Onset Of Schizophrenia Research Articles

Alterations in TRN-anterodorsal thalamocortical circuits affect sleep architecture and homeostatic processes in oxidative stress vulnerable Gclm−/− mice

Schizophrenia is associated with alterations of sensory integration, cognitive processing and both sleep architecture and sleep oscillations in mouse models and human subjects, possibly through changes in thalamocortical dynamics. Oxidative stress (OxS) damage, including inflammation and the impairment of fast-spiking gamma-aminobutyric acid neurons have been hypothesized as a potential mechanism responsible for the onset and development of schizophrenia. Yet, the link between OxS and perturbation of thalamocortical dynamics and sleep remains unclear. Here, we sought to investigate the effects of OxS on sleep regulation by characterizing the dynamics of thalamocortical networks across sleep-wake states in a mouse model with a genetic deletion of the modifier subunit of glutamate-cysteine ligase (Gclm knockout, KO) using high-density electrophysiology in freely-moving mice. We found that Gcml KO mice exhibited a fragmented sleep architecture and impaired sleep homeostasis responses as revealed by the increased NREM sleep latencies, decreased slow-wave activities and spindle rate after sleep deprivation. These changes were associated with altered bursting activity and firing dynamics of neurons from the thalamic reticularis nucleus, anterior cingulate and anterodorsal thalamus. Administration of N-acetylcysteine (NAC), a clinically relevant antioxidant, rescued the sleep fragmentation and spindle rate through a renormalization of local neuronal dynamics in Gclm KO mice. Collectively, these findings provide novel evidence for a link between OxS and the deficits of frontal TC network dynamics as a possible mechanism underlying sleep abnormalities and impaired homeostatic responses observed in schizophrenia.

Motor cortical plasticity in adolescents with early onset schizophrenia: A TMS-EMG study assessing the perturbation effect of intermittent and continuous theta burst stimulation.

Neuroplasticity in adolescents is distinct from that of adults. Literature pertaining to neuroplasticity in schizophrenia is limited to adult populations. We aimed to assess baseline (or resting) cortical excitability and cortical plasticity in adolescents with schizophrenia using the transcranial magnetic stimulation-electromyography (TMS-EMG) protocol. Twenty adolescent cases with schizophrenia and 20 age and gender matched healthy controls were studied using a crossover design. Single pulse TMS elicited resting motor threshold (RMT) and motor evoked potentials (MEPs) were assessed. Cortical plasticity was determined by tracking MEPs after a single session continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) up to 120 min at 12 intervals. Baseline (or resting) cortical excitability was found to be significantly lower in cases compared with controls. Response patterns to cTBS and iTBS were similar between the crossover. While cTBS led to inhibitory response, iTBS had an excitatory effect in both the groups. In the cases, while cTBS led to significantly greater initial inhibitory response, iTBS led to significantly lower excitatory response, compared with controls. The time taken to return to baseline excitability was significantly longer after receiving cTBS for cases, compared with controls. iTBS and cTBS lead to excitatory and inhibitory response, representing classical long-term depression and long-term potentiation effects, respectively, in both cases and controls. We conclude that adolescents with schizophrenia have significantly lower baseline (resting) cortical excitability as well as significantly greater inhibitory plasticity; excitatory plasticity is significantly lower.

Case report on schizophrenia: Application of paplaus model theory in nursing care plan

The term schizophrenia was coined by Eugen Bleuler, it has been derived from the Greek word “schizo” meaning split, and “phren” meaning mind. The point prevalence of schizophrenia is about 1% with equal prevalence in both sexes. The onset of schizophrenia is bimodal in women and often runs a more benign course as compared to men and usually occurs in the late teens or early 20Most devastating disease as this disease strikes the people at the stage when they can show the growth and highest productivity in their lives, mostly in teens or early 20’s, it affects people such a way unable them to return to normal lives: go to job, school to marry, etc.Understanding the severity of this disorder is very important because these clients are always Potential for violence self-directed or at others related to extreme suspiciousness so to Identify the level of suicide precautions needed. If there is a high-risk, does a hospitalization requires? Or if there is a low risk, will the client be safe to go home with supervision from a family member or a friend? For example, does client: Admit previous suicide attempts.,Abuse any substances..Have no peers/friends.,Have any suicide plan.,Contact the family, arrange for crisis counseling. Activate links to self-help groups.,Check for the availability of required supply of medications needed,Initially, provide activities that require minimal concentration (e.g., drawing, playing simple board games),Involve the client in gross motor activities that call for very little concentration (e.g., walking,When the client is at the most depressed state, Involve the client in one-to-one activity.

