Effect of non-pharmacological interventions on source memory processes in the early course of psychosis: A systematic review.

People with a psychotic disorder suffer from major cognitive impairments which prevent their functional recovery. Source memory impairments have been shown to be associated with psychotic symptoms and even to precede their onset. Source memory has thus been hypothesized as a cognitive precursor of psychosis. However, few interventions targeting source memory are included in current therapeutic approaches for early psychosis. AIM: This systematic review aimed to identify non-pharmacological interventions for early psychosis which have impacted source memory processes. METHODS: Studies were selected from nine databases when they included: (a) a non-pharmacological intervention involving a sample of patients with early-onset psychotic disorder or subclinical psychotic symptoms; and (b) effects on source memory processes, measured directly or inferred through an episodic memory task. RESULTS: Thirteen studies were identified, including two cognitive remediation programs and one repetitive transcranial magnetic stimulation treatment that reported beneficial effects on source memory. CONCLUSIONS: Relevant intervention strategies for source memory impairments were identified. This review points up a need to further develop interventions targeting theoretically defined source memory concepts and assess their effects with specific and valid tasks. Recommendations regarding underlying mechanisms which could have a beneficial impact on source memory may provide guidance for the future development of early psychosis interventions.

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.

Childhood abuse and neglect may induce deficits in cognitive precursors of psychosis in high-risk children.

BACKGROUND: Millions of children are born to parents affected by major psychoses. Cognitive dysfunctions seen in patients are already detectable in these children. In parallel, childhood maltreatment increases the risk of adult psychoses through unknown mechanisms. We investigated whether high-risk offspring exposed to abuse/neglect displayed more cognitive precursors of adult psychoses in childhood and adolescence than nonexposed offspring. METHODS: We used a stepwise selection strategy from a 25-year follow-up of 48 densely affected kindreds including 1500 adults (405 patients with schizophrenia or bipolar disorder) to select high-risk offspring aged 6-22 years for inclusion in our study. All offspring were assessed for childhood trauma from direct interviews with the offspring, parents and relatives and from the review of lifetime medical records of parents and children and administered a neuropsychological battery including IQ and 4 of the most impaired neuropsychological domains in psychoses. RESULTS: Our study included 66 high-risk offspring. Those who were exposed to abuse/neglect had significantly lower IQ (effect size [ES] = 0.61) than nonexposed offspring and displayed poorer cognitive performance in visual episodic memory (ES = 0.67) and in executive functions of initiation (ES = 1.01). Moreover, exposed offspring presented more combinations of cognitive deficits that were associated with lower Global Assessment of Functioning scores. LIMITATIONS: Exposure to abuse/neglect was not assessed in the control group, thus the study could not test whether the effect of childhood maltreatment occurred only in a high-risk setting and not in the general population. CONCLUSION: In high-risk youths, maltreatment in childhood/adolescence may negatively impact cognitive domains known to be impaired in adults with psychoses, suggesting an early mediating effect in the association between abuse/neglect and adult psychoses. This finding provides a target for future developmental and preventive research.

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.

Sleep of children with attention deficit hyperactivity disorder: actigraphic and parental reports.

The objectives of this study were to characterize the sleep of children with attention deficit hyperactivity disorder (ADHD), using actigraphy and parental questionnaires, and examine the potentially moderating role of psychostimulant medication and psychiatric comorbidity. Children with ADHD significantly differed from controls on parental and actigraphic measures of sleep, with parental reports indicating more severe sleep disturbances, and actigraphic recordings of longer sleep onset latency, lower sleep efficiency, and lower total sleep time. Both medicated and unmedicated ADHD subgroups differed from the control group on sleep measures, but did not differ from each other. Only the subgroup with comorbid psychiatric symptoms differed from the control group on actigraphic measures. The presence of psychiatric comorbidity, but not psychostimulant medication use, was associated with more severe sleep disturbances. The main implication of these findings is that clinicians should systematically attend to sleep disturbances in children with ADHD, particularly when other psychiatric symptoms are also present.

Sleep, attention, and executive functioning in children with attention-deficit/hyperactivity disorder.

