Adult-onset Schizophrenia Patients Research Articles

Multimodal brain deficits shared in early-onset and adult-onset schizophrenia predict positive symptoms regardless of illness stage.

Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early‐onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early‐onset (EOS) and adult‐onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co‐varying patterns by jointly analyzing three MRI features: fractional amplitude of low‐frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug‐naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub‐cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug‐naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug‐naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.

Differences in patterns of metabolic abnormality and metabolic syndrome between early-onset and adult-onset first-episode drug-naive schizophrenia patients

Although metabolic abnormalities and metabolic syndrome (MetS) often occur in schizophrenia, few studies have investigated them in early-onset schizophrenia (EOS) patients. To our knowledge, this was the first to compare clinical correlates of metabolic abnormalities between first-episode drug-naïve (FEDN) EOS and adult-onset schizophrenia (AOS) patients. A total of 489 Chinese FEDN schizophrenia patients (116 EOS and 373 AOS) and 451 healthy controls were recruited in this cross-sectional study. Blood pressure, waist circumference (WC), Body mass index (BMI), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), glucose, hemoglobin A1c (HbA1c), insulin and insulin resistance were measured. The Positive and Negative Syndrome Scale (PANSS) was applied to evaluate the clinical symptoms of schizophrenia patients, and higher scores on PANSS indicate increased severity. EOS patients had lower rates of: MetS, elevated WC, hypertriglyceridemia, hypercholesterolemia, and hyper-LDLC than EOS patients (all p < 0.05). In EOS patients, WC was positively associated with PANSS general psychopathology score (p = 0.04). In AOS patients, WC (p = 0.01; p = 0.02) and glucose (p < 0.001; p < 0.001) were positively associated with PANSS general psychopathology and total score. HOMA-IR was positively associated with PANSS total score (p = 0.04). Systolic BP, triglycerides and HDLC were main contributors to MetS in AOS (all p < 0.05), but not in EOS. BMI was a risk factor of MetS in EOS, while BMI and HOMA-IR were risk factors of MetS in AOS (all p < 0.05). Our results indicate differences in metabolic abnormalities patterns, risk factors and their association with clinical characteristics between Chinese EOS and AOS patients. Data Availability StatementThe datasets that support the findings of this study are not publically available due to ongoing analyses for further publications, but are available from the corresponding author X.Z. upon reasonable request.

Long-term outcome of early-onset compared to adult-onset schizophrenia: A nationwide Danish register study

ObjectiveEarly-onset schizophrenia (EOS) may have worse outcomes than adult-onset schizophrenia (AOS), but data are scarce. We compared outcomes of EOS vs. AOS. MethodsLongitudinal, register-based study of patients diagnosed with schizophrenia in Denmark between 1996 and 2012, with follow-up until 12/2014. Co-primary outcomes were psychiatric inpatient days during the initial two years after schizophrenia diagnosis and mean number of annual inpatient days for the remaining follow-up. ResultsAltogether, 16,337 patients with schizophrenia were included (EOS = 1223, AOS = 15,114, mean follow-up = 9.5 ± 5.0 years). EOS were hospitalized longer during the first two years than AOS (180.9 ± 171.0 vs 163.4 ± 183.1 days, p < 0.005; IRR = 1.27, 95% CI = 1.19–1.35, p < 0.001), but duration and annual rates thereafter did not differ (EOS = 26.8 ± 57.1 days, AOS = 26.6 ± 56.2 days, p = 0.95; IRR = 1.07, 95% CI = 0.94–1.23, p = 0.30). Fewer EOS patients were never psychiatrically hospitalized (EOS = 17.2%, AOS = 20.1%, p < 0.001), but with no difference in re-admissions in patients diagnosed during hospitalization (EOS = 77.1% vs AOS = 78.1%, p = 0.56). More EOS patients were admitted involuntarily (41% vs. 36%, p < 0.02). AOS patients had more often comorbid substance use disorders during follow-up than EOS (EOS = 21.7%, AOS = 34.2%, p < 0.001). Substance use disorders and out-of-home placement were significantly associated with more inpatient days during both short- and long-term follow-up. ConclusionAlthough EOS was associated with more inpatient days in the first two years after diagnosis, results do not seem to support a generally poorer long-term outcome of EOS compared to AOS. Longer initial hospitalization may be driven by different treatment patterns in child and adolescent vs. adult psychiatry. These data suggest that patient characteristics other than age of onset significantly affect outcomes.

Alterations of plasma cytokine biomarkers for identifying age at onset of schizophrenia with neurological soft signs

Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1β, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.

