bluuebunny/crossref_metadata_2025_split huggingface dataset:
O8.4. ENVIRONMENTAL RISK FACTORS IN BIPOLAR DISORDER AND PSYCHOTIC DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PROSPECTIVE STUDIES
Authors: Rodriguez Victoria , Alameda Luis , Marino Paolo , Trotta Giulia , Spinazzola Edoardo , Matheson Sandra , Laurens Kristin , Murray Robin , Vassos Evangelos 
Published: May 2020

Abstract

Background
There is replicated evidence of a shared genetic load between affective and non-affective psychosis, but much less is known of whether affective psychosis is affected by the same environmental risk factors as well. The aim of this review and meta-analysis is to study the association between specific environmental risk factors of interest previously associated with schizophrenia and later affective psychoses (bipolar disorder and psychotic depression).

Methods
A systematic search of prospective studies was conducted in MEDLINE, EMBASE and PsycINFO databases, supplemented by hand searching. Selected exposures included: paternal age, maternal infection, obstetric and perinatal factors, childhood trauma, childhood infection, urbanicity, migration, stressful life events, head injury and cannabis or substance use. Relevant studies were selected systematically among those fulfilling inclusion criteria, and effect sizes were extracted. Pooled information was presented for those factors with enough number studies to combine extracted effect sizes, while the rest were presented in a narrative way.

Results
Approximately 60 studies addressing the associations between environmental risk factors of interest and later affective psychoses were identified. The compiled studies showed that paternal age, early gestational age, lifetime cannabis use, parental death during childhood and ethnic minority in UK are associated with future development of affective psychosis.

Discussion
These results show that, as per genetics, there may be some overlap in the environmental load between schizophrenia and affective psychosis, suggesting general risks for psychosis rather than diagnostic specific risks. Nonetheless, publish studies for some factors in this subgroup of patients are still scarce. More longitudinal studies addressing specific association between environmental risk factors and affective psychosis are warranted.
O9.6. SYSTEMATIC REVIEW AND META-ANALYSIS OF THE EFFECTS OF CANNABIS USE IN ADOLESCENCE ON IQ IN LONGITUDINAL STUDIES ACCOUNTING PRE-EXPOSURE BASELINE PERFORMANCE
Authors: Power Emmet , Sabherwal Sophie , O’Neill Aisling , Healy Colm , Cotter David , Cannon Mary 
Published: May 2020

Abstract

Background
Cannabis use in adolescence is a known risk factor for developing schizophrenia. Decline in intellectual functioning is a well-studied phenomenon of schizophrenia. Schizophrenia in its first classification was conceptualized as a dementia - ‘Dementia Praecox’ indicating a dominance of effect of cognitive symptoms on functioning at that time. First episode psychosis patients with histories of cannabis use compared to those without cannabis use have superior cognitive functioning suggesting different disease phenotypes. Our aim was to investigate whether cannabis had an effect on full scale IQ in general population samples to further inform understanding of this disease pathway.

Methods
We developed a search strategy through an iterative approach with a qualified information specialist. We searched three databases: Medline, Embase and PsychInfo. We included conference abstracts and full text publications in English. We contacted authors for additional information in cases where an effect size was not calculable. We included longitudinal studies of non-help-seeking young people in the community with a pre-drug exposure standardized measure of IQ prior to the age of 18 and a comparable measure at subsequent follow up. We defined the case group as individuals with a history of heavy cannabis use (more than 25 lifetime uses, at least weekly use for 6 months and/or meeting criteria for a cannabis use disorder) and the control group as similar young people who had no or very minimal experimental exposure to cannabis (&lt;5 lifetime uses). Two reviewers independently extracted the data and assessed for bias using the Newcastle-Ottawa risk of bias tool. We performed random effects meta-analysis in Stata version 14 given expected heterogeneity in measurement of cannabis use across studies.

Results
We identified 7 cohort studies detailed in 6 reports including over 650 subjects and 5600 controls. Study designs included twin cohorts, representative cluster sampled community cohorts and birth cohort studies. Range of follow up was between 2 and 23 years. All studies showed relative decline in IQ of which two were statistically significant. Our findings show that cannabis use in youth is associated with modest IQ differences that equate to approximately to a 2-point decrease in young cannabis users. Studies examining twin pairs showed that twins discordant for cannabis use did not have divergent cognitive trajectories, however these analyses were relatively underpowered to find an effect.

