Nathalie Gingras

Shared Neurocognitive Dysfunctions in Young Offspring at Extreme Risk for Schizophrenia or Bipolar Disorder in Eastern Quebec Multigenerational Families

BACKGROUND Adult patients having schizophrenia (SZ) or bipolar disorder (BP) may have in common neurocognitive deficits. Former evidence suggests impairments in several neuropsychological functions in young offspring at genetic risk for SZ or BP. Moreover, a dose-response relation may exist between the degree of familial loading and cognitive impairments. This study examines the cognitive functioning of high-risk (HR) offspring of parents having schizophrenia (HRSZ) and high-risk offspring of parents having bipolar disorder (HRBP) descending from densely affected kindreds. METHODS The sample consisted of 45 young offspring (mean age of 17.3 years) born to a parent having SZ or BP descending from large multigenerational families of Eastern Québec that are densely affected by SZ or BP and followed up since 1989. The offspring were administered a lifetime best-estimate diagnostic procedure (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) and an extensive standard neuropsychological battery. Raw scores were compared with age- and gender-matched controls. RESULTS The offspring displayed differences in memory and executive functions when compared with controls. Moderate to large effect sizes (Cohen d) ranging from 0.65 to 1.25 (for IQ and memory) were observed. Several of the cognitive dysfunctions were present in both HRSZ and HRBP, even when considering DSM-IV clinical status. CONCLUSIONS HRSZ and HRBP shared several aspects of their cognitive impairment. Our data suggest that the extremely high genetic and familial loading of these HRs may have contributed to a quantitatively increased magnitude of the cognitive impairments in both HR subgroups, especially in memory. These offspring at heightened risk present difficulties in processing information that warrant preventive research.

Clinical diagnoses in young offspring from eastern Québec multigenerational families densely affected by schizophrenia or bipolar disorder

Objective:  The follow‐up since 1989 of a large sample of multigenerational families of eastern Québec that are densely affected by schizophrenia (SZ) or bipolar disorder (BP) has permitted to look at the rates of DSM diagnoses in the young offspring of a SZ parent (HRSZ) and of a BP parent (HRBP) who had an extremely loaded family history.

Deficient relational binding processes in adolescents with psychosis: Evidence from impaired memory for source and temporal context

Introduction. Findings from the literature consistently revealed episodic memory deficits in adolescents with psychosis. However, the nature of the dysfunction remains unclear. Based on a cognitive neuropsychological approach, a theoretically driven paradigm was used to generate valid interpretations about the underlying memory processes impaired in these patients. Methods. A total of 16 inpatient adolescents with psychosis and 19 individually matched controls were assessed using an experimental task designed to measure memory for source and temporal context of studied words. Retrospective confidence judgements for source and temporal context responses were also assessed. Results. On word recognition, patients had more difficulty than controls discriminating target words from neutral distractors. In addition, patients identified both source and temporal context features of recognised items less often than controls. Confidence judgements analyses revealed that the difference between the proportions of correct and incorrect responses made with high confidence was lower in patients than in controls. In addition, the proportion of high-confident responses that were errors was higher in patients compared to controls. Conclusions. These findings suggest impaired relational binding processes in adolescents with psychosis, resulting in a difficulty to create unified memory representations. Our findings on retrospective confidence data point to impaired monitoring of retrieved information that may also impair memory performance in these individuals.

Young offspring at genetic risk of adult psychoses: the form of the trajectory of IQ or memory may orient to the right dysfunction at the right time.

