Publications test

@article{pmid37822873,

title = {Universal method for the isolation of microvessels from frozen brain tissue: A proof-of-concept multiomic investigation of the neurovasculature},

author = {Marina Wakid and Daniel Almeida and Zahia Aouabed and Reza Rahimian and Maria Antonietta Davoli and Volodymyr Yerko and Elena Leonova-Erko and Vincent Richard and René Zahedi and Christoph Borchers and Gustavo Turecki and Naguib Mechawar},

doi = {10.1016/j.bbih.2023.100684},

issn = {2666-3546},

year  = {2023},

date = {2023-12-01},

journal = {Brain Behav Immun Health},

volume = {34},

pages = {100684},

abstract = {The neurovascular unit, comprised of vascular cell types that collectively regulate cerebral blood flow to meet the needs of coupled neurons, is paramount for the proper function of the central nervous system. The neurovascular unit gatekeeps blood-brain barrier properties, which experiences impairment in several central nervous system diseases associated with neuroinflammation and contributes to pathogenesis. To better understand function and dysfunction at the neurovascular unit and how it may confer inflammatory processes within the brain, isolation and characterization of the neurovascular unit is needed. Here, we describe a singular, standardized protocol to enrich and isolate microvessels from archived snap-frozen human and frozen mouse cerebral cortex using mechanical homogenization and centrifugation-separation that preserves the structural integrity and multicellular composition of microvessel fragments. For the first time, microvessels are isolated from postmortem ventromedial prefrontal cortex tissue and are comprehensively investigated as a structural unit using both RNA sequencing and Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). Both the transcriptome and proteome are obtained and compared, demonstrating that the isolated brain microvessel is a robust model for the NVU and can be used to generate highly informative datasets in both physiological and disease contexts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37769672,

title = {International consensus on patient-centred outcomes in eating disorders},

author = {Amelia Austin and Umanga De Silva and Christiana Ilesanmi and Theerawich Likitabhorn and Isabel Miller and Maria da Luz Sousa Fialho and S Bryn Austin and Belinda Caldwell and Chu Shan Elaine Chew and Sook Ning Chua and Suzanne Dooley-Hash and James Downs and Carine El Khazen Hadati and Beate Herpertz-Dahlmann and Jillian Lampert and Yael Latzer and Paulo P P Machado and Sarah Maguire and Madeeha Malik and Carolina Meira Moser and Elissa Myers and Iris Ruth Pastor and Janice Russell and Lauren Smolar and Howard Steiger and Elizabeth Tan and Eva Trujillo-Chi Vacuán and Mei-Chih Meg Tseng and Eric F van Furth and Jennifer E Wildes and Christine Peat and Tracy K Richmond},

doi = {10.1016/S2215-0366(23)00265-1},

issn = {2215-0374},

year  = {2023},

date = {2023-12-01},

journal = {Lancet Psychiatry},

volume = {10},

number = {12},

pages = {966--973},

abstract = {The effectiveness of mental health care can be improved through coordinated and wide-scale outcome measurement. The International Consortium for Health Outcomes Measurement has produced collaborative sets of outcome measures for various mental health conditions, but no universal guideline exists for eating disorders. This Position Paper presents a set of outcomes and measures for eating disorders as determined by 24 international experts from professional and lived experience backgrounds. An adapted Delphi technique was used, and results were assessed through an open review survey. Final recommendations suggest outcomes should be tracked across four domains: eating disorder behaviours and cognitions, physical health, co-occurring mental health conditions, and quality of life and social functioning. Outcomes are collected using three to five patient-reported measures. For children aged between 6 years and 12 years, the measures include the Children's Eating Attitude Test (or, for those with avoidant restrictive food intake disorder, the Eating Disorder in Youth Questionnaire), the KIDSCREEN-10, and the Revised Children's Anxiety and Depression Screener-25. For adolescents aged between 13 years and 17 years, the measures include the Eating Disorder Examination Questionnaire (EDE-Q; or, for avoidant restrictive food intake disorder, the Nine-Item Avoidant Restrictive Food Intake Disorder Screener [NIAS]), the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), the two-item Generalised Anxiety Disorder (GAD-2), the seven-item Generalised Anxiety Disorder (GAD-7), and the KIDSCREEN-10. For adults older than 18 years, measures include the EDE-Q (or, for avoidant restrictive food intake disorder, the NIAS), the PHQ-2, the PHQ-9, the GAD-2, the GAD-7, the Clinical Impairment Assessment, and the 12-item WHO Disability Assessment Schedule 2.0. These questionnaires should be supplemented by information on patient characteristics and circumstances (ie, demographic, historical, and clinical factors). International adoption of these guidelines will allow comparison of research and clinical interventions to determine which settings and interventions work best, and for whom.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37732456,

title = {Atypical brain structure and function in young adults exposed to disaster-related prenatal maternal stress: Project Ice Storm},

author = {Xinyuan Li and Muhammad Naveed Iqbal Qureshi and David P Laplante and Guillaume Elgbeili and Sherri Lee Jones and Xiangyu Long and Vincent Paquin and Gleb Bezgin and Firoza Lussier and Suzanne King and Pedro Rosa-Neto},

doi = {10.1002/jnr.25246},

issn = {1097-4547},

year  = {2023},

date = {2023-12-01},

journal = {J Neurosci Res},

volume = {101},

number = {12},

pages = {1849--1863},

abstract = {Studies have shown that prenatal maternal stress (PNMS) affects brain structure and function in childhood. However, less research has examined whether PNMS effects on brain structure and function extend to young adulthood. We recruited women who were pregnant during or within 3 months following the 1998 Quebec ice storm, assessed their PNMS, and prospectively followed-up their children. T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI were obtained from 19-year-old young adults with (n = 39) and without (n = 65) prenatal exposure to the ice storm. We examined between-group differences in gray matter volume (GMV), surface area (SA), and cortical thickness (CT). We used the brain regions showing between-group GMV differences as seeds to compare between-group functional connectivity. Within the Ice Storm group, we examined (1) associations between PNMS and the atypical GMV, SA, CT, and functional connectivity, and (2) moderation by timing of exposure. Primarily, we found that, compared to Controls, the Ice Storm youth had larger GMV and higher functional connectivity of the anterior cingulate cortex, the precuneus, the left occipital pole, and the right hippocampus; they also had larger CT, but not SA, of the left occipital pole. Within the Ice Storm group, maternal subjective distress during preconception and mid-to-late pregnancy was associated with atypical left occipital pole CT. These results suggest the long-lasting impact of disaster-related PNMS on child brain structure and functional connectivity. Our study also indicates timing-specific effects of the subjective aspect of PNMS on occipital thickness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37551444,

title = {Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations},

author = {Iason Keramidis and Brendan B McAllister and Julien Bourbonnais and Feng Wang and Dominique Isabel and Edris Rezaei and Romain Sansonetti and Phil Degagne and Justin P Hamel and Mojtaba Nazari and Samsoon Inayat and Jordan C Dudley and Annie Barbeau and Lionel Froux and Marie-Eve Paquet and Antoine G Godin and Majid H Mohajerani and Yves De Koninck},

doi = {10.1093/brain/awad250},

issn = {1460-2156},

year  = {2023},

date = {2023-12-01},

journal = {Brain},

volume = {146},

number = {12},

pages = {4903--4915},

abstract = {Disinhibition during early stages of Alzheimer's disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer's disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness of GABAA-mediated inhibition, occurs pre-symptomatically in the hippocampus and prefrontal cortex. KCC2 downregulation was inversely correlated with the age-dependent increase in amyloid-β 42 (Aβ42). Acute administration of Aβ42 caused a downregulation of membrane KCC2. Loss of KCC2 resulted in impaired chloride homeostasis. Preventing the decrease in KCC2 using long term treatment with CLP290 protected against deterioration of learning and cortical hyperactivity. In addition, restoring KCC2, using short term CLP290 treatment, following the transporter reduction effectively reversed spatial memory deficits and social dysfunction, linking chloride dysregulation with Alzheimer's disease-related cognitive decline. These results reveal KCC2 hypofunction as a viable target for treatment of Alzheimer's disease-related cognitive decline; they confirm target engagement, where the therapeutic intervention takes place, and its effectiveness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37973252,

title = {Prospective associations between ADHD symptoms and physical conditions from early childhood to adolescence: a population-based longitudinal study},

author = {Cédric Galera and Ophélie Collet and Massimiliano Orri and Marie Navarro and Laura Castel and Charline Galesne and Claire Reed and Valerie Brandt and Henrik Larsson and Michel Boivin and Richard Tremblay and Sylvana Côté and Samuele Cortese},