Risk Model Assessment in Early-Onset and Adult-Onset Schizophrenia Using Neurological Soft Signs.

Age at onset is one of the most important clinical features of schizophrenia that could indicate greater genetic loadings. Neurological soft signs (NSS) are considered as a potential endophenotype for schizophrenia. However, the association between NSS and different age-onset schizophrenia still remains unclear. We aimed to compare risk model in patients with early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) with NSS. This study included 262 schizophrenia patients, 177 unaffected first-degree relatives and 243 healthy controls. We estimated the discriminant abilities of NSS models for early-onset schizophrenia (onset age < 20) and adult-onset schizophrenia (onset age ≥ 20) using three data mining methods: artificial neural networks (ANN), decision trees (DT) and logistic regression (LR). We then assessed the magnitude of NSS performance in EOS and AOS families. For the four NSS subscales, the NSS performance were greater in EOS and AOS families compared with healthy individuals. More interestingly, there were significant differences found between patients’ families and control group in the four subscales of NSS. These findings support the potential for neurodevelopmental markers to be used as schizophrenia vulnerability indicators. The NSS models had higher discriminant abilities for EOS than for AOS. NSS were more accurate in distinguishing EOS patients from healthy controls compared to AOS patients. Our results support the neurodevelopmental hypothesis that EOS has poorer performance of NSS than AOS. Hence, poorer NSS performance may be imply trait-related NSS feature in EOS.

Self\u2013other recognition impairments in individuals with schizophrenia: a new experimental paradigm using a double mirror

Clinical observations suggest early self-consciousness disturbances in schizophrenia. A double mirror combining the images of two individuals sitting on each side of the mirror was used to study self–other differentiation in 12 individuals with early onset schizophrenia (EOS) and 15 individuals with adult onset schizophrenia (AOS) compared to 27 typically developing controls (TDC) matched on age and sex. The effects of intermodal sensory perception (visual–tactile and visual–kinesthetic) on self–other recognition were also studied. The results showed that EOS and AOS individuals, independently of age and schizophrenia severity, were centered on their own image compared to TDC, with both significant earlier self-recognition and delayed other-recognition during the visual recognition task. In addition, there was no significant effect of intermodal sensory stimulation on self–other recognition in EOS and AOS patients, whereas self-centered functioning was significantly increased by visual–tactile stimulation and decreased by visual–kinesthetic stimulation in TDC. The findings suggest that self–other recognition impairments might be a possible endophenotypic trait of schizophrenia.

Neuropil contraction in relation to Complement C4 gene copy numbers in independent cohorts of adolescent-onset and young adult-onset schizophrenia patients\u2013a pilot study

A recent report suggested Complement 4 (C4A) gene copy numbers (GCN) as risk factors for schizophrenia. Rodent model showed association of C4 with synaptic pruning suggesting its pathophysiological significance (Sekar, A. et al. (2016)). We, therefore, predicted that C4A GCN would be positively correlated with neuropil contraction in the human brain among schizophrenia patients showing more prominent correlations in ventral regions among young adults and dorsal regions among adolescents since neuromaturation progresses dorsoventrally. Whole-brain, multi-voxel, in vivo phosphorus magnetic resonance spectroscopy (31P MRS) assessed neuropil changes by estimating levels of membrane phospholipid (MPL) precursors and catabolites. Increased MPL catabolites and/or decreased MPL precursors indexed neuropil contraction. Digital droplet PCR-based assay was used to estimate C4A and C4B GCN. We evaluated two independent cohorts (young adult-onset early-course schizophrenia (YASZ = 15) and adolescent-onset schizophrenia (AOSZ = 12) patients), and controls matched for each group, n = 22 and 15, respectively. Separate forward stepwise linear regression models with Akaike information Criterion were built for MPL catabolites and precursors. YASZ cohort: Consistent with the rodent model (Sekar, A. et al. 2016)), C4A GCN positively correlated with neuropil contraction (increased pruning/decreased formation) in the inferior frontal cortex and inferior parietal lobule. AOSZ cohort: C4A GCN positively correlated with neuropil contraction in the dorsolateral prefrontal cortex and thalamus. Exploratory analysis of C4B GCN showed positive correlation with neuropil contraction in the cerebellum and superior temporal gyrus among YASZ while AOSZ showed neuropil contraction in the prefrontal and subcortical structures. Thus, C4A and C4B GCN are associated with neuropil contraction in regions often associated with schizophrenia, and may be neuromaturationally dependent.