Objective Neurocognitive dysfunctions analogous to those of adult patients have been detected in children at risk of schizophrenia and bipolar disorder. This led to the following developmental question: Do IQ and memory impairments exhibit different developmental courses from childhood to young adulthood in terms of stability or fluctuations? Methods In a high risk sample, we used a step by step sampling approach to narrow-down the early disease mechanisms. Upstream, we started with a 20-year follow-up of 48 densely affected multigenerational kindreds, including 1500 clinically characterized adult members. We then identified 400 adult members affected by a DSM-IV schizophrenia or bipolar disorder. Downstream, we finally focused on 65 offspring (of an affected parent) aged 7 to 22, who were administered a neuropsychological battery. We then constructed cross-sectional trajectories that were compared to those of controls. Results The childhood IQ deficit displayed a stability until young adulthood. The delay in visual memory exhibited a non-linear two-stage trajectory: a lagging period during childhood followed by a recuperation period from adolescence until adulthood, as supported by a significant Group x Age Periods interaction. No data suggested deterioration between 7 and 22. Conclusion In these offspring at genetic risk, the developmental trajectory of global IQ impairment may not apply to specific domains of cognition such as episodic memory. Different cognitive dysfunctions would mark different developmental courses. The shape of the trajectories might itself have a meaning and provide empirical leads for targeting the right dysfunction at the right time in future prevention research.

The nature of attentional dysfunctions in adolescents hospitalized for a first episode of psychosis.

INTRODUCTION Dysfunctions of attentional processes have been previously described as a significant characteristic associated with psychotic disorders, but the nature of these deficits are insufficiently understood in adolescents experiencing a first episode of psychosis. This study aimed to exhaustively assess attentional processes in psychotic adolescents and their relationships with clinical symptoms and diagnoses. METHODS A total of 24 adolescents hospitalized for a first episode of psychosis and their individually matched controls were assessed using theory-driven attentional tasks. RESULTS No significant differences were found on sustained and selective attention tasks. Patients performed more poorly than controls in a dual-task paradigm, suggesting a divided attention impairment. Significant deficits were also obtained on tasks requiring inhibition and flexibility capacities. No differences were found between schizophrenic and affective subgroups of patients. The intensity of the symptoms of psychosis did not seem to be associated with attentional performances. CONCLUSION These findings suggest that adolescents with a first episode of psychosis show specific rather than global attentional impairments. Sustained and selective attention seems to be preserved, whereas divided attention and attentional control are impaired when compared to controls. The attentional profile seems to be unrelated to either the clinical symptomatology or the diagnosis underlying psychosis. A partial independence between cognition and clinical symptomatology could be hypothesized from these data but remains to be directly assessed in future studies.

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 parents 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.

True and false memories in adolescents with psychosis: Evidence for impaired recollection and familiarity

Introduction. Psychotic patients are impaired on recall and recognition of studied items (true memory) and typically make more false recall (intrusions) and false recognition than controls, reflecting greater susceptibility to false memory. The functional mechanisms underlying these deficits are poorly understood. The aim of this study was to examine recollection and familiarity in true and false memory in psychotic adolescents without long-term exposure to medication and repeated hospitalisations. Methods. Seventeen adolescents with psychosis and 17 matched controls were tested on a DRM false memory paradigm combined with a remember (R)/know (K)/guess (G) procedure. Recall and recognition of targets (studied words), critical lures (associated words) and unrelated distractors were measured. Between-group comparisons were made using t-tests and mixed ANOVAs. Independent estimates for recollection and familiarity were also calculated. Results. True memory was impaired in patients. Similar rates of false memory for critical lures were found in both groups. False memory for unrelated distractors was increased in patients. Contrary to controls, who attributed more R and K responses to targets than lures, patients attributed similar proportions of R and K responses to targets and lures. Furthermore, patients attributed more K responses than controls to all distractors. Conclusions. These findings suggest a deficit in recollection- and familiarity-based memory in psychotic adolescents as well as reliance on preserved gist or meaning-based memory to support poor item-specific memory.

7.2 ELECTRORETINOGRAPHIC ANOMALIES SEEN IN PATIENTS AFFECTED BY SCHIZOPHRENIA OR BIPOLAR DISORDER ARE DETECTABLE EARLY IN CHILDREN BORN TO AN AFFECTED PARENT: IMPLICATIONS FOR THE STAGING OF RISK STATUS IN CHILDHOOD-ADOLESCENCE

