Early-onset Schizophrenia Group Research Articles

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia

BACKGROUND Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

White matter changes and its relationship with clinical symptom in medication-naive first-episode early onset schizophrenia.

Previous studies have highlighted the role of white matter (WM) alterations as biomarkers of the disease state and prognosis of schizophrenia. However, less is known about WM abnormalities in the rarely occurring adolescent early onset schizophrenia (EOS). In this study, T1-weighted and diffusion-weighted images were collected in 56 medication-naive first-episode participants with EOS and 43 healthy controls (HCs). Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA) and mean diffusivity (MD), and investigated their association with clinical feature in participants with EOS. Compared with HCs, decreased MD was found in EOS group most notably in the inferior longitudinal fasciculus, anterior thalamic radiation, inferior fronto-occipital fasciculus and corticospinal tract in the right hemisphere. No significant difference was found in FA between these two groups. The FA values of the forceps minor and the right superior longitudinal fasciculus were suggested to be related to the severity of clinical symptom in participants with EOS. These results provide clues about the neural basis of schizophrenia and a potential biomarker for clinical studies.

Abnormal Brain Structure Morphology in Early-Onset Schizophrenia.

With less exposure to environmental and medication influences, individuals with early-onset schizophrenia (EOS) may provide valuable evidence to study the pathogenesis and phenotypic pattern of schizophrenia.T1-weighted magnetic resonance images were collected in 60 individuals with EOS and 40 healthy controls. Voxel-based morphometry and surface-based morphometry analyzes were performed. Gray matter volume, cortical thickness and cortical surface area were compared between the EOS and healthy controls and among schizophrenia subgroups (with or without family history of schizophrenia). Compared with healthy controls, the EOS group had reduced gray matter volume in the bilateral middle temporal gyrus and reduced cortical thickness in several brain regions. The sporadic early onset schizophrenia and the familial early onset schizophrenia showed different brain structure morphology. These findings suggest that abnormal brain structure morphology, especially in the temporal and frontal lobes, may be an important pathophysiological feature of EOS.

Thalamic Shape Abnormalities Differentially Relate to Cognitive Performance in Early-Onset and Adult-Onset Schizophrenia

Early-onset schizophrenia (EOS) shares many biological and clinical features with adult-onset schizophrenia (AOS), but may represent a unique subgroup with greater susceptibility for disease onset and worsened symptomatology and progression, which could potentially derive from exaggerated neurodevelopmental abnormalities. Neurobiological explanations of schizophrenia have emphasized the involvement of deep-brain structures, particularly alterations of the thalamus, which have been linked to core features of the disorder. The aim of this study was to compare thalamic shape abnormalities between EOS and AOS subjects and determine whether unique behavioral profiles related to these differences. It was hypothesized abnormal thalamic shape would be observed in anterior, mediodorsal and pulvinar regions in both schizophrenia groups relative to control subjects, but exacerbated in EOS. Magnetic resonance T1-weighted images were collected from adult individuals with EOS (n = 28), AOS (n = 33), and healthy control subjects (n = 60), as well as collection of clinical and cognitive measures. Large deformation high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. General linear models were used to compare groups on surface shape features, and Pearson correlations were used to examine relationships between thalamic shape and behavioral measures. Results revealed both EOS and AOS groups demonstrated significant abnormal shape of anterior, lateral and pulvinar thalamic regions relative to CON (all p < 0.007). Relative to AOS, EOS exhibited exacerbated abnormalities in posterior lateral, mediodorsal and lateral geniculate thalamic regions (p = 0.003). Thalamic abnormalities related to worse episodic memory in EOS (p = 0.03) and worse working memory (p = 0.047) and executive functioning (p = 0003) in AOS. Overall, findings suggest thalamic abnormalities are a prominent feature in both early- and late-onset schizophrenia, but exaggerated in EOS and have different brain-behavior profiles for each. The persistence of these abnormalities in adult EOS patients suggests they may represent markers of disrupted neurodevelopment that uniquely relate to the clinical and cognitive aspects of the illness.

