Elisa Rodríguez-Toscano

Psychiatric disorders in child and adolescent offspring of patients with schizophrenia and bipolar disorder: A controlled study

BACKGROUND Early clinical manifestations predating schizophrenia (SZ) and bipolar disorder (BP) have not been fully characterized. Child offspring studies are a valuable opportunity to study the natural history of the illness from its earliest stages. However, there is limited evidence assessing young offspring of SZ and BP simultaneously. We set out to assess rates of psychiatric disorders in child and adolescent offspring of SZ and BP, relative to offspring of community controls, so as to characterize the early phenotype of the disorders comparatively. METHODS SZ and BP parents with offspring aged 7-17years were recruited through adult mental health services of two tertiary hospitals. Community control (CC) parents were recruited from the same geographical area. Ninety BP-offspring, 41 SZ-offspring and 107 CC-offspring were assessed using the K-SADS-PL by child psychiatrists blinded to parental status. Differences in prevalence of psychiatric disorders between groups were adjusted for confounders and for sibling correlation using generalised estimating equations. RESULTS We found a gradient of clinical severity and social disadvantage between SZ, BP and CC-offspring. After adjusting for socio-demographic confounders, SZ and BP-offspring presented higher rates of attention deficit hyperactivity disorder (ADHD) than CC-offspring. ADHD was more prevalent in SZ-offspring than BP-offspring, and BP-offspring presented a higher prevalence of depression than CC-offspring. CONCLUSIONS The higher rates of ADHD in SZ-offspring suggest that abnormal neurodevelopmental processes may exert a stronger influence in SZ than BP. Follow-up of these children will help elucidate the role of ADHD and depression phenotypes in predicting future transition to SZ or BP.

A longitudinal study on the relationship between duration of untreated psychosis and executive function in early-onset first-episode psychosis

BACKGROUND The relationship between duration of untreated psychosis (DUP) and executive function (EF) in patients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms. METHODS A total of 66 subjects were included in the study (19 females [28.8%], mean age 16.2 ± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was estimated using a multivariate linear regression model after removing the effect of intelligence quotient and controlling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up. RESULTS Mean DUP was 65.0 ± 6.9 days (95% confidence interval [CI], 51.2, 78.8). Median DUP was 47.5 days (range 2-180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance [e.v. 10.9%], p=0.007). Only shorter DUP (e.v. 8.7%, p=0.013) and greater severity of baseline negative symptoms (e.v. 10.0%, p=0.008) were significantly associated with greater improvement in EF. CONCLUSIONS In early-onset FEP, shorter DUP was associated with greater improvement in EF over a 2-year follow-up period.

Very Early Brain Damage Leads to Remodeling of the Working Memory System in Adulthood: A Combined fMRI/Tractography Study.

The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI. SIGNIFICANCE STATEMENT Here we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brains ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this “extra” activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI.

Neuropsychological characteristics of child and adolescent offspring of patients with bipolar disorder

BACKGROUND Bipolar disorder (BD) is a severe mental disorder with a strong genetic component. The assessment of child and adolescent offspring of patients diagnosed with BD (BDoff) provides an opportunity to investigate vulnerability factors and the first abnormalities associated with the disorder. Previous literature in child and adolescent BDoff is scarce and controversial. However, some studies concur in identifying significant impairment in executive functions, memory and attention. The present study aims to compare global neuropsychological characteristics of child and adolescent offspring of patients with bipolar disorder with a group of offspring of parentswith no history of psychotic disorder, and to assess the influence of psychopathology on neuropsychological performance. METHODS This research was part of The Bipolar and Schizophrenia Young Offspring Study (BASYS). A group of BDoff (N= 90) and a group of offspring of parents with no history of psychotic disorder (CC) (N = 107) were assessed with a complete neuropsychological battery. Intellectual quotient, working memory, processing speed, verbal memory and learning, visual memory, attention and executive functions were included in the cognitive assessment. RESULTS BDoff showed significantly worse performance in processing speed and immediate recall of visual memory relative to CC. When the presence of any lifetime psychopathology was analysed, the results showed that belonging to the BDoff group was the main explicative factor for the scores obtained in both processing speed and visual memory immediate recall, regardless of the presence of psychopathology. CONCLUSIONS These findings suggest that processing speed and visualmemory should be taken into consideration in future research on vulnerability markers of BD.

