

AimsYoung people with attenuated psychotic symptoms (APS), brief intermittent psychosis, and/or genetic risk and functional deterioration are at high risk for developing psychotic disorders. In a prior trial, family-focused therapy for clinical high risk youth (FFT-CHR) was more effective than brief psychoeducation in reducing APS severity over 6months. This 7-site trial will compare the efficacy of FFT-CHR to a psychoeducational and supportive intervention (enhanced care) on APS and social functioning in CHR individuals over 18 months.MethodsParticipants (N=220, ages 13-25 years) with a CHR syndrome will be randomly assigned to FFT-CHR (18 1-h sessions of family psychoeducation and communication/problem-solving skills training) or enhanced care (3 1-h family psychoeducational sessions followed by 5 individual support sessions), both given over 6months. Participants will rate their weekly progress during treatment using a mobile-enhanced online platform. Family communication will be assessed in a laboratory interactional task at baseline and post-treatment. Independent evaluators will assess APS (primary outcome) and psychosocial functioning (secondary outcome) every 6months over 18 months.ResultsWe hypothesize that, compared to enhanced care, FFT-CHR will be associated with greater improvements in APS and psychosocial functioning over 18 months. Secondarily, improvements in family communication over 6months will mediate the relationship between treatment condition and primary and secondary outcomes over 18 months. The effects of FFT-CHR are predicted to be greater in individuals with higher baseline risk for psychosis conversion.ConclusionsResults of the trial will inform treatment guidelines for individuals at high risk for psychosis.

IntroductionDisturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time.MethodsData were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations.ResultsDisturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar.DiscussionThe critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.

ObjectiveMany psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.MethodsCross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).ResultsACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.ConclusionsAnticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.

BackgroundLatency of the acoustic startle reflex is the time from presentation of the startling stimulus until the response, and provides an index of neural processing speed. Schizophrenia subjects exhibit slowed latency compared to healthy controls. One prior publication reported significant heritability of latency. The current study was undertaken to replicate and extend this solitary finding in a larger cohort.MethodsSchizophrenia probands, their relatives, and control subjects from the Consortium on the Genetics of Schizophrenia (COGS-1) were tested in a paradigm to ascertain magnitude, latency, and prepulse inhibition of startle. Trial types in the paradigm were: pulse-alone, and trials with 30, 60, or 120ms between the prepulse and pulse. Comparisons of subject groups were conducted with ANCOVAs to assess startle latency and magnitude. Heritability of startle magnitude and latency was analyzed with a variance component method implemented in SOLAR v.4.3.1.Results980 subjects had analyzable startle results: 199 schizophrenia probands, 456 of their relatives, and 325 controls. A mixed-design ANCOVA on startle latency in the four trial types was significant for subject group (F(2,973)=4.45, p=0.012) such that probands were slowest, relatives were intermediate and controls were fastest. Magnitude to pulse-alone trials differed significantly between groups by ANCOVA (F(2,974)=3.92, p=0.020) such that controls were lowest, probands highest, and relatives intermediate. Heritability was significant (p&nbsp

Supplemental material, Supplemental_data-1 for Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program by TianHong Zhang, XiaoChen Tang, HuiJun Li, Kristen A Woodberry, Emily R Kline, LiHua Xu, HuiRu Cui, YingYing Tang, YanYan Wei, ChunBo Li, Li Hui, Margaret A Niznikiewicz, Martha E Shenton, Matcheri S Keshavan, William S Stone and JiJun Wang in Australian & New Zealand Journal of Psychiatry

Supplemental material, Supplemental_data-3 for Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program by TianHong Zhang, XiaoChen Tang, HuiJun Li, Kristen A Woodberry, Emily R Kline, LiHua Xu, HuiRu Cui, YingYing Tang, YanYan Wei, ChunBo Li, Li Hui, Margaret A Niznikiewicz, Martha E Shenton, Matcheri S Keshavan, William S Stone and JiJun Wang in Australian & New Zealand Journal of Psychiatry

Supplemental material, Supplemental_data-2 for Clinical subtypes that predict conversion to psychosis: A canonical correlation analysis study from the ShangHai At Risk for Psychosis program by TianHong Zhang, XiaoChen Tang, HuiJun Li, Kristen A Woodberry, Emily R Kline, LiHua Xu, HuiRu Cui, YingYing Tang, YanYan Wei, ChunBo Li, Li Hui, Margaret A Niznikiewicz, Martha E Shenton, Matcheri S Keshavan, William S Stone and JiJun Wang in Australian & New Zealand Journal of Psychiatry

Post-print version of 2018 Molecular Psychiatry paper entitled 'Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program'. Archived after 6-month embargo period, in compliance with Publisher copyright policies & self-archiving (SHERPA / RoMEO). Archive is intended to ensure Green Open Access, in compliance with funding requirements from European Union’s Horizon 2020 research and innovation programme.

Post-print version of 2018 Molecular Psychiatry paper entitled 'Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program'.Archived after 6-month embargo period, in compliancewith Publisher copyright policies & self-archiving (SHERPA / RoMEO). Archive is intended to ensureGreen Open Access, in compliance with funding requirements fromEuropean Union’s Horizon 2020research and innovation programme.