doi = {10.1016/S2352-4642(23)00226-2},

issn = {2352-4650},

year  = {2023},

date = {2023-12-01},

journal = {Lancet Child Adolesc Health},

volume = {7},

number = {12},

pages = {863--874},

abstract = {BACKGROUND: The co-occurrence between attention-deficit hyperactivity disorder (ADHD) and physical conditions is frequent but often goes unrecognised. Most available evidence on the links between ADHD and physical conditions relies on cross-sectional studies. Understanding temporal sequences of associations is key to inform appropriate treatment and preventive strategies. We aimed to assess possible longitudinal associations between ADHD symptoms and a broad range of physical conditions, adjusting for several confounding factors.nnMETHODS: Participants came from the population-based Quebec Longitudinal Study of Child Development. Participants were selected from the Quebec Birth Registry, recruited between October, 1997, and July, 1998, from the province of Quebec, Canada, and followed up in early childhood (n=2120; age 5 months-5 years), middle childhood (n=1750; age 6-12 years), and adolescence (n=1573; age 13-17 years). Main outcome measures included ADHD symptom severity and physical conditions, which were reported by the person most knowledgeable of the child in early childhood, by teachers in middle childhood, and self-reported in adolescence. Multivariable regression analyses were conducted to study the prospective associations between ADHD symptoms and later physical conditions, and physical conditions and later ADHD symptoms, adjusting for multiple confounders.nnFINDINGS: We found several prospective associations between ADHD symptoms and physical conditions including asthma, high BMI (≥1 SD above the mean), epilepsy, dental caries, acute infections, injuries, and sleep problems. After adjusting for key confounding factors, several associations remained: ADHD symptoms in early childhood were associated with later high BMI during middle childhood (odds ratio [OR] 1·19 [95% CI 1·05-1·35]) and adolescence (OR 1·14 [1·01-1·29]), and with unintentional injuries during adolescence (OR 1·10 [1·01-1·21]). ADHD symptoms in middle childhood were significantly associated with later dental caries during adolescence (OR 1·10 [1·01-1·20]). Unintentional injuries in early childhood were associated with later ADHD symptoms in middle childhood (standardised mean difference [SMD] 0·15 [0·05-0·24]) and adolescence (SMD 0·13 [0·04-0·23]), and restless legs syndrome symptoms in middle childhood were associated with later ADHD symptoms in adolescence (SMD 0·15 [0·05-0·25]).nnINTERPRETATION: Our results point to the need to carefully monitor children with ADHD in early or middle childhood for several physical conditions, and to monitor children with particular physical conditions for ADHD symptoms. Our study also calls for policies to promote more integrated health-care systems for children with complex mental and physical needs, bridging the current gap between mental and physical health-care services.nnFUNDING: Québec Government's Ministry of Health, Ministry of Education, and Ministry of Family Affairs; The Lucie and André Chagnon Foundation; the Robert-Sauvé Research Institute of Health and Safety at Work; the Québec Statistics Institute; the Fonds de Recherche du Québec-Santé; the Fonds de Recherche du Québec-Societé et Culture; Canada's Social Science and Humanities Research Council; the Canadian Institutes of Health Research, the Sainte-Justine Research Center; and the French National Research Agency.nnTRANSLATION: For the French translation of the abstract see Supplementary Materials section.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38011563,

title = {Transcriptional signatures of early-life stress and antidepressant treatment efficacy},

author = {Sero Toriano Parel and Shannon N Bennett and Cindy J Cheng and Olivia C Timmermans and Laura M Fiori and Gustavo Turecki and Catherine Jensen Peña},

doi = {10.1073/pnas.2305776120},

issn = {1091-6490},

year  = {2023},

date = {2023-12-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {49},

pages = {e2305776120},

abstract = {Individuals with a history of early-life stress (ELS) tend to have an altered course of depression and lower treatment response rates. Research suggests that ELS alters brain development, but the molecular changes in the brain following ELS that may mediate altered antidepressant response have not been systematically studied. Sex and gender also impact the risk of depression and treatment response. Here, we leveraged existing RNA sequencing datasets from 1) blood samples from depressed female- and male-identifying patients treated with escitalopram or desvenlafaxine and assessed for treatment response or failure; 2) the nucleus accumbens (NAc) of female and male mice exposed to ELS and/or adult stress; and 3) the NAc of mice after adult stress, antidepressant treatment with imipramine or ketamine, and assessed for treatment response or failure. We find that transcriptomic signatures of adult stress after a history of ELS correspond with transcriptomic signatures of treatment nonresponse, across species and multiple classes of antidepressants. Transcriptomic correspondence with treatment outcome was stronger among females and weaker among males. We next pharmacologically tested these predictions in our mouse model of early-life and adult social defeat stress and treatment with either chronic escitalopram or acute ketamine. Among female mice, the strongest predictor of behavior was an interaction between ELS and ketamine treatment. Among males, however, early experience and treatment were poor predictors of behavior, mirroring our bioinformatic predictions. These studies provide neurobiological evidence for molecular adaptations in the brain related to sex and ELS that contribute to antidepressant treatment response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38048480,

title = {Teaching Adolescents With Type 1 Diabetes Self-Compassion (TADS) to Reduce Diabetes Distress: Protocol for a Randomized Controlled Trial},

author = {Saunya Dover and Alexandra Ahmet and Karen Bluth and Brian M Feldman and Ellen B Goldbloom and Gary S Goldfield and Sarah Hamilton and Omar Imran and Adam Khalif and Karine Khatchadourian and Sarah Lawrence and Andrew Leonard and Kuan Liu and Yongdong Ouyang and Corien Peeters and Jai Shah and Noah Spector and Caroline Zuijdwijk and Marie-Eve Robinson},

doi = {10.2196/53935},

issn = {1929-0748},

year  = {2023},

date = {2023-12-01},

journal = {JMIR Res Protoc},

volume = {12},

pages = {e53935},

abstract = {BACKGROUND: Adolescents living with type 1 diabetes (T1D) often experience diabetes distress (DD), a construct distinct from depression or anxiety that refers to the negative emotions that arise from living with and managing diabetes. Self-compassion, which involves being open to one's own suffering and treating oneself with the same care one would show to loved ones, is associated with better psychological and clinical outcomes among individuals with T1D. Self-compassion is a skill that can be taught and therefore represents an opportunity for intervention.nnOBJECTIVE: The overall aim of this study is to assess the effectiveness of a web-based mindful self-compassion for teens (MSC-T) intervention on improving DD, anxiety, depression, diabetes-related disordered eating, and suicidal ideation experienced by youth with T1D (aged between 12 and 17 years) compared with a waitlist control group (standard of care). We will also explore (1) if the effect of the MSC-T intervention changes over time, (2) if the MSC-T intervention has a positive impact on measures of glycemic control, and (3) if the effect of the MSC-T intervention differs based on self-reported gender.nnMETHODS: We will conduct a single-center, parallel-group randomized controlled trial of 140 adolescents with T1D followed for 12 months. Participants will be randomly allocated (using hidden allocation) in a 1:1 ratio to either the MSC-T intervention or the waitlist control group. Our primary outcome is DD, as measured by the Problem Areas in Diabetes-Teen (PAID-T) version at 3 months. Secondary outcomes, assessed at 3 and 12 months, include anxiety (Generalized Anxiety Disorder 7-item [GAD-7] scale), depression (Patient Health Questionnaire-9 [PHQ-9]), diabetes-related disordered eating (Diabetes Eating Problem Survey-Revised [DEPS-R] version), and suicidal ideation (using 1 question from the PHQ-9).nnRESULTS: Study recruitment began in October 2022 and was completed in March 2023, with a total of 141 participants enrolling. Data collection will be ongoing until March 2024. The first results are expected in June 2024.nnCONCLUSIONS: This study will be the first randomized trial to assess the effectiveness of the web-based MSC-T intervention on adolescents with T1D. Given that adolescence is a period where individuals are typically required to assume more responsibility for their diabetes care, providing adolescents with the tools they need to better manage the stress that often accompanies T1D management is paramount.nnTRIAL REGISTRATION: ClinicalTrials.gov NCT05463874; https://clinicaltrials.gov/study/NCT05463874.nnINTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53935.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38054054,

title = {Heterogeneity in the trajectories of psychological distress among late adolescents during the COVID-19 pandemic},

author = {Jean-Philippe Gouin and Alejandro de la Torre-Luque and Yolanda Sánchez-Carro and Marie-Claude Geoffroy and Cecilia Essau},

doi = {10.1002/jcv2.12195},

issn = {2692-9384},

year  = {2023},

date = {2023-12-01},

journal = {JCPP Adv},

volume = {3},

number = {4},

pages = {e12195},

abstract = {BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has constrained opportunities in social, educational and professional domains, leading to developmental challenges for adolescents initiating their transition to adulthood. Meta-analysis indicated that there was a small increase in psychological distress during the first year of the COVID-19 pandemic. However, significant heterogeneity in the psychological response to the COVID-19 pandemic was noted. Developmental antecedents as well as social processes may account for such heterogeneity. The goal of this study was to characterize trajectories of psychological distress in late adolescence during the COVID-19 pandemic.nnMETHODS: 5014 late adolescents born between 2000 and 2002 from the UK Millennium Cohort Study completed online self-reported assessments at three occasions during the first year of the COVID-19 pandemic (May 2020, September/October 2020 and February/March 2021). These surveys assessed psychological distress, loneliness, social support, family conflict, as well as other pandemic stressors. Information on developmental antecedents were obtained when cohort members were 17 years of age.nnRESULTS: Four distinct trajectories class were identified.  (52.13%) experienced low and decreasing levels of psychological distress, while  (31.84%) experienced a small, but significant increase in distress over time and  (8.75%) exhibited a larger increase in distress after the first wave of the pandemic.  (7.29%) experienced elevated psychological distress during the first wave of the pandemic, followed by a decrease in distress in subsequent waves of the pandemic. Larger longitudinal increases in loneliness were noted among individuals in the elevated distress trajectory, compared to other trajectories. Pre-pandemic psychopathology was associated with elevated distress early in the pandemic.nnCONCLUSIONS: The largest trajectory showed low and declining psychological distress, highlighting the resilience of the majority of late adolescents. However, a subgroup of adolescents experienced large increases in psychological distress, identifying a group of individuals more vulnerable to pandemic-related stress.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38062908,

title = {Patient-reported outcome measures in early psychosis: Evaluating the psychometric properties of the single-item self-reported health and self-reported mental health measures in Chennai, India and Montreal, Canada},

