Higher Levels Of Negative Symptoms Research Articles

Adaptive coding of reward in schizophrenia, its change over time and relationship to apathy.

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears to be affected in different domains, especially in the reward domain. Here, we tested adaptive coding of reward in a large group of patients with schizophrenia (n = 86) and control subjects (n = 66). We assessed: (i) the association between adaptive coding deficits and symptoms; (ii) the longitudinal stability of deficits (the same task was performed 3 months apart); and (iii) the stability of results between two experimental sites. We used functional MRI and the monetary incentive delay task to assess adaptation of participants to two different reward ranges: a narrow range and a wide range. We used a region-of-interest analysis to evaluate adaptation within striatal and visual regions. Patients and control subjects underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, with a decreased slope in the narrow reward range with respect to that of control participants, in striatal but not visual regions. This pattern was observed at both research sites. Upon retesting, patients increased their narrow-range slopes, showing improved adaptive coding, whereas control subjects slightly reduced them. At retesting, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal an effect of practice in patients, leading to improvement, with steeper slopes upon retesting. However, in some patients, an excessively steep slope may result in poor discriminability of larger rewards, owing to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (retest, overadaptation) situations might contribute to the multiple motivational symptoms in schizophrenia.

Relationship between perceived coercion and perceived justification of coercive measures – secondary analysis of a randomized-controlled trial

BackgroundSubjective perception of coercion has gained attention as an important outcome. However, little is known about its relation to patients’ appraisal of the justification of coercive measures. The present study aims to analyze the relationship between patients’ appraisal of the justification of coercive measures and their level of perceived coercion.MethodsThis study presents a secondary analysis of the results of a multi-center RCT conducted to evaluate the effects of post-coercion review. Patients who experienced at least one coercive measure during their hospital stay were included in the trial. Participants’ appraisal of the justification of coercive measures was categorized into patient-related and staff-related justifications. Subjective coercion was assessed using the Coercion Experience Scale (CES) and used as dependent variable in a multivariate regression model.Results97 participants who completed the CES were included in the analysis. CES scores were significantly associated with the perception of the coercive measure as justified by staff-related factors (B = 0,540, p < 0,001), as well as with higher level of negative symptoms (B = 0,265, p = 0,011), and with mechanical restraint compared to seclusion (B=-0,343, p = 0,017).ConclusionsPatients’ perceptions of coercive measures as justified by staff-related factors such as arbitrariness or incompetence of staff are related to higher levels of perceived coercion. Multiprofessional efforts must be made to restrict the use of coercive measures and to ensure a transparent and sustainable decision-making process, particularly with patients showing high levels of negative symptoms. Such key elements should be part of all coercion reduction programs.

20-year trajectories of positive and negative symptoms after the first psychotic episode in patients with schizophrenia spectrum disorder: results from the OPUS study.

This study aimed to identify the 20-year trajectories of positive and negative symptoms after the first psychotic episode in a sample of patients with an ICD-10 diagnosis of schizophrenia spectrum disorder, and to investigate the baseline characteristics and long-term outcomes associated with these trajectories. A total of 373 participants in the OPUS trial were included in the study. Symptoms were assessed at baseline and after 1, 2, 5, 10 and 20 years using the Scales for the Assessment of Positive and Negative Symptoms. We used latent class growth mixture modelling to identify trajectories, and multinominal regression analyses to investigate predictors of membership to identified trajectories. Five trajectories of positive symptoms were identified: early continuous remission (50.9% of the sample), stable improvement (18.0%), intermittent symptoms (10.2%), relapse with moderate symptoms (11.9%), and continuous severe symptoms (9.1%). Substance use disorder (odds ratio, OR: 2.83, 95% CI: 1.09-7.38, p=0.033), longer duration of untreated psychosis (OR: 1.02, 95% CI: 1.00-1.03, p=0.007) and higher level of negative symptoms (OR: 1.60, 95% CI: 1.07-2.39, p=0.021) were predictors of the relapse with moderate symptoms trajectory, while only longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.030) predicted membership to the continuous severe symptoms trajectory. Two trajectories of negative symptoms were identified: symptom remission (51.0%) and continuous symptoms (49.0%). Predictors of the continuous symptoms trajectory were male sex (OR: 3.03, 95% CI: 1.48-6.02, p=0.002) and longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.034). Trajectories displaying continuous positive and negative symptoms were linked to lower neurocognition, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) (z-score: -0.78, CI: -1.39 to -0.17, for continuous positive symptoms; z-score: -0.33, CI: -0.53 to -0.13, for continuous negative symptoms). The same trajectories were also linked to higher use of antipsychotic medication at 20-year follow-up (continuous positive symptoms: 78%; continuous negative symptoms: 67%). These findings suggest that the majority of patients with first-episode schizophrenia spectrum disorder have a trajectory with early stable remission of positive symptoms. Long duration of untreated psychosis and comorbid substance abuse are modifiable predictors of poor trajectories for positive symptoms in these patients. In about half of patients, negative symptoms do not improve over time. These symptoms, in addition to being associated with poor social and neurocognitive functioning, may prevent patients from seeking help.

