Influence of Sensory Monitoring on Speech Breathing Planning Processes: An Exploratory Study in Aging Speakers Reporting Dyspnea.

PURPOSE: Previous studies have suggested that inspirations during speech pauses are influenced by the length of adjacent utterances, owing to respiratory motor planning and physiological recovery processes. The goal of this study was to examine how attention to respiratory sensations may influence these processes in aging speakers with dyspnea, by measuring the effect of sensory monitoring on the relationship between utterance length and the occurrence of inspirations, as well as on functional voice and respiratory measures. METHOD: Seventeen adults aged 50 years and older with complaints of voicing-related dyspnea completed a repeated-measures protocol consisting of a 2-week baseline phase and a 4-week sensory monitoring phase. Audiovisual recordings of semistructured speech and self-report questionnaires were collected at study onset, after the baseline phase, and after the sensory monitoring phase. Repeated-measures logistic regressions were conducted to examine changes in the relationship between utterance length and the occurrence of inspirations in adjacent pauses, and repeated-measures analyses of variance were used to investigate any changes in functional voice and respiratory measures. RESULTS: Planning and recovery processes appeared to remain constant across the baseline phase. From postbaseline to postsensory monitoring timepoints, a strengthening of the relationship between the presence of an inspiration during a speech pause and the length of the subsequent-but not preceding-utterance was noted. Significant improvements were noted in voice-related handicap from study onset to postsensory monitoring, but no changes were reported in respiratory comfort during speech. CONCLUSIONS: Results suggest that respiratory planning processes, that is, the ability to plan breath intakes based on the length of upcoming utterances, may be modifiable behaviorally through targeted sensory monitoring. Further studies are warranted to validate the proposed role of respiratory sensation awareness in achieving skilled temporal coordination between voicing and breathing.

Impact of Transplant Body Mass Index and Post-Transplant Weight Changes on the Development of Chronic Lung Allograft Dysfunction Phenotypes.

INTRODUCTION: Chronic lung allograft dysfunction (CLAD) is a lung transplant complication for which four phenotypes are recognized: Bronchiolitis obliterans syndrome (BOS), Restrictive allograft syndrome (RAS), mixed and undefined phenotypes. Weight gain is common after transplant and may negatively impact lung function. Study objectives were to describe post-transplant weight trajectories of patients who developed (or did not) CLAD phenotypes and examine the associations between BMI at transplant, post-transplant changes in weight and BMI, and the risk of developing these phenotypes. METHODS: Adults who underwent a bilateral lung transplant between 2000 and 2020 at our institution were categorized as having (or not) one of the four CLAD phenotypes based on the proposed classification system. Demographic, anthropometric, and clinical data were retrospectively collected from medical records and analyzed. RESULTS: Study population included 579 recipients (412 [71.1%] CLAD-free, 81 [14.0%] BOS, 20 [3.5%] RAS, 59 [10.2%] mixed, and 7 [1.2%] undefined phenotype). Weight gains of greater amplitude were seen in recipients with restrictive phenotypes than CLAD-free and BOS patients within the first five years post-transplant. While the BMI category at transplant was not statistically associated with the risk of developing CLAD phenotypes, an increase in weight (Hazard ratio [HR]: 1.04, 95% CI [1.01-1.08]; P = .008) and BMI (HR: 1.13, 95% CI [1.03-1.23]; P = .008) over the post-transplant period was associated with a greater risk of RAS. CONCLUSION: Post-LTx gain in weight and BMI modestly increased the risk of RAS, adding to the list of unfavorable outcomes associated with weight gain following transplant.

Evaluation of the effects of blue-enriched white light on cognitive performance, arousal, and overall appreciation of lighting.