Enhanced Resting-State Functional Connectivity of the Nucleus Accumbens in First-Episode, Medication-Naïve Patients With Early Onset Schizophrenia.

There is abundant evidence that early onset schizophrenia (EOS) is associated with abnormalities in widespread regions, including the cortical, striatal, and limbic areas. As a main component of the ventral striatum, the nucleus accumbens (NAc) is implicated in the pathology of schizophrenia. However, functional connection patterns of NAc in patients with schizophrenia, especially EOS, are seldom explored. A total of 78 first-episode, medication-naïve patients with EOS and 90 healthy controls were recruited in the present study, and resting-state, seed-based functional connectivity (FC) analyses were performed to investigate temporal correlations between NAc and the rest of the brain in the two groups. Additionally, correlation analyses were done between regions showing group differences in NAc functional integration and clinical features of EOS. Group comparison found enhanced FC of the NAc in the EOS group relative to the HCs with increased FC in the right superior temporal gyrus and left superior parietal gyrus with the left NAc region of interest (ROI) and elevated FC in left middle occipital gyrus with the right NAc ROI. No significant associations were found between FC strength and symptom severity as well as the age of the patients. Our findings reveal abnormally enhanced FC of the NAc with regions located in the temporal, parietal, and occipital areas, which were implicated in auditory/visual processing, sensorimotor integration, and cognitive functions. The results suggest disturbed relationships between regions subserving reward, salience processing, and regions subserving sensory processing as well as cognitive functions, which may deepen our understanding of the role of NAc in the pathology of EOS.

Response of Antipsychotic Drugs in Health Section Late-onset and Early-onset Schizophrenia in the Vindhya Region, Central India: A Prospective Cohort Study

Introduction: Previous studies were predominantly on earlyonset schizophrenia with little emphasis on clinical profile, therapeutic responsiveness and various investigational, biochemical and neuroimaging variables in Late-onset Schizophrenia (LOS), which is an emerging concern in elderly morbidity, and differs significantly from Early-onset Schizophrenia (EOS). Aim: To study the clinical profile, and response to various antipsychotic drugs in LOS and compare it with EOS. Materials and Methods: A clinical prospective cohort study was conducted in Shyam Shah Medical College, Rewa Madhya Pradesh, India, from January 2020 to June 2021, with baseline and follow-up assessment of psychotic and cognitive symptoms after four weeks using PANSS (Positive and Negative Syndrome Scale), MoCA (Montreal Cognitive Assessment) and BPRS (Brief Psychiatric Rating Scale) scales. A total of 51 patients were included in the study, divided into two groups of early and late onset, attending the out-patient and in-patient services during the period at the center and concomitant treatment with antipsychotics for four weeks. Statistical analysis was done in Statistical Package for Social Sciences (SPSS) version 21.0 with p-value of 0.05. Results: A total of 51 patients, 27 in EOS group and 24 in LOS were included and analysed in the present study. The demographic profile of late and EOS varied in mean age with EOS at 30.11 years and LOS at 57.66 years), gender distribution predominantly males (n=19) in EOS and predominantly females (n=20) in LOS) and the average age of onset of EOS was 22.05 years and LOS was 55.54 years. The duration of illness in EOS 7.98 years and LOS was 2.12 years. The mean Positive and Negative Syndrome Scale score at baseline for EOS was 1.92±1.07 and LOS was 2.83±0.56 and four weeks for EOS was 1.70±0.91 and LOS was 2.83±0.56. The response in Positive and Negative Syndrome Scale at 4 weeks as well as individual domain scale score such as hallucinations, suspiciousness, blunted effect, emotional withdrawal, active social avoidance showed significant results in both EOS and LOS. Conclusion: Schizophrenia can manifest for the first time in late life and manifestations of stringently defined schizophrenia is by no means confined to onset at younger ages. Although there are undoubted similarities between the symptoms of EOS and LOS, there are also clear differences, especially demographic and clinical characteristics, early identification of which will help in adequate intervention and prevention of further morbidity in the elderly.

