Effect of Disrupted-in-Schizophrenia 1 gene on treatment response in patients with a first episode of psychosis

IntroductionThere is substantial evidence suggesting that individual variability in antipsychotic treatment response could be genetically determined. Disrupted-in-Schizophrenia 1 (DISC1) gene has been previously associated to the illness and to treatment response in a sample of patients suffering from psychosis. However, there is a lack of studies on the effect of DISC1 on treatment response in samples of first episode psychosis.ObjectivesThe aim of this study was to explore the relation between variations in DISC1 gene and treatment response to antipsychotics in a sample of drug-naïve patients with a first episode of psychosis.MethodsTwo hundred and twenty Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys), rs6675281 (Leu607Phe) and rs1000731. Early (6 weeks) response to antipsychotic treatment was assessed with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects.ResultsWe found a significant association between rs1000731 and treatment response. Thus, those patients homozygous for the G allele of rs1000731 were more frequently non-responders, measured with SANS, after 6 weeks of treatment, than those carrying the A allele (X2 = 4.019; P = 0.032). Moreover, when analysing the clinical improvement longitudinally, we observed that those patients carrying the A allele for the rs1000731 presented a greater improvement in positive symptoms dimension (F = 8.905; P = 0.003).ConclusionsOur results suggest a minor contribution to antipsychotic drug response of genetic alterations in the DISC1 gene.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Early psychosis in young women

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.789 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S7-S7

Author(s):

A. Riecher-Rössler

Keyword(s):

Young Women ◽

Help Seeking ◽

Negative Symptoms ◽

Stress Reactivity ◽

Psychotic Symptoms ◽

First Episode ◽

Seeking Behavior ◽

Drug Naïve ◽

Competing Interest ◽

The University

IntroductionIt is well known that young women are at lower risk for schizophrenic psychoses than young men. However, little is known about the peculiarities of emerging psychosis in young women.ObjectivesTo describe characteristics of emerging psychosis in women.MethodsWithin the FePsy (Früherkennung von Psychosen = early detection of psychosis) study at the University of Basel Psychiatric Clinics we have examined consecutively all patients with a first episode of psychosis (FEP) or an at-risk mental state (ARMS) referred to us between 2000 and 2015.ResultsWomen did not significantly differ from men regarding psychopathology, neither in the ARMS nor in the FEP group. This was true for positive as well as negative symptoms and basic symptoms. Interestingly, women had a higher correlation of self-rating with observer-rating regarding psychotic symptoms. Duration of untreated psychosis was significantly lower in women than in men. Women seek help more quickly than men and their first contact is more often their partner.Regarding neurocognition women showed a slightly better performance in verbal tasks. They also had higher prolactin levels and larger pituitary volumes, even when drug-naive.Transition to psychosis occurred as often and as quickly in women as in men.ConclusionsThere are only few gender differences in patients with emerging psychosis, which resemble mainly those found in the general population, with women showing a better help-seeking behavior, being more partner-oriented, having a better verbal performance and potentially also a higher stress reactivity [1].Disclosure of interestThe author has not supplied his declaration of competing interest.

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T119. NO DIFFERENCE BETWEEN VOLITIVE AND EXPRESSIVE NEGATIVE SYMPTOMS FOR EARLY TREATMENT RESPONSE IN FIRST EPISODE OF PSYCHOSIS ANTIPSYCHOTIC NAïVE PATIENTS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.679 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S276-S276

Author(s):

Bernardo Haguiara ◽

Gabriela Koga Tonsig ◽

Simão Kagan ◽

Daniel Cavalcante ◽

Cristiano Noto ◽

...

Keyword(s):