Introduction: Light's non-visual effects on the biological clock, cognitive performance, alertness, and mental health are getting more recognized. These are primarily driven by blue light, which triggers specific retinal cells containing melanopsin. Traditionally, research on light has relied on correlated color temperature (CCT) as a metric of its biological influence, given that bluer light corresponds to higher Kelvin values. However, CCT proves to be an inadequate proxy of light's biological effects. A more precise metric is melanopic Equivalent Daylight Illuminance (mel-EDI), which aligns with melanopsin spectrum. Studies have reported positive cognitive impacts of blue-enriched white light. It's unclear if the mixed results are due to different mel-EDI levels since this factor wasn't assessed. Method: Given recent recommendations from experts to aim for at least 250 mel-EDI exposure daily for cognitive benefits, our aim was to assess if a 50-minute exposure to LED light with 250 mel-EDI could enhance concentration and alertness, without affecting visual performance or comfort compared to conventional lighting producing around 150 mel-EDI. To ensure mel-EDI's impact, photopic lux levels were kept constant across conditions. Conditions were counterbalanced, parameters included subjective sleepiness (KSS; Karolinska Sleepiness Scale), concentration (d2-R test), visual performance (FrACT; Freiburg Visual Acuity and Contrast Test), general appreciation (VAS; Visual Analogous Scale), preferences and comfort (modified OLS; Office Lighting Survey). Results: The experimental light significantly reduced sleepiness (p = 0.03, Cohen's d = 0.42) and also decreased contrast sensitivity (p = 0.01, Cohen's d = 0.50). The conventional light was found to be more comfortable (p = 0.002, Cohen's d = 0.62), cheerful (p = 0.02, Cohen's d = 0.46) and pleasant (p = 0.005, Cohen's d = 0.55) while the experimental light was perceived as brighter (p = 0.004, Cohen's d = 0.58) and tended to be more stimulating (p = 0.10). Notably, there was a preference for conventional lighting (p = 0.004, Cohen's d=0.56) and concentration was equally improved in both conditions. Discussion: Despite the lack of further improvement in concentration from exposure to blue-enriched light, given the observed benefits in terms of vigilance, further research over an extended period would be justified. These findings could subsequently motivate cognitive optimization through lighting for workers that would benefit from artificial lighting such as in northern regions.

Heterogeneity in the longitudinal courses of global functioning in children at familial risk of major psychiatric disorders: Association with trauma and familial characteristics.

OBJECTIVES: The extent to which heterogeneity in childhood risk trajectories may underlie later heterogeneity in schizophrenia (SZ), bipolar disorder (BP), and major depressive disorder (MDD) remains a chief question. Answers may optimally be found by studying the longitudinal trajectories of children born to an affected parent. We aimed to differentiate trajectories of global functioning and their sensitive periods from the age of 6 to 17 years in children at familial risk (FHRs). METHODS: First, a latent class mixed model analysis (LCMM) was applied to yearly ratings of the Children's Global Assessment Scale (CGAS) from the age of 6 to 17 years in 170 FHRs born to a parent affected by DSM-IV SZ (N = 37), BP (N = 82) or MDD (N = 51). Then, we compared the obtained Classes or trajectories of FHRs in terms of sex, parental diagnosis, IQ, child clinical status, childhood trauma, polygenic risk score (PRS), and outcome in transition to illness. RESULTS: The LCMM on yearly CGAS trajectories identified a 4-class solution showing markedly different childhood and adolescence dynamic courses and temporal vulnerability windows marked by a functioning decline and a degree of specificity in parental diagnosis. Moreover, IQ, trauma exposure, PRS level, and timing of later transition to illness differentiated the trajectories. Almost half (46%) of the FHRs exhibited a good and stable global functioning trajectory. CONCLUSIONS: FHRs of major psychiatric disorders show heterogeneous functional decline during development associated with parental diagnosis, polygenic risk loading, and childhood trauma.

Nutritional management of people living with cystic fibrosis throughout life and disease continuum: Changing times, new challenges.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding for the ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The management of CF disease has evolved in recent decades from treating downstream disease manifestations affecting the airways, the lungs and the gastrointestinal system to addressing the CFTR gene defect. The advent of CFTR modulators, which correct the functionality of the defective CFTR, contributes to reshaping the landscape of CF demographics, prognosis and therapies, including nutritional management. A spectrum of clinical manifestations is emerging within the same patient population where undernutrition and nutritional deficiencies coexist with excessive weight gain and metabolic derangements. Such contrasting presentations challenge current practices, require adjustments to traditional approaches, and involve more individualised interventions. This narrative review examines the current state of knowledge on the nutritional management of people living with cystic fibrosis from early life to adulthood in the era of CFTR modulation.