Discussion
Our findings demonstrate the harmful effects of cannabis use on brain development in young people. These findings are of public health importance and provide further evidence for the detrimental effects of early cannabis use on mental health and cognition.
O11.4. INTERACTOME OVERLAP BETWEEN SCHIZOPHRENIA AND COGNITION
Authors: Koch Elise , Rosenthale Brin , Lundquist Anders , Chen Chi-Hua , Kauppi Karolina 
Published: May 2020

Abstract

Background
Cognitive impairments constitute a core feature of schizophrenia, and a genetic overlap between schizophrenia and cognitive functioning in healthy individuals has been identified. However, due to the high polygenicity and complex genetic architecture of both traits, overlapping biological pathways have not yet been identified between schizophrenia and normal cognitive ability. Network medicine offers a framework to study biologically meaningful gene networks through protein-protein interactions among risk genes. Here, established network-based methods were used to further reveal the biological relatedness of schizophrenia and cognition.

Methods
The protein interactome was used to examine the genetic link between schizophrenia risk genes and genes associated with cognitive performance in healthy individuals. First, we used a method called network separation to examine if there is an overlap between schizophrenia and cognition in the interactome network space. Then, we used network propagation analyses to identify schizophrenia risk genes that are close to cognition-associated genes in the interactome network space. Gene ontology and pathway enrichment analysis was performed to describe the function of this gene set.

Results
Network separation analyses showed a profound interactome overlap between schizophrenia risk genes and genes associated with cognitive performance (SAB = -0.22, z-score = -6.80, p = 5.38e-12). We identified 140 schizophrenia risk genes that are close to cognition-associated genes in the interactome. Risk genes close to cognition were enriched for pathways including long-term potentiation and Alzheimer’s disease, and included genes with a role in neurotransmitter systems implemented in cognition, such as glutamate and dopamine, that were not part of the direct genetic overlap. Moreover, schizophrenia risk genes close to cognition included 45 druggable genes not yet used as drug targets.

Discussion
These results pinpoint schizophrenia risk genes of particular interest for further examination in schizophrenia patient groups to reveal the genetic architecture of cognitive impairments in schizophrenia, of which some are druggable genes with potential as candidate targets for cognitive enhancing drugs.
O11.5. INCREASED INFLAMMATION AND MACROPHAGE INFILTRATION IS ASSOCIATED WITH ALTERED SUBEPENDYMAL ZONE NEUROGENESIS IN SCHIZOPHRENIA BUT NOT BIPOLAR DISORDER
Authors: North Hayley , Weissleder Christin , Bitar Maina , Fullerton Janice M , Sager Rachel , Barry Guy , Webster Maree J , Shannon Weickert Cynthia 
Published: May 2020

Abstract

Background
Inflammation is implicated in the pathogenesis of schizophrenia and bipolar disorder. Inflammation regulates neurogenesis, and markers for stem cells and neuronal progenitors are reduced in schizophrenia and bipolar disorder in the subependymal zone (SEZ) – the brain’s largest region of neurogenesis. This research aimed to discover core differences in gene expression and cellular composition in the SEZ in psychiatric disorders that may contribute to dysregulated neurogenesis.

Methods
We performed total RNA sequencing in the SEZ of 20 post-mortem schizophrenia and 21 control brains. Quantitative PCR (qPCR) and immunohistochemistry were performed in 32 schizophrenia and 32 control overlapping cases and 29 bipolar disorder cases. Immunohistochemistry was used for quantification and localisation of CD163+ macrophages. Cluster-analysis of IL6, IL6R, IL1R1 and SERPINA3 expression defined low and high inflammation subgroups, which were used to compare neurogenesis marker expression.

Results
Out of &gt;60,000 genes, the most significantly differentially expressed gene in schizophrenia was CD163, a macrophage marker, which was increased 3.3 times compared to controls and confirmed by qPCR. Abundant CD163+ macrophages were located surrounding blood vessels, in the parenchyma and seem to infiltrate throughout the SEZ where neural stem and progenitor cells typically reside. Macrophage cell density was increased in schizophrenia compared to controls and bipolar disorder (by 29% and 61%; p = 0.017 and p = 0.002 respectively). CD163 expression positively correlated with the quiescent neural stem cell marker GFAPδ (r = 0.56, p = 0.001), and negatively correlated with neuronal progenitor marker ASCL1 (r = - 0.40, p = 0.032) in schizophrenia but not bipolar disorder. Cluster analysis of inflammatory gene expression revealed 40% of schizophrenia but only 10% of control cases were highly inflamed. The high inflammation schizophrenia subgroup had increased CD163 and GFAPδ expression but decreased ASCL1 expression (all p &lt; 0.026).