S214. Neuropil Contraction in Relation to Complement C4 Gene Copy Number in Independent Cohorts of Adolescent-Onset and Young Adult-Onset Schizophrenia Patients

A recent report suggested Complement 4 (C4A) gene copy number repeats (CNR) as risk factors for schizophrenia. Rodent model suggested pathophysiological significance of these associations by demonstrating increased synaptic pruning. We, thus, predicted that C4A CNR would be positively correlated with increased neuropil contraction in the human brain among schizophrenia patients showing more prominent correlations in ventral regions among young adults and dorsal regions among adolescents since neuromaturation progresses dorsoventrally.

S112. RELATION BETWEEN EARLY-ONSET PSYCHOSIS AND FORMAL THOUGHT DISORDER IN SCHIZOPHRENIA

BackgroundFormal thought disorder is one of the fundamental features of schizophrenia. Early onset schizophrenia (EOS) is strongly related to poor prognosis and illness outcomes. The aim of this study is to investigate the relation of EOS and formal thought disorder in schizophrenia.MethodsThis research was a retrospective study. Data regarding the patients with schizophrenia were obtained from two separate studies conducted at Dokuz Eylul University.Thought disorder scores were compared between 32 patients with early onset schizophrenia (EOS; age ≤ 18) and 120 patients with adult onset schizophrenia (AOS; age > 18). Also, we looked at the effect of Duration of Untreated Psychosis (DUP). We further categorized these two sets as short DUP (short DUP; ≤ 6 month) and long DUP (long DUP; > 6 month) groups.ResultsSchizophrenia patients with early onset showed significantly higher scores compared to adult onset schizophrenia patients with regards to poverty of speech (U= 1525.50; p = .037) and peculiar sentences (U= 1613.50; p = .043).DiscussionEarly onset schizophrenia patients had significant formal thought disorder abnormalities. Formal thought disorder may have some developmental characteristics which indicate an important dimension related to prognosis and outcome of schizophrenia. Also, DUP may have potential effect over formal thought disorder.

Comparing illness presentation, treatment and functioning between patients with adolescent- and adult-onset psychosis

Studies have shown that early- and adult-onset schizophrenia patients differ in pre-morbid traits, illness presentation, psychopathology, and prognosis. We aimed to compare adult-onset patients (age range 26–55 years) with an adolescent-onset cohort (15–25 years) in demographics, illness presentation and functioning at baseline. Participants were from two territory-wide early intervention services for adolescent-onset (n=671) and adult-onset psychosis patients (n=360) in Hong Kong. The adolescent-onset cohort had their initial psychotic episode from 2001–2003; retrospective data collection was done through systematic case note review. The adult-onset cohort was recruited for a larger interventional study from 2009–2011; information was collected via face-to-face interviews. Adult-onset psychosis was significantly associated with more females, fewer smokers, more non-local birth, more full-time employment, better functioning, poorer medication adherence, more psychiatric hospitalization and fewer with schizophrenia than adolescent-onset psychosis (mean age: 20.4). The effect sizes were small, except for medication adherence where a robust effect was found. No group difference in DUP was found. The finding that adult-onset patients had better functioning challenges the view that adolescent- and adult-onset psychoses share a similar prognostic trajectory. Implications for adapting intervention processes for adolescent- and adult-onset psychosis are discussed.

Executive function in early- and adult onset schizophrenia

BackgroundThe goal of this study was to investigate differences in executive functioning between patients with early-onset and adult-onset schizophrenia spectrum psychoses at the time of first treatment. MethodsNeuropsychological tests covering executive functioning domains were performed for 20 adolescents with early-onset schizophrenia (EOS) close to first treatment and 90 first episode patients with adult onset schizophrenia (AOS) in addition to 66 adolescent- and 127 adult age and gender matched healthy controls. ResultsBoth EOS and AOS patients had significantly poorer executive performance than their age- and gender matched healthy counterparts. Both healthy adolescent controls and EOS patients had poorer executive performance than their adult counterparts. However, there were no differences in executive functioning between EOS and AOS patients after controlling for the levels of their age matched healthy control groups. Substituting EOS/AOS status with other age-at-onset thresholds had no effect. ConclusionsWe find the same relative levels of executive dysfunction in EOS- and AOS groups at the time of first treatment. This does not necessarily contradict previous findings of more severe dysfunction in EOS patients over time, but indicates an interaction between the disorder and the maturational processes that only can be investigated through longitudinal studies.