Evaluation of electroretinography (ERG) parameters as a biomarker for ADHD.

BACKGROUND: The retina is recognized as an accessible part of the brain due to their common embryonic origin. The electroretinogram (ERG) has proven to be a valuable tool for detecting schizophrenia and bipolarity. We therefore investigated its ability to detect ADHD. METHODS: The cone and rod luminance response functions of the ERG were recorded in 26 ADHD subjects (17 women and 9 men) and 25 controls (16 women and 9 men). RESULTS: No significant differences were found between the mixed groups, but sexual dysmorphia was observed in the significant results. In males, a significant prolonged cone a-wave latency was observed in the ADHD group. In females, we observed a significant decrease in the cone a- and b-wave amplitudes and a trend for a prolonged cone b-wave latency as well as a higher scotopic mixed rod-cone a-wave in the ADHD group. CONCLUSION: The data obtained in this study show the potential of the ERG to detect ADHD, warranting further large-scale studies.

New-onset Obesity After Lung Transplantation: Incidence, Risk Factors, and Clinical Outcomes.

BACKGROUND: Lung transplant (LTx) recipients who gain weight after transplantation may experience an upward shift in body mass index (BMI) that places them in the obese category. The incidence, risk factors, and impact on metabolic health and mortality of new-onset obesity have not been documented in the LTx setting. METHODS: This single-center retrospective study included 564 LTx recipients. Individuals were stratified according to their BMI trajectories from pretransplant evaluation up to 10 y posttransplant. New-onset obesity was defined as a pretransplant BMI <30 kg/m 2 and posttransplant BMI >30 kg/m 2 . The incidence, risk factors, and posttransplant diabetes mellitus, metabolic syndrome, and mortality of recipients with new-onset obesity were compared with those of nonobese (BMI <30 kg/m 2 , pre/post-LTx), consistently obese (BMI >30 kg/m 2 , pre/post-LTx), and obese recipients with weight loss (BMI >30 kg/m 2 pre-LTx, BMI <30 kg/m 2 post-LTx). RESULTS: We found that 14% of recipients developed obesity after transplantation. Overweight individuals (odds ratio [OR]: 9.01; 95% confidence interval [CI] [4.86-16.69]; P < 0.001) and candidates with chronic obstructive pulmonary disease (OR: 6.93; 95% CI [2.30-20.85]; P = 0.001) and other diagnoses (OR: 4.28; 95% CI [1.22-14.98]; P = 0.023) were at greater risk. Multivariable regression analysis showed that new-onset obesity was associated with a greater risk of metabolic syndrome (hazard ratio: 1.70; 95% CI [1.17-2.46]; P = 0.005), but not of posttransplant diabetes mellitus, than nonobesity. Recipients with new-onset obesity had a survival comparable to that of consistently obese individuals. CONCLUSIONS: A greater understanding of the multifaceted nature of post-LTx obesity may lead to interventions that are better tailored to the characteristics of these individuals.

Long-term bone mineral density changes and fractures in lung transplant recipients with cystic fibrosis.