Treatment Response ◽

Negative Symptoms ◽

Real Life ◽

First Episode ◽

Antipsychotic Treatment ◽

Social Avoidance ◽

F Test ◽

The Social ◽

Highly Correlated

Abstract Background Negative symptoms are associated with a range of poor clinical and real-life functioning outcomes in people with schizophrenia. The division of negative symptoms into two separate factors, named “expressive deficits” and “social amotivation” could enable more accurate analysis and the development of new therapeutic tools. We aim to investigate whether the different symptoms that make up the negative dimension at baseline differently predict treatment response in first episode psychosis (FEP) antipsychotic naïve patients. Methods Patients with FEP (n=80), without previous use of antipsychotics, were recruited at an emergency service in São Paulo, Brazil, between 2014 and 2019. Individuals were assessed at admission and after 10 weeks of follow-up. Patients with schizophrenia, schizoaffective disorder and schizophreniform disorder were included. The diagnosis was confirmed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I). Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at the baseline and after 10 weeks of treatment. The “expressive deficits” factor was defined as the sum of the six following items of the PANSS: N1 (blunted affect), N3 (poor rapport), N6 (lack of spontaneity and flow of conversation), G5 (mannerisms and posturing), G7 (motor retardation), G13 (disturbance of volition). The “social amotivation” factor was defined as the sum of N2 (emotional withdrawal), N4 (passive/apathetic social withdrawal) and G16 (active social avoidance). To evaluate treatment response, we used the difference between the PANSS score at baseline and after ten weeks of follow-up (delta-PANSS). We performed three linear regressions, one using the “expressive deficits” factor, one using the “social amotivation” factor and another using the total negative symptom score at baseline. Results The mean age was 26.01 years old (SD ± 7.2), and the majority was male (58.75%). “Expressive deficits” (p=0.005, R-squared=0.084, F-test=8.28, β=8.24, df=78), “social amotivation” (p=0.009, R-squared=0,072, F-test=7.14, β=5.59, df=78); and negative symptoms (p=0.002, R-squared=0.105, F-test=10.23, β=9.08, df=78) at baseline behaved similarly in relation to delta-PANSS. All measures of negative symptoms are highly correlated to PANSS total at both time points. Discussion The results were different from our initial hypothesis of worse outcome for patients with higher expressive negative symptoms. We found that negative symptoms overall and both subdomains are highly correlated to PANSS total in acute phase in early stages, what can explain the association to better outcomes with antipsychotic treatment. Longer follow-up can help us to investigate whether differences between the subdomains of negative symptoms can be observed in more stable patients.

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Changes in the cytokine profile in first episode, drug-naïve patients with psychosis after short-term antipsychotic treatment

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.382 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S371-S371

Author(s):

P. Petrikis ◽

P. Voulgari ◽

V. Boumba ◽

D. Archimandriti ◽

P. Skapinakis ◽

...

Keyword(s):

Antipsychotic Medication ◽

Transforming Growth Factor ◽

Serum Levels ◽

Psychotic Symptoms ◽

First Episode ◽

Enzyme Linked Immunosorbent Assay ◽

Antipsychotic Treatment ◽

Before And After ◽

Drug Naïve ◽

Competing Interest

IntroductionAn increasing body of evidence suggests that antipsychotic medication can cause immunological changes that could be attributed to the amelioration of psychotic symptoms or the metabolic side effects of the drugs. So far, the results of the studies remain controversial.ObjectiveOur aim was to compare the levels of interleukin (IL) IL-2, IL-6 and transforming growth factor-β2 (TGF-β2) in drug-naïve, first-episode patients with psychosis before and after six weeks of antipsychotic medication.MethodsThirty-nine first episode patients with psychosis were enrolled in the study. Serum levels of IL-2, IL-6 and TGF-β2 were measured by enzyme linked immunosorbent assay (ELISA) before and six weeks after the initiation of antipsychotic medication. In addition, clinical psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsSerum levels of IL-2 were significantly higher in the study group six weeks after the initiation of antipsychotic treatment (P < 0.001) while TGF-β2 levels were decreased (P < 0.001) and IL-6 levels were slightly reduced (P < 0.004).ConclusionThe changes in cytokine levels may be attributed to the action of antipsychotic medication and the remission of psychopathology. The reduction in TGF-β2 levels is observed in all patients and with all antipsychotic medications used. TGF-β2 may be a marker of clinical efficacy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Indication of depot antipsychotic treatment in the view of slovak psychiatrists

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.2040 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S553-S553

Author(s):

M. Zelman

Keyword(s):

