Early-onset Schizophrenia Research Articles

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.

Neurocognitive and social cognitive impairments in remission and symptomatic states of early-onset schizophrenia spectrum disorders.

Previous studies demonstrated neurocognitive impairments in early-onset schizophrenia (EOS) and other psychotic spectrum disorders (PSD). This study aimed to compare remitted and symptomatic cases in terms of neurocognition and theory of mind (ToM). 50 healthy controls (HC) and 106 patients diagnosed schizophrenia in remission (EOS-R, n = 38), symptomatic schizophrenia (EOS-S, n = 34), and other PSD (n = 34) were included in our study. The Positive and Negative Symptom Scale, Columbia-Suicide Severity Rating Scale, Reactive and Proactive Aggression Questionnaire were used to evaluate psychopathology. A cognitive battery was conducted to measure verbal learning/memory, visual learning/memory, executive functions (EF), inhibition, processing speed (PS), verbal fluency skills. Reading Mind in Eyes Test (RMET) and Faux-Pas tests were implemented to assess ToM. Principal Component Analysis was used to identify cognitive domain scores. Patient groups had poorer performance in cognitive domains than the HC group. The cognitive impairment and psychopathology levels of EOS-R and the PSD groups were comparable for all cognitive domains. The EOS-S group also had poorer scores in Rey verbal learning score (d = 0.87), RMET (d = 0.72), verbal fluency (d = 0.66), PS/EF (d = 0.82) and visual learning/memory (d = 0.83) test scores than the PSD group. Only RMET (d = 0.72) and executive function/processing speed domain (d = 0.63) were significantly impaired in the EOS-S group than the EOS-R group Cognitive impairments seen in remitted psychotic disorders were on the same continuum. Impaired EF/PS and ToM skills could be a cognitive marker for symptomatic illness in youth.

The “Revolving Door Phenomenon” in Patients with Early Onset Schizophrenia: A Multicenter Study

The “Revolving Door Phenomenon” in Patients with Early Onset Schizophrenia: A Multicenter Study

Very Early-Onset Schizophrenia in a 7-Year-Old Girl

Schizophrenia most commonly starts during early adulthood but it can emerge during childhood. Pediatric schizophrenia is used to describe schizophrenia occurring before 18 years of age. It can further be categorized into early onset type which occurs prior to 18 years and the very early onset type occurring prior to 13 years.
 Miss AD, a 7-year-old female presented to our facility about 1 year ago with a 3-months history of illness. Initially, she stopped communicating with anyone; there was associated social withdrawal, sluggishness and decline in her academics. A few weeks later, she started talking and laughing to herself and 2 weeks prior to presentation, she started seeing strange things in clear consciousness and claiming her classmates were ganging up against her. Her teachers and parents were ignorant of the nature of her illness at the onset and as such, she was maltreated.
 At presentation, a diagnosis of very early onset schizophrenia was made and she was commenced on treatment with oral Risperidone which was gradually increased over a period of 1 year of her ongoing treatment to 2mg total daily dosage. Additionally, oral chlorpromazine and Benzhexol were added; she is currently on 50mg nocte and 0.125mg daily respectively. During the course of her treatment, she showed significant improvement but no complete remission, residual symptoms such as starring on-end with occasional talking and laughing to herself persisted.

Disassociated and concurrent structural and functional abnormalities in the drug-naïve first-episode early onset schizophrenia