Distinct Thalamic Abnormalities Differentially Relate to Cognition in Early-Onset Relative to Adult-Onset Schizophrenia

Early-onset schizophrenia (EOS) shares many biological and clinical features with adult-onset schizophrenia (AOS). However, EOS may represent a subgroup with greater susceptibility for disease progression and presentation. The neurobiology of schizophrenia is known to involve deep-brain structures, particularly the thalamus. The aim of this study was to compare thalamic shape abnormalities between EOS and AOS group and determine whether unique behavioral profiles related to these differences.

Cognitive Performance in Early-Onset Schizophrenia and Attention-Deficit/Hyperactivity Disorder: A 25-Year Follow-Up Study.

Early-Onset Schizophrenia (EOS) and Attention Deficit-Hyperactivity Disorder (ADHD) are early- onset neurodevelopmental disorders associated with cognitive deficits. The current study represents the first attempt to compare these groups on a comprehensive cognitive test battery in a longitudinal design over 25 years in order to enhance our knowledge of particular patterns resulting from the interaction between normal maturational processes and different illness processes of these disorders. In the baseline study, 19 adolescents with schizophrenia were compared to 20 adolescents with ADHD and 30 healthy controls (HC), all between 12 and 18 years of age. After 13 years (T2) and after 25 years (T3) they were re-evaluated with the cognitive test battery. A cognitive Composite Score was used in a linear mixed model. The EOS group had a significant cognitive stagnation or deterioration from T1 to T2 compared to HC. However, the EOS group had the most positive change from T2 to T3, supporting a stable level of cognitive performance over the 25 year span. The ADHD group improved or had similar development as the HC group from T1 to T2. They continued to improve significantly compared to the HC group from T2 to T3. Individuals in the EOS group performed more impaired on the cognitive composite score compared to the HC group and the ADHD group at all three time points. Results might indicate a neurodevelopmental pathway of EOS with subnormal cognitive development specific in adolescence. In comparison, the ADHD group had a more consistent cognitive maturation supporting a maturational delay hypothesis of ADHD.

Self-reported sensory responsiveness patterns in typically-developing and early-onset schizophrenia adolescents: Its relationship with schizotypal and autistic traits

Altered behavioural responses to sensory stimuli, including both hypo- and hyper-reactivity, have been found in individuals with schizophrenia. However, how specific sensory responsiveness patterns are associated with symptomatology of schizophrenia remains largely unknown. The present study aimed to examine sensory responsiveness in typically-developing (TD) adolescents (n = 98) and adolescents with early-onset schizophrenia (EOS) (n = 29) and investigate the relationship between schizotypal traits and sensory responsiveness patterns. All participants completed the Adult/Adolescent Sensory Profile (AASP), the Schizotypal Personality Questionnaire (SPQ) and the Autism Spectrum Quotient (AQ). Results showed that higher levels of hypersensitivity and hyposensitivity coexisted in EOS patients and were correlated with positive and negative symptoms of schizophrenia. Atypical sensory experiences except for sensory seeking were found to be positively correlated with higher levels of schizotypal traits regardless of diagnostic status. Moreover, the strength and pattern of such correlations were comparable in both EOS and TD groups. This study also provided evidence that higher levels of autistic traits would intensify the positive correlation between schizotypal traits and sensory responsiveness abnormalities, suggesting an additive effect of co-occurring schizotypal and autistic traits on atypical sensory experiences. These findings extend previous research by depicting sensory responsiveness patterns in younger populations with schizophrenia, and may have implications for future development of sensory-related interventions in clinical settings.

Emotional Education in Early Onset Schizophrenia and Asperger's Syndrome.