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.

Exploring substance use as rule-violating behaviour during inpatient treatment of offender patients with schizophrenia.

BackgroundRule‐violating behaviour in the form of substance misuse has been studied primarily within the context of prison settings, but not in forensic psychiatric settings.AimsOur aim was to explore factors that are associated with substance misuse during hospitalisation in patients among those patients in a Swiss forensic psychiatric inpatient unit who were suffering from a disorder along the schizophrenia spectrum.MethodsFrom a database of demographic, clinical and offending data on all residents at any time between 1982 and 2016 in the forensic psychiatric hospital in Zurich, 364 cases fulfilled diagnostic criteria for schizophrenia or a schizophrenia‐like illness and formed our sample. Any confirmed use of alcohol or illicit substances during admission (yes/no) was the dependent variable. Its relationship to all 507 other variables was explored by machine learning. To counteract overfitting, data were divided into training and validation set. The best model from the training set was tested on the validation set.ResultsSubstance use as a secure hospital inpatient was unusual (15, 14%). Prior substance use disorder accounted for so much of the variance (AUC 0.92) that it was noted but excluded from further models. In the resulting model of best fit, variables related to rule breaking, younger age overall and at onset of schizophrenia and nature of offending behaviour, substance misuse as a minor and having records of complications in prior psychiatric treatment were associated with substance misuse during hospitalisation, as was length of inpatient treatment. In the initial model the AUC was 0.92. Even after removal of substance use disorder from the final model, performance indicators were meaningful with a balanced accuracy of 67.95, an AUC of 0.735, a sensitivity of 81.48% and a specificity of 57.58%.ConclusionsSubstance misuse in secure forensic psychiatric hospitals is unusual but worthy of clinical and research consideration because of its association with other rule violations and longer hospitalisation. More knowledge is needed about effective interventions and rehabilitation for this group.

Age-dependent patterns of schizophrenia genetic risk affect cognition

Cognition shares substantial genetic overlap with schizophrenia, yet it remains unclear whether such genetic effects become significant during developmental periods of elevated risk for schizophrenia, such as the peak age of onset. We introduce an investigative framework integrating epidemiological, developmental, and genetic approaches to determine whether genetic effects shared between schizophrenia and cognition are significant across periods of differing risk for schizophrenia onset, and whether these effects are shared with depression. 771 European-American participants, including 636 (ages 15–84 years) from families with at least two first-degree relatives with schizophrenia and 135 unrelated controls, were divided into three age-risk groups based on ages relative to epidemiological age of onset patterns for schizophrenia: Pre-Peak (before peak age-of-onset: 15 to 22 years), Post-Peak (after peak age-of-onset: 23–42 years), and Plateau (during plateau of age-of-onset: over 42 years). For general cognition and 11 specific cognitive traits, we estimated genetic correlations with schizophrenia and with depression within each age-risk group. Genetic effects shared between deficits in general cognition and schizophrenia were nonsignificant before peak age of onset, yet were high and significant after peak age of onset and during the plateau of onset. These age-dependent genetic effects were largely consistent across specific cognitive traits and not transdiagnostically shared with depression. Schizophrenia genetic effects appear to influence cognitive traits in an age-dependent manner, supporting late developmental and perhaps neurodegenerative models that hypothesize increased expression of schizophrenia risk genes during and after the peak age of risk. Our findings underscore the utility of cognitive traits for tracking schizophrenia genetic effects across the lifespan.

The effects of fetal or neonatal hypoxia and genetic variants on age at onset of schizophrenia