Schizophrenia which is an abnormally developmental disease has been widely reported to show abnormal brain structure and function. Enhanced functional integration is a predominant neural marker for brain mature. Abnormal development of structure and functional integration may be a biomarker for early diagnosis of schizophrenia. Fifty-five patients with early onset schizophrenia (EOS) and 79 healthy controls were enrolled in this study. Voxel-based morphometry (VBM) and functional connectivity density (FCD) were performed to explore gray matter volume (GMV) lesion, abnormal functional integration, and concurrent structural and functional abnormalities in the brain. Furthermore, the relationships between abnormalities structural and function and clinical characteristics were evaluated in EOS. Compared with healthy controls, EOS showed significantly decreased GMV in the bilateral OFC, frontal, temporal, occipital, parietal and limbic system. EOS also showed decreased FCD in precuneus and increased FCD in cerebellum. Moreover, we found concurrent changes of structure and function in left lateral orbitofrontal cortex (lOFC). Finally, correlation analyses did not find significant correlation between abnormal neural measurements and clinical characteristic in EOS. The results reveal disassociated and bound structural and functional abnormalities patterns in EOS suggesting structural and functional measurements play different roles in delineating the abnormal patterns of EOS. The concurrent structural and functional changes in lOFC may be a biomarker for early diagnosis of schizophrenia. Our findings will deepen our understanding of the pathophysiological mechanisms in EOS.

Associations of Neurocognition and Social Cognition With Brain Structure and Function in Early-Onset Schizophrenia.

BackgroundCognitive impairment is a core feature of schizophrenia that is more serious in patients with early-onset schizophrenia (EOS). However, the neuroimaging basis of cognitive functions, including neurocognition and social cognition, remains unclear in patients with EOS.MethodsForty-three patients with EOS underwent structural and resting state functional magnetic resonance imaging scans. Brain structure and function were evaluated through the analysis of brain gray matter volume (GMV) and amplitude of low-frequency fluctuations (ALFF). They underwent comprehensive assessments for neurocognition (verbal memory, verbal expression, attention, and executive function) and social cognition (theory of mind and attributional bias). Correlation analyses were conducted to detect the potential link between cognitive function indices and brain imaging parameters.ResultsFirst, neurocognition was linked to brain structure characterized by higher immediate recall scores associated with increased GMV in the left temporal pole, higher verbal fluency scores associated with increased GMV in the left temporal pole: middle temporal gyrus, and higher Stroop-word scores associated with increased GMV in the right middle frontal gyrus. Second, social cognition was related to brain function characterized by lower sense of reality scores associated with increased ALFF in the left precentral gyrus, higher scores of accidental hostility bias associated with increased ALFF in the right middle temporal gyrus, and higher scores of accidental aggression bias associated with increased ALFF in the left precentral gyrus.ConclusionThese findings may add to the existing knowledge about the cognitive function-brain relationship. They may have clinical significance for studying the mechanism of neurocognitive and social cognitive impairment in patients with EOS and providing potential neural targets for their treatment and intervention.

Neurocognitive profile of adolescents with early-onset schizophrenia and their unaffected siblings

Background We investigated the neurocognitive profiles of Early-Onset Schizophrenia (EOS; onset before age 18) and paired unaffected siblings and the little-studied effect of age-of-onset and duration of illness on cognitive performance. Methods 31 EOS probands, and 31 of their siblings, had four cognitive domains assessed: (a) Memory: California Verbal Learning Test, and the Wechsler Memory Scale-Revised; (b) Working memory: Digit Span; (c) Attention: Degraded-Stimulus Continuous Performance Test, Span of Apprehension (SPAN), and Trail Making Test (TMT) part A; (d) Executive function: Wisconsin card sorting task, and TMT part B. Diagnosis was confirmed using the structured clinical interview for DSM-IV. Results While EOS showed a generalised neurocognitive deficit (0.25–0.50 effect size) compared with siblings, across all cognitive domains, significantly greater patient deficits were observed with, working memory, attention, and executive function and minimal differences for digit span forward, block design and false alarms on the SPAN-12 confirmed by repeated measures MANOVA. Patients with earlier onset (12–15) showed greater deficits on false alarm and digits backward scores. Siblings showed individual cognitive task profiles similar to patients, confirming familial effects. EOS showed much more variable scores than siblings with more individual tasks showing 2 SD deficits than siblings. Long duration patients had greater z-score variability across tasks. Conclusions Duration of illness was a more important characteristic in patients with onset 16 and over than in younger onset patients with comparable durations. Both the similarity of sibling pair profiles and greater patient variability across task provide further support for neurobiological heterogeneity in schizophrenia.