author = {Neha Nair and Aarati Taksal and Greeshma Mohan and Thara Rangaswamy and Ramachandran Padmavati and Norbert Schmitz and Ashok Malla and Srividya N Iyer},

doi = {10.1111/eip.13485},

issn = {1751-7893},

year  = {2023},

date = {2023-12-01},

journal = {Early Interv Psychiatry},

abstract = {AIM: Patient-reported outcome measures (PROMs) provide valuable information and promote shared decision-making but are infrequently used in psychosis. Self-rated Health (SRH) and Self-rated Mental Health (SRMH) are single-item PROMs in which respondents rate their health and mental health from 'poor' to 'excellent'. We examined the psychometric properties of the SRH and SRMH in early psychosis services in Chennai, India and Montreal, Canada.nnMETHODS: Assessments were completed in Tamil/English in Chennai and French/English in Montreal. Test-retest reliability included data from 59 patients in Chennai and Montreal. Criterion validity was examined against clinician-rated measures of depression, anxiety, positive and negative symptoms, and a quality-of-life PROM for 261 patients in Chennai and Montreal.nnRESULTS: SRH and SRMH had good to excellent test-retest reliability (ICC >0.63) at both sites and in English and Tamil (but not French). Results for criterion validity were mixed. In Montreal, low SRH was associated with not being in positive symptom remission, and poorer functioning and quality of life. SRH was associated only with functioning in Chennai. No associations were found for SRMH in Montreal. In Chennai, low SRMH was associated with not being in positive symptom remission and poorer functioning.nnCONCLUSIONS: Patient-reported outcome measures may perform differently across contexts as a potential function of variations in sociodemographics, illness characteristics/course, understandings of health/mental health, and so forth. More work is needed to understand if discrepancies between PROMs and CROMs indicate poor validity of PROMs or 'valid' differences between patient and clinician perceptions. Our work suggests that single-item PROMs can be feasibly integrated into clinical settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38102388,

title = {The vocal side of empathy: neural correlates of pain perception in spoken complaints},

author = {Maël Mauchand and Jorge L Armony and Marc D Pell},

doi = {10.1093/scan/nsad075},

issn = {1749-5024},

year  = {2023},

date = {2023-12-01},

journal = {Soc Cogn Affect Neurosci},

volume = {19},

number = {1},

abstract = {In the extensive neuroimaging literature on empathy for pain, few studies have investigated how this phenomenon may relate to everyday social situations such as spoken interactions. The present study used functional Magnetic Resonance Imaging (fMRI) to assess how complaints, as vocal expressions of pain, are empathically processed by listeners and how these empathic responses may vary based on speakers' vocal expression and cultural identity. Twenty-four French participants listened to short utterances describing a painful event, which were either produced in a neutral-sounding or complaining voice by both in-group (French) and out-group (French Canadian) speakers. Results suggest that the perception of suffering from a complaining voice increased activity in the emotional voice areas, composed of voice-sensitive temporal regions interacting with prefrontal cortices and the amygdala. The Salience and Theory of Mind networks, associated with affective and cognitive aspects of empathy, also showed prosody-related activity and specifically correlated with behavioral evaluations of suffering by listeners. Complaints produced by in- vs out-group speakers elicited sensorimotor and default mode activity, respectively, suggesting accent-based changes in empathic perspective. These results, while reaffirming the role of key networks in tasks involving empathy, highlight the importance of vocal expression information and social categorization processes when perceiving another's suffering during social interactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38129480,

title = {Peripheral clock gene oscillations are perturbed in neonatal and adult rat offspring raised under adverse limited bedding conditions},

author = {Claire-Dominique Walker and Tara C Delorme and Silke Kiessling and Hong Long and Nicolas Cermakian},

doi = {10.1038/s41598-023-47968-y},

issn = {2045-2322},

year  = {2023},

date = {2023-12-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {22886},

abstract = {Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in postnatal development. Since peripheral oscillators can be influenced by maternal feeding and behavior, we investigated whether exposure to the adverse environmental conditions of limited bedding (LB) during postnatal life would alter rhythmicity in the SCN, adrenal gland and liver in neonatal (postnatal day PND10), juvenile (PND28) and adult rats. We also examined locomotor activity in adults. Limited bedding increased nursing time and slightly increased fragmentation of maternal behavior. Exposure to LB reduced the amplitude of Per2 in the SCN on PND10. Adrenal clock gene expression (Bmal1, Per2, Cry1, Rev-erbα, Dbp) and corticosterone secretion were rhythmic at all ages in NB offspring, whereas rhythmicity of Bmal1, Cry1 and corticosterone was abolished in neonatal LB pups. Circadian gene expression in the adrenal and liver was well established by PND28. In adults, liver expression of several circadian genes was increased at specific daytimes by LB and the microstructure of locomotor behavior was altered. Thus, changes in maternal care and behavior might provide important signals to the maturing peripheral oscillators and modify, in particular their output functions in the long-term.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38234857,

title = {Five dominant dimensions of brain aging are identified via deep learning: associations with clinical, lifestyle, and genetic measures},

author = {Zhijian Yang and Junhao Wen and Guray Erus and Sindhuja T Govindarajan and Randa Melhem and Elizabeth Mamourian and Yuhan Cui and Dhivya Srinivasan and Ahmed Abdulkadir and Paraskevi Parmpi and Katharina Wittfeld and Hans J Grabe and Robin Bülow and Stefan Frenzel and Duygu Tosun and Murat Bilgel and Yang An and Dahyun Yi and Daniel S Marcus and Pamela LaMontagne and Tammie L S Benzinger and Susan R Heckbert and Thomas R Austin and Shari R Waldstein and Michele K Evans and Alan B Zonderman and Lenore J Launer and Aristeidis Sotiras and Mark A Espeland and Colin L Masters and Paul Maruff and Jurgen Fripp and Arthur Toga and Sid O'Bryant and Mallar M Chakravarty and Sylvia Villeneuve and Sterling C Johnson and John C Morris and Marilyn S Albert and Kristine Yaffe and Henry Völzke and Luigi Ferrucci and Nick R Bryan and Russell T Shinohara and Yong Fan and Mohamad Habes and Paris Alexandros Lalousis and Nikolaos Koutsouleris and David A Wolk and Susan M Resnick and Haochang Shou and Ilya M Nasrallah and Christos Davatzikos},

doi = {10.1101/2023.12.29.23300642},

year  = {2023},

date = {2023-12-01},

journal = {medRxiv},

abstract = {Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan. Herein, we leverage a state-of-the art deep representation learning method, Surreal-GAN, and present both methodological advances and extensive experimental results that allow us to elucidate the heterogeneity of brain aging in a large and diverse cohort of 49,482 individuals from 11 studies. Five dominant patterns of neurodegeneration were identified and quantified for each individual by their respective (herein referred to as) R-indices. Significant associations between R-indices and distinct biomedical, lifestyle, and genetic factors provide insights into the etiology of observed variances. Furthermore, baseline R-indices showed predictive value for disease progression and mortality. These five R-indices contribute to MRI-based precision diagnostics, prognostication, and may inform stratification into clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37482283,

title = {The relationship between negative symptoms and MATRICS neurocognitive domains: A meta-analysis and systematic review},

author = {Christy Au-Yeung and Danielle Penney and Jesse Rae and Hannah Carling and Libby Lassman and Martin Lepage},

doi = {10.1016/j.pnpbp.2023.110833},

issn = {1878-4216},

year  = {2023},

date = {2023-12-01},

journal = {Prog Neuropsychopharmacol Biol Psychiatry},

volume = {127},

pages = {110833},

abstract = {BACKGROUND: Negative symptoms (NS) are a core symptom domain in schizophrenia spectrum disorders and are associated with poorer social and vocational functioning, and with increased likelihood and durations of hospital admission. NS are not well understood, limiting available interventions. However, numerous studies have reported associations between neurocognitive domains and NS severity. Thus, one promising area in understanding NS is in relation to neurocognition. Currently, the specificity of the relationship between NS and neurocognition is unknown, meaning that there is no consensus regarding which neurocognitive domain is most strongly associated with NS. There is a need to systematically examine the relationship between NS and various neurocognitive domains within study samples.nnMETHODS: A systematic search of Ovid PsycINFO, Ovid MEDLINE and Web of Science was performed for articles published since 2004 (year of MATRICS Consensus publication). Inclusion criteria were: 1) individuals with schizophrenia spectrum disorders, first episode psychosis or clinical high risk 2) assessed all six MATRICS neurocognitive domains (processing speed, attention, working memory, verbal learning & memory, visual learning & memory, reasoning & problem solving), 3) reported correlations between all six MATRICS neurocognitive domains and global NS. A three-level random effects hierarchical meta-analysis was performed to assess the relationship between NS (global, expressive, and experiential dimensions) and the six MATRICS neurocognitive domains.nnRESULTS: 21 studies were included in the review (n = 3619). All MATRICS neurocognitive domains had small significant correlations with global NS (r = -0.16 to -0.20, p < 0.0001). This relationship was significantly moderated by diagnosis and the moderating effect of sex/ gender trended on significance. Analysis of a subset of the studies revealed that MATRICS neurocognitive domains also had small significant correlations with the two NS dimensions, expressive and experiential. Correlations were stronger with the expressive NS dimension.nnCONCLUSIONS: This review is novel in assessing the relationship between multiple neurocognitive domains and NS within the same sample, by synthesizing close to two decades of research. Our results suggest that there is a non-specific relationship between neurocognition and NS, and that expressive NS may have a stronger relationship with neurocognitive functioning-based on the MATRICS classification of neurocognition and the neurocognitive assessments used in the included studies. This has implications on our understanding of NS and neurocognition, as well as their treatments. As we gain better understanding of the directionality of the NS-cognition relationship, it could suggest that NS, particularly in the expressive domain, could be improved by targeting cognition globally or that neurocognitive treatments could be more effective if NS are addressed first. Further implications of these results are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37837812,