The objective of this study was to investigate potential relationships between two measures of sleep impairments (i.e., sleep duration and sleep efficiency [SE]) and attention and executive functioning in children with attention-deficit/hyperactivity disorder (ADHD). Parents of 43 children (mean age = 10 ± 1.8 years) with ADHD completed sleep and behavioral questionnaires. Children also wore a wrist actigraph for seven nights and were subsequently assessed with the Conners' continuous performance test (CPT)-2. A significant relationship was found between lower SE and increased variability in reaction time on the CPT. Shorter sleep duration was associated with a range of executive functioning problems as reported by the parents. The relationships between sleep duration and the executive functioning measures held even after controlling for age, gender, and use of medication, but not the relationships with SE. These results suggest that sleep quantity is an important correlate of executive functioning in children with ADHD.

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.

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.

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.

Superior estimation abilities in two autistic spectrum children.

Anecdotal reports of superior estimation abilities in autistic individuals (e.g., Sacks, 1985) have never been confirmed empirically. We present here case studies of 2 children with autistic spectrum diagnoses and report remarkable abilities in estimation for several quantifiable dimensions. K.T. and G.T. were tested at 9 years of age for estimation of rank, numerosity, time, weight, length, surface, distance, and precise enumeration for small numbers. Their performances were compared to those of 6 age- and IQ- matched comparison children. K.T. demonstrated a superior level of performance in estimating rank (e.g., which set has larger numerosity?) but his performance in other tasks was average. G.T. displayed outstanding performance in estimating numerosity, time, weight, surface, length, and distance, with average performance in other tasks. These results show that certain autistic spectrum individuals may develop superior and highly specialized abilities in estimation. We discuss these findings in relation to the role of "veridical mapping" in the development of special ability (Mottron, Dawson, & Soulieres, 2009; Mottron, Dawson, Soulieres, Hubert, & Burack, 2006a). Veridical mapping is the detection of isomorphism within a code, between two codes, or between one code and isomorphic elements of the world. Within this framework, it is proposed that estimation abilities, like absolute pitch, rely on the ability to map a verbal code with a specific magnitude of a psychophysical dimension.

Three profiles of language abilities in toddlers with an expressive vocabulary delay: variations on a theme.

PURPOSE: The presence of an expressive vocabulary delay (EVD) in the context of otherwise harmonious development has been the main criterion used to define language delay in 2-year-olds. To better understand the communicative functioning of these children, other variables must be considered. In this study, the aim was to delineate and characterize clusters of 2-year-olds with EVD by measuring other language variables in these children. METHOD: Language and related variables were measured in 68 francophone children with EVD. RESULTS: In a cluster analysis, 2 language variables--(a) language expression and engagement in communication and (b) language comprehension--yielded 3 clusters ranging from weak language ability to high scores on both variables. Further differences were found between these clusters with regard to 2 correlates of lexical acquisition--namely, size of the expressive vocabulary and cognitive development. CONCLUSION: These results shed new light on the notion of heterogeneity in toddlers who present with an EVD by proposing subgroups among them. A follow-up investigation of these participants is ongoing.

Familiarity and recollection processes in patients with recent-onset schizophrenia and their unaffected parents.

Episodic memory deficits are present in patients with schizophrenia (SZ) and their unaffected relatives and could be considered as a cognitive indicator of genetic vulnerability to SZ. The present study, involving patients with SZ as well as their parents, used experimental tasks specifically designed to disentangle the contribution of familiarity and recollection processes to episodic memory. The performance of patients with SZ (n=26) and their unaffected parents (n=35) was compared with that of healthy control groups matched on socio-demographic variables (controls of patients, n=26; controls of parents, n=35) on two memory tasks assessing recollection and familiarity. The first task was designed to investigate item recognition and memory for item-spatial context associations whereas the second targeted item-item associations. The results revealed an overall episodic memory deficit in patients with SZ, encompassing both familiarity and recollection, while unaffected parents showed a dysfunction restricted to the recollection process. Our study highlights differences and similarities in the source of the episodic memory deficit found in patients with SZ and their unaffected parents, and it suggests that recollection could act as a cognitive endophenotype of SZ. The results also suggest that use of experimental tasks represents a promising method in the search of cognitive endophenotypes in SZ.

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.

Atomoxetine and neuropsychological function in children with attention-deficit/hyperactivity disorder: results of a pilot study.