Negative Symptoms ◽

Atypical Antipsychotics ◽

Young Patients ◽

First Episode ◽

Antipsychotic Treatment ◽

Depot Antipsychotic ◽

Treatment Research ◽

Competing Interest ◽

Oral Antipsychotic ◽

Depot Form

With the increasing number of atypical antipsychotics in depot form, there emerges question about plus and cons of their use in schizophrenia patients. We focused on the opinion of Slovak psychiatrists about use of this treatment in some specific situations of schizophrenia treatment. Research was realized via questionnaire on psychiatrists (n = 47) from ambulant and hospital care, during one conference in June 2015. First part of the questionnaire was focused on the preference of oral or depot form of antipsychotic treatment. Depot form would be indicated by psychiatrists (in more than 89%) when low compliance, anosognosia or frequent episodes. On the contrary, oral antipsychotic treatment is preferred in young patients or employed patients. The type of symptoms (e.g. positive, negative) has relatively small impact on the preference of treatment, where the preferences of each type were the lowest (fewer than 36%). According to the opinion of psychiatrists, depot antipsychotic treatment is not suitable in first episode of disorder (according to 81% of respondents), otherwise in second or third episode it would not be chosen by 6% of asked psychiatrists.From the aspects of the choice between atypical or typical depot, atypical antipsychotics in depot form were favored when presence of adverse reactions (80%), occurrence of negative symptoms (65%) and short duration of disorder (58%). Typical depot was preferred by psychiatrists in patients with chronic states.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Clinical correlates of first episode schizophrenia-a comparative study

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20180296 ◽

2018 ◽

Vol 6 (2) ◽

pp. 551

Author(s):

Kathir M. ◽

Pugazhendhi K. ◽

Ravishankar J.

Keyword(s):

Family History ◽

Negative Symptoms ◽

Suicide Attempts ◽

Social Withdrawal ◽

First Episode ◽

Positive Symptoms ◽

Major Mental Disorder ◽

History Of ◽

Drug Naïve ◽

First Episode Schizophrenia

Background: Schizophrenia is a major mental disorder which has to be assessed early and managed actively even though long term functional outcome remains relatively poor. The aim of the study is to analyze negative symptoms, suicidal risk and substance use in first episode schizophrenics in comparison with multi-episode schizophrenics.Methods: 30 patients with drug naive first episode schizophrenia and 30 patients with multi episode schizophrenia, who attended the outpatient department of Psychiatry, Government Stanley Medical College, Chennai, Tamilnadu, India were studied to compare predisposing factors and spectrum of symptoms for Schizophrenia for a period of one year (January 2010-December 2010). Psychiatric questionnaire by Michael C. Hilton, DAST by Harvey A. Skinner, AUDIT by WHO, Suicide risk scale by National Health and Medical Research Council, PANSS by SR Kay were used to assess patients.Results: Unemployment and family history of suicide attempts were observed more in drug naive first episode schizophrenics. 90% of these patients had completed their primary education while 47% of multi-episode schizophrenics were illiterates. Positive symptoms (delusions, hallucinatory behaviour and suspiciousness) and negative symptoms (blunted affect, emotional withdrawal and social withdrawal) were observed more in first episode schizophrenics while PANSS, DAST, AUDIT scores did not find any differences between both the groups.Conclusions: In our study, the first episode schizophrenia patients were more educated, more unemployed and had more family history of suicide, elevated sub score of positive symptoms as measured by PANSS. Relative assessment of violence and serious behavior problems that are related to positive symptoms must be done and managed with anti psychotics.

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Predictors of antipsychotic treatment response in patients with first-episode schizophrenia, schizoaffective and schizophreniform disorders

The British Journal of Psychiatry ◽

10.1192/bjp.185.1.18 ◽

2004 ◽

Vol 185 (1) ◽

pp. 18-24 ◽

Cited By ~ 102

Author(s):

Diana O. Perkins ◽

Jeffrey A. Lieberman ◽

Hongbin Gu ◽

Mauricio Tohen ◽

Joseph McEvoy ◽

...

Keyword(s):

Clinical Response ◽

Treatment Response ◽

Negative Symptoms ◽

Positive Symptom ◽

First Episode ◽

Antipsychotic Treatment ◽

Duration Of Untreated Psychosis ◽

First Episode Schizophrenia ◽

Relationship Of ◽

The Relationship

BackgroundDuration of untreated psychosis (DUP) may contribute to the observed heterogeneity of the treatment response in first-episode schizophrenia.AimsTo examine the relationship of DUP and premorbid function with clinical outcomes following up to 2 years of antipsychotic treatment.MethodFor a subsample (n = 191) of subjects participating in a clinical trial, DUP and premorbid function were prospectively compared with clinical response to olanzapine or haloperidol.ResultsShorter DUP and good premorbid function each independently are associated with better clinical response, including improvement in overall psychopathology and negative symptoms. Premorbid function also is associated with positive symptom, social and vocational outcomes.ConclusionsEarlier antipsychotic treatment is associated with better outcomes in first-episode schizophrenia. Poor premorbid function could indicate an illness subtype less likely to respond to antipsychotic treatment regardless of when it is instituted.

