First-episode Psychotic Patients Research Articles

Duration of untreated psychosis and its associated sociodemographic and clinical factors in first-episode psychosis: A study from Eastern Nepal.

Duration of untreated psychosis (DUP) is considered an important factor in outcome. Individual, familial and illness factors may prolong DUP. Little data on this issue is available from the country of Nepal. The purpose of the present study was to assess DUP in patients with first-episode psychosis and identify associations with patients' socio-demographic and clinical factors. A cross-sectional, descriptive study was conducted in the department of psychiatry, of Tertiary Hospital in the Eastern part of Nepal. Eighty-six patients were enrolled. ICD-10 was used to make the diagnosis. Nottingham Onset Schedule-DUP version (NOS-DUP) was used to assess DUP. Positive and Negative Syndrome Scale (PANSS) was used to assess patients' clinical symptoms. The mean (SD) DUP was 21.4 (42.1) months and median DUP was 3.0 months (IQR = 23.5). Participants from mountainous region, the unemployed, having an insidious onset of illness, and patients with a diagnosis of schizophrenia had significantly longer DUP (P < .005). Duration of untreated psychosis was also positively correlated with negative symptoms (r = .42, (P < .001) and total PANSS score (r = .42, P < .001). Duration of untreated psychosis in first-episode psychotic patients was relatively long (compared to studies in other countries), and was found to be positively associated with mountainous regions of Nepal, being unemployed, having an insidious onset of illness, and having a diagnosis of schizophrenia. Programs and educational efforts are needed to ensure early treatment of patients with first-episode psychosis, especially in the mountainous rural areas of Nepal.

Evaluating the association of vitamin D3, parathyroid hormone, and C-reactive protein serum levels in patients with an acute psychotic episode: a cross-sectional study in tertiary centre in Iran

BackgroundThe high impact of vitamin D on brain development and its relationship with inflammatory markers in the clinical course of psychiatric disorders have compelled researchers to investigate the potential association between vitamin D levels, C-reactive protein (CRP) levels, and the incidence of mental disorders. In the present study, we aimed to compare the serum levels of vitamin D and its related markers, including calcium, phosphorus, and parathyroid hormone (PTH), along with CRP, in 3 groups of patients with acute psychotic episodes, including schizophrenia, bipolar disorder, and methamphetamine-induced psychosis, with a standard control group of the Iranian population.MethodsThis descriptive cross-sectional study was conducted at a psychiatric hospital in Tehran, Iran, and involved a total of 185 subjects. The subjects included four groups: acute phase of schizophrenia (n = 49), acute manic episodes of bipolar disorder (n = 43), methamphetamine-induced psychotic disorder (n = 46), and control group (n = 47). Among 138 patients in acute psychotic episodes, 33 patients were in their first episode of psychosis, while 105 patients were in acute exacerbation of their chronic psychotic disorders. The Brief Psychiatric Rating Scale (BPRS) was measured by an expert attending psychiatrist for all patients. Then, serum levels of calcium, phosphorus, parathormone, vitamin D, and CRP were assessed in all study groups.ResultsAmong our 185 study subjects, it was observed that individuals with higher education levels and those who were married had a lower prevalence of mental disorders. In all patient groups, the serum levels of CRP were significantly higher, and PTH levels were significantly lower than in the control group (p < 0.001). The serum levels of calcium, phosphorus, and vitamin D were not statistically significantly different between the patient and control groups of the study. In chronic psychotic patients, CRP levels were significantly higher (p < 0.031), and vitamin D levels were significantly lower (p < 0.044) compared to first-episode psychotic patients.ConclusionThis study suggests that CRP levels are significantly higher and PHT level is significantly lower in acute psychotic patients. Moreover, vitamin D levels were significantly lower in chronic psychotic patients compared to first-episode psychotic patients.

Basal-Forebrain Cholinergic Nuclei Alterations are Associated With Medication and Cognitive Deficits Across the Schizophrenia Spectrum.