Discussion
Increased macrophages in the SEZ is a key difference in schizophrenia pathology and potentially drives heightened inflammation in a subgroup. Inflammation has varied effects on different stages of neurogenesis in schizophrenia but not bipolar disorder, implicating divergent mechanisms leading to reduced neurogenesis in each psychiatric condition. In schizophrenia, macrophages and high inflammation seem to reduce neuronal differentiation and sustain neural stem cell quiescence, likely blunting stem cell proliferation. Therefore, reduced SEZ neurogenesis across the lifespan in schizophrenia may contribute to the widely reported inhibitory interneuron deficits.
T12. THE RELATIONSHIP OF INTESTINAL PERMEABILITY FACTORS WITH SOCIODEMOGRAPHIC AND PHYSICAL HEALTH FACTORS AND PANSS SCORES IN SCHIZOPHRENIA PATIENTS AND HEALTHY CONTROLS
Authors: Borkent Jenny , Sommer Iris E C , Haarman Bartholomeus C M 
Published: May 2020

Abstract

Background
Recent studies have pointed to the gut-brain axis as a new venue for treatment of psychiatric disorders, with increased inflammation stemming from increased intestinal permeability to further affect brain functioning in a significant subset of patients. Yet, this line of research is still in its infancy, with multiple studies showing increased intestinal permeability in schizophrenia and bipolar disorders, demonstrated as translocation of food and bacterial antigens, as well as intestinal microbiome disturbances.

Methods
Therefore, we measured intestinal permeability markers soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in schizophrenia patients and healthy controls. Intestinal permeability markers were compared to several sociodemographic, including age, gender and BMI, and physical health variables, including CRP, glucose, cholesterol, triglycerides, HDL, LDL and non-HDL, and Positive and Negative Syndrome Scale (PANSS) scores. Of the control group (n = 43), 76.7% was male, with a mean age of 25.1 years. Of the schizophrenia group (n = 105) 75.2 % was male, with a mean age of 27.4 years and an average PANSS score of 57.2.

Results
Levels of LBP and sCD14 were not significantly different between schizophrenia patients and controls. LBP and sCD14 levels were neither correlated in the control group, nor in the schizophrenia group. In the control group Females had elevated LBP levels compared to males (p &lt; 0.01), but not in the schizophrenia group. Quantitative levels of LBP, but not sCD14, correlated with triglycerides in the schizophrenia group (R2 = 0.049, p &lt; 0.05). Furthermore, quantitative levels of sCD14, but not LBP, correlated with CRP in the schizophrenia group (R2 = 0.078, p &lt; 0.05). Finally, LBP levels in patients correlated with PANSS negative scores (R2 = 0.055, p &lt; 0.05). Neither a correlation of LBP and sCD14 with age, nor with BMI was observed in both the control and the schizophrenia group.

Discussion
In conclusion, these intestinal permeability markers showed few differences between the schizophrenia and the control group. We found weak, yet significant correlations with triglycerides, CRP and severity of negative symptoms, which may be caused by poor eating habits or metabolic syndrome leading to leaky gut in the more severely affected patients. These results are not in line with results of Severance et al. (2013), who performed a similar analysis and found differences in intestinal permeability markers between a control group and a schizophrenia group. Furthermore, they did observe a positive correlation between sCD14 and LBP in both the control and the schizophrenia group. The difference between that study and our current findings may stem from the different patients samples, as we assessed patients in their first five years after diagnosis, when metabolic syndrome was less abundant.
T15. MISMATCH NEGATIVITY INDICES AS A PROGNOSTIC FACTOR FOR REMISSION IN SCHIZOPHRENIA
Authors: Shim Se-Hoon , Lim Eunsung , Park Sung-Yong , Jang Seung-Ho , Bahk Won-Myong , Kwon Young-Joon , Yoon Bo-Hyun 
Published: May 2020

Abstract

Background
Mismatch negativity (MMN) is an event-related potential component when a sequence of relatively standard stimuli is interrupted by the infrequent presentation of deviant stimuli. MMN is known to be associated with neuro-cognition and functional outcomes. Also, abnormally decreased MMN has often been reported in schizophrenia. Remission and recovery rates are related to the neuro-cognition of patients with schizophrenia. The present study explored the relationship of MMN with remission in patients with schizophrenia.