title = {Profiles of patients with substance-related disorders who dropped out or not from addiction treatment},

author = {Marie-Josée Fleury and Zhirong Cao and Guy Grenier and Christophe Huỳnh},

doi = {10.1016/j.psychres.2023.115532},

issn = {1872-7123},

year  = {2023},

date = {2023-11-01},

journal = {Psychiatry Res},

volume = {329},

pages = {115532},

abstract = {This longitudinal study identified profiles of patients with substance-related disorders (SRD) who did or did not drop out of specialized addiction treatment, integrating various patterns of outpatient service use. Medical administrative databases of Quebec (Canada) were used to investigate a cohort of 16,179 patients with SRD who received specialized addiction treatment. Latent class analysis identified patient profiles, based on multi-year outpatient service use. Four patient profiles related to treatment dropout were identified: patients who did not drop out and were low service users (Profile 1); patients who did not drop out and were high service users (Profile 2); patients who dropped out and were low service users (Profile 3); patients who dropped out and were high service users (Profile 4). Profile 1 had the best health and social conditions, while Profile 4 had the worst. The risks of being frequent emergency department users, being hospitalized or dying were highest in Profile 4, followed by Profiles 3, 2 and 1. Assertive treatment programs may be suited to Profile 4 and intensive case management programs to Profile 3. Collaborative care with higher psychosocial interventions and regularity of care may be extended to Profile 2 and interventions integrating motivational treatment to Profile 1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37804598,

title = {Risk stratification for treating people at ultra-high risk for psychosis: A cost-effectiveness analysis},

author = {Olajumoke M Ologundudu and Lena Palaniyappan and Lauren E Cipriano and Ben F M Wijnen and Kelly K Anderson and Shehzad Ali},

doi = {10.1016/j.schres.2023.09.015},

issn = {1573-2509},

year  = {2023},

date = {2023-11-01},

journal = {Schizophr Res},

volume = {261},

pages = {225--233},

abstract = {People who are at ultra-high risk (UHR) for psychosis receive clinical care with the aim to prevent first-episode psychosis (FEP), regardless of the risk of conversion to psychosis. An economic model from the Canadian health system perspective was developed to evaluate the cost-effectiveness of treating all with UHR compared to risk stratification over a 15-year time horizon, based on conversion probability, expected quality-of-life and costs. The analysis used a decision tree followed by a Markov model. Health states included: Not UHR, UHR with <20 % risk of conversion to FEP (based on the North American Prodrome Longitudinal Study risk calculator), UHR with ≥20 % risk, FEP, Remission, Post-FEP, and Death. The analysis found that: risk stratification (i.e., only treating those with ≥20 % risk) had lower costs ($1398) and quality-adjusted life-years (0.055 QALYs) per person compared to treating all. The incremental cost-effectiveness ratio for 'treat all' was $25,448/QALY, and suggests treating all may be cost-effective. The model was sensitive to changes to the probability of conversion.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37852259,

title = {Massively parallel functional dissection of schizophrenia-associated noncoding genetic variants},

author = {Christine K Rummel and Miriam Gagliardi and Ruhel Ahmad and Alexander Herholt and Laura Jimenez-Barron and Vanessa Murek and Liesa Weigert and Anna Hausruckinger and Susanne Maidl and Barbara Hauger and Florian J Raabe and Christina Fürle and Lucia Trastulla and Gustavo Turecki and Matthias Eder and Moritz J Rossner and Michael J Ziller},

doi = {10.1016/j.cell.2023.09.015},

issn = {1097-4172},

year  = {2023},

date = {2023-11-01},

journal = {Cell},

volume = {186},

number = {23},

pages = {5165--5182.e33},

abstract = {Schizophrenia (SCZ) is a highly heritable mental disorder with thousands of associated genetic variants located mostly in the noncoding space of the genome. Translating these associations into insights regarding the underlying pathomechanisms has been challenging because the causal variants, their mechanisms of action, and their target genes remain largely unknown. We implemented a massively parallel variant annotation pipeline (MVAP) to perform SCZ variant-to-function mapping at scale in disease-relevant neural cell types. This approach identified 620 functional variants (1.7%) that operate in a highly developmental context and neuronal-activity-dependent manner. Multimodal integration of epigenomic and CRISPRi screening data enabled us to link these functional variants to target genes, biological processes, and ultimately alterations of neuronal physiology. These results provide a multistage prioritization strategy to map functional single-nucleotide polymorphism (SNP)-to-gene-to-endophenotype relations and offer biological insights into the context-dependent molecular processes modulated by SCZ-associated genetic variation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37740852,

title = {Disorganized Communication and Social Dysfunction in Schizophrenia: Emerging Concepts and Methods},

author = {Emmanuel Olarewaju and Guillaume Dumas and Lena Palaniyappan},

doi = {10.1007/s11920-023-01462-4},

issn = {1535-1645},

year  = {2023},

date = {2023-11-01},

journal = {Curr Psychiatry Rep},

volume = {25},

number = {11},

pages = {671--681},

abstract = {PURPOSE OF REVIEW: In this review, we embrace the emerging field of second-person neuroscience to address disorganization in schizophrenia. We argue that the focus of interest for disorganization is the interpersonal space where shared mental processes ('social mind') occur based on the bio-behavioural synchrony between two (or more) interacting people. We lay out several bio-behavioural measures that can capture the component parts of this process. In particular, we highlight the real-time imaging technology of hyperscanning that enables multi-person analysis of naturalistic social interaction. We illustrate how these measures can be used in empirical studies by posing disorganization as a problem of interpersonal processing.nnRECENT FINDINGS: Traditionally, disorganized speech and behaviour have been studied as the product of hidden cognitive processes ('private mind'). A dysfunction in these processes was attributed to the brain afflicted by the illness ('brain-bound mechanisms'). But this approach has contributed to challenges in measuring and quantifying disorganization. Consequently, the single-brain focus has not provided satisfactory clarity or led to effective treatments for persistent social dysfunction in schizophrenia. Social dysfunction is a core feature of schizophrenia. This dysfunction arises from disorganized interpersonal interaction that typifies the social profile of affected individuals. We outline challenges in employing several emerging concepts and methods and how they can be addressed to investigate the mechanisms of social dysfunction in schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37738630,

title = {Brain MRI research in neurodegenerative dementia: time to deliver on promises},

author = {Simon Ducharme},

doi = {10.1093/brain/awad320},

issn = {1460-2156},

year  = {2023},

date = {2023-11-01},

journal = {Brain},

volume = {146},

number = {11},

pages = {4403--4404},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38012135,

title = {Cortical reactivation of spatial and non-spatial features coordinates with hippocampus to form a memory dialogue},

author = {HaoRan Chang and Ingrid M Esteves and Adam R Neumann and Majid H Mohajerani and Bruce L McNaughton},

doi = {10.1038/s41467-023-43254-7},

issn = {2041-1723},

year  = {2023},

date = {2023-11-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {7748},

abstract = {Episodic memories comprise diverse attributes of experience distributed across neocortical areas. The hippocampus is integral to rapidly binding these diffuse representations, as they occur, to be later reinstated. However, the nature of the information exchanged during this hippocampal-cortical dialogue remains poorly understood. A recent study has shown that the secondary motor cortex carries two types of representations: place cell-like activity, which were impaired by hippocampal lesions, and responses tied to visuo-tactile cues, which became more pronounced following hippocampal lesions. Using two-photon Ca imaging to record neuronal activities in the secondary motor cortex of male Thy1-GCaMP6s mice, we assessed the cortical retrieval of spatial and non-spatial attributes from previous explorations in a virtual environment. We show that, following navigation, spontaneous resting state reactivations convey varying degrees of spatial (trajectory sequences) and non-spatial (visuo-tactile attributes) information, while reactivations of non-spatial attributes tend to precede reactivations of spatial representations surrounding hippocampal sharp-wave ripples.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37950055,

title = {Repeated multi-domain cognitive training prevents cognitive decline, anxiety and amyloid pathology found in a mouse model of Alzheimer disease},

author = {Jogender Mehla and Scott H Deibel and Hadil Karem and Nancy S Hong and Shakhawat R Hossain and Sean G Lacoursiere and Robert J Sutherland and Majid H Mohajerani and Robert J McDonald},

doi = {10.1038/s42003-023-05506-6},

issn = {2399-3642},

year  = {2023},

date = {2023-11-01},

journal = {Commun Biol},

volume = {6},

number = {1},

pages = {1145},

abstract = {Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer's disease. To investigate this protective effect, 3-month-old APP mice were exposed to repeated single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, & 9 months. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for all groups. Then, mice were sacrificed, and their brains were assessed for pathology. APP mice given multi-domain cognitive training compared to APP control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. Additionally, multi-domain cognitive training improved anxiety in APP mice as evidenced by measuring thigmotaxis behavior in the Morris water maze. There were mild reductions in microgliosis in the brain of APP mice with single-domain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37884281,

title = {Brain structural correlates of psychopathic traits in elite female combat-sports athletes},

author = {Eduardo González-Alemañy and Anelin Dayris Rodríguez Olivera and María Antonieta Bobes and Jorge L Armony},