The cholinergic system is altered in schizophrenia. Particularly, patients' volumes of basal-forebrain cholinergic nuclei (BFCN) are lower and correlated with attentional deficits. It is unclear, however, if and how BFCN changes and their link to cognitive symptoms extend across the schizophrenia spectrum, including individuals with at-risk mental state for psychosis (ARMS) or during first psychotic episode (FEP). To address this question, we assessed voxel-based morphometry (VBM) of structural magnetic resonance imaging data of anterior and posterior BFCN subclusters as well as symptom ratings, including cognitive, positive, and negative symptoms, in a large multi-site dataset (n = 4) comprising 68 ARMS subjects, 98 FEP patients (27 unmedicated and 71 medicated), 140 patients with established schizophrenia (SCZ; medicated), and 169 healthy controls. In SCZ, we found lower VBM measures for the anterior BFCN, which were associated with the anticholinergic burden of medication and correlated with patients' cognitive deficits. In contrast, we found larger VBM measures for the posterior BFCN in FEP, which were driven by unmedicated patients and correlated at-trend with cognitive deficits. We found no BFCN changes in ARMS. Altered VBM measures were not correlated with positive or negative symptoms. Results demonstrate complex (posterior vs. anterior BFCN) and non-linear (larger vs. lower VBM) differences in BFCN across the schizophrenia spectrum, which are specifically associated both with medication, including its anticholinergic burden, and cognitive symptoms. Data suggest an altered trajectory of BFCN integrity in schizophrenia, influenced by medication and relevant for cognitive symptoms.

Evidence of innate immune dysfunction in first-episode psychosis patients with accompanying mood disorder

BackgroundInflammation and increases in inflammatory cytokines are common findings in psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Meta-analyses of studies that measured circulating cytokines have provided evidence of innate inflammation across all three disorders, with some overlap of inflammatory cytokines such as IL-6 and TNF-α. However, differences across disorders were also identified, including increased IL-4 in BD that suggest different immune mechanisms may be involved depending on the type of disorder present.MethodsWe sought to identify if the presence or absence of an affective disorder in first-episode psychotic (FEP) patients was associated with variations in cytokine production after stimulation of peripheral blood mononuclear cells (PBMC). 98 participants were recruited and grouped into healthy controls (n = 45) and first-episode psychosis patients (n = 53). Psychosis patients were further grouped by presence (AFF; n = 22) or lack (NON; n = 31) of an affective disorder. We cultured isolated PBMC from all participants for 48 h at 37 °C under four separate conditions; (1) culture media alone for baseline, or the following three stimulatory conditions: (2) 25 ng/mL lipopolysaccharide (LPS), (3) 10 ng/mL phytohemagglutinin (PHA), and (4) 125 ng/ml α-CD3 plus 250 ng/ml α-CD28. Supernatants collected at 48 h were analyzed using multiplex Luminex assay to identify differences in cytokine and chemokine production. Results from these assays were then correlated to patient clinical assessments for positive and negative symptoms common to psychotic disorders.ResultsWe found that PBMC from affective FEP patients produced higher concentrations of cytokines associated with both innate and adaptive immunity after stimulation than non-affective FEP patients and healthy controls. More specifically, the AFF PBMC produced increased tumor necrosis fctor (TNF)-α, interleukin (IL)-1β, IL-6, and others associated with innate inflammation. PBMC from AFF also produced increased IL-4, IL-17, interferon (IFN)γ, and other cytokines associated with adaptive immune activation, depending on stimulation. Additionally, inflammatory cytokines that differed at rest and after LPS stimulation correlated with Scale for the Assessment of Negative Symptoms (SANS) scores.ConclusionsOur findings suggest that immune dysfunction in affective psychosis may differ from that of primary psychotic disorders, and inflammation may be associated with increased negative symptoms. These findings could be helpful in determining clinical diagnosis after first psychotic episode.

The association of cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients: a cross sectional study

IntroductionCognitive impairment is common in first-episode psychosis patients and often associated with poor quality of life and functional impairment. However, most literature on this association is from high income countries and not low resource countries like Uganda. We aimed to determine the association between cognitive impairment with quality of life and functional impairment in Ugandan first-episode psychosis patients.MethodsAt Butabika national psychiatric hospital of Uganda, we enrolled 94 first-episode psychosis patients aged 18–60 years with a confirmed first-episode of psychosis and no previous treatment with antipsychotic medication. Neuropsychological assessment was performed using the MATRICS consensus cognitive battery (MCCB). Quality of life and functional impairment were assessed using the brief version of the World Health Organisation Quality of Life scale (WHOQOL-BREF) and the MINI International Neuropsychiatric Inventory (MINI) respectively. Linear regression analyses determined the association between impairment in different cognitive domains with various quality of life and functional impairment domains while controlling for age, gender and level of education.ResultsHigh scores in the reasoning and problem solving cognitive domain were associated with better quality of life in the psychological domain of WHOQOL-BREF (p = 0.029). For functional impairment, high cognitive scores in the domains of speed of processing (p = 0.018), reasoning and problem solving (p = 0.015), working memory (p = 0.017) and visual learning and memory (p = 0.002) were associated with psychosis “having a greater impact on other members of the family” on the MINI. Higher scores in the social cognition domain were associated with “less aggressive and disruptive behaviour” (p = 0.003).ConclusionCognitive impairment in Ugandan first-episode psychotic patients is associated with both poorer quality of life and functional impairment. Remediation of cognitive function may be a plausible intervention to improve outcomes in Ugandan first-episode psychosis patients.

