Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample

Background

There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.

Methods

We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.

Results

Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).

Conclusion

The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.     

Neuropsychological Impairment in Prodromal,First-Episode,and Chronic Psychosis: Assessing RBANS Performance

BackgroundCognitive deficits are observed throughout all developmental phases of psychosis. However, prior studies have usually focused on a limited illness period and used a wide variety of cognitive instruments. Therefore, it has been difficult to characterize or highlight cognitive functioning in different stages of psychosis.MethodWe administered the RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) tests to 4 participant subgroups, including healthy volunteers (controls, HC, n = 28), subjects at high risk for clinical psychosis (prodrome, CHR, n = 27), first-episode schizophrenia patients (FE-Sz, n = 26), and mid-term and long-term chronic schizophrenia patients (Ch-Sz, n =147). Comparison, correlation, and regression analyses of RBANS index scores were assessed among groups. We examined clinical outcomes over 2 years between the CHR and HC subjects, and RBANS domains were used as possible predictors for conversion to psychosis.ResultsPerformance on all RBANS domains was significantly impaired during a post-onset stage of psychosis (FE-Sz and Ch-Sz), and RBANS scores declined along with disease progression. Regression analyses showed that for CHR and HC subjects, baseline impairment in delayed memory (DM) significantly predicted conversion to psychosis. Additionally, partial correlations showed that for FE-Sz and Ch-Sz subjects, DM was the only correlate with a later stage of psychosis.ConclusionsCognitive deficits broadly emerged, and diminished functioning followed along with disease progression. Impairment in DM is perhaps one domain that helps us understand the development of psychosis. A critical need is to monitor and treat memory functioning for psychotic patients throughout all phases of the disease.     

The Impact of Social Deprivation on Paranoia,Hallucinations, Mania and Depression: The Role of Discrimination Social Support,Stress and Trust

The negative implications of living in a socially unequal society are now well documented. However, there is poor understanding of the pathways from specific environmental risk to symptoms. Here we examine the associations between social deprivation, depression, and psychotic symptoms using the 2007 Adult Psychiatric Morbidity Survey, a cross-sectional dataset including 7,353 individuals. In addition we looked at the mediating role of stress, discrimination, trust and lack of social support. We found that the participants'' neighbourhood index of multiple deprivation (IMD) significantly predicted psychosis and depression. On inspection of specific psychotic symptoms, IMD predicted paranoia, but not hallucinations or hypomania. Stress and trust partially mediated the relationship between IMD and paranoid ideation. Stress, trust and a lack of social support fully mediated the relationship between IMD and depression. Future research should focus on the role deprivation and social inequalities plays in specific manifestations of psychopathology and investigate mechanisms to explain those associations that occur. Targeting the mediating mechanisms through appropriate psychological intervention may go some way to dampen the negative consequences of living in an unjust society; ameliorating economic injustice may improve population mental health.     

Psychological processes mediating the association between developmental trauma and specific psychotic symptoms in adults: a systematic review and meta‐analysis

Experiencing psychological trauma during childhood and/or adolescence is associated with an increased risk of psychosis in adulthood. However, we lack a clear knowledge of how developmental trauma induces vulnerability to psychotic symptoms. Understanding the psychological processes involved in this association is crucial to the development of preventive interventions and improved treatments. We sought to systematically review the literature and combine findings using meta‐analytic techniques to establish the potential roles of psychological processes in the associations between developmental trauma and specific psychotic experiences (i.e., hallucinations, delusions and paranoia). Twenty‐two studies met our inclusion criteria. We found mediating roles of dissociation, emotional dysregulation and post‐traumatic stress disorder (PTSD) symptoms (avoidance, numbing and hyperarousal) between developmental trauma and hallucinations. There was also evidence of a mediating role of negative schemata, i.e. mental constructs of meanings, between developmental trauma and delusions as well as paranoia. Many studies to date have been of poor quality, and the field is limited by mostly cross‐sectional research. Our findings suggest that there may be distinct psy­chological pathways from developmental trauma to psychotic phenomena in adulthood. Clinicians should carefully ask people with psychosis about their history of developmental trauma, and screen patients with such a history for dissociation, emotional dysregulation and PTSD symptoms. Well conducted research with prospective designs, including neurocognitive assessment, is required in order to fully understand the biopsychosocial mechanisms underlying the association between developmental trauma and psychosis.     

Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity,Cognition and Antipsychotic Medication

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.     