Neuropsychological characteristics of child and adolescent offspring of patients with schizophrenia or bipolar disorder

BACKGROUND Schizophrenia (SZ) and bipolar disorder (BD) are considered neurobiological disorders which share some clinical, cognitive and neuroimaging characteristics. Studying child and adolescent offspring of patients diagnosed with bipolar disorder (BDoff) or schizophrenia (SZoff) is regarded as a reliable method for investigating early alterations and vulnerability factors for these disorders. This study compares the neuropsychological characteristics of SZoff, BDoff and a community control offspring group (CC) with the aim of examining shared and differential cognitive characteristics among groups. METHODS 41 SZoff, 90 BDoff and 107 CC were recruited. They were all assessed with a complete neuropsychological battery which included intelligence quotient, working memory (WM), processing speed, verbal memory and learning, visual memory, executive functions and sustained attention. RESULTS SZoff and BDoff showed worse performance in some cognitive areas compared with CC. Some of these difficulties (visual memory) were common to both offspring groups, whereas others, such as verbal learning and WM in SZoff or PSI in BDoff, were group-specific. CONCLUSIONS The cognitive difficulties in visual memory shown by both the SZoff and BDoff groups might point to a common endophenotype in the two disorders. Difficulties in other cognitive functions would be specific depending on the family diagnosis.

Clinical, Cognitive, and Neuroimaging Evidence of a Neurodevelopmental Continuum in Offspring of Probands With Schizophrenia and Bipolar Disorder

Background Studies in child and adolescent offspring of patients with schizophrenia or bipolar disorders may help understand the influence of neurodevelopmental factors on the premorbid phenotype of these disorders. Aims To assess whether a combination of neurodevelopmental factors discriminates between young offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) and community controls (CcO). To assess the association between these factors and rates of psychiatric diagnoses in high risk (HR) youth. Methods One hundred thirty-three HR offspring (47 SzO and 86 BpO) and 84 CcO, aged 6-17, underwent cross-sectional clinical, neurocognitive, and structural neuroimaging assessment. Information on perinatal events and early childhood development was also obtained. General linear mixed models were performed to assess group discrimination and association with lifetime axis I psychiatric disorders. Results Multivariate analyses revealed that greater neurological soft signs (NSS), less total grey matter volume (GMV) and a higher frequency of obstetric complications discriminated HR offspring from CcO. When comparing each group individually, greater NSS and a higher frequency of obstetric complications discriminated SzO from CcO, and BpO from CcO, while lower intelligence also discriminated SzO from CcO and from BpO. Within HR offspring, lower intelligence and less total GMV were associated with lifetime incidence of psychiatric disorders. Conclusions Both SzO and BpO showed evidence of neurodevelopmental insult, although this may have a greater impact in SzO. Lower intelligence and less total GMV hold potential as biomarkers of risk for psychiatric disorders in HR youth.

Temperament in child and adolescent offspring of patients with schizophrenia and bipolar disorder

Shared vulnerability in offspring of individuals with schizophrenia (SzO) and bipolar disorder (BpO) might manifest early during development through common temperament traits. Temperament dimensions in child and adolescent BpO (N = 80), SzO (N = 34) and the offspring of community controls (CcO) (N = 101) were assessed using the Revised Dimensions of Temperament Survey. The association between temperament dimensions and lifetime psychopathology (including threshold and subthreshold DSM-IV-TR diagnoses) and current socio-academic adjustment was assessed using logistic regression. Fully adjusted models showed that both BpO and SzO scored significantly lower in the positive mood dimension and in the adaptability factor than CcO, with small–medium effect sizes (Cohen’s d ~ 0.3–0.5). BpO also scored lower in the activity factor and the activity dimensions than CcO (Cohen’s d ~ 0.3). Lower scores in the positive mood dimension were associated with increased risk of impaired adjustment both in BpO [OR 2.30, 95% CI (1.18–4.46)] and in SzO [OR 2.87, 95% CI (1.07–7.66)]. In BpO, lower scores in positive mood were also associated with increased likelihood of internalizing [OR 1.84, 95% CI (1.28–2.64)] and externalizing disorders [OR 1.48, 95% CI (1.01–2.18)]; in SzO, higher scores in activity and flexibility were associated with increased likelihood of internalizing [OR 2.31, 95% CI (1.22–4.38)] and externalizing disorders [OR 3.28, 95% CI (1.2–9)], respectively. Early difficulties in emotion regulation might represent a shared vulnerability phenotype in BpO and SzO. The identification of extreme temperament traits could help to characterize subgroups at greater risk of psychopathology and impaired adjustment, in which targeted interventions are warranted.