IntroductionFetal or neonatal hypoxia (FoNH) is a known risk factor for schizophrenia. It has been hypothesized that FoNH induced expression of schizophrenia susceptibility genes (Schmidt-Kastner et al. 2012, Giannopoulou et al. 2018).ObjectivesTo test this hypothesis, we explore the effects of FoNH and some genetic variants on age at onset (AAO) of schizophrenia.MethodsThe study included 1670 patients (women 1021 (61.1%), mean age 34.6 (SD 13.6), mean age at disease onset 25.4 (10.5) years) with ICD-10 diagnosis of schizophrenia or schizoaffective psychosis. The effects of FoNH in interaction with sex, family history (FH) and genetic variants on AAO of schizophrenia were evaluated. Polymorphisms rs2514218 DRD2 (n=943), Val66Met BDNF (n=820) and VNTR AS3MT (n=804) were genotyped.ResultsAmong all patients studied 179 (10.8%) had experienced FoNH. Regression model showed that FoNH, sex and FH of schizophrenia contribute significantly (p=0.000) to AAO. In the FoNH group, AAO was lower compared to the group without FoNH (20.7 (6.2) vs 25.5 (10.) years). When comparing men and women, there was a difference between FoNH and non- FoNH subgroups only in women (p=0.000). No interaction between FH and FoNH was observed though positive FH had an effect on AAO. There was the interaction effect of VNTR AS3MT and FoNH on AAO. In the FoNH group, carriers of 2 repeats had younger AAO compared to the carriers homozygous for 3 repeat variant (19.6 (4.9) vs 22. (7.6) years).ConclusionsWe demonstrate the interaction effects of FoNH and VNTR AS3MT polymorphism on AAO of schizophrenia.DisclosureNo significant relationships.

Clinical Indicators of Symptom Dimensions and Cognitive Ability in Schizophrenia

IntroductionSchizophrenia is a heterogeneous disorder and it is unknown what causes individual variability in symptoms and cognitive ability.Objectives To examine the association between nine clinical predictors measurable at the onset of schizophrenia and five phenotype dimensions: positive, negative (diminished expressivity), negative (motivation and pleasure), disorganised symptoms and cognitive ability.Methods852 participants (mean age 49 years old) with a diagnosis of schizophrenia or schizoaffective depression were included from the CardiffCOGS cross-sectional sample. Phenotype dimensions were created using confirmatory factor analysis and a 5-factor model. Associations were tested using linear regression, adjusting for age and sex. A Bonferroni correction was applied for (p<1.1x10-3) for multiple testing.ResultsAge of onset of psychosis was significantly associated with positive symptoms (β=-0.18, p=4.0 x10-6). Lower premorbid IQ was associated with diminished expressivity (β=-0.25, p= 7.0x10-13), reduced motivation and pleasure (β=-0.23, p= 4.3x10-11), disorganised symptoms (β=-0.14, p= 7.6x10-5) and reduced cognition (β=0.54, p= 4.8x10-77). Poor premorbid social adjustment held associations with all except positive. Developmental delay was associated with reduced cognition (β=-0.35, p= 4.3x10-5). Cannabis use (year before onset), psychosocial stressors (within 6 months), childhood abuse and family history of schizophrenia held no associations.ConclusionsClinical indicators measurable at schizophrenia onset are associated with lifetime symptom variability. A younger psychosis onset is associated with more severe positive symptoms, suggesting possible age-targeted management. Pre-established links of lower premorbid IQ with poor premorbid social adjustment and negative symptom severity with cognition are strengthened. Further investigation could potentially improve diagnosis and guide treatment choice for aspects of schizophrenia with poor outcomes.DisclosureNo significant relationships.

Pharmacogenetic testing in schizophrenia in real clinical practice: before or after antipsychotic -induced adverse drug reactions development?

IntroductionSchizophrenia is socially significant mental disorder characterized by early onset and high time and financial expenditure on treatment. Antipsychotics (APs) are highly effective against positive and negative symptoms, but at same time have a wide range of adverse drug reactions (ADRs). APs efficiency and safety are variable and depend on characteristics of genetically determined mechanisms (transportation, biotransformation, and elimination).ObjectivesInvestigation role of pharmacogenetic testing (PhGT) on example of clinical case of severe ADRs in 47-year-old woman with schizophrenia.MethodsPatient’s medical history analysis; clinical observation; biochemical serum analysis; therapeutic drug monitoring; PhGT.ResultsThe clinical case of a woman with schizophrenia who has been noted to be unresponsive to APs for some years after schizophrenia onset. She was found to be homozygous for nonfunctional SNVs CYP2D6*4 and CYP2C9*2, heterozygous for CYP1A1*2A, which was reason for complete shutdown of isoenzymes 2D6, 2C9 and 1A1 activity and development of ADRs in use of initial doses of several APs, as well as for an increase in severity of ADRs with schizophrenia positive symptoms aggravation with an even slower titration of APs daily dose not only with polytherapy, but also with monotherapy. So, not recommented APs for patient: aripiprazole, haloperidol, zuclopenthixol, cariprazine, quetiapine, paliperidone, risperidone, thioridazine, sertindole, asenapine, alimemazine, chlorpromazine, etc. (CYP2D6); haloperidol, clozapine, olanzapine, perphenazine, promazine (CYP2C9); carefully: haloperidol, olanzapine, perospirone (СYP1A1).ConclusionsThis rare case demonstrates PhGT importance before APs therapy, because the patient had very high risk AP – induced ADRs. She needed PhGt before APs use, but not after severe ADRs during 12 years.DisclosureNo significant relationships.