Cannabis use disorder and dissociation: A report from a prospective first-episode psychosis study

BackgroundCannabis is the most used recreational drug worldwide. Its use can increase the risk of developing psychotic disorders and exacerbate their course. However, the relationship between cannabis use and dissociative symptoms has been scarcely investigated. AimsTo examine differences in psychotic and dissociative symptoms, and in functioning in first-episode psychotic patients (FEPp) using cannabis compared with those not using cannabis. MethodsBetween January 2014 and December 2019, seventy FEPp with cannabis use disorder (N = 35) and without it (N = 35) were recruited in psychiatric inpatient facilities in the Italian regions of Lazio and Piemonte. All subjects were assessed at FEP, after 4 and 8 months, using the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF) scale and the Dissociative Experiences Scale – II (DES-II). Detailed information on the pattern of cannabis and other substance use were collected. ResultsFEP using cannabis showed higher levels of positive symptomatology, dissociative experiences and worse functioning than their non-user counterpart, despite a comparable antipsychotic treatment. At an eight-month prospective evaluation, FEP using cannabis still showed higher levels of positive symptomatology and dissociation. Moreover, global functioning worsened over time in FEPp using cannabis, whereas it improved those not using it. DiscussionOur findings suggest that a greater degree of dissociation and positive symptoms at FEPp and their persistence over time may characterise cannabis-associated psychosis. Both these factors might explain the overall functioning worsening over time that we observed in the cannabis-user group compared to the functioning improvement in the non-user group.

Dissociation as a causal pathway from sexual abuse to positive symptoms in the spectrum of psychotic disorders

BackgroundAlthough numerous studies have supported the role of childhood maltreatment in the etiology of psychosis, underlying mechanisms have not been well understood yet. The present study aimed to investigate the mediating role of particular forms of dissociation in the relationship between five major types of childhood abuse and psychotic symptoms among patients with schizophrenia spectrum and other psychotic disorders.MethodsIn this cross-sectional correlation study, 70 first-episode psychotic patients and 70 chronic psychotic patients were selected by systematic random sampling (with the sampling interval of 3) from among inpatients and outpatients referring to Baharan Psychiatric hospital, Zahedan, Iran, and were matched based on age, gender, and education level. Moreover, 70 age-, gender-, and education level-matched community controls were recruited from hospital staff and their relatives and friends. All of the participants completed a research interview and questionnaires. Data on experiences of childhood maltreatment, psychosis, dissociation, and demographics were collected and analyzed by SPSS V25 software.ResultsThe obtained results revealed that the mean scores of sexual abuse, emotional abuse, and physical abuse were higher in psychotic patients than community controls (without any significant difference between first-episode psychotic patients and chronic psychotic patients). Furthermore, the highest mean scores of dissociative experiences belonged to chronic psychotic patients. Multiple-mediation also indicated that absorption and dissociative amnesia played a mediating role in the relationship between sexual abuse and positive symptoms. Moreover, this study demonstrated the role of physical abuse in predicting psychotic symptoms even in the absence of sexual abuse.ConclusionsThis study illustrated specific associations among childhood maltreatment, dissociative experiences, and psychotic symptoms in the clinical population. Thus, to provide appropriate interventions, patients with schizophrenia spectrum and other psychotic disorders were asked about a wide range of possible adverse childhood experiences and dissociative experiences. Nevertheless, further studies using prospective or longitudinal designs need to be carried out to realize the differential contribution of various forms of childhood maltreatment and their potential interactions, more precisely.