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Gut microbial biomarkers for the treatment response in first-episode, drug-naïve schizophrenia: a 24-week follow-up study

Translational Psychiatry ◽

10.1038/s41398-021-01531-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xiuxia Yuan ◽

Yunpeng Wang ◽

Xue Li ◽

Jiajun Jiang ◽

Yulin Kang ◽

...

Keyword(s):

Treatment Response ◽

First Episode ◽

Antipsychotic Treatment ◽

Follow Up Study ◽

Α Diversity ◽

Microbial Biomarkers ◽

Significant Difference ◽

Drug Naïve ◽

Risperidone Treatment

AbstractPreclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.

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Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis

Psychological Medicine ◽

10.1017/s0033291713000330 ◽

2013 ◽

Vol 44 (1) ◽

pp. 37-50 ◽

Cited By ~ 25

Author(s):

J. M. Pelayo-Terán ◽

F. J. Diaz ◽

R. Pérez-Iglesias ◽

P. Suárez-Pinilla ◽

R. Tabarés-Seisdedos ◽

...

Keyword(s):

Negative Symptoms ◽

Cannabis Use ◽

Three Dimensions ◽

First Episode ◽

Antipsychotic Treatment ◽

Short Term ◽

Positive Dimension ◽

Negative Dimension ◽

Drug Naïve ◽

Term Response

BackgroundTrajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.MethodThis pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.ResultsPatients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.ConclusionsOur results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

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T121. BLUNTED AFFECT EARLY PROGRESSION IN DRUG-NAïVE FIRST EPISODE SCHIZOPHRENIA PATIENTS: 10-WEEK FOLLOW UP

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.681 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S277-S277

Author(s):

Simão Kagan ◽

Luccas Coutinho ◽

Daniel Cavalcante ◽

Mariane Noto ◽

André Nakamura ◽

...

Keyword(s):

Negative Symptoms ◽

Demographic Data ◽

First Episode ◽

Antipsychotic Treatment ◽

Intensity Score ◽

Symptom Intensity ◽

Neurobiological Substrates ◽

Drug Naïve ◽

First Episode Schizophrenia

Abstract Background The study of individual negative symptoms is encouraged as they may have separate neurobiological substrates and require specific therapeutic strategies. Blunted affect is a decrease in the observed expression of emotion and may be more fluctuant than expected. We aim to investigate early trajectories of blunted affect in first episode schizophrenia (FES) patients without previous antipsychotic-treatment. Methods We included 82 first episode psychosis antipsychotic naïve patients meeting the DSM-IV criteria for schizophrenia, schizoaffective or schizophreniform disorder. All participant started risperidone (1-4mg) after the first assessment. Socioeconomic and demographic data were collected at baseline. Positive and Negative Syndrome Scale (PANSS) was applied at both assessments. PANSS negative component item N1 was used to access blunted affect. Participants were divided into three groups for each assessment according to their N1 score: (i) absence of symptoms - score 1 or 2; (ii) Mild intensity - score 3 or 4; and (iii) Severe intensity - score 5 to 7. Results Mean age was 25.77 (sd: ±7.27) years-old and 61% were male. Mean total PANSS was 92.74 (sd: ± 22.37) at baseline and 65.54 (sd: ± 20.42) at follow up. Mean risperidone dose at follow up was 3.71 (± 1.51). Forty three (52%) study participants had persistence of blunted affect at 10-week follow up regardless of symptom intensity. Sixteen (19.5%) patients never displayed blunted affect. In fact, the most common trajectories include participants who persists with the same symptom severity (n=48). Symptoms improved in 17 participants and got worse in 17 as well. Only one participant started the study without symptom and evolved to high intensity at follow up, while no participant started the study with high severity symptoms and evolved to absence of symptoms. Discussion Our study suggests that blunted affect exhibit different trajectories, but its intensity tends to remain stable over short-term follow up. Blunted affect may be unresponsive to risperidone at the beginning of treatment. Most of the previous studies addressed trajectories of negative symptoms as a group. Only few addressed the progression of blunted affect and, to the best of our knowledge, this is the first to use a sample of drug-naïve FES patients. Also, we selected only participants in use of risperidone after first assessment in order to reduce bias. A sample of drug naïve FES patients brings opportunities like assessing the course of blunted affect at an early phase of the condition and reducing confounders such as chronicity and exposure to antipsychotics.

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