In this study, we aim to verify how emotional training can improve empathy and theory of mind (ToM) in patients diagnosed with early onset schizophrenia and Asperger’s syndrome. The study design includes 100 subjects divided into two experimental groups and two control groups. The two experimental groups followed a rational emotive behavior therapy (REBT) protocol. The two control groups instead underwent cognitive behavioral psychotherapy training. Analysis of Variance (ANOVA) was applied to analyze the difference between the Asperger’s syndrome (AS) and early onset schizophrenia (EOS) groups, pre and post training. Our analysis shows that the AS group improved post emotional training but only when emotions were internalized, as demonstrated by the improvement of the scores in the post-treatment eye test (ET) but not in the emotional quotient (EQ) test. The EOS group instead showed post-training improvement, not only concerning skills leading to internalizing emotions but also in empathy, as demonstrated by the improvement of EQ and Reflective Functioning Questionnaire (RFQ) test scores. These scores remained lower than in the control group. Finally, our findings reveal that the value of the treatment was more considerable for the EOS group than for the AS group due to the improvement in first- and second-order ToM skills and an improvement of empathic skills in the first group, followed by the group comprising AS subjects. In the AS group, the treatment only favored the enhancement of first-order ToM skills; however, this improved quality of life and social adaptation.

Abnormal Thalamocortical Circuit in Adolescents With Early-Onset Schizophrenia

Thalamic circuit imbalance characterized by increased sensorimotor-thalamic connectivity and decreased prefrontal-thalamic connectivity has been consistently observed in adult-onset schizophrenia (AOS), although it is unclear whether this pattern is also a feature of early-onset schizophrenia (EOS). If this is the case, thalamic circuit imbalance can be considered as a core mechanistic defect in schizophrenia, unconfounded by the age of onset. A total of 116 adolescents with EOS (63 drug-naive EOS) and 55 matched healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging scans. To define the specific location of the thalamic subregions in thalamocortical circuit, 16 atlas-based thalamic subdivisions were used in functional connectivity analysis. The EOS group showed increased sensorimotor-thalamic connectivity and decreased prefrontal-cerebello-thalamic connectivity, consistent with AOS. Sensorimotor-thalamic hyperconnectivity was more prominent than prefrontal-thalamic hypoconnectivity, which was circumscribed to the medial prefrontal cortex (mPFC), in EOS. Of note, the EOS group specifically exhibited strengthened thalamic connectivity with the salience network (SN). In addition, the EOS showed a more prominent disruption of the lateral thalamic nuclear connectivity. Thalamic dysconnectivity observed in the EOS extends the observations from adult patients. Sensorimotor-thalamic hyperconnectivity is critical for the expression of schizophrenia phenotype irrespective of the age of onset, raising the possibility of aberrant but accelerated functional network maturation in EOS. The specific thalamocortical dysconnectivity involving the SN and mPFC may underlie the distinctive features of multi-modal hallucinations and heightened emotional valence of psychosis seen in EOS.

Associations between cognition and internalizing problems in young adults with early-onset schizophrenia: A 13-year follow-up study

The present follow-up study examines the associations between cognition and parent-rated internalizing problems among adolescents with early-onset schizophrenia (EOS) at baseline (T1) and self-rated internalizing problems 13 years later (T2). Twelve individuals (8 male/4 female) with EOS and 30 healthy controls (16 male/14 female) were included in the study. All were between 12 and 18 years of age at T1. Internalizing problems were measured with the Achenbach System of Empirically Based Assessment Internalizing Scale. Cognition was examined with a neuropsychological test battery measuring auditory attention/working memory, visuomotor processing, cognitive flexibility and verbal memory. Compared to healthy controls, the EOS group had significant cognitive deficits and more internalizing problems both at T1 and T2. There was no correlation between parent-rated internalizing problems at T1 and self-rated internalizing problems at T2 in the EOS group. However, deficits in auditory attention/working memory at T1 were significantly associated with internalizing problems at T2. A focus on improving the treatment of cognitive impairments may be important in preventing the development of internalizing problems in young patients with schizophrenia. The small sample size of the study is a limitation and further research is recommended.