The Psychosis Recent Onset GRoningen Survey (PROGR-S): Defining Dimensions and Improving Outcomes in Early Psychosis

Psychotic disorders are among the most complex medical conditions. Longitudinal cohort studies may offer further insight into determinants of functional outcome after a psychotic episode. This paper describes the Psychosis Recent Onset in GRoningen Survey (PROGR-S) that currently contains data on 1076 early-episode patients with psychosis, including symptoms, personality, cognition, life events and other outcome determinants. Our goal in this report is to give an overview of PROGR-S, as a point of reference for future publications on the effect of cognition, personality and psychosocial functioning on outcomes. PROGR-S contains an extensive, diagnostic battery including anamnesis, biography, socio-demographic characteristics, clinical status, drug use, neuropsychological assessment, personality questionnaires, and physical status tests. Extensive follow-up data is available on psychopathology, physical condition, medication use, and care consumption. Sample characteristics were determined and related to existing literature. PROGR-S (period 1997–2009, n = 718) included the majority of the expected referrals in the catchment area. The average age was 27 (SD = 8.6) and two-thirds were male. The average IQ was lower than that in the healthy control group. The majority had been diagnosed with a psychotic spectrum disorder. A substantial number of the patients had depressive symptoms (479/718, 78%) and current cannabis or alcohol use (465/718, 75%). The level of community functioning was moderate, i.e. most patients were not in a relationship and were unemployed. The PROGR-S database contains a valuable cohort to study a range of aspects related to symptomatic and functional outcomes of recent onset psychosis, which may play a role in the treatment of this complex and disabling disorder. Results reported here show interesting starting points for future research. Thus, we aim to investigate long-term outcomes on the basis of cognition, personality, negative symptoms and physical health. Ultimately, we hope that this paper will contribute improving the health of patients with psychotic disorders.     

Hypogonadism Due to Hyperprolactinemia and Subsequent First Episode of Psychosis

BackgroundHyperprolactinemia causes hypogonadotrophic hypogonadism. Hyperprolactinemia can be pre-existing in some patients with schizophrenia. Dopamine is the most important prolactin-inhibiting factor, and dopaminergic hyperactivity has been implicated in the pathophysiology of psychosis.ObjectiveSince dopamine is a prolactin-inhibiting factor and dopamine imbalanced has been implicated in the pathophysiology of psychotic disorders, we investigated the probable relationship between hyperprolactinemia and the development of psychotic symptoms, in a patient with hypogonadism due to hyperprolactnemia and subsequent first episode of psychosis. Since dopamine is a prolactin-inhibiting factor and dopamine imbalance has been implicated in the pathophysiology of psychotic disorders, we investigated the probable relationship between hyperprolactinemia and the development of psychotic symptoms.MethodsWe present the case of a patient with hypogonadism secondary to chronic, untreated hyperprolactinemia who developed acute psychotic symptoms.ResultsPsychotic symptoms resolved soon after treatment with aripiprazole in conjunction with cabergoline, with a concomitant decrease in serum prolactin level.ConclusionThis is an interesting case illustrating a complicated relationship among hypogonadism secondary to a prolactinoma and dopamine and psychosis.     

Elucidating the role of muscarinic receptors in psychosis

Muscarinic receptors have been implicated in the regulation of cognition and psychosis based on pharmacological evidence from pre-clinical and clinical studies. Muscarinic agonists have shown promise in the clinic in improving cognition and reducing psychotic episodes in Alzheimer's patients. However, lack of selective muscarinic ligands has limited their use due to troublesome side effects observed at higher doses. Without selective ligands, it has been difficult to assign a specific muscarinic receptor subtype to these high order mental processes. Recent development of muscarinic receptor knockout mice has provided additional tools to investigate cognition and psychosis in behavioral assays and to determine the receptor subtypes associated with parasympathomimetic physiology. Biochemical studies indicate that the M1 receptor plays a significant role in regulating G alpha q-mediated signal transduction in the hippocampus and cortex. Behavioral studies suggest that the M4 receptor is involved in movement regulation and prepulse inhibition of the startle reflex, a measure of attention. These findings support a role for the development of M1 and M4 receptor agonists for diseases in which symptoms include cognitive impairment and psychotic behaviors.     