BACKGROUND: Little is known about long-term bone mineral density (BMD) changes and fractures in lung transplant recipients with cystic fibrosis (CF). We examined femur and lumbar spine (LS) BMD changes in men and women with CF up to 10 years post-transplant and documented post-transplant fracture prevalence. METHODS: Retrospective study of individuals who had undergone a lung transplant (2000-2015) and had a pre-transplant and at least one BMD measurement after transplant. Vertebral fractures were assessed on chest computed tomography scans and other fractures abstracted from medical records. RESULTS: The cohort consisted of 131 individuals; 53% males, median age: 28 years [interquartile range: 24-35] and 31% having pre-transplant low bone mass. Most recipients were given bisphosphonates after transplant with proportion reaching 94% at 10 years. Up to 10 years post-transplant, men experienced positive or little change in LS BMD, indicating minimal loss from pre-transplant values. In contrast, women displayed negative changes in BMD up to 5 years post-transplant before recovering pre-transplant BMD values by 10 years. Similar patterns were observed at the femur BMD where men demonstrated a lower bone loss and faster recovery towards pre-transplant values than women. After transplant, 88% of recipients maintained their pre-transplant bone status, 3% experienced an improvement, mostly progressing from low bone mass to normal status whereas 9% had a deterioration of their pre-transplant bone status. Twenty-seven recipients suffered fractures in the post-transplant period. CONCLUSIONS: These findings underline that lung recipients with CF remain at risk of skeletal fragility despite prompt initiation of post-transplant anti-osteoporosis therapy.

Trends, Determinants, and Impact on Survival of Post-Lung Transplant Weight Changes: A Single-center Longitudinal Retrospective Study.

BACKGROUND: Weight gain is commonly seen in lung transplant (LTx) recipients. Although previous studies have focused on weight changes at fixed time periods and relatively early after transplant, trends over time and long-term weight evolution have not been described in this population. The study objectives were to document weight changes up to 15 years post-LTx and assess the predictors of post-LTx weight changes and their associations with mortality. METHODS: Retrospective cohort study of LTx recipients between January 1, 2000, and November 30, 2016 (n = 502). Absolute weight changes from transplant were calculated at fixed time periods (6 mo, 1, 2, 5, 10, and 15 y), and continuous trends over time were generated. Predictors of weight changes and their association with mortality were assessed using linear and Cox regression analysis. RESULTS: LTx recipients experienced a gradual increase in weight, resulting from the combination of multiple weight trajectories. Interstitial lung disease diagnosis negatively predicted post-LTx weight changes at all time points, whereas transplant body mass index categories were significant predictors at earlier time points. Patients with a weight gain of >10% at 5 years had a better survival (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.20-0.66), whereas a 10% weight loss at earlier time points was associated with worse survival (1 y: HR, 2.04; 95% CI, 1.22-3.41 and 2 y: HR, 2.37; 95% CI, 1.22-4.58). CONCLUSIONS: Post-LTx weight changes display various trajectories, are predicted to some extent by individual and LTx-related factors, and have a negative or positive impact on survival depending on the time post-LTx. These results may lead to a better individualization of weight management after transplant.

Nutritional Requirements of Lung Transplant Recipients: Challenges and Considerations.

An optimal nutritional status is associated with better post-transplant outcomes and survival. Post-lung transplant nutrition management is however particularly challenging as lung recipients represent a very heterogeneous group of patients in terms of age, underlying diseases, weight status and presence of comorbidities. Furthermore, the post-transplant period encompasses several stages characterized by physiological and pathophysiological changes that affect nutritional status of patients and necessitate tailored nutrition management. We provide an overview of the current state of knowledge regarding nutritional requirements in the post-lung transplant period from the immediate post-operative phase to long-term follow-up. In the immediate post-transplantation phase, the high doses of immunosuppressants and corticosteroids, the goal of maintaining hemodynamic stability, the presence of a catabolic state, and the wound healing process increase nutritional demands and lead to metabolic perturbations that necessitate nutritional interventions. As time from transplantation increases, complications such as obesity, osteoporosis, cancer, diabetes, and kidney disease, may develop and require adjustments to nutrition management. Until specific nutritional guidelines for lung recipients are elaborated, recommendations regarding nutrient requirements are formulated to provide guidance for clinicians caring for these patients. Finally, the management of recipients with special considerations is also briefly addressed.

The Impact of Waiting List BMI Changes on the Short-term Outcomes of Lung Transplantation.