Clinical Predictors of Duration of Untreated Psychosis: Exploring Psychosocial and Clinical Predictors of Duration of Untreated Psychosis in First-Episode Psychotic Patients in Mzuzu, Malawi

The duration of untreated Psychosis (DUP) is a modifiable factor in the management and outcome of patients with psychosis. However, its predictive factors have not been studied much in Malawi. Our study was aimed at determining the psychosocial and clinical predictors of DUP in first episode psychosis in Malawi. A quantitative cross-sectional study, using secondary data from an early intervention study project was done in Mzuzu, Malawi. We analysed 140 adult participants enrolled in early intervention project in 2010. Data was collected using abstraction sheet to target predictive factors. We conducted univariate and multivariate logistic regression at confidence interval of 95%. We described the mean DUP, and looked at relationship of clinical and psychosocial factors with DUP. Most participants were male (60%, n=84) and single (51.4%, n=72). The median age of male participants was 31 years (Range=18 to 60), lower than females 35 years (Range=18 to 65). (what were the numbers of females). The majority of the participants' highest education level was secondary school (63.6%, n=89), and most had DUP of ≥ 6 months (74%, n=103). We found mean DUP of 42 months (SD= ±71). Employment status, diagnosis of schizophrenia (OR=10.93, 95% C.I 3.08-38.89), and negative symptoms of psychosis were associated with DUP of ≥ 6 months. Public self-consciousness and social quality of life were associated with long DUP. Our study shows psychosocial and clinical factors that predict long DUP in Malawi. This highlights the need to target these factors when working on first episode psychosis for a better outcome.

First-Episode Psychotic Patients Showed Longitudinal Brain Changes Using fMRI With an Emotional Auditory Paradigm.

Most previous longitudinal studies of functional magnetic resonance imaging (fMRI) in first-episode psychosis (FEP) using cognitive paradigm task found an increased activation after antipsychotic medications. We designed an emotional auditory paradigm to explore brain activation during emotional and nonemotional word processing. This study aimed to analyze if longitudinal changes in brain fMRI BOLD activation is present in patients vs. healthy controls. A group of FEP patients (n = 34) received clinical assessment and had a fMRI scan at baseline and follow-up (average, 25-month interval). During the fMRI scan, both emotional and nonemotional words were presented as a block design. Results were compared with a pair of healthy control group (n = 13). Patients showed a decreased activation at follow-up fMRI in amygdala (F = 4.69; p = 0.04) and hippocampus (F = 5.03; p = 0.03) compared with controls. Middle frontal gyrus was the only area that showed a substantial increased activation in patients (F = 4.53; p = 0.04). A great heterogeneity in individual activation patterns was also found. These results support the relevance of the type of paradigm in neuroimaging for psychosis. This is, as far as we know, the first longitudinal study with an emotional auditory paradigm in FEP. Our results suggested that the amygdala and hippocampus play a key role in psychotic disease. More studies are needed to understand the heterogeneity of response at individual level.

Erectile dysfunction in patients with first-episode psychosis.

Sexual dysfunction is more prevalent in psychotic patients than in the nonpsychotic population. The objective of this study was to identify correlations between serum prolactin levels, testosterone levels and erectile dysfunction in patients with first-episode psychosis (n=40) compared to age-matched healthy controls (n=40). All subjects underwent clinical evaluation, international index of erectile function (IIEF5) score assessment and measurement of serum prolactin and total testosterone levels. In first-episode psychotic patients, the IIEF-5 score and total testosterone levels were significantly lower, while serum prolactin levels were higher. We concluded that men with first-episode psychosis are at an increased risk for development of erectile dysfunction, and increased duration of untreated psychosis leads to a higher incidence of erectile dysfunction and hyperprolactinemia.

Changes in motor preparation affect the sensory consequences of voice production in voice hearers

BackgroundAuditory verbal hallucinations (AVH) are a cardinal symptom of psychosis but are also present in 6–13% of the general population. Alterations in sensory feedback processing are a likely cause of AVH, indicative of changes in the forward model. However, it is unknown whether such alterations are related to anomalies in forming an efference copy during action preparation, selective for voices, and similar along the psychosis continuum. By directly comparing psychotic and nonclinical voice hearers (NCVH), the current study specifies whether and how AVH proneness modulates both the efference copy (Readiness Potential) and sensory feedback processing for voices and tones (N1, P2) with event-related brain potentials (ERPs). MethodsControls with low AVH proneness (n = 15), NCVH (n = 16) and first-episode psychotic patients with AVH (n = 16) engaged in a button-press task with two types of stimuli: self-initiated and externally generated self-voices or tones during EEG recordings. ResultsGroups differed in sensory feedback processing of expected and actual feedback: NCVH displayed an atypically enhanced N1 to self-initiated voices, while N1 suppression was reduced in psychotic patients. P2 suppression for voices and tones was strongest in NCVH, but absent for voices in patients. Motor activity preceding the button press was reduced in NCVH and patients, specifically for sensory feedback to self-voice in NCVH. ConclusionsThese findings suggest that selective changes in sensory feedback to voice are core to AVH. These changes already show in preparatory motor activity, potentially reflecting changes in forming an efference copy. The results provide partial support for continuum models of psychosis.