Schizophrenia and the COVID-19 pandemic: A narrative review from the biomedical perspective.

The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic in 2020 caused a rapid worsening of global mental health. Patients with severe mental disorders, including schizophrenia, are at higher risk of being infected. The neuroinvasive potential of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed. The aim of this article was to present a narrative and comprehensive review of multidimensional associations between schizophrenia and COVID-19 with special emphasis on common biological pathways. Online searches were performed in the PubMed database and covered the publication period until September 17, 2022. Search terms included "psychosis", "schizophrenia", "inflammation" and "COVID-19". Viewed as a neuroinflammatory state, schizophrenia shares several neurobiological mechanisms with the COVID-19. Environmental stress, common comorbidities of schizophrenia and adverse effects of antipsychotic treatment are associated with the higher severity and mortality of the COVID-19. Additionally, more frequent relapses of psychosis have been observed, and might be related to lower treatment adherence. In the context of clinical manifestation, higher level of negative symptoms has been identified among patients with schizophrenia during the pandemic. Improvements in mental health care policy and treatment adjustment are necessary to protect people with schizophrenia who are the population that is particularly vulnerable to the consequences of the COVID-19 pandemic. Future research will show if prenatal infection with the SARS-CoV-2 increases a risk of psychosis.

Primary and secondary negative symptoms severity and the use of psychiatric care resources in schizophrenia spectrum disorders: A 3-year follow-up longitudinal retrospective study

Negative symptoms represent one of the core features of schizophrenia spectrum disorders (SSD), strongly correlated with low remission rates, poor real-world functioning, and worse quality of life. Despite the body of evidence attesting the role of negative symptoms in determining worse outcomes in SSD, few studies have directly investigated their impact on the use of psychiatric services and even fewer research have examined the differential impact between primary versus secondary negative symptoms.The present study aims to investigate whether SSD subjects with high levels of primary and of secondary negative symptoms at an index hospitalization show a different use of psychiatric services in the subsequent 3 years. A total of 429 subjects were included in the study. Results show that SSD patients with high levels of negative symptoms are characterized by an overall greater use of high-cost resources, with more admissions in the hospital acute care psychiatric ward and in high intensity residential inpatient services. Moreover, while primary negative symptoms appear to play a role in determining a greater use of psychiatric services, high levels of secondary negative symptoms are associated with an increased use of most psychiatric resources, especially of high-cost ones.In conclusion, negative symptoms have a relevant impact on the pattern of psychiatric resources utilization in SSD patients. While scientific research continues to look for effective treatments for primary negative symptoms, clinicians should pay particular attention to secondary negative symptoms, as these also have important consequences but may benefit from appropriate treatment.

Evaluating how treatment adherence influences cognitive remediation outcomes

BackgroundThere is evidence that Cognitive Remediation (CR) is an efficacious approach to reduce cognitive and functioning difficulties in people with schizophrenia. However, there is still a limited understanding of what influences different treatment responses. Treatment adherence has been suggested as one factor but has not been investigated systematically. AimTo investigate how the number of CR sessions completed influences treatment outcomes. MethodThis study used data from six randomised controlled trials comparing CR to a control condition. Instrumental variable analysis was used to evaluate the effect of number of treatment sessions on cognitive and functional outcomes. Logistic regression analysis was conducted to identify significant predictors of session attendance. ResultsA total of 440 participants with schizophrenia spectrum diagnosis were considered. Participants were mostly men (71.6%) and had a mean age of 39.6 (SD 10.69). A higher number of CR sessions led to larger improvements in executive function and processing speed at end of therapy. However, number of sessions did not influence outcomes for working memory and functioning. Younger age and higher levels of negative symptoms at baseline were associated with higher treatment attendance. ConclusionThese findings highlight the importance of treatment adherence and underscore the importance of massed practice, at least for some cognitive outcomes. While it may be complex to assess a single session's contribution to outcome in a dose-response fashion, accessing more sessions seems associated with some cognitive benefits. Observing a relationship to functioning may require longer therapy.