S197. OBSTETRIC COMPLICATIONS, NEUROCOGNITION, AND SCHIZOPHRENIA

BackgroundSchizophrenia is a disorder with a heterogeneous genetic and neurobiological background that influences early brain development. The symptoms is the behavioural outcome of deviations in early neurodevelopment, including prenatal insults such as obstetric complications (OC). OC have been linked to an increased risk for schizophrenia in offspring, especially in early-onset schizophrenia (EOS). Extensive cognitive deficits occur in EOS, whereof executive function is one of the best documented. Cognitive dysfunction reflects underlying abnormalities in the brain neurodevelopment, and is considered to be an intermediate variable between OC and schizophrenia. Our research group (Teigset et al, 2016) is the only study that has investigated the relationship between OC and cognition in EOS. This study aimed to examine the frequency of OC in EOS compared to controls, and also investigate the relationship between OC and neurocognitive dysfunction. In the present presentation we will focus upon executive function and report the findings when comparing the same sample of patients and controls as in the Teigset et al study.MethodsNineteen EOS patients and 53 healthy controls were tested with the MATRICS Consensus Cognitive Battery(MCCB), and two tests for assessment of executive functioning. The selected subtests for measuring executive function were the D-KEFS Color Word Interference Test (Stroop) and the Wisconsin Card Sorting Test. WCST assesses perseverative responses and failure to maintain set, and the Stroop assesses time in seconds for completing the Inhibition and Switching conditions. The cognitive measures were combined with data from the Norwegian Birth Registry (NMBR). Information on OC was collected from the NMBR containing information about all births in Norway, including information about maternal health before and during pregnancy, and any complications arising during pregnancy or birth. The registry includes information about medication during pregnancy, labor interventions, birth complications, maternal complications after birth, whether this was a live birth, any diagnoses in the child or evidence of congenital abnormalities.ResultsGroup differences in OC were studied with Student’s t-tests and Chi-square tests. The association between OC and cognitive function were studied using linear regression analyses. The results indicated no group differences in OC in EOS and healthy controls. However, a shorter gestational length in the EOS group led to significant decreases in the overall neurocognitive composite score (MCCB), in processing speed and in the two executive function tasks.DiscussionOur findings indicate that a shorter gestational length did not increase the risk for developing EOS, but was significantly associated with the cognitive difficulties in this group. In particular, executive functioning were affected, a finding in line with those of Brown et al (2009), showing that prenatal infections were associated with impaired executive function. Interestingly, reductions in neurocognitive performance among those exposed to OC was less extensive in the healthy control group with the same labor-conditions, which may indicate a greater effect of OC on neuropsychological development in schizophrenia. In conclusion, gestational length does not increase the risk for developing EOS, but significantly affects the cognitive difficulties - particularly executive function - seen among cases.

Gestational length affects neurocognition in early-onset schizophrenia

Obstetric complications (OC) have been linked to an increased risk for schizophrenia in offspring, especially in early-onset schizophrenia (EOS). Extensive cognitive deficits occur in EOS, although no study has yet to investigate the relationship between OC and cognition in EOS. This study aims to examine the frequency of OC in EOS compared to controls, and also investigates the relationship between OC and neurocognitive dysfunction in the two groups. Nineteen EOS patients and 53 healthy controls were tested with the MATRICS Consensus Cognitive Battery (MCCB), and the cognitive measures were combined with OC data from the Norwegian Birth Registry. The results indicated no group differences in OC in EOS and healthy controls, but a shorter gestational length in the EOS group led to significant decreases in the overall neurocognitive composite score, and in processing speed. This suggests that the poorer neuropsychological performances commonly found in EOS may be partly attributable to the length of gestation. The worsened neurocognitive functioning did not appear among controls, so gestational length had a different impact on the two groups. Our findings indicated that a shorter gestational length did not increase the risk for developing EOS, but did significantly affect the cognitive difficulties in this group.