Evidence for a Shared Etiological Mechanism of Psychotic Symptoms and Obsessive-Compulsive Symptoms in Patients with Psychotic Disorders and Their Siblings

The prevalence of obsessive-compulsive disorder in subjects with psychotic disorder is much higher than in the general population. The higher than chance co-occurrence has also been demonstrated at the level of subclinical expression of both phenotypes. Both extended phenotypes have been shown to cluster in families. However, little is known about the origins of their elevated co-occurrence. In the present study, evidence for a shared etiological mechanism was investigated in 3 samples with decreasing levels of familial psychosis liability: 987 patients, 973 of their unaffected siblings and 566 healthy controls. The association between the obsessive-compulsive phenotype and the psychosis phenotype c.q. psychosis liability was investigated. First, the association was assessed between (subclinical) obsessive-compulsive symptoms and psychosis liability. Second, in a cross-sib cross-trait analysis, it was examined whether (subclinical) obsessive-compulsive symptoms in the patient were associated with (subclinical) psychotic symptoms in the related unaffected sibling. Evidence was found for both associations, which is compatible with a partially shared etiological pathway underlying obsessive-compulsive and psychotic disorder. This is the first study that used a cross-sib cross-trait design in patients and unaffected siblings, thus circumventing confounding by disease-related factors present in clinical samples.     

Neuropsychological and Socio-Occupational Functioning in Young Psychiatric Outpatients: A Longitudinal Investigation

Background

Clinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning.

Methods

At baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome.

Results

Good socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome.

Conclusions

Neuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches.     

Approches cognitivo-comportementales de groupe dans la prise en charge précoce de jeunes adultes schizophrènes

One hundred and fifty young psychotic adults are treated at the Montreal Sacré-c?ur hospital’s specialized clinic for the treatment of first psychotic episodes. The clinic’s principal objective is the early intervention in the development of the psychotic process to ultimately decrease the length of time the psychosis remains untreated and avoid the deterioration of the cognitive, relational and social functioning of these young adults. This objective is achieved through the establishment of an important and long lasting therapeutic relationship, the use of new-generation anti-psychotic drugs, family-oriented intervention and the participation in a group cognitive-behavioural psychotherapy program. This program is divided into five sub-programs according to a continuum of social and cognitive functioning, ranging from weak to strong. The therapeutic activities of every subprogram are developed stepwise, and their sequence is determined by the resolution of the first psychotic episode as well as by the social integration of the participants. In this article, the authors present the structure and the functioning of the clinic. They also present the organization, and the general objectives, of the program as well as the different cognitive and behavioural strategies aimed at resolving the principal problems encountered by young adults at the time of their first psychotic episodes.     

Social Functioning Trajectories of Young First-Episode Psychosis Patients with and without Cannabis Misuse: A 30-Month Follow-Up Study

The aim of the study was to investigate trajectories of social functioning in young people with first-episode psychosis (FEP) with and without cannabis misuse using a secondary analysis of data from the Episode-II trial. Forty-two young people with FEP and comorbid cannabis use disorder were compared with 39 young people with FEP but without a cannabis use disorder. Social functioning was assessed every 6 months during a 30-month follow-up. Multilevel linear growth curve modeling was used to compare the social functioning trajectories over time for those with and without cannabis misuse. Cannabis misuse was not associated with social functioning at baseline assessment. Over a 30-month follow-up, FEP patients without cannabis disorder showed significant improvements in their social functioning, whereas patients with cannabis misuse at baseline displayed no such improvement. Patients with and without cannabis misuse differed significantly in their levels of social functioning after 24 months. Similar results were obtained after adjusting for potential confounders (i.e., age, gender, negative symptoms, premorbid functioning, DSM-IV diagnoses, baseline social functioning and other substance use). In the context of a specialized early intervention service, patients with cannabis misuse at baseline did not attain the improvements in social outcomes observed in their counterparts without cannabis misuse. There is a need to develop effective interventions to reduce cannabis misuse to ultimately improve social outcomes in young people with psychosis.     

Weight change and cognitive function: findings from the Women's Health Initiative Study of Cognitive Aging

Although studies exploring relationships between obesity and cognitive impairment in the elderly are conflicting, literature suggests that overweight and obesity may be protective against cognitive impairment and dementia in older women. We examine the associations between changes in weight and waist circumference (WC) with global and domain-specific cognitive function in a large, well-defined cohort of 2,283 older, postmenopausal women (aged 65-79) prospectively followed through the Women's Health Initiative (WHI) Study of Cognitive Aging (WHISCA). We assessed the associations between changes in weight and WC collected up to 5 years before WHISCA enrollment and mean levels of global and domain-specific cognitive performance across an average of 5.4 years of subsequent follow-up. There was a lack of associations between weight and cognition in women who remained stable or gained weight. The only significant relationships observed were in association with weight loss (P ≤ 0.05), most likely signaling incipient disease. Moreover, cognition was not related to changes in WC. Relationships were largely independent of initial BMI, self-reported caloric intake or dieting. The lack of associations between weight gain and cognition in women is consistent with the existing literature.     