doi = {10.1111/ejn.16171},

issn = {1460-9568},

year  = {2023},

date = {2023-11-01},

journal = {Eur J Neurosci},

volume = {58},

number = {10},

pages = {4255--4263},

abstract = {Psychopathy is characterized by glibness and superficial charm, as well as a lack of empathy, guilt and remorse, and is often accompanied by antisocial behaviour. The cerebral bases of this syndrome have been mostly studied in violent subjects or those with a criminal history. However, the antisocial component of psychopathy is not central to its conceptualization, and in fact, psychopathic traits are present in well-adjusted, non-criminal individuals within the general population. Interestingly, certain psychopathy characteristics appear to be particularly pronounced in some groups or professions. Importantly, as these so-called adaptive or successful psychopaths do not show antisocial tendencies or have significant psychiatric comorbidities, they may represent an ideal population to study this trait. Here, we investigated such a group, specifically elite female judo athletes, and compared them with matched non-athletes. Participants completed psychopathy, anger, perspective-taking and empathic concern questionnaires and underwent structural magnetic resonance imaging (MRI). Grey matter volume (GMV) was computed using voxel-based morphometry from the T1-weighted images. Athletes scored significantly higher in primary psychopathy and anger and lower in empathy and perspective taking. They also exhibited smaller GMV in the right temporal pole, left occipital cortex and left amygdala/hippocampus. GMV values for the latter cluster significantly correlated with primary psychopathy scores across both groups. These results confirm and extend previous findings to a little-studied population and provide support for the conceptualization of psychopathy as a dimensional personality trait which not only is not necessarily associated with antisocial behaviour but may potentially have adaptive value.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37885906,

title = {Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders},

author = {John M Felt and Natan Yusupov and Karra D Harrington and Julia Fietz and Zhenyu Zach Zhang and Martin J Sliwinski and Nilam Ram and Kieran J O'Donnell and  and Michael J Meaney and Frank W Putnam and Jennie G Noll and Elisabeth B Binder and Chad E Shenk},

doi = {10.1016/j.ynstr.2023.100577},

issn = {2352-2895},

year  = {2023},

date = {2023-11-01},

journal = {Neurobiol Stress},

volume = {27},

pages = {100577},

abstract = {BACKGROUND: Early life adversity and psychiatric disorders are associated with earlier declines in neurocognitive abilities during adulthood. These declines may be preceded by changes in biological aging, specifically epigenetic age acceleration, providing an opportunity to uncover genome-wide biomarkers that identify individuals most likely to benefit from early screening and prevention.nnMETHODS: Five unique epigenetic age acceleration clocks derived from peripheral blood were examined in relation to latent variables of general and speeded cognitive abilities across two independent cohorts: 1) the Female Growth and Development Study (FGDS;  = 86), a 30-year prospective cohort study of substantiated child sexual abuse and non-abused controls, and 2) the Biological Classification of Mental Disorders study (BeCOME;  = 313), an adult community cohort established based on psychiatric disorders.nnRESULTS: A faster pace of biological aging (DunedinPoAm) was associated with lower general cognitive abilities in both cohorts and slower speeded abilities in the BeCOME cohort. Acceleration in the Horvath clock was significantly associated with slower speeded abilities in the BeCOME cohort but not the FGDS. Acceleration in the Hannum clock and the GrimAge clock were not significantly associated with either cognitive ability. Accelerated PhenoAge was associated with slower speeded abilities in the FGDS but not the BeCOME cohort.nnCONCLUSIONS: The present results suggest that epigenetic age acceleration has the potential to serve as a biomarker for neurocognitive decline in adults with a history of early life adversity or psychiatric disorders. Estimates of epigenetic aging may identify adults at risk of cognitive decline that could benefit from early neurocognitive screening.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37961792,

title = {From jamais to déjà vu: The respective roles of semantic and episodic memory in novelty monitoring and involuntary memory retrieval},

author = {Louis Renoult and J Bruno Debruille},

doi = {10.1017/S0140525X23000158},

issn = {1469-1825},

year  = {2023},

date = {2023-11-01},

journal = {Behav Brain Sci},

volume = {46},

pages = {e373},

abstract = {Barzykowski and Moulin's model proposes that déjà vu and involuntary autobiographical memories are the result of a continuously active memory system that tracks the novelty of situations. Déjà vu would only have episodic content and concern interpretation of prior experiences. We argue that these aspects of the model would gain to be clarified and explored further and we suggest possible directions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37963865,

title = {Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes},

author = {Eamon Fitzgerald and Mojun Shen and Hannah Ee Juen Yong and Zihan Wang and Irina Pokhvisneva and Sachin Patel and Nicholas O'Toole and Shiao-Yng Chan and Yap Seng Chong and Helen Chen and Peter D Gluckman and Jerry Chan and Patrick Kia Ming Lee and Michael J Meaney},

doi = {10.1038/s41467-023-42300-8},

issn = {2041-1723},

year  = {2023},

date = {2023-11-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {7120},

abstract = {Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38010651,

title = {Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease},

author = {Cristiano Schaffer Aguzzoli and Pâmela C L Ferreira and Guilherme Povala and João Pedro Ferrari-Souza and Bruna Bellaver and Carolina Soares Katz and Hussein Zalzale and Firoza Z Lussier and Francieli Rohden and Sarah Abbas and Douglas T Leffa and Marina Scop Medeiros and Joseph Therriault and Andréa L Benedet and Cécile Tissot and Stijn Servaes and Nesrine Rahmouni and Arthur Cassa Macedo and Gleb Bezgin and Min Su Kang and Jenna Stevenson and Vanessa Pallen and Ann Cohen and Oscar L Lopez and Dana L Tudorascu and William E Klunk and Victor L Villemagne and Jean Paul Soucy and Eduardo R Zimmer and Lucas P Schilling and Thomas K Karikari and Nicholas J Ashton and Henrik Zetterberg and Kaj Blennow and Serge Gauthier and Victor Valcour and Bruce L Miller and Pedro Rosa-Neto and Tharick A Pascoal},

doi = {10.1001/jamanetworkopen.2023.45175},

issn = {2574-3805},

year  = {2023},

date = {2023-11-01},

journal = {JAMA Netw Open},

volume = {6},

number = {11},

pages = {e2345175},

abstract = {IMPORTANCE: Neuropsychiatric symptoms are commonly encountered and are highly debilitating in patients with Alzheimer disease. Understanding their underpinnings has implications for identifying biomarkers and treatment for these symptoms.nnOBJECTIVE: To evaluate whether glial markers are associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum.nnDESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted from January to June 2023, leveraging data from the Translational Biomarkers in Aging and Dementia cohort at McGill University, Canada. Recruitment was based on referrals of individuals from the community or from outpatient clinics. Exclusion criteria included active substance abuse, major surgery, recent head trauma, safety contraindications for positron emission tomography (PET) or magnetic resonance imaging, being currently enrolled in other studies, and having inadequately treated systemic conditions.nnMAIN OUTCOMES AND MEASURES: All individuals underwent assessment for neuropsychiatric symptoms (Neuropsychiatry Inventory Questionnaire [NPI-Q]), and imaging for microglial activation ([11C]PBR28 PET), amyloid-β ([18F]AZD4694 PET), and tau tangles ([18F]MK6240 PET).nnRESULTS: Of the 109 participants, 72 (66%) were women and 37 (34%) were men; the median age was 71.8 years (range, 38.0-86.5 years). Overall, 70 had no cognitive impairment and 39 had cognitive impairment (25 mild; 14 Alzheimer disease dementia). Amyloid-β PET positivity was present in 21 cognitively unimpaired individuals (30%) and in 31 cognitively impaired individuals (79%). The NPI-Q severity score was associated with microglial activation in the frontal, temporal, and parietal cortices (β = 7.37; 95% CI, 1.34-13.41; P = .01). A leave-one-out approach revealed that irritability was the NPI-Q domain most closely associated with the presence of brain microglial activation (β = 6.86; 95% CI, 1.77-11.95; P = .008). Furthermore, we found that microglia-associated irritability was associated with study partner burden measured by NPI-Q distress score (β = 5.72; 95% CI, 0.33-11.10; P = .03).nnCONCLUSIONS AND RELEVANCE: In this cross-sectional study of 109 individuals across the AD continuum, microglial activation was associated with and a potential biomarker of neuropsychiatric symptoms in Alzheimer disease. Moreover, our findings suggest that the combination of amyloid-β- and microglia-targeted therapies could have an impact on relieving these symptoms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38036458,

title = {Access to a regular primary care physician among young people with early psychosis in Ontario, Canada},

author = {Rebecca Rodrigues and Jennifer N S Reid and Joshua C Wiener and Suzanne Archie and Richard G Booth and Chiachen Cheng and Arlene G MacDougall and Lena Palaniyappan and Bridget L Ryan and Aristotle Voineskos and Paul Kurdyak and Saadia Hameed Jan and Kelly K Anderson and },

doi = {10.1111/eip.13487},

issn = {1751-7893},

year  = {2023},

date = {2023-11-01},

journal = {Early Interv Psychiatry},

abstract = {AIM: Access to a primary care physician in early psychosis facilitates help-seeking and engagement with psychiatric treatment. We examined access to a regular primary care physician in people with early psychosis, compared to the general population, and explored factors associated with access.nnMETHODS: Using linked health administrative data from Ontario (Canada), we identified people aged 14-35 years with a first diagnosis of nonaffective psychotic disorder (n = 39 449; 2005-2015). We matched cases to four randomly selected general population controls based on age, sex, neighbourhood, and index date (n = 157 796). We used modified Poisson regression to estimate prevalence ratios (PR) for access to a regular primary care physician in the year prior to first diagnosis of psychotic disorder, and the sociodemographic and clinical factors associated with access.nnRESULTS: A larger proportion of people with early psychosis had a regular primary care physician, relative to the general population (89% vs. 68%; PR = 1.30, 95%CI = 1.30-1.31). However, this was accounted for by a higher prevalence of comorbidities among people with psychosis, and this association was no longer present after adjustment (PR = 0.97, 95%CI = 0.97, 0.98). People with early psychosis who were older, male, refugees and those residing in lower income or high residential instability neighbourhoods were less likely to have a regular primary care physician.nnCONCLUSION: Approximately one in ten young people with early psychosis in Ontario lack access to a regular primary care physician. Strategies to improve primary care physician access are needed for management of physical comorbidities and to ensure continuity of care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37858179,