Methods
Forty patients with schizophrenia were recruited and divided into two groups, with or without remission, according to the Remission in Schizophrenia Working Group criteria (RSWGcr). For assessments of symptom severity, cognitive function and functional outcome, scale such as Positive and Negative Syndrome Scale (PANSS), K-WAIS-IV, and Global Assessment of Functioning (GAF) were measured. MMN of the patients were evaluated at the frontocentral site. A regression analysis was used to identify the factors that significantly predicted symptom improvement and remission including MMN at frontal site assessed at baseline, and anticipated clinical variables as predictive factors.

Results
MMN amplitudes in frontal sites were further decreased in the groups without remission compared to the groups with remission. MMN amplitude was significantly correlated with measures of symptom change and functional outcome measurements in patients with schizophrenia. Regression analysis revealed that symptom severity and MMN significantly predicted remission in patients with schizophrenia. Symptom improvement significantly predicted PANSS at baseline, illness duration, and antipsychotic dose, as did MMN amplitude at frontal site.

Discussion
This study explored the relationship of MMN with remission in patients with schizophrenia. The remitted patients with schizophrenia showed larger MMN amplitude in frontal electrode site than those of non-remitted patients. MMN in frontal sites was correlated with symptom improvement and functional outcomes through PANSS and GAF scales. The present study found that MMN was significantly correlated with variables related to remission such as PANSS and GAF evaluated at 6 months later. MMN indexes appears to be a promising candidate for predicted factor of remission of schizophrenia.
T19. GLUTAMATE AND RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA
Authors: Egerton Alice , McQueen Grant , Sendt Kyra-Verena , Gillespie Amy , Lally John , Borgan Faith , Howes Oliver , Barker Gareth J , Stone James , McGuire Philip , MacCabe James 
Published: May 2020

Abstract

Background
The mechanisms that underlie and may mediate the therapeutic response to clozapine in treatment resistant schizophrenia (TRS) are unclear. Basic science studies have indicated that clozapine may modulate brain glutamate, but this has not yet been investigated in man. The aim of this study was to determine whether clozapine alters brain glutamate levels in patients with TRS, and the associations with clinical outcome.

Methods
The study included patients with TRS who were about to start clozapine as part of their normal clinical care. Glutamate levels were measured in the anterior cingulate cortex (ACC) and right caudate nucleus using proton magnetic resonance spectroscopy (1H-MRS) before clozapine initiation (n=37) and again after 12-weeks of clozapine treatment (n=27). Symptoms were principally assessed using the PANSS. 1H-MRS scans were also acquired in a comparator group of healthy volunteers (n = 16).

Results
Over the 12 weeks of clozapine treatment there was a significant reduction in glutamate in the caudate (n = 22, F = 7.61 P &lt; 0.05) but not in the ACC. The percentage reduction in caudate glutamate was positively associated with the percentage reduction in total PANSS score (n = 23, r = 0.42, P = 0.04). ACC Glx (glutamate plus glutamine) prior to clozapine initiation was higher in patients with TRS than in healthy volunteers (P=0.03).

Discussion
Improvements in symptoms following clozapine initiation in TRS may be related to reductions in glutamate in the caudate nucleus. In contrast, ACC glutamate levels appear to remain high during the first three months of clozapine treatment.
T24. CHANGES IN TELOMERE LENGTH IN YOUNG PEOPLE WITH FIRST EPISODE PSYCHOSIS: A 12-MONTHS FOLLOW-UP STUDY
Authors: Ayora Mirian , Fraguas David , Recio Sandra , Diaz-Caneja Covadonga M , Blasco Maria A , Arango Celso 
Published: May 2020

Abstract

Background
Cellular aging is associated with the appearance of several chronic organic diseases, and many neuropsychiatric disorders such as schizophrenia spectrum disorders, which include psychotic disorders. Telomeres are one of the biomarkers of this cellular aging. Researches have shown that shorter telomere length is a biomarker of oxidation and cellular aging. Recent studies have concluded that patients with a first psychotic episode (FEP) have shorter telomere length than healthy controls (HC). However, there is no published data on the change in telomere length in the first years of illness.
The purpose of this study is to evaluate the changes in telomere length measured in peripheral blood mononuclear cells (PBMCs) in a sample of patients with early-onset psychosis and healthy subjects.