Late onset schizophrenia and delusional disorder: activity of platelet energy, glutamate, and glutathione metabolizing enzymes

IntroductionAlterations of glutamate, energy and glutathione metabolism contribute to the pathogenesis of psychotic disordersObjectivesRevealing clinical-biological correlations in patients with late onset schizophrenia and delusional disorder by determining clinical parameters and activity of platelet enzymes of energy, glutamate, and glutathione metabolism.Methods27 women of 45-80 years old were studied, with late onset schizophrenia or delusional disorder. Activity of platelet cytochrome c-oxidase (COX), glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione-S-transferase (GST), and scores by PANSS, HAMD, MMSE, and CGI-S were evaluated twice: before and after the 28-th day of treatment. Activity of COX, GDH, GR, and GST was measured once in 23 women of 44-81 years old comprising the control group.ResultsAs compared with controls, only GDH activity was found significantly decreased (before and after treatment, p<0.001). Clusterisation of patients by enzymatic activities resulted in 3 clusters significantly different by COX, GDH and GST. Significant correlations were found between enzymatic activities and scores by psychometric scales: in the cluster 1 (n=9) baseline COX activity correlated with scores by PANSS positive subscale (R=0.9, p=0.001) and with scores by MMSE (R=-0.9, p=0.002); in the cluster 2 (n=12) GR activity after treatment negatively correlated with scores by PANSS (R=-0.9, p=0.001), PANSS negative subscale (R=-0.8, p=0.004), and CGI-S (R=-0.9, p=0.001).ConclusionsThe revealed correlations between enzymatic activities and clinical parameters give hope on detection of useful biochemical markers which, after enlargement of patients’ group with late onset psychotic disorders, would be validated for prediction of the pharmacotherapy efficiency and outcome of treatment.DisclosureNo significant relationships.

The Relationships Among Metal Homeostasis, Mitochondria, and Locus Coeruleus in Psychiatric and Neurodegenerative Disorders: Potential Pathogenetic Mechanism and Therapeutic Implications.

While alterations in the locus coeruleus-noradrenergic system are present during early stages of neuropsychiatric disorders, it is unclear what causes these changes and how they contribute to other pathologies in these conditions. Data suggest that the onset of major depressive disorder and schizophrenia is associated with metal dyshomeostasis that causes glial cell mitochondrial dysfunction and hyperactivation in the locus coeruleus. The effect of the overactive locus coeruleus on the hippocampus, amygdala, thalamus, and prefrontal cortex can be responsible for some of the psychiatric symptoms. Although locus coeruleus overactivation may diminish over time, neuroinflammation-induced alterations are presumably ongoing due to continued metal dyshomeostasis and mitochondrial dysfunction. In early Alzheimer's and Parkinson's diseases, metal dyshomeostasis and mitochondrial dysfunction likely induce locus coeruleus hyperactivation, pathological tau or α-synuclein formation, and neurodegeneration, while reduction of glymphatic and cerebrospinal fluid flow might be responsible for β-amyloid aggregation in the olfactory regions before the onset of dementia. It is possible that the overactive noradrenergic system stimulates the apoptosis signaling pathway and pathogenic protein formation, leading to further pathological changes which can occur in the presence or absence of locus coeruleus hypoactivation. Data are presented in this review indicating that although locus coeruleus hyperactivation is involved in pathological changes at prodromal and early stages of these neuropsychiatric disorders, metal dyshomeostasis and mitochondrial dysfunction are critical factors in maintaining ongoing neuropathology throughout the course of these conditions. The proposed mechanistic model includes multiple pharmacological sites that may be targeted for the treatment of neuropsychiatric disorders commonly.