title = {Description of patients with eating disorders by general practitioners: a cohort study and focus on co-management with depression},

author = {Jean Sébastien Cadwallader and Massimiliano Orri and Caroline Barry and Bruno Falissard and Christine Hassler and Caroline Huas},

doi = {10.1186/s40337-023-00901-0},

issn = {2050-2974},

year  = {2023},

date = {2023-10-01},

journal = {J Eat Disord},

volume = {11},

number = {1},

pages = {185},

abstract = {BACKGROUND: International guidelines often state that general practitioners (GPs) provide early management for most patients with eating disorders (EDs). GP management of EDs has not been studied in France. Depressive disorders are often a comorbidity of EDs. The aims of this study were to describe in France the characteristics of people with all subcategories of EDs (Anorexia Nervosa, Bulimia Nervosa, ED Not Otherwise Specified) managed by their GPs and to study the management temporality between depression and all subcategories of EDs.nnMETHODS: Retrospective cohort study of patients with EDs visiting French GPs. Data collected from 1994 through 2009 were extracted from the French society of general electronic health record. A descriptive analysis of the population focused on depression, medication such as antidepressants and anxiolytics, and the management temporality between depression and EDs.nnRESULTS: 1310 patients aged 8 years or older were seen at least once for an ED by a GP participating in the database out of 355,848 patients, with a prevalence rate of 0.3%. They had a mean age of 35.19 years, 82.67% were women. 41.6% had anorexia nervosa, 26.4% bulimia nervosa, and 32% an ED not otherwise specified. Overall, 32.3% had been managed at least once for depression, and 18.4% had been prescribed an antidepressant of any type at least once. Benzodiazepines had been prescribed at least once for 73.9% of the patients treated for depression. Patients with an ED seen regularly by their GP ("during" profile) received care for depression more frequently than those with other profiles. 60.9% had a single visit with the participating GP for their ED Treatment and management for depression did not precede care for EDs.nnCONCLUSIONS: Data extracted from the French society of general practice were the only one available in France in primary care about EDs and our study was the only one on this topic. The frequency of visits for EDs was very low in our general practice-based sample. Depressive disorders were a frequent comorbidity of EDs. GPs could manage common early signs of depression and EDs, especially if they improved their communication skills and developed collaborative professional management.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37847817,

title = {Exploring the Relationship Between Suicidality and Persistent Negative Symptoms Following a First Episode of Psychosis},

author = {Joseph Ghanem and Massimiliano Orri and Laura Moro and Katie M Lavigne and Delphine Raucher-Chéné and Ashok Malla and Ridha Joober and Martin Lepage},

doi = {10.1093/schbul/sbad146},

issn = {1745-1701},

year  = {2023},

date = {2023-10-01},

journal = {Schizophr Bull},

abstract = {BACKGROUND AND HYPOTHESIS: Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups.nnSTUDY DESIGN: In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS).nnSTUDY RESULTS: Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms.nnCONCLUSION: We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37749258,

title = {APOEε4 potentiates amyloid β effects on longitudinal tau pathology},

author = {João Pedro Ferrari-Souza and Bruna Bellaver and Pâmela C L Ferreira and Andréa L Benedet and Guilherme Povala and Firoza Z Lussier and Douglas T Leffa and Joseph Therriault and Cécile Tissot and Carolina Soares and Yi-Ting Wang and Mira Chamoun and Stijn Servaes and Arthur C Macedo and Marie Vermeiren and Gleb Bezgin and Min Su Kang and Jenna Stevenson and Nesrine Rahmouni and Vanessa Pallen and Nina Margherita Poltronetti and Ann Cohen and Oscar L Lopez and William E Klunk and Jean-Paul Soucy and Serge Gauthier and Diogo O Souza and Gallen Triana-Baltzer and Ziad S Saad and Hartmuth C Kolb and Thomas K Karikari and Victor L Villemagne and Dana L Tudorascu and Nicholas J Ashton and Henrik Zetterberg and Kaj Blennow and Eduardo R Zimmer and Pedro Rosa-Neto and Tharick A Pascoal},

doi = {10.1038/s43587-023-00490-2},

issn = {2662-8465},

year  = {2023},

date = {2023-10-01},

journal = {Nat Aging},

volume = {3},

number = {10},

pages = {1210--1218},

abstract = {The mechanisms by which the apolipoprotein E ε4 (APOEε4) allele influences the pathophysiological progression of Alzheimer's disease (AD) are poorly understood. Here we tested the association of APOEε4 carriership and amyloid-β (Aβ) burden with longitudinal tau pathology. We longitudinally assessed 94 individuals across the aging and AD spectrum who underwent clinical assessments, APOE genotyping, magnetic resonance imaging, positron emission tomography (PET) for Aβ ([F]AZD4694) and tau ([F]MK-6240) at baseline, as well as a 2-year follow-up tau-PET scan. We found that APOEε4 carriership potentiates Aβ effects on longitudinal tau accumulation over 2 years. The APOEε4-potentiated Aβ effects on tau-PET burden were mediated by longitudinal plasma phosphorylated tau at threonine 217 (p-tau217) increase. This longitudinal tau accumulation as measured by PET was accompanied by brain atrophy and clinical decline. Our results suggest that the APOEε4 allele plays a key role in Aβ downstream effects on the aggregation of phosphorylated tau in the living human brain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37536439,

title = {Early tactile stimulation influences the development of Alzheimer's disease in gestationally stressed APP  adult offspring  mice},

author = {Shakhawat R Hossain and Hadil Karem and Zahra Jafari and Bryan E Kolb and Majid H Mohajerani},

doi = {10.1016/j.expneurol.2023.114498},

issn = {1090-2430},

year  = {2023},

date = {2023-10-01},

journal = {Exp Neurol},

volume = {368},

pages = {114498},

abstract = {Alzheimer's disease (AD) is associated with cerebral plaques and tangles, reduced synapse number, and shrinkage in several brain areas and these morphological effects are associated with the onset of compromised cognitive, motor, and anxiety-like behaviours. The appearance of both anatomical and behavioural symptoms is worsened by stress. The focus of this study was to examine the effect of neonatal tactile stimulation on AD-like behavioural and neurological symptoms on APP  mice, a mouse model of AD, who have been gestationally stressed. Our findings indicate that neonatal tactile stimulation improves cognition, motor skills, and anxiety-like symptoms in both gestationally stressed and non-stressed adult APP mice and that these alterations are associated with reduced Aβ plaque formation. Thus, tactile stimulation appears to be a promising non-invasive preventative strategy for slowing the onset of dementia in aging animals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37531809,

title = {Weak-hyperactive hippocampal CA1 neurons in the prodromal stage of Alzheimer's disease in hybrid App × Thy1-GCaMP6s mice suggest disrupted plasticity},

author = {Samsoon Inayat and Brendan B McAllister and HaoRan Chang and Sean G Lacoursiere and Ian Q Whishaw and Robert J Sutherland and Majid H Mohajerani},

doi = {10.1016/j.neurobiolaging.2023.06.002},

issn = {1558-1497},

year  = {2023},

date = {2023-10-01},

journal = {Neurobiol Aging},

volume = {130},

pages = {154--171},

abstract = {This study investigated the impact of familial Alzheimer's disease (AD)-linked amyloid precursor protein (App) mutations on hippocampal CA1 neuronal activity and function at an early disease stage in App × Thy1-GCaMP6s (A-TG) mice using calcium imaging. Longitudinal assessment of spatial behavior at 12 and 18 months of age identified an early disease stage at 12 months when there was significant amyloid beta pathology with mild behavioral deficits. Hippocampal CA1 neuronal activity and event-related encoding of distance and time were therefore assessed at 12 months of age in several configurations of an air-induced running task to assess the dynamics of cellular activity. Neurons in A-TG mice displayed diminished (weaker) and more frequent (hyperactive) neuronal firing that was more pronounced during movement compared to immobility. Responsive neurons showed configuration-specific deficits in distance and time encoding with impairment in adapting their responses to changing configurations. These results suggest that at an early stage of AD in the absence of full-blown behavioral deficits, weak-hyperactive neuronal activity may induce impairments in sensory perception of changing environments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37861419,

title = {Combinations and Temporal Associations Among Precursor Symptoms Before a First Episode of Psychosis},

author = {Vincent Paquin and Ashok K Malla and Srividya N Iyer and Martin Lepage and Ridha Joober and Jai L Shah},