BACKGROUND: Obesity and underweight are associated with a higher postlung transplantation (LTx) mortality. This study aims to assess the impact of the changes in body mass index (BMI) during the waiting period for LTx on early postoperative outcomes. METHODS: Medical records of 502 consecutive cases of LTx performed at our institution between 1999 and 2015 were reviewed. Patients were stratified per change in BMI category between pre-LTx assessment (candidate BMI) and transplant BMI as follows: A-candidate BMI, less than 18.5 or 18.5 to 29.9 and transplant BMI, less than 18.5; B-candidate BMI, less than 18.5 and transplant BMI, 18.5 to 29.9; C-candidate BMI, 18.5 to 29.9 and transplant BMI, 18.5 to 29.9; D-candidate BMI, 30 or greater and transplant BMI, 18.5 to 29.9; and E-candidate BMI, 30 or greater or 18.5 to 29.9 and transplant BMI, 30 or greater. Our primary outcome was in-hospital mortality and secondary outcomes were length of mechanical ventilation, intensive care unit length of stay (LOS), hospital LOS and postoperative complications. RESULTS: BMI variation during the waiting time was common, as 1/3 of patients experienced a change in BMI category. Length of mechanical ventilation (21 days vs 9 days; P = 0.018), intensive care unit LOS (26 days vs 15 days; P = 0.035), and rates of surgical complications (76% vs 44%; P = 0.018) were significantly worse in patients of group E versus group D. Obese candidates who failed to decrease BMI less than 30 by transplant exhibited an increased risk of postoperative mortality (odds ratio, 2.62; 95% confidence interval, 1.01-6.48) compared with patients in group C. Pre-LTx BMI evolution had no impact on postoperative morbidity and mortality in underweight patients. CONCLUSIONS: Our results suggest that obese candidates with an unfavorable pretransplant BMI evolution are at greater risk of worse post-LTx outcomes.

Impaired rib bone mass and quality in end-stage cystic fibrosis patients.

BACKGROUND: Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients. We therefore examined rib specimens resected at the time of lung transplant in CF patients to measure parameters of bone quantity and quality. METHODS: In this exploratory study, we analysed 19 end-stage CF and 13 control rib specimens resected from otherwise healthy lung donors. BMD, bone microarchitecture, static parameters of bone formation and resorption and microcrack density of rib specimens were quantified by imaging, histomorphometric and histological methods. Variables reflecting the mineralization of ribs were assessed by digitized microradiography. The degree of bone mineralization (g/cm3) and the heterogeneity index of the mineralization (g/cm3) were calculated for trabecular and cortical bone. RESULTS: Compared to controls, CF ribs exhibited lower areal and trabecular volumetric BMD, decreased trabecular thickness and osteoid parameters, and increased microcrack density, that was particularly pronounced in specimens from patients with CF-related diabetes. Static parameters of bone resorption were similar in both groups. Degree of mineralization of total bone, but not heterogeneity index, was increased in CF specimens. CONCLUSION: The combination of reduced bone mass, altered microarchitecture, imbalanced bone remodeling (maintained bone resorption but decreased formation), increased microdamage and a small increase of the degree of mineralization, may lead to decreased bone strength, which, when coupled with chronic coughing and chest physical therapy, may provide an explanation for the increased incidence of rib fractures previously reported in this population.

Liability indicators aggregate many years before transition to illness in offspring descending from kindreds affected by schizophrenia or bipolar disorder.

Objectives: Offspring born to patients with affective and non-affective psychoses display indicators of brain dysfunctions that affected parents carry. Such indicators may help understand the risk trajectory. Methods: We followed up the clinical/developmental trajectories of 84 young offspring born to affected parents descending from the Quebec kindreds affected by schizophrenia or bipolar disorder. We longitudinally characterized childhood trajectories using 5 established risk indicators: cognitive impairments, psychotic-like experiences, non-psychotic DSM diagnosis and episodes of poor functioning, trauma and drug use. Results: Overall, offspring individually presented a high rate of risk indicators with 39% having 3 or more indicators. Thirty-three offspring progressed to an axis 1 DSM-IV disorder, 15 of whom transitioned to a major affective or non-affective disorder. The relative risks for each risk indicator were low in these vulnerable offspring (RR = 1.92 to 2.99). Remarkably, transitioners accumulated more risk indicators in childhood-adolescence than non-transitioners (Wilcoxon rank test; Z = 2.64, p = 0.008). Heterogeneity in the risk trajectories was observed. Outcome was not specific to parent's diagnosis. Conclusion: Young offspring descending from kindreds affected by major psychoses would accumulate risk indicators many years before transition. A clustering of risk factors has also been observed in children at risk of metabolic-cardiovascular disorders and influences practice guidelines in this field. Our findings may be significant for the primary care surveillance of millions of children born to affected parents in the G7 nations. Future longitudinal risk research of children at genetic risk should explore concurrently several intrinsic and environmental risk modalities to increase predictivity.