Are Executive Functions Deficits in Early-Onset Chronic Schizophrenia More Severe than in Adult-Onset Chronic Schizophrenia?

ObjectiveThe research on the age of schizophrenia onset and cognitive impairments leads to contradictory conclusions. It is still unknown whether neurocognitive deficits in early-onset schizophrenia (EOS) are more intense than adulthood-onset schizophrenia (AOS). The study aimed to examine specific aspects of the executive functions of chronic outpatients with different ages of schizophrenia onset.MethodTwo clinical groups (EOS and AOS) consisted of 60 chronic outpatients with schizophrenia recruited from the community-based support system. The executive functions were measured with the Wisconsin Card Sorting Test (WCST), Trail Making Test A&B (TMT A&B), verbal fluency task (VFT), and the N-back test. Obtained results were compared to control groups consisting of 40 healthy subjects, matched with age, sex, and years of education, respectively.ResultsThere were no differences in various aspects of executive dysfunctions between EOS and AOS outpatients. The outpatients in general, had lower scores than healthy controls regardless of their age of symptom onset. The most important finding suggests that some cognitive domains (visual working memory and processing speed) in presented schizophrenia patients were similar to those in healthy controls.Despite the demographic differences, both clinical groups present the same level of executive functioning. In addition, similar to the healthy participants, the outpatients had no problems in working memory and processing speed.ConclusionsThese observations suggest that EOS might not be associated with more severe cognitive deterioration. Moreover, the stabilization or improvement of their functioning might be linked with long-term psycho-social rehabilitation and modern pharmacotherapy.

Treatment Approaches for First Episode and Early-Phase Schizophrenia in Adolescents and Young Adults: A Delphi Consensus Report from Europe.

PurposeAlthough first-episode psychosis (FEP) in youth, particularly early-onset schizophrenia (EOS), is managed similarly to adult-onset schizophrenia, few antipsychotics are approved for people aged 13–18 years. We aimed to explore areas of uncertainty in EOS management and provide evidence-based recommendations to mental health specialists. We used the Delphi methodology to gain knowledge in areas lacking evidence-based strategies. This standardized methodology consists of the development of a questionnaire by content experts, which is then submitted to a broader panel of professionals (panelists) to survey their level of agreement on the topics proposed.Materials and MethodsThe developed questionnaire covered patient management from diagnosis to maintenance treatment and was administered to a broader panel of specialists across Europe. Based on an analysis of responses received in this first round, the items that needed further insight were submitted to the panel for a second round and then reanalysed.ResultsAn initial set of 90 items was developed; in round I, consensus was reached for 83/90 items (92%), while it was reached for 7/11 (64%) of the items sent out for rerating in round II. Feedback for rounds I and II was obtained from 54/92 and 48/54 approached experts, respectively. There was broad agreement on diagnostic standards, multimodal approaches and focus on adverse events, but uncertainty in terms of pharmacological strategies (including clozapine) in case of failure and antipsychotic dosing in younger patients.ConclusionDespite knowledge about diagnostic clues and integrated management of EOS, this study highlights the lack of standardization in treating EOS, with safety arguments having a major role in the decision-making process. Targeted clinical trials and systematic dissemination across Europe of current scientific evidence on the value of early intervention services is hoped to contribute to standardized and improved quality care for patients with early-phase psychosis and schizophrenia.

Clozapine for Management of Childhood and Adolescent-Onset Schizophrenia: A Systematic Review and Meta-Analysis.

Background: Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term "childhood and adolescent-onset schizophrenia (CAOS)" for either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS. Methods: We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the title, abstract, and full article review, 18 studies qualified (double-blind RCTs n = 4; OLS n = 4; observational studies n = 7; case reports n = 3). Results: Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks) and long term (2-9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and hypersalivation were commonly reported (90%), constipation was next in frequency (13%-50%). Neutropenia was seen in 6%-15% of cases and agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8%-22%), treatment-onset diabetes was less frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen. Conclusions: Limited studies indicate that clozapine is a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of CAOS.