doi = {10.1093/schbul/sbad152},

issn = {1745-1701},

year  = {2023},

date = {2023-10-01},

journal = {Schizophr Bull},

abstract = {BACKGROUND AND HYPOTHESIS: Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we aimed to investigate combinations and temporal associations among precursor symptoms.nnSTUDY DESIGN: Participants were from PEPP-Montréal, a catchment-based early intervention program for FEP. Through semistructured interviews, collateral from relatives, and a review of health and social records, we retrospectively measured the presence or absence of 29 precursor symptoms, including 9 subthreshold psychotic and 20 nonpsychotic symptoms. Sequences of symptoms were derived from the timing of the first precursor symptom relative to the onset of FEP.nnSTUDY RESULTS: The sample included 390 participants (68% men; age range: 14-35 years). Combinations of precursor symptoms most frequently featured depression, anxiety, and substance use. Of 256 possible pairs of initial and subsequent precursor symptoms, many had asymmetrical associations: eg, when the first symptom was suspiciousness, the incidence rate ratio (IRR) of subsequent anxiety was 3.40 (95% confidence interval [CI]: 1.79, 6.46), but when the first symptom was anxiety, the IRR of subsequent suspiciousness was 1.15 (95% CI: 0.77, 1.73).nnCONCLUSIONS: A detailed examination of precursor symptoms reveals diverse clinical profiles that cut across diagnostic categories and evolve longitudinally prior to FEP. Their identification may contribute to risk assessments and provide insights into the mechanisms of illness progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37804203,

title = {Neuroanatomical and cognitive biomarkers of alpha-synuclein propagation in a mouse model of synucleinopathy prior to onset of motor symptoms},

author = {Stephanie Tullo and Aline S Miranda and Esther Del Cid-Pellitero and Mei Peng Lim and Daniel Gallino and Anoosha Attaran and Raihaan Patel and Vladislav Novikov and Megan Park and Flavio H Beraldo and Wen Luo and Irina Shlaifer and Thomas M Durcan and Timothy J Bussey and Lisa M Saksida and Edward A Fon and Vania F Prado and Marco A M Prado and M Mallar Chakravarty},

doi = {10.1111/jnc.15967},

issn = {1471-4159},

year  = {2023},

date = {2023-10-01},

journal = {J Neurochem},

abstract = {Significant evidence suggests that misfolded alpha-synuclein (aSyn), a major component of Lewy bodies, propagates in a prion-like manner contributing to disease progression in Parkinson's disease (PD) and other synucleinopathies. In fact, timed inoculation of M83 hemizygous mice with recombinant human aSyn preformed fibrils (PFF) has shown symptomatic deficits after substantial spreading of pathogenic alpha-synuclein, as detected by markers for the phosphorylation of S129 of aSyn. However, whether accumulated toxicity impact human-relevant cognitive and structural neuroanatomical measures is not fully understood. Here we performed a single unilateral striatal PFF injection in M83 hemizygous mice, and using two assays with translational potential, ex vivo magnetic resonance imaging (MRI) and touchscreen testing, we examined the combined neuroanatomical and behavioral impact of aSyn propagation. In PFF-injected mice, we observed widespread atrophy in bilateral regions that project to or receive input from the injection site using MRI. We also identified early deficits in reversal learning prior to the emergence of motor symptoms. Our findings highlight a network of regions with related cellular correlates of pathology that follow the progression of aSyn spreading, and that affect brain areas relevant for reversal learning. Our experiments suggest that M83 hemizygous mice injected with human PFF provides a model to understand how misfolded aSyn affects human-relevant pre-clinical measures and suggest that these pre-clinical biomarkers could be used to detect early toxicity of aSyn and provide better translational measures between mice and human disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37796588,

title = {Improving Children's Mental Health Literacy Through the Cocreation of an Intervention and Scale Validation: Protocol for the CHILD-Mental Health Literacy Research Study},

author = {Florence Francis-Oliviero and Céline Loubières and Christine Grové and Alexandra Marinucci and Rebecca Shankland and Réda Salamon and Emmanuelle Perez and Laure Garancher and Cédric Galera and Elsa Gaillard and Massimiliano Orri and Juan Luis González-Caballero and Ilaria Montagni},

doi = {10.2196/51096},

issn = {1929-0748},

year  = {2023},

date = {2023-10-01},

journal = {JMIR Res Protoc},

volume = {12},

pages = {e51096},

abstract = {BACKGROUND: Children's mental health is a public health priority, with 1 in 5 European children younger than 12 years having a behavioral, developmental, or psychological disorder. Mental health literacy (MHL) is a modifiable determinant of mental health, promoting psychological well-being and reducing mental health problems. Despite its significance, no interventions or scales currently exist for increasing and measuring MHL in this population.nnOBJECTIVE: This study has dual objectives: (1) cocreating and evaluating an intervention on children's MHL, and (2) developing and validating a scale that measures children's MHL.nnMETHODS: Our study focuses on children aged 9-11 years attending primary school classes in various settings, including urban and rural areas, and priority education zones within a French department. Using a participatory research approach, we will conduct workshops involving children, parents, teachers, and 1 artist to cocreate an intervention comprising multiple tools (eg, a pedagogical kit and videos). This intervention will undergo initial evaluation in 4 classes through observations, interviews, and satisfaction questionnaires to assess its viability. Concurrently, the artist will collaborate with children to create the initial version of the CHILD-MHL scale, which will then be administered to 300 children. Psychometric analyses will validate the scale. Subsequently, we will conduct a cluster randomized controlled trial involving a minimum of 20 classes, using the CHILD-MHL scale scores as the primary end point to evaluate the intervention's efficacy. Additional interviews will complement this mixed methods evaluation. Both the intervention and the scale are grounded in the Child-Focused MHL model.nnRESULTS: The first tool of the intervention is the pedagogical kit Le Jardin du Dedans, supported by the public organization Psycom Santé Mentale Info and endorsed by UNICEF (United Nations Children's Fund) France. The second tool is a handbook by the Pan American Health Organization and the World Health Organization, which is addressed to teachers to sensitize them to children's mental health problems. The third is a 5-page supplementary leaflet produced by the nongovernmental organization The Ink Link, which teaches children the notion of MHL. Finally, we produced 56 items of the MHL Scale and listed existing education policies for children's mental health.nnCONCLUSIONS: After its robust evaluation, the intervention could be extended to several schools in France. The scale will be the first in the world to measure children's MHL. It will be used not only to evaluate interventions but also to provide data for decision makers to include MHL in all educational policies. Both the intervention and the scale could be translated into other languages.nnINTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51096.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38495338,

title = {The impact of quality control on cortical morphometry comparisons in autism},

author = {Saashi A Bedford and Alfredo Ortiz-Rosa and Jenna M Schabdach and Manuela Costantino and Stephanie Tullo and Tom Piercy and  and Meng-Chuan Lai and Michael V Lombardo and Adriana Di Martino and Gabriel A Devenyi and M Mallar Chakravarty and Aaron F Alexander-Bloch and Jakob Seidlitz and Simon Baron-Cohen and Richard A I Bethlehem},

doi = {10.1162/imag_a_00022},

issn = {2837-6056},

year  = {2023},

date = {2023-10-01},

journal = {Imaging Neurosci (Camb)},

volume = {1},

pages = {1--21},

abstract = {Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons, and a growing body of work has demonstrated the importance of careful quality control (QC) and evaluated the impact of image and image-processing quality. However, the growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. One of the most important aspects of MRI quality is the accuracy of processed outputs, which have been shown to impact estimated neurodevelopmental trajectories. Here, we evaluate whether the quality of surface reconstructions by FreeSurfer (one of the most widely used MRI processing pipelines) interacts with clinical and demographic factors. We present a tool, FSQC, that enables quick and efficient yet thorough assessment of outputs of the FreeSurfer processing pipeline. We validate our method against other existing QC metrics, including the automated FreeSurfer Euler number, two other manual ratings of raw image quality, and two popular automated QC methods. We show strikingly similar spatial patterns in the relationship between each QC measure and cortical thickness; relationships for cortical volume and surface area are largely consistent across metrics, though with some notable differences. We next demonstrate that thresholding by QC score attenuates but does not eliminate the impact of quality on cortical estimates. Finally, we explore different ways of controlling for quality when examining differences between autistic individuals and neurotypical controls in the Autism Brain Imaging Data Exchange (ABIDE) dataset, demonstrating that inadequate control for quality can alter results of case-control comparisons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38441079,

title = {Studying Psychosis Using Natural Language Generation: A Review of Emerging Opportunities},

author = {Lena Palaniyappan and David Benrimoh and Alban Voppel and Roberta Rocca},

doi = {10.1016/j.bpsc.2023.04.009},

issn = {2451-9030},

year  = {2023},

date = {2023-10-01},

journal = {Biol Psychiatry Cogn Neurosci Neuroimaging},

volume = {8},

number = {10},

pages = {994--1004},

abstract = {Disrupted language in psychotic disorders, such as schizophrenia, can manifest as false contents and formal deviations, often described as thought disorder. These features play a critical role in the social dysfunction associated with psychosis, but we continue to lack insights regarding how and why these symptoms develop. Natural language generation (NLG) is a field of computer science that focuses on generating human-like language for various applications. The theory that psychosis is related to the evolution of language in humans suggests that NLG systems that are sufficiently evolved to generate human-like language may also exhibit psychosis-like features. In this conceptual review, we propose using NLG systems that are at various stages of development as in silico tools to study linguistic features of psychosis. We argue that a program of in silico experimental research on the network architecture, function, learning rules, and training of NLG systems can help us understand better why thought disorder occurs in patients. This will allow us to gain a better understanding of the relationship between language and psychosis and potentially pave the way for new therapeutic approaches to address this vexing challenge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37713573,

title = {Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies},

author = {Rudolf Uher and Barbara Pavlova and Joaquim Radua and Umberto Provenzani and Sara Najafi and Lydia Fortea and Maria Ortuño and Anna Nazarova and Nader Perroud and Lena Palaniyappan and Katharina Domschke and Samuele Cortese and Paul D Arnold and Jehannine C Austin and Michael M Vanyukov and Myrna M Weissman and Allan H Young and Manon H J Hillegers and Andrea Danese and Merete Nordentoft and Robin M Murray and Paolo Fusar-Poli},