Methods
This study included 10 young patients with FEP (50% female, mean age 18.4 years) and 10 young HC (60% female, mean age 16.4 years). PBMCs telomere length was determined using high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at baseline and 12-month follow-up. We analysed in our sample of patients if there are significant differences according to the diagnosis and antipsychotic treatment.

Results
At baseline, we did not find significant differences in telomere length between FEP patients and HC. After one-year follow-up, it was found that telomere length is shorter in patients with FEP than in HC (p=0.007).
The diagnostics in the patients’ group were: 60% schizophrenia and 40% other diagnoses (20% psychosis not specified and 20% bipolar disorder). There was no significant difference between changes in telomeres length and diagnosis (p = 0.840).
The antipsychotic treatment in the patients’ group after 12 months was: 20% risperidone, 50% aripiprazole, 10% clozapine, 10% paliperidone and 10% quetiapine. We didn′t find a strong association between the shortening of telomeres and the cumulative dose of antipsychotics.

Discussion
This is one of the first studies where it has been analysed a longitudinal data of telomere length. It is shown that patients with the first episode of psychosis have significantly shorter telomere length than healthy controls. Changes in telomere length during the first years of illness can represent an early marker of accelerated cellular aging. Further studies are needed with a larger sample to know mechanisms responsible for accelerating aging and the role of oxidative stress in the pathogenesis of psychosis.
T29. CHILDHOOD PSYCHOPATHOLOGY ACROSS 12 YEARS PREDICTS ADULT PSYCHOTIC-LIKE EXPERIENCES: A PARALLEL TWO-PART PIECEWISE LATENT GROWTH CURVE MODEL
Authors: Ka-Yee Wong Keri , Francesconi Marta , Flouri Eirini 
Published: May 2020

Abstract

Background
The prevalence of childhood psychopathology fluctuates across the lifespan, yet studies often adopt linear growth curve models (LGM) of estimation that assumes constant linear growth and do not account for the comorbidity between internalizing and externalizing behaviors in predicting later psychosis. This study tests whether internalizing and externalizing behaviors in early childhood (4–9 years) and adolescence (11–16 years) are best modelled by a two-part parallel piecewise growth model (2-PGM) or a single LGM (4–16 years) and whether specific developmental periods better predict psychotic-like experiences (PLEs) in adulthood (18 years).

Methods
Parent-rated child’s psychopathology on the Strengths and Difficulties Questionnaire (Goodman, 2006) at ages 4, 6, 8, 9, 11, 13, and 16 years from the Avon Longitudinal Study of Parents and Children were first modelled by a parallel LGM, then a 2-PGM, to predict clinician-rated adult PLEs. Models were re-run controlling for confounds assessed prior to age 4 years (i.e., child’s gender, verbal IQ, socioeconomic status, maternal education, prior diagnosis of mental health issues, and stressful life experiences at 42 months).

Results
Considering internalizing and externalizing problem behaviors in tandem, a 2-PGM fit the data better than a LGM (CFI/TLI = .97/.96, 2(129) = 781.63, p &lt; .001, RMSEA = .033, 90%CI[.031-.035], WRMR = 1.32, N = 4717). Controlling for confounds, internalizing symptoms at baseline (b = .130, p = .004) and changes (b = .196, p &lt; .001) in early childhood best predicted adult PLEs, but not changes in adolescent internalizing/externalizing symptoms. Females were more likely than males to be in the definite/suspected PLEs group at 18 years (b = .078, p = .006). Findings suggest that maternal reports of internalizing problem behaviors, particularly in primary school years, provide predictive utility of clinician-assessed PLEs.

Discussion
Using a 2-PGM technique may better identify important developmental windows of assessment and intervention for PLEs than LGM. Findings have important theoretical and practical implications for mental health research.