Cognitive structure from childhood to adulthood in kindreds densely affected by schizophrenia and bipolar disorder.

The developmental aspects of cognitive structures from childhood until adulthood and across different levels of risk for psychopathology have been little studied. The aim of the current study was to explore the cognitive factorial structure in subsamples from highly familial and densely affected kindreds of schizophrenia and bipolar disorder - i.e. affected adult members, non-affected adult members and high-risk youth. The same neuropsychological battery was administered in a sample of 480 participants: schizophrenia and bipolar patients (n=51), young high-risk offspring (n=61), non-affected adult relatives of patients (n=96), and controls (n=272). Exploratory Factorial Analysis was performed in the control sample and yielded a 5-factor solution: verbal comprehension, processing speed/working memory, visual learning and memory, verbal learning and memory, reasoning and problem solving. Confirmatory factor analysis indicated that the hierarchical 5-factor solution was well suited for the young high-risk offspring, the non-affected adult relatives of patient and the patients. A hierarchical model with a "g" factor was a good fit for all subsamples. These results suggest that cognitive impairments may aggregate in highly familial individuals.

Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment.

Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response.

[Cognitive-behavioural therapy in early psychosis: an open study in a clinical setting]. / La thérapie cognitivo-comportementale des psychoses en début d'évolution: étude ouverte en milieu clinique.

OBJECTIVE: Meta-analysis results confirm that cognitive-behavioural therapy in psychosis (CBTp) is efficient for persistent symptoms. However, external validity remains unexplored. CBTp in early psychosis (in the first 5 years after diagnosis) seems especially relevant, given a possible impact on long-term course. However, the few studies that experimented with CBTp with this population had poor results. They all introduced therapy during an acute psychotic phase and most of them performed a limited number of sessions. Therefore, our introductory open study aimed to evaluate the efficiency of a 25-session Australian CBTp program, introduced during a stable phase in Quebec patients with early psychosis. METHOD: The Active Cognitive Psychotherapy for Early Psychosis program was offered to 20 patients aged 14 years or older, at a rate of 1 weekly session during 6 months. RESULTS: The acceptance rate was 75%, the mean session compliance rate was 84%, and participants were satisfied with the program. Pre- and post-CBTp analyses indicated statistically significant improvements of psychotic symptomatology, which were maintained at 6-month follow-up. Self-criticism improvement was also statistically significant, post-CBTp. CONCLUSION: CBTp seems to be appropriate in our clinical settings, including with adolescents. Moreover, the treatment dosage used seems to foster session compliance.

Verbal and visual memory impairments among young offspring and healthy adult relatives of patients with schizophrenia and bipolar disorder: selective generational patterns indicate different developmental trajectories.