IMPACT OF FAMILIAL AND ENVIRONMENTAL RISK FACTORS ON AGE OF ONSET OF SCHIZOPHRENIA

ABSTRACT &#x0D; Objectives: 1.To determines impact of familial risk factor i.e. positive family history of schizophrenia on age of onset of schizophrenia.&#x0D; 2. To determine impact of environmental risk factor i.e. substance misuse on age of onset of schizophrenia.&#x0D; Materials and Methods: In this cross sectional analytical study, 430 patients were enrolled from OPD in Sarhad Hospital for Psychiatric Diseases Peshawar through convenience non probability sampling technique. First Data was dichotomized on the basis of positive and negative family history of schizophrenia. Later on data was again dichotomized on the basis of positive and negative history of substance misuse. Frequency and percentage were calculated for categorical variable while mean and standard deviation for continuous variables. Independent-samples T test was used while comparing categorical variable with continuous variable and Chi-square test was used while comparing two categorical variables in between them.&#x0D; Results: The mean age of onset of schizophrenia was 22.28 years with early onset in males than females. In those with familial schizophrenia, the mean ages of onset of schizophrenia in males and females were 22.35 and 22.05 years while in those with sporadic cases, the mean age of onset of schizophrenia in males and females were 21.83 and 25.43 years respectively. Moreover non-tobacco substances and cannabinoids were having statistically significant impact on age of onset of schizophrenia.&#x0D; Conclusion: There was significant gender difference in age at onset of schizophrenia and substance misuse. Family history of schizophrenia eliminates the gender difference in age at onset of schizophrenia. Moreover non-tobacco substances and cannabinoids misuse can cause early onset of schizophrenia.

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.

Cognitive functions in late-onset psychosis

The review discusses cognitive functions in late-onset schizophrenia and very late-onset schizophrenia-like psychosis compared to cognition in normal aging, early-onset schizophrenia, and neurodegenerative diseases. The problem of the dynamics of the state of the cognitive functions in patients with late-onset schizophrenic psychoses is highlighted, and prospects for further research are discussed. Patients with late-onset schizophrenic psychosis are characterized by more pronounced cognitive deficits compared to normal aging, but less severe than cognitive changes observed in early-onset schizophrenia. Late-onset schizophrenia may be a heterogeneous condition in terms of cognitive dysfunction.

Early-onset schizophrenia in Riga’s Children’s Clinical University Hospital 2012-2021 – epidemiology and associated factors

Early-onset schizophrenia in Riga’s Children’s Clinical University Hospital 2012-2021 – epidemiology and associated factors

Very early onset schizophrenia in Dandy-Walker variant: A case report

The Sri Lanka Journal of Psychiatry (SLJP) is a peer-reviewed, open access journal published bi annually by the Sri Lanka College of Psychiatrists.The Journal publishes original papers, brief reports including case reports and commentaries relevant to psychiatry and allied sciences. The Sri Lanka Journal of Psychiatry is committed to maintaining and conforming to the editorial and ethical standards recommended by the International Committee of Medical Journal Editors.Cover“Perseverance”. These tenacious fishermen in Mannar continue their livelihood despite numerous difficulties. L. N. P. Samarasinghe, Acting Consultant Psychiatrist, Base Hospital Nikaweratiya, Sri Lanka.

A Pilot Study on Early-Onset Schizophrenia Reveals the Implication of Wnt, Cadherin and Cholecystokinin Receptor Signaling in Its Pathophysiology.

Early-Onset Schizophrenia (EOS) is a very rare mental disorder that is a form of schizophrenia occurring before the age of 18. EOS is a brain disease marked by an early onset of positive and negative symptoms of psychosis that impact development and cognitive functioning. Clinical manifestations commonly include premorbid features of Autism Spectrum Disorder (ASD), attention deficits, Intellectual Disability (ID), neurodevelopmental delay, and behavioral disturbances. After the onset of psychotic symptoms, other neuropsychiatric comorbidities are also common, including obsessive-compulsive disorder, major depressive disorder, expressive and receptive language disorders, auditory processing, and executive functioning deficits. With the purpose to better gain insight into the genetic bases of this disorder, we developed a pilot project performing whole exome sequencing of nine trios affected by EOS, ASD, and mild ID. We carried out gene prioritization by combining multiple bioinformatic tools allowing us to identify the main pathways that could underpin the neurodevelopmental phenotypes of these patients. We identified the presence of variants in genes belonging to the Wnt, cadherin and cholecystokinin receptor signaling pathways.