The effects of catechol-O-methyltransferase single nucleotide polymorphisms on positive and negative symptoms of schizophrenia: A systematic review and meta-analysis.

The catechol-O-methyltransferase (COMT) gene is thought to have an important role in the etiopathogenesis of schizophrenia, but there are conflicting results regarding its role in clinical presentation. We aimed to elucidate the relationship between the single nucleotide polymorphisms (SNPs) in the COMT gene and the severity of positive and negative symptoms. In order to investigate the relationship, the PubMed, PubMed Central, Scopus, and Cochrane CENTRAL databases were screened for eligible articles. Thirty-eight studies, including 4443 adult patients with schizophrenia, were included in the quantitative analyses, and four studies were qualitatively assessed. Quantitative analyses were performed for acutely ill and clinically stable patient subgroups regarding the different genotypes of rs4680 SNP. Our results showed that the severity of negative symptoms was higher in patients who were rs4680 Met homozygous compared to Val/Met heterozygotes only in acutely ill samples. There was no other significant difference between genotypes. Meta-regression did not reveal any significant moderator effect on the difference in negative symptoms. General psychopathology, positive, negative, and total psychotic symptom levels also were similar between Val homozygotes and Met carriers. Nonetheless, there are some limitations in the study. First, SNPs except for rs4680 were under-researched because of the limited number of studies. Second, high heterogeneity across studies was the main concern. Our results suggested that the COMT rs4680 Met allele was associated with higher levels of negative symptoms within acutely ill patients. Future studies should focus on specific patient subgroups to reveal the moderating effects of SNPs.

Modifiable predictors of self-reported and performance-based functioning in individuals with schizophrenia-spectrum disorders and high levels of negative symptoms

Individuals with schizophrenia who have high negative symptoms are at high risk for poor functional outcomes. However, the determinants of psychosocial functioning in this group are not well understood. We aimed to examine modifiable predictors of both objective, performance-based functional capacity and social skills, and self-reported functioning in individuals with schizophrenia and schizoaffective disorder and high negative symptoms. Fifty-five adults with moderate-to-severe negative symptoms were administered measures of neuropsychological performance, performance-based functional capacity and social competence, self-reported functioning, psychiatric symptom severity, defeatist/asocial beliefs, and intrinsic motivation. In the context of multiple significant predictor variables identified through bivariate correlations, multiple regression models showed that neuropsychological performance was the only significant predictor of performance-based functional capacity; neuropsychological performance and motivation/pleasure negative symptoms were significant predictors of performance-based social competence. For two different measures of self-reported functioning, intrinsic motivation, asocial beliefs, and diminished expression emerged as significant predictors. Neurocognitive ability was a better predictor of performance-based functional skills whereas motivation and beliefs more strongly predicted self-reported real-world functioning. The findings of this study suggest a complex picture of predictors of performance-based functional capacity (objective neuropsychological functioning) and self-reported functioning (motivation and beliefs), underscoring the clinical and scientific utility of including both self-reported and objective measures of functioning to identify treatment approach. Individuals with high negative symptoms and a cognitive/functional skills deficit may benefit from interventions such as cognitive remediation or skills training, whereas individuals with motivational difficulties may benefit from treatments such as cognitive behavioral therapy.