T24. CHANGES IN TELOMERE LENGTH IN YOUNG PEOPLE WITH FIRST EPISODE PSYCHOSIS: A 12-MONTHS FOLLOW-UP STUDY

BackgroundCellular 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.MethodsThis 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.ResultsAt 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.DiscussionThis 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.

T91. THE POSITIVE AND NEGATIVE SYNDROME SCALE SUPERIOR TO A SELF-REPORT QUESTIONNAIRE IN THE PHARMACOTHERAPY MONITORING AND OUTCOME SURVEY

BackgroundAiming to improve the quality of care for patients with a psychotic disorder, the ongoing Pharmacotherapy Monitoring Outcome Survey (PHAMOUS) started in 2006 in four large mental health care organizations in the Northern Netherlands, by adding it to the at that time mandatory Routine Outcome Monitoring program. However, since the cuts in the financial budgets for mental health care, research nurses are increasingly experiencing time-pressure in the assessments. The Positive and Negative Syndrome Scale (PANSS), part of the assessment, is a time-consuming interview, taking approximately 30 minutes. Therefore, we developed and validated a short self-report questionnaire assessing positive psychotic symptoms, the Brief Positive Symptoms Questionnaire (BPSQ).MethodsThe BPSQ was added to PHAMOUS and filled in once by patients in four mental health care institutions in 2017 and 2018. The BPSQ consists of nine items and takes about 2–3 minutes to complete. It was validated against the PANSS positive scale and two items of the Health of the Nations Outcome Scale (HoNOS), with item 6 assessing the problems that patients experience due to hallucinations and delusions and item 8 assessing further mental and behavioural problems.ResultsBPSQ data were obtained from n=287 patients (mean age 47.1 years, 67.6% male). The PANSS was assessed in n=244 and HoNOS data were available for n=156 patients. Scores of one patient were considered unreliable and thus removed from the data set. The BPSQ had a Cronbach’s alpha of .81. Spearman’s correlation coefficient of the BPSQ and the PANSS positive scale was significant (ρ(243) = .63, p < .05). Correlations between the BPSQ and HoNOS items 6 and 8 were significant (ρ(155) = .488, p < .05 and ρ(155) = .251, p < .05 respectively). Post hoc analysis showed that the more severely psychotic the patients were, the less the BPSQ and the PANSS positive scale were corresponding.DiscussionGiven the medium correlation of the BPSQ with the PANSS positive scale and the low concurrent validity with the two relevant HoNOS items, we argue that the widely used and validated PANSS is indispensable in the PHAMOUS assessment of positive symptoms in a chronic population with psychotic disorders. Replication of this study in first-episode psychotic patients is recommended.

Aripiprazole Long-Acting Injection During First Episode Schizophrenia—An Exploratory Analysis

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18–26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive (p < 0.001) and negative (p < 0.001) symptoms and in general psychopathology (p < 0.001) and decrease in global severity (p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness.

L-Arginine metabolism before and after 10 weeks of antipsychotic treatment in first-episode psychotic patients