Social Cognition in Individuals at Ultra-High Risk for Psychosis: A Meta-Analysis

Objective

Treatment in the ultra-high risk stage for a psychotic episode is critical to the course of symptoms. Markers for the development of psychosis have been studied, to optimize the detection of people at risk of psychosis. One possible marker for the transition to psychosis is social cognition. To estimate effect sizes for social cognition based on a quantitative integration of the published evidence, we conducted a meta-analysis of social cognitive performance in people at ultra high risk (UHR).

Methods

A literature search (1970-July 2015) was performed in PubMed, PsychINFO, Medline, Embase, and ISI Web of Science, using the search terms ‘social cognition’, ‘theory of mind’, ‘emotion recognition’, ‘attributional style’, ‘social knowledge’, ‘social perception’, ‘empathy’, ‘at risk mental state’, ‘clinical high risk’, ‘psychosis prodrome’, and ‘ultra high risk’. The pooled effect size (Cohen’s D) and the effect sizes for each domain of social cognition were calculated. A random effects model with 95% confidence intervals was used.

Results

Seventeen studies were included in the analysis. The overall significant effect was of medium magnitude (d = 0.52, 95% Cl = 0.38–0.65). No moderator effects were found for age, gender and sample size. Sub-analyses demonstrated that individuals in the UHR phase show significant moderate deficits in affect recognition and affect discrimination in faces as well as in voices and in verbal Theory of Mind (TOM). Due to an insufficient amount of studies, we did not calculate an effect size for attributional bias and social perception/ knowledge. A majority of studies did not find a correlation between social cognition deficits and transition to psychosis, which may suggest that social cognition in general is not a useful marker for the development of psychosis. However some studies suggest the possible predictive value of verbal TOM and the recognition of specific emotions in faces for the transition into psychosis. More research is needed on these subjects.

Conclusion

The published literature indicates consistent general impairments in social cognition in people in the UHR phase, but only very specific impairments seem to predict transition to psychosis.     

Social Cognitive Role of Schizophrenia Candidate Gene GABRB2

The occurrence of positive selection in schizophrenia-associated GABRB2 suggests a broader impact of the gene product on population fitness. The present study considered the possibility of cognition-related GABRB2 involvement by examining the association of GABRB2 with psychosis and altruism, respectively representing psychiatric and psychological facets of social cognition. Four single nucleotide polymorphisms (SNPs) were genotyped for quantitative trait analyses and population-based association studies. Psychosis was measured by either the Positive and Negative Syndrome Scale (PANSS) or antipsychotics dosage, and altruism was based on a self-report altruism scale. The minor alleles of SNPs rs6556547, rs1816071 and rs187269 in GABRB2 were correlated with high PANSS score for positive symptoms in a Han Chinese schizophrenic cohort, whereas those of rs1816071 and rs1816072 were associated with high antipsychotics dosage in a US Caucasian schizophrenic cohort. Moreover, strongly significant GABRB2-disease associations were found among schizophrenics with severe psychosis based on high PANSS positive score, but no significant association was observed for schizophrenics with only mild psychosis. Interestingly, in addition to association with psychosis in schizophrenics, rs187269 was also associated with altruism in healthy Han Chinese. Furthermore, parallel to correlation with severe psychosis, its minor allele was correlated with high altruism scores. These findings revealed that GABRB2 is associated with psychosis, the core symptom and an endophenotype of schizophrenia. Importantly, the association was found across the breadth of the psychiatric (psychosis) to psychological (altruism) spectrum of social cognition suggesting GABRB2 involvement in human cognition.     