doi = {10.1002/wps.21147},

issn = {1723-8617},

year  = {2023},

date = {2023-10-01},

journal = {World Psychiatry},

volume = {22},

number = {3},

pages = {433--448},

abstract = {The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37883082,

title = {Perinatal Trajectories of Maternal Depressive Symptoms in Prospective, Community-Based Cohorts Across 3 Continents},

author = {Michelle Z L Kee and Andrea Cremaschi and Maria De Iorio and Helen Chen and Tina Montreuil and Tuong Vi Nguyen and Sylvana M Côté and Kieran J O'Donnell and Gerald F Giesbrecht and Nicole Letourneau and Shiao Yng Chan and Michael J Meaney},

doi = {10.1001/jamanetworkopen.2023.39942},

issn = {2574-3805},

year  = {2023},

date = {2023-10-01},

journal = {JAMA Netw Open},

volume = {6},

number = {10},

pages = {e2339942},

abstract = {IMPORTANCE: Depressive symptoms during pregnancy influence the development and health of the offspring, underscoring the need for timely intervention. However, the course of depressive symptoms across the perinatal period remains unclear, thus complicating screening and referral guidelines.nnOBJECTIVE: To examine the course and stability of depressive symptoms across the perinatal period in multiple, ethnically diverse independent observational cohorts.nnDESIGN, SETTING, AND PARTICIPANTS: This cohort study included self-reported depressive symptoms at multiple time points from 7 prospective cohorts spanning 3 continents (United Kingdom: Avon Longitudinal Study of Parents and Children from 1991 to 1995; Canada: Maternal Adversity, Vulnerability and Neurodevelopment from 2003 to 2007; Montreal Antenatal Well-being Study from 2019 to 2022; Alberta Pregnancy Outcomes and Nutrition from 2009 to 2014; and Singapore: Growing Up in Singapore Toward Healthy Outcomes from 2009 to 2013; Singapore Preconception Study of Long-Term Maternal and Child Outcomes from 2015 to 2019; and Mapping Antenatal Maternal Stress from 2019 to 2022). Participants were recruited either during preconception or pregnancy and observed into the postnatal period. All data from each cohort were analyzed from July 2022 to April 2023.nnMAIN OUTCOMES AND MEASURES: Self-reported depressive symptoms from pregnancy to 2 years following childbirth using either the Edinburgh Postnatal Depression Scale or the Center for Epidemiological Studies Depression were analyzed independently within each cohort using item response theory (IRT) techniques. K-means clustering was used to identify groups of participants with similar trajectories.nnRESULTS: A total of 11 563 pregnant women (mean [SD] age, 29 [5] years; 569 [4.9%] East Asian women; 304 [2.6%] Southeast Asian women; 10 133 [87.6%] White women) self-reported depressive symptoms from pregnancy to 2 years following childbirth. Analytic methods from Item Response Theory identified 3 groups of mothers based on depressive symptoms: low, mild, and high levels in each of the 7 cohorts. Mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onwards. Mothers with clinical levels of depressive symptoms likewise showed stable trajectories from pregnancy into the postnatal period.nnCONCLUSIONS AND RELEVANCE: In this study, trajectories of depressive symptoms remained stable from pregnancy across the perinatal period, a finding that conflicts with a continuing emphasis on postpartum or postnatal onset of depression that persists in some health policy guidelines. Interventions and public health initiatives should focus on reducing depressive symptoms during pregnancy in addition to following birth.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37884562,

title = {Transcriptional dissection of symptomatic profiles across the brain of men and women with depression},

author = {Samaneh Mansouri and André M Pessoni and Arturo Marroquín-Rivera and Eric M Parise and Carol A Tamminga and Gustavo Turecki and Eric J Nestler and Ting-Huei Chen and Benoit Labonté},

doi = {10.1038/s41467-023-42686-5},

issn = {2041-1723},

year  = {2023},

date = {2023-10-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {6835},

abstract = {Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37773255,

title = {Finding normal-to-better neurocognitive indexes in individuals with schizotypal traits using a social role task},

author = {Mingyi Diao and Ilya Demchenko and Gifty Asare and Jingyan Quan and J Bruno Debruille},

doi = {10.1038/s41537-023-00394-5},

issn = {2754-6993},

year  = {2023},

date = {2023-09-01},

journal = {Schizophrenia (Heidelb)},

volume = {9},

number = {1},

pages = {66},

abstract = {Schizophrenia patients make more errors and have longer reaction times (RTs) than healthy controls in most cognitive tasks. Deficits are also observed in subclinical participants having high scores on the schizotypal personality questionnaire (SPQ). They are accompanied by smaller amplitudes of the event-related brain potentials (ERPs) that index attention and semantic- and working-memory. These functions are thus thought to be impaired in individuals having various schizophrenia attributes (SzAs). Nevertheless, normal RTs were recently found in SzAs during a particular self-referential task where half of the stimuli were names of extraordinary social roles (e.g., genius). Each name (ordinary or extraordinary) was presented individually, and participants were asked to decide whether or not they would consider themselves performing the role at any moment of their lives. To further test an absence of cognitive deficits in this task, the ERPs elicited by names of social roles were also examined in 175 healthy participants. The absence of longer RTs in high- than in low-SPQs was replicated. Moreover, the ERPs of high SPQs had larger occipital N1s, larger P2s and larger occipital N400s than those of low SPQs while late positive potentials (LPPs) were of similar amplitudes. Such results are consistent with clinical observations of greater attention and faster processing of stimuli related to extraordinary/delusional beliefs. Further studies should test whether the cognitive deficits found in SzAs are due to the use of tasks and stimuli that are less within their focus of interest than within that of healthy controls.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37667020,

title = {Brain health in ethnically minority youth at risk for psychosis},

author = {Rachel A Rabin and Lena Palaniyappan},

doi = {10.1038/s41386-023-01719-9},

issn = {1740-634X},

year  = {2023},

date = {2023-09-01},

journal = {Neuropsychopharmacology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37725642,

title = {Allostatic load in children: The cost of empathic concern},

author = {Desiree Y Phua and Helen Chen and Fabian Yap and Yap Seng Chong and Peter D Gluckman and Birit F P Broekman and Johan G Eriksson and Michael J Meaney},

doi = {10.1073/pnas.2217769120},

issn = {1091-6490},

year  = {2023},

date = {2023-09-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {39},

pages = {e2217769120},

abstract = {Early-life adversity affects long-term health outcomes but there is considerable interindividual variability in susceptibility to environmental influences. We proposed that positive psychological characteristics that reflect engagement with context, such as being concerned about people or performance on tasks (i.e., empathic concern), could moderate the interindividual variation in sensitivity to the quality of the early environment. We studied 526 children of various Asian nationalities in Singapore (46.6% female, 13.4% below the poverty line) with longitudinal data on perinatal and childhood experiences, maternal report on empathic concern of the child, and a comprehensive set of physiological measures reflecting pediatric allostatic load assessed at 6 y of age. The perinatal and childhood experiences included adversities and positive experiences. We found that cumulative adverse childhood experience was positively associated with allostatic load of children at 6 y of age at higher levels of empathic concern but not significantly associated at lower levels of empathic concern. This finding reveals evidence for the importance of empathic concern as a psychological characteristic that moderates the developmental impact of environmental influences, serving as a source for vulnerability to adversities in children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37549631,

title = {Sex and cell-specific gene expression in corticolimbic brain regions associated with psychiatric disorders revealed by bulk and single-nuclei RNA sequencing},

author = {Eamon Fitzgerald and Danusa Mar Arcego and Mo Jun Shen and Nicholas O'Toole and Xianglan Wen and Corina Nagy and Sara Mostafavi and Kelly Craig and Patricia Pelufo Silveira and Nirmala Arul Rayan and Josie Diorio and Michael J Meaney and Tie-Yuan Zhang},

doi = {10.1016/j.ebiom.2023.104749},

issn = {2352-3964},

year  = {2023},

date = {2023-09-01},

journal = {EBioMedicine},

volume = {95},

pages = {104749},

abstract = {BACKGROUND: There are sex-specific differences in the prevalence, symptomology and course of psychiatric disorders. However, preclinical models have primarily used males, such that the molecular mechanisms underlying sex-specific differences in psychiatric disorders are not well established.nnMETHODS: In this study, we compared transcriptome-wide gene expression profiles in male and female rats within the corticolimbic system, including the cingulate cortex, nucleus accumbens medial shell (NAcS), ventral dentate gyrus and the basolateral amygdala (n = 22-24 per group/region).nnFINDINGS: We found over 3000 differentially expressed genes (DEGs) in the NAcS between males and females. Of these DEGs in the NAcS, 303 showed sex-dependent conservation DEGs in humans and were significantly enriched for gene ontology terms related to blood vessel morphogenesis and regulation of cell migration. Single nuclei RNA sequencing in the NAcS of male and female rats identified widespread sex-dependent expression, with genes upregulated in females showing a notable enrichment for synaptic function. Female upregulated genes in astrocytes, Drd3+MSNs and oligodendrocyte were also enriched in several psychiatric genome-wide association studies (GWAS).nnINTERPRETATION: Our data provide comprehensive evidence of sex- and cell-specific molecular profiles in the NAcS. Importantly these differences associate with anxiety, bipolar disorder, schizophrenia, and cross-disorder, suggesting an intrinsic molecular basis for sex-based differences in psychiatric disorders that strongly implicates the NAcS.nnFUNDING: This work was supported by funding from the Hope for Depression Research Foundation (MJM).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}