Neural Abnormalities in Fear Generalization in Schizophrenia and Associations With Negative Symptoms

BackgroundAssociative learning and memory processes, including the generalization of previously learned associations, may be altered in schizophrenia. Deficits in schizophrenia in stimulus generalization, one of the simplest forms of memory, could interfere with the ability to efficiently categorize related, similar information, potentially leading to impairments in daily functioning. MethodsTo measure generalization in schizophrenia, 37 individuals with a nonaffective psychotic disorder and 32 demographically matched healthy control subjects underwent a Pavlovian fear conditioning and generalization procedure, which accounted for variation in perceptual ability across participants, while undergoing functional magnetic resonance imaging. Skin conductance and neural responses to conditioned (CS+), neutral (CS−), and generalization stimuli were measured. Explicit memory ratings reflecting successful generalization were also collected after the scanning, as well as measures of symptom severity. ResultsCompared with healthy control subjects, individuals with nonaffective psychotic disorders showed significant deficits in fear generalization across multiple measurements, with impairments in memory ratings and reductions in activation and deactivation of the salience and default networks, respectively, during fear generalization. Moreover, in the psychotic disorder group, greater behavioral and neural abnormalities in generalization were associated with higher levels of negative symptoms. ConclusionsFear generalization is impaired in psychotic illness. Given that successful generalization relies on a dynamic balance between excitatory and inhibitory neurotransmission, these results reveal a potentially quantifiable mechanism linked to negative symptoms that can be investigated further in future human and experimental animal studies.

BDNF affects the mediating effect of negative symptoms on the relationship between age of onset and cognition in patients with chronic schizophrenia

The age of onset of schizophrenia is related to variability in cognitive function and clinical characters, and negative symptoms and cognitive function share similar features that could be closely connected. Alterations in brain-derived neurotrophic factor (BDNF) expression and the Val66Met (rs6562) polymorphism are involved in the pathogenesis of the disease, but few studies have explored its influence on the associations of age of onset, cognitive function and clinical symptoms in schizophrenia. The clinical symptoms of a total of 573 patients with chronic schizophrenia were assessed by using the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The serum BDNF level and Val66Met polymorphism were measured after the assessment. Our results showed the following: (1) patients with an earlier age of onset exhibited more negative symptoms and cognitive deficits, as well as lower levels of serum BDNF; (2) negative symptoms and cognitive function showed negative and positive correlations with age of onset, respectively, and worse cognitive function was associated with a high level of negative symptoms and a low level of serum BDNF; and (3) the moderated mediation analyses indicated that negative symptoms partially mediated the relationship between age of onset and cognitive deficits, which was moderated by serum BDNF. The mediating effect of negative symptoms exhibited a Met allele dose-dependent tendency. These results indicate that age of onset, cognitive function, and clinical symptoms of schizophrenia exhibit different relationships under different serum BDNF levels and BDNF Val66met polymorphisms.

Клінічні особливості медикаментозного комплаєнса пацієнтів зі змішаною деменцією, ускладненою галюцинаторно-параноїдними розладами

У дослідженні взяли участь 72 пацієнти зі змішаною деменцією, ускладненою галюцинаторно-параноїдними розладами. В основну групу ввійшли 49 пацієнтів із частковим і неповним медичним комплаєнсом, у контрольну – 23 пацієнти з повним медичним комплаєнсом. У обстежених установлено особливості медикаментозного комплаєнса. Виявлено фактори, що впливають на зниження медичного комплаєнса: відмова / ухилення від прийому призначених лікарем ліків і процедур; негативне ставлення до препаратів, що приймають, та низька оцінка їхньої ефективності; відсутність або часткова критика хвороби та її проявів; коморбідність зі зловживанням алкоголю; низький рівень соціального функціонування та соціальної підтримки; низький рівень терапевтичного альянсу; високий рівень негативної симптоматики.

M148. NORMALIZATION IN REWARD PROCESSING DURING INITIAL TREATMENT MAY PREDICT LONG-TERM CLINICAL OUTCOME IN ANTIPSYCHOTIC NAïVE SCHIZOPHRENIA PATIENTS