Schizophrenia in Klinefelter Syndrome.

Klinefelter syndrome is the most common sex chromosome disorder in males, typically characterized by an extra X chromosome. The authors of this report present a case of early onset schizophrenia in a patient with Klinefelter syndrome.

A Case Series of Very Late-onset Schizophrenia-like Psychosis: Is It a Dimension of Dementia?

Emerging research has shown that there may be a subset of patients who develop a first-break psychosis later in life when they are over 60 years of age. Very late-onset schizophrenia-like psychosis (VLOSLP) differs from early-onset schizophrenia in a few very important ways that lead us to believe that there may be a distinct pathologic process involved. We present 4 cases of females with psychotic symptoms that first appeared after the patients were 60 years of age. We conducted a literature review and found that our older adult psychiatric unit is not alone in struggling with diagnoses for these individuals. Some of these patients have a disease that will progress to a neurocognitive disorder, but a large group of others will remain cognitively intact. Fortunately, the treatment for both processes is very similar, but studies have shown that patients with VLOSLP will need significantly lower doses of antipsychotics compared with those with early-onset schizophrenia. It remains unclear if VLOSLP is a unique disorder, a prodrome to dementia, or a different condition that is not yet understood. Further research is needed to develop comprehensive treatment for patients with VLOSLP.

Efficacy and Safety of Lurasidone in Children and Adolescents: Recommendations for Clinical Management and Future Research.

Lurasidone is a novel azapirone derivative and atypical antipsychotic agent with a high binding affinity for dopaminergic (D2), serotoninergic (5-HT2A), and 5-HT7 receptors (antagonist), a moderate affinity for 5- HT1A receptors (partial agonist), and no appreciable affinity for histaminergic (H1) and muscarinic (M1) receptors. It was recently included by the European Medication Agency among the in-label pharmacological treatments for children and adolescents affected by early onset schizophrenia. As a dopamine and serotonin antagonist, lurasidone acted on a variety of receptors and showed its efficacy both as an antipsychotic and an activating compound. Administered with food or within 30 minutes from a meal, it presents sufficient bioavailability and does not interact with most of the other drugs during metabolism. With little effects on hormones and weight gain, potential procognitive profile due to its 5-HT7 antagonism, and reduced extrapyramidal side effects, lurasidone could be a good choice in terms of both effectiveness and tolerability, particularly for patients headed towards a long-term treatment. This article aims to summarize the available scientific evidence from the literature on the use of lurasidone in children and adolescents and to provide recommendations for clinical management and future research.

A Selective Review of the Excitatory-Inhibitory Imbalance in Schizophrenia: Underlying Biology, Genetics, Microcircuits, and Symptoms.

Schizophrenia is a chronic disorder characterized by specific positive and negative primary symptoms, social behavior disturbances and cognitive deficits (e.g., impairment in working memory and cognitive flexibility). Mounting evidence suggests that altered excitability and inhibition at the molecular, cellular, circuit and network level might be the basis for the pathophysiology of neurodevelopmental and neuropsychiatric disorders such as schizophrenia. In the past decades, human and animal studies have identified that glutamate and gamma-aminobutyric acid (GABA) neurotransmissions are critically involved in several cognitive progresses, including learning and memory. The purpose of this review is, by analyzing emerging findings relating to the balance of excitatory and inhibitory, ranging from animal models of schizophrenia to clinical studies in patients with early onset, first-episode or chronic schizophrenia, to discuss how the excitatory-inhibitory imbalance may relate to the pathophysiology of disease phenotypes such as cognitive deficits and negative symptoms, and highlight directions for appropriate therapeutic strategies.