Exploring the behavioral and cognitive phenotype of KBG syndrome

KBG syndrome is a neurodevelopmental disorder, caused by dominant mutations in ANKRD11, that is characterized by developmental delay/intellectual disability, mild craniofacial dysmorphisms, and short stature. Behavior and cognition have hardly been studied, but anecdotal evidence suggests higher frequencies of ADHD‐symptoms and social‐emotional impairments. In this study, the behavioral and cognitive profile of KBG syndrome will be investigated in order to examine if and how cognitive deficits contribute to behavioral difficulties. A total of 18 patients with KBG syndrome and a control group consisting of 17 patients with other genetic disorders with comparable intelligence levels, completed neuropsychological assessment. Age‐appropriate tasks were selected, covering overall intelligence, attention, memory, executive functioning, social cognition and visuoconstruction. Results were compared using Cohen's d effect sizes. As to behavior, fewer difficulties in social functioning and slightly more attentional problems, hyperactivity, oppositional defiant behavior and conduct problems were found in the KBG syndrome group. Regarding cognitive functioning, inspection of the observed differences shows that patients with KBG syndrome showed lower scores on sustained attention, cognitive flexibility, and visuoconstruction. In contrast, the KBG syndrome group demonstrated higher scores on visual memory, social cognition and emotion recognition. The cognitive profile of KBG syndrome in this sample indicates problems in attention and executive functioning that may underlie the behavior profile which primarily comprises impulsive behavior. Contrary to expectations based on previous (case) reports, no deficits were found in social cognitive functioning. These findings are important for counseling purposes, for tailored education planning, and for the development of personalized intervention.     

Default Mode Network Connectivity as a Function of Familial and Environmental Risk for Psychotic Disorder

Background

Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.

Methods

Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.

Results

There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.

Discussion

Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.     

Infant Growth after Preterm Birth and Mental Health in Young Adulthood

Objectives

Faster growth after preterm birth benefits long-term cognitive functioning. Whether these benefits extend to mental health remains largely unknown. We examined if faster growth in infancy is associated with better self-reported mental health in young adults born preterm at very low birth weight (VLBW) (<1500g).

Study Design

As young adults, participants of the Helsinki Study of Very Low Birth Weight Adults self-reported symptoms of depression and attention deficit/hyperactivity disorder (ADHD) (n = 157) and other psychiatric problems (n = 104). As main predictors of mental health outcomes in linear regression models, we used infant weight, length, and head circumference at birth, term, and 12 months of corrected age, and growth between these time points. Growth data were collected from records and measures at term and at 12 months of corrected age were interpolated. Additionally, we examined the moderating effects of intrauterine growth restriction.

Results

Size at birth, term, or 12 months of corrected age, or growth between these time points were not associated with mental health outcomes (p-values >0.05). Intrauterine growth restriction did not systematically moderate any associations.

Conclusions

Despite the high variability in early growth of VLBW infants, the previously described association between slow growth in infancy and poorer cognitive functioning in later life is not reflected in symptoms of depression, ADHD, and other psychiatric problems. This suggests that the development of cognitive and psychiatric problems may have dissimilar critical periods in VLBW infants.     

Longitudinal Associations between Adolescent Psychotic Experiences and Depressive Symptoms

Background

Psychotic experiences are prevalent in community samples and are highly correlated with depressive symptoms. This study aimed to investigate the longitudinal associations between psychotic experiences and depressive symptoms between adolescence and young adulthood.

Method

Prospective cohort study with a 6 year follow-up in a community sample of 7632 adolescents and young adults. Depressive symptoms were assessed with the Short Moods and Feelings Questionnaire and psychotic experiences with a semi-structured clinical interview at 12 and 18 years. Longitudinal and cross-sectional associations were investigated with regression and structural equation models.

Results

Depressive symptoms and psychotic experiences were associated at each time-point (12 years r = 0.486 [95% CI 0.457, 0.515]; 18 years r = 0.286 [95% CI 0.233, 0.339]) and there were longitudinal within-phenotype associations (depressive symptoms r = 0.252 [95% CI 0.205, 0.299]; psychotic experiences r = 0.662 [95% CI 0.595, 0.729]). There was an across-phenotype association between psychotic experiences at 12 and depressive symptoms at 18 r = 0.139 [95% CI 0.086, 0.192; p<0.001], but no association between depressive symptoms at 12 and psychotic experiences at 18 r = −0.022 [95% CI −0.032, 0.077; p = 0.891].

Conclusions

Longitudinal across-phenotype associations were substantially weaker than cross-sectional associations or within-phenotype longitudinal associations. Whilst psychotic experiences at 12 years were associated with a small increase in depression at 18 years, depression at 12 years was not associated with psychotic experiences at 18 years once across-phenotype cross-sectional and within-phenotype longitudinal associations were accounted for. This suggests that the biological mechanisms underlying depression at this age do not increase subsequent risk of psychotic experiences once they resolve.     

Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of socio‐demographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.5 ± 17.6 months after initial assessment. Eighty‐nine participants with 22q11DS (age range: 8‐30 years; mean 16.1 ± 4.7) were assessed using the Structured Interview for Psychosis‐Risk Syndromes. Information on Axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders, and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non‐UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high‐risk samples. Nevertheless, the relatively high transition rate in non‐UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.