Agmatine is an endogenous NMDA (N-methyl-d-aspartate) antagonist which is synthesized from l-Arginine and described as a novel neurotransmitter. Agmatine is considered to play an important role for the development of schizophrenia. The aim of the present study is to explore the role of agmatine and l-arginine metabolism in medication-naive first-episode psychosis (FEP). We conducted a case control study in medication-naive patients with FEP (n = 40). The healthy volunteers with no family history of schizophrenia (n = 35) matched for age, gender and education level were selected as a control group. The patients were recruited to the study and followed up for 10 weeks. The plasma l-arginine, l-citrulline, l-ornithine and agmatine levels were measured using modified liquid chromatography/mass spectrometry. The plasma levels of l-arginine, l-citrulline and agmatine (p < 0.0001), but not l-ornithine and agmatinase (p > 0.05), were significantly increased during baseline analysis. After 10 weeks of treatment, plasma l-arginine and l-citrulline levels were still significantly increased (p < 0.05) while l-ornithine and agmatinase levels remained unchanged (p > 0.05). Conversely, plasma agmatine levels were significantly decreased after the treatment (p < 0.0001). Positive and negative predictive values of agmatine used for evaluating the diagnostic accuracy were 95.1% and 97.1%, respectively (p < 000.1). This is the first study of arginine metabolism and agmatine in medication-naive first-episode patients and provides evidence of increased levels of an endogenous NMDA antagonist which decreases following antipsychotic treatment.

Affective versus non-affective first episode psychoses: A longitudinal study

ObjectiveThis study aimed to assess (1) whether there were clinical, neuropsychological and functional differences between and within affective and non-affective psychoses at baseline and two years-follow-up and (2) to explore clinical and neuropsychological predictors of psychosocial functioning in the whole sample. MethodThis is a subanalysis from a multicentre, naturalistic, longitudinal prospective study (‘Phenotype-genotype and environmental interaction. Application of a predictive model in first psychotic episodes’). The sample consisted of 192 patients with a first psychotic episode (FEP): 142 with non-affective psychoses and 50 with affective psychoses. Student t-tests, paired t-tests, Pearson correlations, ANOVAs and regression analyses were performed. ResultsAt baseline, the groups differed in perseverative errors (WCST), Premorbid Adjustment Scale (PAS), family history of psychiatric disorder, negative (PANSS) and manic symptoms (YMRS). At two years follow-up, the groups differed in all the PANSS subscales and in depressive symptoms assessed by the MADRS. When the whole sample was considered, the regression model which best explained the estimated variance in functioning at follow-up (41%) was composed by PANSS total score and verbal fluency assessed by the FAS (COWAT). ConclusionsWe found clinical and neurocognitive differences at baseline which decreased in the follow-up. Reduced performances at baseline in executive functions in combination with symptom severity (PANSS) were predictors of FEP patients’ poor functional outcome.

Tracking single membrane targets of human autoantibodies using single nanoparticle imaging

BackgroundOver the past decade, an increasing number of neurological and neuropsychiatric diseases have been associated with the expression of autoantibodies directed against neuronal targets, including neurotransmitter receptors. Although cell-based assays are routinely used in clinics to detect the presence of immunoglobulins, such tests often provide heterogeneous outcomes due to their limited sensitivity, especially at low titers. Thus, there is an urging need for new methods allowing the detection of autoantibodies in seropositive patients that cannot always be clinically distinguished from seronegative ones. New methodHere we make a case for single nanoparticle imaging approaches as a highly sensitive antibody detection assay. Through high-affinity interactions between functionalized nanoparticles and autoantibodies that recognize extracellular domains of membrane neuronal targets, single nanoparticle imaging allows a live surface staining of transmembrane proteins and gives access to their surface dynamics. Results and comparison with existing method(s)We show here that this method is well-suited to detect low titers of purified immunoglobulin G (IgG) from first-episode psychotic patients and demonstrate that these IgG target glutamatergic N-Methyl-d-Aspartate receptors (NMDAR) in live hippocampal neurons. The molecular behaviors of targeted membrane receptors were indistinguishable from those of endogenous GluN1 NMDAR subunit and were virtually independent of the IgG concentration present in the sample contrary to classical cell-based assays. ConclusionsSingle nanoparticle imaging emerges as a real-time sensitive method to detect IgG directed against neuronal surface proteins, which could be used as an additional step to rule out ambiguous seropositivity diagnoses.

Altered serum levels of vascular endothelial growth factor in first-episode drug-naïve and chronic medicated schizophrenia

There is much evidence of a relationship between alterations in the brain's regional cellular energy metabolism and blood flow in schizophrenic. Vascular endothelial growth factor (VEGF) plays a role in the pathogenesis of neuropsychiatric illnesses. So, we compared serum VEGF levels in drug-naïve first-episode psychotic (FEP) and chronically medicated schizophrenic to examine if a correlation existed between VEGF and psychopathological symptoms. The serum VEGF levels were assessed in 46 FEP patients, 47 chronic medicated patients and 50 healthy controls. Symptoms of schizophrenia were evaluated with the Positive and Negative Syndrome Scale (PANSS) and sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure serum VEGF levels. VEGF levels were significantly lower in FEP patients compared to both chronically medicated schizophrenic patients and healthy controls, while VEGF levels in chronically medicated patients were markedly higher than in healthy controls. Furthermore, a significant correlation was detected between the levels and the PANSS negative subscale among patient groups. However, no significant correlation was observed between VEGF and clinical variables in patients. This study suggested that imbalanced neurotrophic factors may be associated with the onset of schizophrenia, but subsequent increased VEGF may be related to medication or other factors in disease progression.