Age of onset by sex in schizophrenia: Proximal and distal characteristics

BackgroundEarlier schizophrenia onset in men relative to women has been a consistent finding in the literature, but a nuanced understanding of underlying reasons remains elusive. Further consideration should be given to factors associated with sex differences in age of onset. MethodParticipants with schizophrenia were derived from the 2010 Australian Survey of High Impact Psychosis (n = 857). The SHIP survey constituted a representative, population-based study of almost 1.5 million Australian adults seen at various mental health services, and assessed personal health information, psychiatric comorbidities as well as psychosis illness and treatment. Hierarchical clustering was employed to identify age of onset by sex. Within-sex comparisons on distal and proximal factors affecting age of onset were conducted. ResultsUsing modal age, two and three clusters were respectively found in men (early versus late onset) and women (early versus mid versus late onset). Early onset groups in both sexes had an increased family history of psychosis compared to older onset, but other risk factors were not consistent across the sexes. Less premorbid impairment was noted in females with middle to later onset schizophrenia. ConclusionThese findings further inform our understanding of the pathogenesis of schizophrenia. Added explorations of trends in older onset schizophrenia cohorts is especially important.

Fibroblast Growth Factor 9 as a Potential Biomarker for Schizophrenia

Preclinical and clinical studies have suggested that fibroblast growth factor (FGF) system contributed to the onset and development of schizophrenia (SCZ). However, there was no strong clinical evidence to link an individual FGF with SCZ. In this study, we aim to measure blood FGF9 levels in the patients with SCZ with and/or without medication, and test whether FGF9 has a potential to be a biomarker for SCZ. We recruited 130 patients with SCZ and 111 healthy individuals, and the ELISA and qRT-PCR assays were used to measure serum FGF9 levels in the participants. ELISA assay demonstrated that serum FGF9 protein levels were dramatically reduced in first-episode, drug-free patients, but not in chronically medicated patients when compared to healthy control subjects. Further analysis showed that treatment of the first-episode, drug-free SCZ patients with antipsychotics for 8 weeks significantly increased the serum FGF9 levels. In addition, we found that blood FGF9 mRNA levels were significantly lower in first-onset SCZ patients than controls. Under the receiver operating characteristic curve, the optimal cutoff values for FGF9 protein level as an indicator for diagnosis of drug-free SCZ patients was projected to be 166.4 pg/ml, which yielded a sensitivity of 0.955 and specificity of 0.86, and the area under the curve was 0.973 (95% CI, 0.954-0.993). Furthermore, FGF9 had good performance to discriminate between drug-free SCZ patients and chronically medicated patients, the optimal cutoff value for FGF9 concentration was projected to be 165.035 pg/ml with a sensitivity of 0.86 and specificity of 0.919, and the AUC was 0.968 (95% CI, 0.944, 0.991). Taken together, our results for the first time demonstrated the dysregulation of FGF9 in SCZ, and FGF9 has the potential to be served as a biomarker for SCZ.

A rare case of early onset childhood schizophrenia with predominant negative symptoms

Early onset childhood schizophrenia (<13 years) is often a rare disorder with an estimated prevalence of 1 in 30,000 children. The disease is characterized by hallucinations, delusions and cognitive impairments. It tends to present insidiously with a premorbid period of developmental delay or regression with declining academics. Often, the diagnosis of early onset schizophrenia is missed or sometimes misdiagnosed as pervasive developmental disorders. We here present a rare case of 10-year-old boy who showed behavioural abnormalities suggestive of psychosis.

Circular RNA: A novel and potential regulator in pathophysiology of schizophrenia.

Circular RNAs (CircRNAs) are a sub-class of non-coding RNA, which are covalently closed at the ends through a non-canonical process called, backsplicing from the precursor linear RNAs. These molecules are involved in several biological phenomena including regulation of gene expression, synaptic plasticity, and cognition. Several studies have shown that circRNA are present abundantly inside the mammalian brain and they are believed to be associated with the development of neurons and neuronal functions. It is also evident that alterations in intracellular and extracellular levels of circRNAs are linked with various neurological and neuropsychiatric disorders including schizophrenia (SZ). Detailed studies of circRNAs are required to decode the molecular mechanism behind the onset of SZ and the related biological activities during disease progression. This can help unravel their role in this neurobehavioral disorder and develop effective therapeutics against the disease. The present review mainly focuses on the expression and activities of the circRNAs in the post-mortem brain, peripheral blood, and exosomes. It also gives an insight into the role of circRNA interaction with RNA binding proteins (RBPs) and nucleotide modification and their therapeutic potential in the context of schizophrenia.