OBJECTIVE: Memory deficits have been shown in patients affected by schizophrenia (SZ) and bipolar (BP)/mood disorder. We recently reported that young high-risk offspring of an affected parent were impaired in both verbal episodic memory (VEM) and visual episodic memory (VisEM). Understanding better the trajectory of memory impairments from childhood to adult clinical status in risk populations is crucial for early detection and prevention. In multigenerational families densely affected by SZ or BP, our aim was to compare the memory impairments observed in young nonaffected offspring with memory functioning in nonaffected adult relatives and patients. METHODS: For 20 years, we followed up numerous kindreds in the Eastern Québec population. After having characterized the Diagnostic and Statistical Manual of Mental Disorders phenotypes, we assessed cognition (N = 381) in 3 subsamples in these kindreds and in controls: 60 young offspring of a parent affected by SZ or BP, and in the adult generations, 92 nonaffected adult relatives and 40 patients affected by SZ or BP. VEM was assessed with the California Verbal Learning Test and VisEM with the Rey figures. RESULTS: The VEM deficits observed in the offspring were also found in adult relatives and patients. In contrast, the VisEM impairments observed in the young offspring were present only in patients, not in the adult relatives. CONCLUSION: Implications for prevention and genetic mechanisms can be drawn from the observation that VEM and VisEM would show distinct generational trajectories and that the trajectory associated with VisEM may offer a better potential than VEM to predict future risk of developing the disease.

Association of polyaminergic loci with anxiety, mood disorders, and attempted suicide.

BACKGROUND: The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate and distinct risk alleles. As several of these polymorphisms are associated with gene expression, these findings may provide mechanisms to explain the alterations in polyamine metabolism which have been observed in psychiatric disorders.

Retinal response to light in young nonaffected offspring at high genetic risk of neuropsychiatric brain disorders.

BACKGROUND: In neuropsychiatric brain disorders, such as schizophrenia (SZ) and bipolar disorder (BD), the biased effect of chronic drug therapy and the toxic effect of illness once installed constitute obstacles to the identification of valid biomarkers. Such biomarkers could lie at the level of retinal function where anomalies have already been reported in adults suffering from neuropsychiatric disorders. Here, we report a specific electroretinographic (ERG) anomaly in young nonaffected and nonmedicated offspring at high genetic risk (HR) of these disorders. METHODS: Electroretinography was performed in 29 HR offspring having one parent affected by DSM-IV SZ or BD (mean age: 20.8 years, SD 4.4) and 29 healthy control subjects (mean age: 20.6 years, SD 4.2). The HRs' parents descended from multigenerational families affected by SZ or BD. RESULTS: Rod ERG (b-wave amplitude at V(max)) in HRs was significantly lower than control subjects (p < .0001; effect size of -1.47), whereas the cone ERG V(max) showed no difference (p = .27). No effects of gender, age, and seasons of testing were observed. The anomaly in retinal response (rod V(max) b-wave amplitude) was observed independently of parents' diagnosis (SZ; p = .007, effect size of -1.09; BD: p < .0001, effect size of -1.88) and was present in both the younger and older HRs (effect size of -1.6 and -1.8, respectively). CONCLUSIONS: A rod retinal response anomaly before the age of the disease incidence may represent an early and specific biomarker of risk with meaning for further genetic and prevention research.

Classification of hypersensitivity pneumonitis: a hypothesis.

BACKGROUND: Regardless of the causative antigen, hypersensitivity pneumonitis (HP) is usually classified as 'acute', 'subacute' or 'chronic'. Considerable confusion still surrounds this classification because there are no widely accepted criteria to distinguish the various stages. The objective of this study was to determine whether the current classification of HP truly reflects categories of patients with distinct clinical features. METHODS: Data obtained from a large prospective multicenter cohort study (the HP Study) were used to divide a cohort of patients with HP into a limited number of categories (clusters) with maximally differing clinical patterns, without prejudgment. The results of this cluster analysis were compared with the current classification of HP (acute, subacute or chronic). RESULTS: 168 patients were included in the analysis. A 2-cluster solution best fitted the data. Patients in cluster 1 (41 patients) had more recurrent systemic symptoms (chills and body aches) and normal chest radiographs than those in cluster 2 (127 patients) who showed significantly more clubbing, hypoxemia, restrictive patterns on pulmonary function tests and fibrosis on high-resolution computed tomography (HRCT). All p values were <0.0001, using Fisher's exact test. Nodular opacities were seen on HRCT as often in cluster 1 as in cluster 2. There was considerable disagreement between the current classification of HP and the results of our analysis. CONCLUSION: The current classification of acute, subacute and chronic HP is not supported by our analysis. Subacute HP is particularly difficult to define.