P.3.b.046 - Environmental predictive factors of cognition in first episode psychotic patients

1. Tunbridge, EM; Weickert CS; Kleinman JE, Herman MM; Chen J, Kolachana BS, Harrison PJ, Weinberger DR. Catechol-o-methyltransferase enzyme activity and protein expression in human prefrontal cortex across the postnatal lifespan. 2007. Cerebral Cortex.17(5):1206-12. 2. Moreno D, Moreno-Iniguez M, Vigil D, Castro-Fornieles J, Ortuno F, Gonzalez-Pinto A, et al. Obstetric complications as a risk factor for first psychotic episodes in childhood and adolescence. Eur Child Adolesc Psychiatry. 2009; 18(3): 180-4. 3. Agerbo E, Sullivan PF, Vilhjalmsson BJ, Pedersen CB, Mors O, Borglum AD, et al. Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis. JAMA Psychiatry. 2015; 72(7): 635-41. BRACKGROUND In recent years, evidence for the influence of environmental factors on the development of schizophrenia and other psychoses has become wellestablished1. Indeed, schizophrenia patients have demonstrated greater sensitivity and increased manifestations of psychotic symptoms in response to mild stressors2.

P.7.d.011 Association between duration of untreated psychosis and functionality within family environment in early-onset first episode psychosis

variance has been performed by group, age and IQ. Age, IQ and severity (CGI, C-GAS) effects were analyzed by Pearson’s correlation; single emotions by repeated measures. Statistical significance required two-tailed p 0.05. Results: Drug-free ADHD and ASD children were significantly slower than TDCs in both FR in FR (RTc: ASD p= 0.01, ADHD p< 0.001; RTe: ASD e ADHD p< 0.001) and IFE (RTc: ASD p= 0.001, ADHD p= 0.022; RTe: ASD p= 0.004). ASD were also slower compared with TDCs in MFE4 (RTc p = 0.039, RTe p = 0.05). Both drug-free ADHD and ASD appeared less accurate than TDCs in MFE4 (ASD p= 0.007, ADHD p= 0.002) and IFE (ASD p= 0.004, ADHD p= 0.005), but not in FR. When processing ‘surprise’, both the ASD and ADHD group exhibited longer RTc compared to TDCs (ASD p< 0.001, ADHD p= 0.018). MPH treatment induced a significant improvement in facial recognition abilities both in speed (RTc: p = 0.023) and accuracy (p< 0.001); increased accuracy has also been observed in IFE (p = 0.004) and MFE tasks (p< 0.001), especially in ‘Happiness’ recognition (p< 0.001). Discussion: The results suggest that specific information processing deficits during face recognition and identification of facial emotions stimuli are present in both ADHD and ASD compared to TDC, with some differences between them. These data highlight the utility, in both ADHD and ASD children, of specific neuropsychological tasks to better characterize strengths and difficulties in their cognitive/affective functioning, in order to develop specific and efficient treatment strategies. Preliminary results suggest that MPH facilitates emotion recognition, whilst not influencing processing speed, confirming recent evidence of MPH regulatory effect not only on inhibitory fronto–striatal circuitry but even its effect in attenuating abnormal activity within affective circuits involved in emotional processing [3].

Diagnosis and clinical symptom description in offspring of patients with bipolar disorder

European Child and Adolescent Psychiatry is Europes only peer-reviewed journal entirely devoted to child and adolescent psychiatry. It aims to further a broad understanding of psychopathology in children and adolescents. Empirical research is its foundation, and clinical relevance is its hallmark. European Child and Adolescent Psychiatry welcomes in particular papers covering neuropsychiatry, cognitive neuroscience, genetics, neuroimaging, pharmacology, and related fields of interest. Contributions are encouraged from all around the world.A1-01 Research and Getting Published