This pilot longitudinal study using measures from parents and teachers evaluated the effects of flexible doses of atomoxetine (ATX) on neuropsychological and functional outcomes in 21 children with attention-deficit/hyperactivity disorder (ADHD) (mean age, 8.0 +/- 1.3 years; inattentive subtype, 71.4%; combined subtype, 28.6%). Among 16 children completing 6 months of ATX treatment, neuropsychological function measured by the NEPSY instrument found significant improvement from baseline in the memory and learning domain (p = 0.01); this change was also seen in an age- and sex-matched healthy control group (p = 0.011). The patient group showed significant improvement on the Test of Everyday Attention (TEA-Ch) and parent and teacher versions of the Behavior Rating Inventory of Executive Function (BRIEF), which assess attentional and executive processes, respectively. Functional improvement was also observed on the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) and parent and teacher versions of the ADHD Rating Scale (ADHDRS-IV), and the investigator-rated Clinical Global Impressions-Severity (CGI-S) scale evidenced reductions in ADHD symptoms. These findings suggest that potential benefits of ATX treatment may extend beyond reduction of core ADHD symptoms to amelioration of some neuropsychological and functional deficits.

Effects of phonological and semantic cuing on encoding and retrieval processes in adolescent psychosis.

The aim of this study was to investigate the effects of cuing on encoding and retrieval processes in adolescent psychosis. Patients and controls were instructed to learn word lists under three conditions: no cue, phonological cue, and semantic cue. Memory performance was measured with free and cued recalls. In free recall, both groups showed higher performance with semantic than with phonological encoding cues, but patients had no advantage from semantic cuing relative to no cue, contrary to controls. Patients' performance improved from free to cued recall, but this was not sufficient to normalize their performance. Impaired strategic processes may lead to encoding and retrieval difficulties in patients.

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.

Systematic review of the literature on characteristics of late-talking toddlers.

BACKGROUND: Research has investigated late-talking toddlers because they are at great risk of continuing to experience language-learning difficulties once they enter school and hence are candidates for early intervention. It is also important to consider this group of children with regards to the immediate characteristics which are detrimental to their development and for which early intervention has become increasingly available. AIMS: To review the literature on late-talking toddlers in order to identify the characteristics of this population whose importance has been clearly demonstrated, identify sources of incongruence in findings, and to underscore aspects of language delay at 2 years of age and characteristics about which additional knowledge is needed. MAIN CONTRIBUTION: The review highlights the need to define the language difficulties found in late-talking toddlers based on clinical profiles that go beyond the criterion of an expressive vocabulary delay. It also underscores the association between vocabulary delay and characteristics of the child such as social-emotional development and characteristics of the socio-familial environment such as language stimulation. CONCLUSIONS: Future research should take into account the lack of homogeneity observed within the population of children with a vocabulary delay at 2 years of age and attempt to identify subgroups within late-talking toddlers. It should also consider a multifactorial perspective of child development to further the understanding of this phenomenon.

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.

Use of the Hayling task to measure inhibition of prepotent responses in normal aging and Alzheimer's disease.

This study measures the effect of Alzheimer's disease (AD) and normal aging on the inhibition of prepotent responses. AD patients, normal aged controls, and young subjects were tested with the Hayling task, which measures the ability to inhibit a semantically constrained response, and with the Stroop procedure. AD patients showed a severe deficit in both error rates and response time on the Hayling task. Inhibition was also impaired on the Stroop procedure, both when using raw performance and when using an inhibition score that controlled for reading and naming speed. Normal aged participants showed modest impairment relative to young controls on both tests. Examination of individual performance in AD patients indicated that the impairment was found in most patients on the Hayling test but in only a subgroup of patients on the Stroop test.

Effect of manipulation and irrelevant noise on working memory capacity of patients with Alzheimer's dementia.

The effect of manipulation and distracting noise on immediate serial recall was measured in patients with dementia of the Alzheimer type (DAT), neurologically healthy elderly individuals, and young adults. In Experiment 1, the authors compared serial word recall with word recall in alphabetical order. Alphabetical recall requires the active manipulation of the contents of working memory. Findings indicated that DAT patients were severely impaired in the alphabetical recall task, whereas the performance of neurologically healthy elderly participants was comparable with the performance of young adult participants. In Experiment 2, the authors investigated the effect of different irrelevant auditory backgrounds on immediate digit recall. In this task, both elderly participants and DAT patients performed similarly to the group of young adult participants, indicating comparable efficacy to resist auditory distraction.