BackgroundDecreased functional magnetic resonance (fMRI) signaling in ventral striatum during reward anticipation has been a consistent finding in unmedicated patients with schizophrenia. Antipsychotic medication may normalize this, which has been associated with improvement in psychotic symptoms. Whether this initial treatment response predict long term clinical outcome have not been examined previously. We here present unique data from a cohort of antipsychotic näive patients, who was examined before and after six weeks of antipsychotic monotherapy, and again after six years of naturalistic treatment. We hypothesized that improved reward related fMRI-signaling in striatum during initial treatment will be associated with less severe symptoms and a higher level of function after six years.MethodsAntipsychotic-naïve, first episode patients with schizophrenia and matched healthy controls were examined at three timepoints: Baseline, after six weeks and after six years. During the first six weeks, patients were treated with a D2/3 antagonist, after which they switched to a naturalistic clinical setting. At all three timepoints, fMRI was obtained while participants played a monetary rewarding game. Mean contrast signal during anticipation of salient events was extracted from predefined regions of interest in nucleus accumbens and caudatus. Additionally, symptom severity and level of function were assessed in patients. Remission after six years was defined by the Andreasen criteria.Long term changes in patients were analyzed with paired t-test. Repeated measures ANOVA was used to compare fMRI signal in patients and controls over time. Changes in fMRI signal during the first six weeks was compared between remitted and unremitted patients with students t-test. Correlations between symptom severity, level of function and fMRI signal up were analyzed with Spearman or Pearson as appropriate.ResultsLong term follow-up data on fMRI and psychopathology was obtained from 25 patients and 28 controls 6.7 (4.3–8.7) years after baseline examinations. In patients, symptomatology and level of function was improved (all p<0.001), and remission criteria was met by 12 (48%) of the patients.Repeated measures ANOVA of the extracted fMRI contrast signal at baseline and six years showed a group*time interaction in left Nucleus accumbens (F=4.8, p= 0.038) and left caudatus (F= 4.08, p=0=049). Mean contrast signal increased in patients but decreased in healthy controls.Change in contrast signal in left caudatus during the first six weeks of treatment differed between remitted and non-remitted patients (t=2.2, p=0.044). An increase in signal during initial treatment was found in patients later being in remission, which was not observed in non-remitted patients.Decreased fMRI contrast signal in left caudatus at six years follow up was associated with a higher level of negative symptoms (r=-0.44, p=0.02) and a lower level of function (r=0.45, p=0.02).DiscussionIn this long-term follow up study, half of the patients were in remission 4–8 years after their first schizophrenia diagnosis. These individuals were characterized by a normalization of reward anticipation signaling in left striatal regions during their initial treatment with a selective D2/3 antagonist. Schizophrenia is a diagnosis with a heterogeneous outcome, and prognostic biomarkers are still missing. The present results suggest that normalization in reward processing during initial antipsychotic treatment may predict remission six years later. Although these results need to be reproduced, they do support the notion, that patients responding to antipsychotic treatment are characterized by changes in striatal function, which may be predictive for long-term outcome.

S236. QUALITY OF LIFE AND ASSOCIATION WITH SYMPTOMS IN PATIENTS WITH SCHIZOPHRENIA SIX YEARS AFTER FIRST EPISODE PSYCHOSES

BackgroundQuality of Life in patients with schizophrenia is an important part of successful treatment outcome. Our previous results showed, that despite symptomatic improvement after six weeks of antipsychotic treatment, the overall Quality of Life was not improved.The aim of the present study is to explore Quality of Life after six years, and the association with symptomatic remission or symptoms in general.The following hypothesizes were tested: Quality of life will be improved after six years, and patients in remission will report a better Quality of Life compared to patients not in remission. Further, low Quality of Life will be associated with high level of negative symptoms.MethodsIn this study 69 antipsychotic drug-naïve, first episode patients with schizophrenia (ICD-10) were included between 2009–2013, and 31 patients where re-examined after 6.7 years (range 4.2–8.3).Quality of Life was reported by answering a validated questionnaire counting 18 questions, divided into three domains: Housing Situation, Social Relations and Life Satisfaction. Higher scores indicate higher satisfaction within the domain.Symptoms were assessed using Positive and Negative Syndrome Scale (PANSS) at baseline and follow up. Additionally, at follow up negative symptoms were assessed with Brief Negative Symptoms Scale (BNSS), focusing on three domains: Anhedonia, Asociality, and Avolition.For statistical analysis, Spearman Rank, paired T-test and Mann-Whitney U-test were used.ResultsThe overall Quality of Life was improved (p=0.013) after six years. The improvement was found in Housing Situation (p<0.001) and Social Relation (p<0.001) but not in Life Satisfaction (p=0.9)Symptomatic remission was observed in 15 (48%) patients. Quality of Life in patients in remission did not differ from patients without remission (p=0.16)Patients improved in PANSS total, positive, negative and general score (all p<0.001). A negative correlation was observed between Quality of Life (Social Relations) and PANSS-negative (r=-0.40, p<0.05), and PANSS-total score (r=-0.43 p<0.05), and between Quality of Life (Life Satisfaction) and PANSS-general (r=-0.53, p<0.01) and PANSS-total score(r=-0.44, p=0.05). There was no correlation between Quality of Life and positive symptoms.All three Quality of Life subdomains correlated with BNSS total (p<0.05, r<-0.42). This was driven by a high correlation with Anhedonia (all r<-0.55, all p<0.005) and Asociality (all r<-0.51, all p<0.005) but no correlation with Avolition.DiscussionPatients in this study improved their subjective Quality of Life over a six-year period. This improvement was found within their Social Relations and an improved Housing Situation. In contrast, there was no improvement in patients’ Life Satisfaction.Remission was found in half of the patients. Although Quality of life was associated with total symptom severity, it seemed to be independent of symptomatic remission. Quality of life was most associated with the level of negative symptoms, especially with Anhedonia and Asociality. This is in line with previous findings of associations between negative symptoms and the ability to maintain social relations and to function in everyday life. The results underline the importance of increased focus on negative symptoms.