Early onset schizophrenia with an underlying epileptiform disorder-a case report

Early onset schizophrenia with an underlying epileptiform disorder-a case report

Schizophrenia: A developmental disorder with a risk of non-specific but avoidable decline

The onset of schizophrenia is determined by biological and social risk factors operating predominantly during development. These result in subtle deviations in brain structure and cognitive function. Striatal dopamine dysregulation follows, causing abnormal salience and resultant psychotic symptoms. Most people diagnosed as having schizophrenia do not progressively deteriorate; many improve or recover. However, poor care can allow a cycle of deterioration to be established, stress increasing dopamine dysregulation, leading to more stress consequent on continuing psychotic experiences, and so further dopamine release. Additionally, long-term antipsychotics can induce dopamine supersensitivity with resultant relapse and eventually treatment resistance. Some patients suffer loss of social and cognitive function, but this is a consequence of the hazards that afflict the person with schizophrenia, not a direct consequence of genetic predisposition. Thus, brain health and cognition can be further impaired by chronic medication effects, cardiovascular and cerebrovascular events, obesity, poor diet, and lack of exercise; drug use, especially of tobacco and cannabis, are likely to contribute. Poverty, homelessness and poor nutrition which become the lot of some people with schizophrenia, can also affect cognition. Regrettably, the model of progressive deterioration provides psychiatry and its funders with an alibi for the effects of poor care.

Early-life factors associated with increased risk of disability pension in the national real-world schizophrenia FACE-SZ cohort study.

Among severe psychiatric disorders, schizophrenia has one of the highest impacts on professional and personal functioning with important indirect costs including disability pension allowance for the patients with the more severe forms of schizophrenia. To explore early-life factors associated with disability pension in schizophrenia. 916 patients were consecutively recruited at a national level in 10 expert centers and received a comprehensive standardized evaluation. Their disability pension status and early-life variables were reported from medical records and validated scales. Eight factors were explored: age, male sex, parental history of severe mental illness, childhood trauma exposure, education level, childhood ADHD, early age at schizophrenia onset and duration of untreated psychosis. 739 (80.7%) participants received a disability pension. In the multivariate model, early age at schizophrenia onset and low education level were associated with disability pension independently of age and sex while no significant association was found for parent history of severe mental illness, childhood trauma, childhood ADHD or duration of untreated psychosis. Low education level and early age at schizophrenia onset seem the best predictors of increased risk of disability pension in schizophrenia.

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.

Drug-Induced Hyperprolactinemia and Hyponatremia - Biological Markers of Unfavorable Evolution in Schizophrenia

Adverse reactions to psychotropic medication can be considered as risk indicators for an unfavorable evolution of patients with schizophrenia, based on particular pathogenic mechanisms that can be used in the personalized therapeutic approach. The combination of antidepressants with antipsychotic drugs in schizophrenia has a risk of synergistic action of excessive blockade of dopamine receptors, which causes hyperprolactinemia. Primary hyponatremia occurs during pregnancy and can be an important marker for signaling neurodevelopmental abnormalities, while secondary hyponatremia has a major clinical dimension and is induced by psychotropic drugs. The pathogenic mechanisms presented can be objectified by neuroimaging examinations that bring benefits in the diagnostic accuracy and re-evaluation of the therapeutic approach, especially in correlation with the severity of biological markers such as prolactin and sodium. The persistence of high prolactin and low sodium levels is an alarm signal that announces a negative evolution of the patient or a major risk of severe cardiac, metabolic, vascular or renal comorbidities. Recognition of pathogenic mechanisms of neurodevelopment, including ventriculomegaly, hyponatremia, focal cortical dysplasia, hippocampal or temporal lobe lesions, in association with a positive history of neonatal or febrile seizures, requires prophylaxis due to high risk of onset of schizophrenia in childhood. Fetal cortical dysplasia is associated with the risk of neonatal seizures. This vulnerability favors the appearance of febrile convulsions or enuresis with changes in brain structure. Enuresis may be an important marker of neurodevelopmental potential for schizophrenia. Neonatal seizures are correlated with hyponatremia and severe hypertension, which appeared in the third trimester of pregnancy, can trigger eclampsia. Neuroimaging monitoring in patients with neurodevelopmental abnormalities, hyperprolactinemia and primary or secondary hyponatremia, acquires a major importance, being able to delimit the boundary between a functional lesion, potentially reversible, with an irreversible lesion.