Abstract Background Adult patients having schizophrenia, bipolar disorder or major depression display indicators of brain dysfunctions that may be detectable in healthy children-adolescents at genetic risk, such as those born to an affected parent (Maziade, New Eng J Med 2017; Schizophr Res 2013). For instance, cognitive deficits are displayed by both adult patients and children at risk (Maziade, Schizophr Bull 2011). We had reported that schizophrenia patients present diminished amplitudes and delayed latencies of rod and cone photoreceptor responses (Hébert, Schizophr Res, 2015) and we recently found that bipolar patients have similar ERG anomalies. We had also reported preliminary data in a small sample of 29 children born to an affected parent showing that young offspring had rod diminished amplitudes (Hébert, Biol Psychiatry 2010). The present objectives were i) under the hypothesis that offspring would display many of the ERG anomalies that schizophrenia or mood disorder patients carry (Hébert, Schizophr Res 2015; Prog Neuropsychopharmacol Biol Psychiatry 2017), to look for cone and rod response anomalies in a large sample of young high-risk offspring; ii) to describe the relationship between ERG anomalies and other risk endophenotypes in the offspring; and iii) look at the relationship between ERG anomalies and the risk clusters already shown to predict later transition to illness. Methods The sample consisted of 84 young offspring (aged 6 to 27) of a parent affected by schizophrenia or bipolar disorder, compared to 224 healthy controls balanced for age and sex. Full-field cone and rod ERG was measured in non-dilated eyes for all subjects. In the young offspring, we also collected measures of different cognitive domains, attenuated symptoms of psychosis, non-psychotic DSM diagnosis and/or an episode of poor GAF functioning in childhood-adolescence, childhood trauma, and cannabis use (Paccalet, Schizophr Res 2016). Results In comparison to controls the offspring displayed three ERG anomalies that were observed in adult patients: prolonged cone b-wave latency (p=0.04), diminished rod b-wave amplitude (p=0.04) and prolonged rod b-wave latency (p=0.006). These ERG anomalies were shared by offspring of a parent with schizophrenia or bipolar disorder, an observation of ERG commonality that we had made in adult patients. The three ERG amplitude and latency anomalies tended to aggregate in a child at risk, a trend we also observed in another endophenotype modality such as deficits in different cognitive domains. However, in these high-risk children and adolescents, the patterns of aggregation suggest that ERG anomalies would depict another risk pathway than that marked by cognitive deficits. Discussion First, ERG anomalies in high-risk children have neurobiological implications for future research on the illness neurodevelopment. Second, as found for other modalities of risk endophenotypes in children at genetic risk (Maziade, New Eng J Med 2017), multiple rod and cone ERG anomalies tended to cluster together in a child. Such an aggregation may be compatible with the multifactorial polygenic theory with a threshold. Remarkably, a clustering of risk indicators is also observed in children at risk of metabolic cardiovascular disorders and is presently considered in practice guidelines for these children. The clustering of risk indicators may provide an empirical basis for the staging of the risk status of children at genetic risk and has immediate implications for their longitudinal surveillance in the clinic.

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.

Over-reliance on gist memory in adolescents with psychosis

When healthy persons produce actions associated with novel objects, they confuse similar actions more often than dissimilar actions. It is not known whether they habitually confuse some action dimensions over others. This is applicable to the study of limb apraxia, a disorder impairing the production of actions associated with common objects, in which patients do habitually confuse certain movement dimensions. In this study, novel objects were associated with actions consisting of simple action dimensions (pulling, sliding, and twisting), or combinations of these dimensions (e.g., simultaneously slide and twist). Participants learned to pair novel objects, actions and nonword names. On test trials, participants were shown a novel object, asked to recall its name, and asked to demonstrate its action. When participants confused similar actions (e.g., produced’twist and slide’ instead of ’slide’), errors were classified according to which dimension was added or omitted. Chi Square analyses on the errors indicated that (1) addition errors were more frequent than omissions, (2) participants added a ’twist’ dimension more often than slide or pull (3) participants omitted the slide dimension more than twist or pull. The overproduction of addition errors in healthy participants may relate to apraxic behaviour. In limb apraxia, the actions produced in response to pictured objects are augmented: a movement dimension may be exaggerated (e.g., the extent of hammering/pounding motion) or movement features (e.g., a hand posture) from previous actions may intrude on the performance of subsequent actions.