Investigating Cognitive and Clinical Predictors of Real-Life Functioning, Functional Capacity, and Quality of Life in Individuals at Ultra-High Risk for Psychosis

Abstract A substantial proportion of individuals at ultra-high risk (UHR) for psychosis show long-term functional impairments, which may have profound consequences for the individual and society. Finding predictors of these functional impairments is critical to inform on the individual’s functional prognosis and potentially develop targeted interventions. This study used data from 91 UHR individuals participating in a randomized, clinical trial, that were followed up at 12 months, to elucidate on clinical, neuro- and social-cognitive predictors of UHR individuals’ functional outcome in the domains of social- and role functioning, quality of life, and functional capacity. The proportion of UHR individuals showing a poor social- and role outcome at 12-month follow-up was 50% and 63%, respectively. Worse social outcome was predicted by higher levels of negative symptoms, reduced processing speed, and impaired baseline social functioning explaining 52% of the variance. Worse role outcome was predicted by impaired role functioning at baseline, explaining 25% of the variance. Quality of life impairments were predicted by better theory of mind explaining 4% of the variance, and functional capacity social skills deficits were predicted by impaired baseline social skills explaining 20% of the variance. Our findings indicate that processing speed and negative symptoms may contribute to social- and role-functioning deficits, and while aspects of social cognition may also relate to social- and role functioning, baseline-functional impairments seem to be a strong contributor to persistent impairments in functioning and quality of life. If replicated, our findings suggest the need for future studies investigating the effect of pro-functional interventions targeting baseline functioning and targeted cognitive domains in UHR.

Lipid alterations in adolescents with early-onset psychosis may be independent of antipsychotic medication

BackgroundDyslipidemia and insulin resistance (HOMA-IR) are cardiovascular risk factors prevalent in patients with psychosis. Whether these factors are intrinsic or affected by lifestyle or antipsychotic medication (AP) is unclear. Therefore, we investigated lipid profiles, HOMA-IR, and psychotic phenotypes in patients aged 12–18 years with early-onset psychosis (EOP) with and without AP exposure. MethodWe measured fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG), insulin, and glucose in patients with EOP (n = 39) and healthy controls (HC) (n = 66). Diet information was not available. Negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). We used univariate analysis of variance to compare TC/HDL-C ratios and TG and HOMA-IR values, controlling for body mass index (BMI) and AP exposure. We assessed the explained variance of having EOP using multiple regression analysis. ResultsPatients with and without AP exposure had significantly higher TC/HDL-C (p = 0.003, p = 0.029) and TG values (p < 0.001, p = 0.021) than HC. Significantly increased HOMA-IR scores were found only in AP-exposed patients (p = 0.037). EOP significantly increased the explained variance for TC/HDL-C and TG, but not for HOMA-IR. Patients with a PANSS negative score > 21 had significantly higher levels of TG than those with low scores (p = 0.032). ConclusionOur results suggest that lipid alterations predate AP treatment in adolescents with EOP. Higher levels of negative symptoms and AP further increase metabolic risk. The preliminary findings propose that subclinical dyslipidemia may be intrinsic to EOP.