Assessment of real-world daily-living skills in early-onset schizophrenia trough the Life Skills Profile scale

BackgroundAdolescents with early-onset schizophrenia (EOS) have marked deficits in their functional outcome. However, few short and reliable instruments for assessing real-world functioning have been specifically validated in EOS. The Life Skills Profile (LSP) is a brief scale widely used in schizophrenia and considered one of the optimal instruments for assessing real-world daily living skills. The purpose of this study was to examine the usefulness and the feasibility of the LSP to assess daily living skills in EOS. MethodsThe sample included 53 clinically and pharmacologically stabilized adolescent patients with EOS and 53 healthy adolescents. Content review of the scale and internal consistency analysis were conducted in the EOS group. A subgroup of 30 patients was re-assessed over a 10-day interval to establish the test–retest reliability. Measures of functional outcome were used to assess convergent validity, and measures of intelligence and symptoms were used to assess divergent validity. Discriminant validity was analyzed through logistic analysis and the receiver-operating characteristic curve. ResultsThe LSP and its subscales showed high reliability, adequate internal consistency and adequate convergent and divergent validity. The LSP was also found to be a sensitive instrument for detecting differences between patients and healthy adolescents, correctly classifying 84% of the sample. The estimated area under the curve was 0.925 (95% CI 0.875–0.976). ConclusionsThe LSP showed adequate psychometric characteristics in adolescents with EOS and appeared to be a valid, reliable and time-efficient instrument for use in clinical practice and research settings to assess real-world daily-living skills in EOS.

Dimensions of positive symptoms in late versus early onset psychosis

Casenote studies have characterized late onset schizophrenia (LOS) and related psychoses as somewhat different symptomatically from patients with an early onset schizophrenia (EOS). This study examined a range of phenomenological aspects of delusions and hallucinations as well as traditional symptom measures in both groups. 34 LOS and 235 EOS completed the Positive and Negative Syndrome Scale, the Psychotic Symptom Rating Scales, and the Beck Depression and Anxiety inventories. Subgroups experiencing delusions were compared matching for chronological age and gender, and also when matched for chronicity and gender. Delusions were very common at over 80% in both groups. LOS participants with delusions exhibited greater suspiciousness/paranoia, greater belief-conviction, and reduced insight when compared with the EOS group. These findings remained when matching for chronicity of illness, but disappeared when matching for chronological age. Hallucinations were surprisingly rarer in LOS (35%) than EOS (57%), with half the LOS group reporting whispers rather than clearly audible sounds. In general, anxiety, depression, and distress were as marked in LOS and EOS. Similarities between EOS and LOS far outweighed the differences across a range of symptoms and measures. Greater delusional conviction, paranoia, and poorer insight in LOS were associated with the later age of onset rather than relating to chronicity of illness. As belief-conviction in LOS was not associated with increased grandiosity, disorientation, or unusualness of thought content, as it was in EOS, delusional conviction may be determined somewhat differently later in life.

Comprehensive segmentation of subcortical brain volumes in early onset schizophrenia reveals limited structural abnormalities

Structural brain abnormalities are well documented in adult schizophrenia, but there are few studies of brain structures in early onset schizophrenia (EOS) and findings are inconsistent. Most previous EOS studies have been limited to global morphometric measures, such as whole gray matter (GM) or cerebrospinal fluid (CSF), or to single brain structures. The purpose of this study was to compare specific volumes and hemispheric lateralization in a large number of subcortical brain structures, between EOS patients and a healthy control group. High-resolution structural magnetic resonance images (MRI) and automatic brain volume segmentation were performed on 18 EOS patients and 33 healthy controls (11–18years). A total of 29 brain structures were studied. The patients showed marked bilateral enlargements of the lateral ventricles and of the fourth ventricle, and bilateral enlargement of the caudate nuclei compared to the controls. For all other subcortical brain structures, there were no significant differences between the EOS group and the healthy control group, contrary to findings from the majority of morphometric studies of childhood or adult onset schizophrenia.

Neurocognition and functional outcome in early-onset schizophrenia and attention-deficit/hyperactivity disorder: A 13-year follow-up.