S153. WHERE IS THE ABNORMAL BRAIN ACTIVITY IN FIRST EPISODE PSYCHOSIS?

BackgroundRecent review about functional magnetic resonance imaging (fMRI) in first episode psychosis (FEP) concluded that there is an abnormal connectivity involving the frontal temporal pathway similar to found in chronic schizophrenia (Mwansisya et al., 2017). Besides, thalamic circuits were also altered in chronic schizophrenia patients (Li et al., 2017). The present work gives a wider review of studies using functional magnetic resonance imaging techniques (fMRI) on first-episode psychotic patients, specifically focus on the main areas involved.MethodsThe review was made in accordance with the PRISMA guidelines (Moher et al., 2009). For each study, the following factors were extracted: anatomical location of the main finding and type of functional abnormality (hypo and hyperactivation). A total of 3 different databases (Pubmed, Web of Knowledge, PsycInfo) were reviewed. Thirty-five of 643 (from 2000 to 31st October 2017) neuroimaging papers were analyzed.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) showed 52% of activity abnormalities (55% was hypoactivation). Temporal lobe showed 51% of functional activity altered (61% was hypoactivity). The ventrolateral prefrontal cortex (VLPFC) presented 28% of aberrant fMRI (75% was hyperactivity). Thalamus presented alteration activity with 20% (71% was hypoactivity). The Cingulate was also altered during activation with 20% of patients (85% was hypoactivity). Finally, functional alterations of the Amygdala were present in 14% of the selected patients (80% was hypoactivation).DiscussionThis larger review suggests that there are several possible areas apart from fronto temporal pathways (Mwansisya et al., 2017), that have to be taken into account at the early course of psychosis, such as lymbic system, thalamo-cortical networks and cingulate. These functional activation abnormalities seem to be different to the reported in the previous review. The different results seem to be clearly influenced by the kind of paradigm. Moreover, our finding is not in concordance with the suggestion that thalamic alterations became only prominent at the chronic phase of psychosis (Li et al., 2017).

42.3 METABOLOMICS APPROACHES TO STUDY METABOLIC CO-MORBIDITIES IN PSYCHOTIC DISORDERS

BackgroundPsychotic patients are at high risk for developing obesity, metabolic syndrome and type 2 diabetes. These metabolic co-morbidities are hypothesized to be related to both treatment side-effects as well as to metabolic changes occurring during the psychosis. Earlier metabolomics studies have shown that blood metabolite levels are predictive of insulin resistance and type 2 diabetes in the general population as well as sensitive to the effects of antipsychotics. Here we aimed to identify the metabolite profiles predicting future weight gain and other metabolic abnormalities in psychotic patients.MethodsWe applied metabolomics to investigate serum metabolite profiles in a prospective study setting in 36 first-episode psychosis patients during the first year of the antipsychotic treatment and 19 controls. Two analytical platforms with broad analytical coverage were used. Molecular lipids were analysed by ultra-high performance liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC_QTOFMS) and polar metabolites were analysed by two-dimensional gas chromatography coupled to TOFMS (GCxGC-TOFMS). Ongoing prospective metabolomics studies ae focusing on the subjects in at-risk mental state.ResultsWhile corroborating several earlier findings when comparing cases and controls and the effects of the antipsychotic medication, we also found that prospective weight gain in psychotic patients was associated with increased levels of triacylglycerols with low carbon number and double-bond count at baseline and independent of obesity, that is, lipids known to be associated with increased liver fat.DiscussionThe first-episode psychotic patients who rapidly gain weight in the follow-up have early metabolic disturbances which are associated with insulin resistance and fatty liver. Our studies suggest that metabolite profiles may be used to identify the psychotic patients most vulnerable to develop metabolic co-morbidities, and may point to a pharmacological approach to counteract the antipsychotic-induced weight gain.