Deviation from expected cognitive ability is a core cognitive feature of schizophrenia related to neurophysiologic, clinical and psychosocial functioning

Cognitive functioning in schizophrenia is characterized by a generalized impairment in current cognitive ability based on traditional population-based norms. However, these norms assume a normal cognitive trajectory and do not directly account for illness-related declines from expected cognitive potential. Indeed, schizophrenia patients exhibit even greater deviation between their observed and expected cognitive functioning based on expanded norms that leverage premorbid variables resistant to illness-related features. The current study further quantified the extent to which illness-related features account for this deviation from expectation and assessed its relationship to neurophysiologic (mismatch negativity, P3a, theta oscillations), clinical, and psychosocial functioning in schizophrenia patients. Expected cognitive ability (PENN-CNB global cognition) in patients (n = 684) was calculated using healthy comparison subject (n = 660) weighted regression based on premorbid variables resistant to illness-related decline (demographics, single-word reading, parental education). The magnitude of any deviation between current (observed) and regression-predicted (expected) cognitive ability was calculated. Results indicated that 24% (n = 164) of the total patient population exhibited significant (≥-1.96 SD) deviation between observed and expected global cognitive ability. Interestingly, 20% of the total patient population (n = 136) had “normal” range cognitive performance when using traditional population-based norms, but also had significant deviation from expected cognitive ability. The magnitude of this deviation was associated with more severe neurophysiologic abnormalities, longer illness duration, higher levels of negative symptoms, and worse psychosocial functioning. Assessment of cognitive deviation is thus a complementary metric for characterizing the severity of illness-related cognitive declines in patients, while also reflecting the expression and severity of key endophenotypes of schizophrenia.

The impact of gender and childhood abuse on age of psychosis onset, psychopathology and needs for care in psychosis patients

Gender is associated with several features of psychotic disorders, including age of illness onset, symptomatology, a higher prevalence of history of childhood sexual abuse (CSA) and needs for care. Childhood sexual abuse is associated with adverse mental health consequences but as there is a gender difference in stress reactivity, there may be a differential impact of CSA on psychopathology, age of psychosis onset and needs for care in First Episode Psychosis (FEP) patients. We hypothesized that a history of abuse would be associated with lowering of age of onset, increased symptomatology and more unmet needs in women but not men. A total of 444 FEP patients have been recruited within the context of the GET UP trial. Symptomatology has been assessed using the PANSS scale, needs for care with the CAN scale and childhood abuse with the CECA-Q scale. Childhood sexual abuse was more frequent among female patients [22.6% in women vs 11.6% in men (OR = 0.45, p < 0.01)], whereas there was no gender difference in the prevalence of childhood physical abuse (29.0% in women vs 31.7% in men). Childhood abuse was associated with higher levels of negative symptoms in both men and women, with a reduced age of onset in women only and little increase in needs for care in both men and women. Our results seem to suggest that childhood sexual abuse in female FEP patients may be linked to a more severe form of psychosis whose presentation is characterized by earlier age of onset and higher levels of negative symptoms and we can also speculate that gender-specific protective factors in women, but not in men, may be outweighed by the consequences of childhood abuse.

S122. 3-YEAR NEGATIVE SYMPTOM TRAJECTORY AND ITS RELATIONSHIP WITH SYMPTOM AND FUNCTIONAL OUTCOMES IN FIRST-EPISODE NON-AFFECTIVE PSYCHOSIS: A PROSPECTIVE 13-YEAR FOLLOW-UP STUDY