The relation between neurocognitive impairments and functional outcome has been documented in both early onset schizophrenia (EOS) and attention-deficit/hyperactivity disorder (ADHD), but less is known about the long-term relation between these factors. The present study investigates how neurocognition at baseline is related to measures of functional outcome at 13-year follow-up in subjects with EOS and ADHD. Subjects with EOS (n = 15), ADHD (n = 19), and healthy controls (n = 30) were followed up 13 years after initial assessment. All subjects were between 12 and 18 years of age at baseline and between 24 and 30 at follow-up. They were retested at T2 with the same comprehensive neurocognitive test battery as used at T1, and reassessed with various symptom and behavior ratings and functional outcome measures. Both groups were characterized by reduced functional outcome at follow-up, although of different magnitude and type, compared with healthy controls. In the EOS group, neurocognitive baseline measures were associated with social functioning at follow-up (η2 between .26 and .41), while for the ADHD group, no significant predictions were found. Adolescents with EOS and ADHD are characterized by poor functional outcome compared with healthy controls when reassessed as young adults. Executive function, memory and attention were related to social and community functioning in EOS. For ADHD no significant predictions were found although functional outcome was poor. For both groups treatment should focus on training of social skills and activities of daily living to enhance the long-term functional outcome. For EOS cognitive remediation should also be considered.

Deficient maturation of aspects of attention and executive functions in early onset schizophrenia

The few existing long-term, neuropsychological follow-up studies of early onset schizophrenia (EOS) patients have reported relative stability in some cognitive functions but abnormal developmental trajectories in verbal memory, set shifting, aspects of attention, and speed of information processing throughout late adolescence into early adulthood. The current 5-year follow-up study compared the development of specific cognitive functions in EOS patients (N = 17) from the time of first-episode to chronic phase with that of healthy controls (N = 38) and secondarily to patients with other early onset, non-organic, non-affective psychoses (EOP) (N = 11). Speed of processing of executive functions, set shifting, and attention improved significantly in the healthy controls and reflected continuous functional maturation during late adolescence and early adulthood. The developmental progression of attention and set shifting but not speed of processing of executive functions was significantly subnormal in EOS patients. Other specific cognitive functions that had attained functional maturity in the healthy controls before or around the time of the baseline assessment showed normal development in EOS patients during the follow-up period, indicating stable cognitive deficits. These results suggest post-onset developmental deficits in two out of the three aspects of attention and executive functions that have protracted maturational trajectories and that overlap the age of onset of EOS. No significant difference in the development of any specific cognitive function was found between the EOS and EOP group.

YSFC01-01 - Neural correlates of verbal working memory dysfunction in early-onset schizophrenia: a functional magnetic resonance imaging study

ObjectivesWorking memory (WM) deficits are among the core cognitive abnormalities in schizophrenia. WM is subserved by widely distributed fronto-parietal networks and is undergoing robust development during adolescence. Studying the neural correlates of WM dysfunction in early-onset schizophrenia (EOS) will advance our understanding of aberrant neurodevelopmental processes in the disorder.MethodNineteen patients with EOS aged 13-19 and 20 matched healthy participants underwent functional Magnetic Resonance Imaging (fMRI) as they performed a N-back verbal WM task with 3 levels of difficulty (1-back, 2-back, 3-back). Following matching for task performance, 14 patients were compared to 20 controls, using non-parametric whole brain and region of interest approaches followed by psycho-physiological interaction analysis (PPI) with seed voxel from the left parietal cluster.ResultsRegions within the left prefrontal cortex, the left insula and bilateral anterior cingulate cortex showed reduced activation in EOS patients compared to healthy participants at the 2-back condition. In addition, ROI analysis at the same condition revealed hypoactivation in the EOS group with large effect sizes for left prefrontal and parietal regions. The PPI results revealed negative functional connectivity in the healthy participants’ group but not in EOS between left parietal and right parietal and bilateral frontal regions.ConclusionsOur results support compromised function within the left prefrontal-cingulate network and left insula during the N-Back verbal WM task in patients with EOS compared to healthy participants. They also indicate the possibility of more widespread fronto-parietal network dysfunction, most noted in the left hemisphere in the disorder.