Disease and genetic contributions toward local tissue volume disturbances in schizophrenia: A tensor‐based morphometry study

Structural brain deficits, especially frontotemporal volume reduction and ventricular enlargement, have been repeatedly reported in patients with schizophrenia. However, it remains unclear whether brain structural deformations may be attributable to disease-related or genetic factors. In this study, the structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 65 first-degree nonpsychotic relatives of schizophrenia patients, 27 community comparison (CC) probands, and 73 CC relatives were examined using tensor-based morphometry (TBM) to isolate global and localized differences in tissue volume across the entire brain between groups. We found brain tissue contractions most prominently in frontal and temporal regions and expansions in the putamen/pallidum, and lateral and third ventricles in schizophrenia patients when compared with unrelated CC probands. Results were similar, though less prominent when patients were compared with their nonpsychotic relatives. Structural deformations observed in unaffected patient relatives compared to age-similar CC relatives were suggestive of schizophrenia-related genetic liability and were pronounced in the putamen/pallidum and medial temporal regions. Schizophrenia and genetic liability effects for the putamen/pallidum were confirmed by regions-of-interest analysis. In conclusion, TBM findings complement reports of frontal, temporal, and ventricular dysmorphology in schizophrenia and further indicate that putamen/pallidum enlargements, originally linked mainly with medication exposure in early studies, also reflect a genetic predisposition for schizophrenia. Thus, brain deformation profiles revealed in this study may help to clarify the role of specific genetic or environmental risk factors toward altered brain morphology in schizophrenia.

The contributions of disease and genetic factors towards regional cortical thinning in schizophrenia: The UCLA family study

Objective Cortical thickness reductions in prefrontal and temporal cortices have been repeatedly observed in patients with schizophrenia. However, it remains unclear whether regional variations in cortical thickness may be attributable to disease-related or genetic-liability factors. Method The structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 66 first-degree non-psychotic relatives of schizophrenia patients, 27 community comparison (CC) probands and 77 CC relatives were examined using cortical pattern matching methods to map and compare highly localized changes in cortical gray matter thickness between groups defined by biological risk for schizophrenia. Results Schizophrenia patients showed marked cortical thinning primarily in frontal and temporal cortices when compared to unrelated CC probands. Results were similar, though less pronounced when patients were compared with their non-psychotic relatives. Cortical thickness reductions observed in unaffected relatives compared to age-similar CC relatives suggestive of schizophrenia-related genetic liability were marginal, surviving correction for the left parahippocampal gyrus and inferior occipital cortex only. Conclusions Observations of pronounced fronto/temporal cortical thinning in schizophrenia patients replicate prior findings. The lack of marked cortical thickness alterations in non-psychotic relatives of patients, suggests that disease processes are primary contributors toward cortical thickness reductions in the disorder. However, genetic factors may have a larger influence on abnormalities in the medial temporal lobe.

Voxel-based structural magnetic resonance imaging (MRI) study of patients with early onset schizophrenia

BackgroundInvestigation into the whole brain morphology of early onset schizophrenia (EOS) to date has been sparse. We studied the regional brain volumes in EOS patients, and the correlations between regional volume measures and symptom severity.MethodsA total of 18 EOS patients (onset under 16 years) and 18 controls matched for age, gender, parental socioeconomic status, and height were examined. Voxel-based morphometric analysis using the Brain Analysis Morphological Mapping (BAMM) software package was employed to explore alterations of the regional grey (GM) and white matter (WM) volumes in EOS patients. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).ResultsEOS patients had significantly reduced GM volume in the left parahippocampal, inferior frontal, and superior temporal gyri, compared with the controls. They also had less WM volume in the left posterior limb of the internal capsule and the left inferior longitudinal fasciculus. The positive symptom score of PANSS (higher values corresponding to more severe symptoms) was negatively related to GM volume in the bilateral posterior cingulate gyrus. The negative symptom score was positively correlated with GM volume in the right thalamus. As for the association with WM volume, the positive symptom score of PANSS was positively related to cerebellar WM (vermis region), and negatively correlated with WM in the brain stem (pons) and in the bilateral cerebellum (hemisphere region).ConclusionOur findings of regional volume alterations of GM and WM in EOS patients coincide with those of previous studies of adult onset schizophrenia patients. However, in brain regions that had no overall structural differences between EOS patients and controls (that is, the bilateral posterior cingulate gyrus, the right thalamus, the cerebellum, and the pons), within-subject analysis of EOS patients alone revealed that there were significant associations of the volume in these areas and the symptom severity. These findings suggest that at an early stage of the illness, especially for those with onset before brain maturation, a wide range of disturbed neural circuits, including these brain regions that show no apparent morphological changes, may contribute to the formation of the symptomatology.