BackgroundNegative symptoms are a core feature of schizophrenia and are a major determinant of functional impairment. Few studies have been conducted to examine patterns of longitudinal course of negative symptoms in the early stage of illness. Differential relationships of negative symptom trajectories with long-term clinical and functional outcomes remain to be clarified. This study aimed to investigate patterns of negative symptom trajectories over 3 years, utilizing latent class growth analysis (LCGA), in patients presenting with first-episode non-affective psychosis. Predictive capacity of symptom trajectories on 13-year functional and negative symptom outcomes was also examined.MethodsOne hundred thirty-six Chinese patients aged 18–55 years presenting with DSM-IV first-episode schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder or delusional disorder were assessed at clinical stabilization for first psychotic episode (baseline), 1, 2, 3 and 13 years of follow-up. Assessments encompassing premorbid adjustment, baseline symptom and cognitive profiles and functional levels were conducted. Negative symptoms were measured by High Royds Evaluation of Negativity (HEN) Scale. Individual class membership of negative symptoms derived from LCGA was based on HEN ratings at baseline, 1, 2 and 3-year follow-up.ResultsThree distinct negative symptom trajectories were identified including low-stable (59.6%, n=81), moderate-stable (29.4%, n=40) and high-increasing (11.0%, n=15) trajectories. Multinomial regression analysis revealed that poorer premorbid adjustment, lower baseline cognitive composite scores and more severe baseline depression predicted high-increasing trajectory membership (Nagelkerke pseudo R2=0.339, Model χ2=277.96, p<0.01). At 13 years, 88 patients (64.7%) completed follow-up assessment, with attrition analysis indicating lack of significant differences in demographic, premorbid and baseline characteristics between completers and non-completers. Analysis of covariance (controlling for premorbid adjustment, baseline cognition and depression) followed by post-hoc comparison analyses found that high-increasing trajectory was significantly associated with poorer global functional outcome and higher negative symptom levels at 13-year follow-up.DiscussionOur results indicate that 11% of first-episode non-affective psychosis patients displayed persistently high levels of negative symptoms with gradual symptom worsening over 3-year follow-up. This trajectory membership was predictive of poorer negative symptom and functional outcomes 13 years after presentation. High-increasing negative symptom trajectory identified in the initial 3 years of treatment for first-episode psychosis may represent a subgroup of patients having markedly elevated risk of developing deficit syndrome in the later course of illness.

T123. PERSISTENT NEGATIVE SYMPTOMS IN FIRST EPISODE PSYCHOSIS: PREVALENCE, PREDICTORS AND PROGNOSIS

BackgroundNegative symptoms are a core component of schizophrenia. These symptoms have been shown to impact on a range of outcomes, and often are resistant to pharmacological and psychosocial interventions treatment. The goal of this study was to investigate the prevalence, baseline predictors and long-term impact of persistent negative symptoms (PNS) within a large representative cohort of people with first episode psychosis.MethodsThe study had prospective design. Patients recruited into the OPUS trial (1998–2000) with a first time diagnosis within the schizophrenia spectrum (F20-28) were included. People were classified with persistent negative symptoms, if they experienced enduring negative symptoms that were not secondary to psychotic symptoms, depression or due to medication side effects. Clinical data collected at baseline, 1 year, 2 years and 10 years was used to identify predictors of PNS and long-term outcomes.ResultsFull clinical data was available on 369 people. A total of 90 people (24%) displayed PNS, two years after diagnosis. Significant univariable predictors of PNS at baseline were low functioning, male sex, cannabis use, poor pre-morbid social functioning and high levels of negative symptoms. People that displayed PNS had significantly lower functioning and higher levels of psychopathology at 10 year follow-up. A total 3% of people with PNS were recovered at 10 year follow-up compared to rate of 20% recovered without PNS (OR 7.42, p<0.01).DiscussionA significant proportion of the cohort displayed persistent negative symptoms and these symptoms significantly impacted on long-term outcomes. Researchers and clinicians need to continue to develop effective interventions that can ameliorate these symptoms and potentially impact on illness prognosis within schizophrenia.

Psychopathological Symptoms and Satisfaction with Mental Health in Patients with Schizophrenia

Background: The patient’s view of their mental health is a central aspect in research and practice. Yet, little is known about which psychopathological symptoms are linked with patients’ satisfaction with their mental health. We aimed to identify these symptoms in patients with schizophrenia. Methods: An individual patient data meta-analysis was conducted with data from 2,488 patients from 8 independent studies. Satisfaction with mental health was rated on a 7-point scale, and symptoms were observer-rated using identical items from the Brief Psychiatric Rating Scale and the Positive and Negative Symptom Scale. Mixed multilevel univariate followed by multivariate regression models were used to identify symptoms associated with satisfaction with mental health. Results: In univariate regressions, all subscales – not age and gender – were associated with mental health satisfaction. In the multivariate regression, only affective and negative symptoms were significantly associated with a lower satisfaction with mental health, explaining 22.5% of the variance. Conclusions: Observer-rated psychopathological symptoms are linked to patients’ mental health satisfaction. In addition to affective symptoms – which are commonly negatively linked with satisfaction ratings – a higher level of negative symptoms makes patients less satisfied with their mental health, whilst positive and other symptoms do not influence mental health satisfaction.