Greater Severity Of Negative Symptoms Research Articles

Network analysis of discrete emotional states measured via ecological momentary assessment in schizophrenia.

Prior studies demonstrate that schizophrenia (SZ) is associated with abnormalities in positive and negative emotional experience that predict clinical presentation. However, it is unclear whether specific discrete emotions within the broader positive/negative categories are driving those symptom associations. Further, it is also unclear whether specific emotions contribute to symptoms in isolation or via networks of emotional states that dynamically interact across time. The current study used network analysis to evaluate temporally dynamic interactions among discrete emotional states experienced in the real world as assessed via Ecological Momentary Assessment (EMA). Participants included 46 outpatients with chronic SZ and 52 demographically matched healthy controls (CN) who completed 6days of EMA that captured reports of emotional experience and symptoms derived from monetary surveys and geolocation based symptom markers of mobility and home location. Results indicated that less dense emotion networks were associated with greater severity of negative symptoms, whereas more dense emotion networks were associated with more severe positive symptoms and mania. Additionally, SZ evidenced greater centrality for shame, which was associated with greater severity of positive symptoms. These findings suggest that positive and negative symptoms are associated with distinct profiles of temporally dynamic and interactive emotion networks in SZ. Findings have implications for adapting psychosocial therapies to target specific discrete emotional states in the treatment of positive versus negative symptoms.

The deficit subtype of schizophrenia is associated with a pro-inflammatory phenotype but not with altered levels of zonulin: Findings from a case-control study

There is evidence that subclinical inflammation and increased gut permeability might be involved in the pathophysiology of schizophrenia. Less is known about these phenomena in patients with the deficit subtype of schizophrenia (D-SCZ) characterized by primary and enduring negative symptoms. Therefore, in the present study we aimed to compare the levels of zonulin (the marker of gut permeability) and immune-inflammatory markers in patients with D-SCZ, those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). A total of 119 outpatients with schizophrenia and 120 HCs were enrolled. The levels of 26 immune-inflammatory markers and zonulin were determined in serum samples. The following between-group differences were significant after adjustment for multiple testing and the effects of potential confounding factors: 1) higher levels of interleukin(IL)− 1β and C-reactive protein (CRP) in patients with D-SCZ compared to those with ND-SCZ and HCs; 2) higher levels of tumor necrosis factor-α and RANTES in both groups of patients with schizophrenia compared to HCs and 3) higher levels of IL-17 in patients with D-SCZ compared to HCs. No significant between-group differences in zonulin levels were found. Higher levels of IL-1β and CRP were associated with worse performance of attention after adjustment for age, education and chlorpromazine equivalents. Also, higher levels of IL-1β were correlated with greater severity of negative symptoms after adjustment for potential confounding factors. In conclusion, individuals with D-SCZ are more likely to show subclinical inflammation. However, findings from the present study do not support the hypothesis that this phenomenon is secondary to increased gut permeability.

A-172 Evaluating Associations Between the Five Negative Symptom Domains and Cognition in Schizophrenia

Abstract Objective: Recently, factor analysis has supported a five-factor model of negative symptoms in schizophrenia (anhedonia, avolition, alogia, asociality, and blunted affect). Associations between these unique negative symptom domains and neurocognition are yet to be examined. The following study investigates relationships between the five distinct negative symptoms and cognitive functioning. Methods: Outpatients diagnosed with schizophrenia (n=245) were assessed during periods of clinical stability for negative symptom severity using the Brief Negative Symptom Scale (BNSS). The MATRICS Consensus Cognitive Battery (MCCB) was used to assess seven domains of neurocognition, including processing speed, working memory, verbal learning, visual learning, reasoning, problem solving, and social cognition. To evaluate external correlates, the five-domain negative symptoms were correlated with measures of neurocognition. Results: Greater negative associations were found between the five negative symptom domains with processing speed, attention, working memory, social cognition, and overall MCCB scores. Correlational analyses demonstrated the strongest negative relationships between the domain of attention with alogia and blunted affect. Conclusions: The present study examined unique associations between cognitive abilities and the five negative symptom domains. Strong negative associations were found between negative symptoms and distinct measures of neurocognition, indicating a unique variance in cognitive performance correlates with severity of negative symptoms. Results suggest greater severity of negative symptoms is associated with greater impairments in select neurocognitive domains. Further research using analytic approaches would offer additional support for this hypothesis. Findings have implications for developing differential treatments targeting the five negative symptom domains separately, as they may have distinct underlying pathophysiological and neurocognitive mechanisms.

Pathoplastic effects of metabolic disorders in severe mental illness

IntroductionPatients with severe mental illness (SMI) have a higher risk of weight gain, dyslipidemia and insulin-resistance. It was observed that insulin resistance has a pathoplastic effect: in Schizophrenia it was associated with a greater severity of negative symptoms, whereas in Bipolar Disorder it was associated with more chronicity and rapid cycling. Moreover a correlation was observed between obesity and a worse outcome in Bipolar Disorder type I.ObjectivesWe aimed at assessing the influence of dysmetabolisms on clinical characteristics in patients with SMI.MethodsWe recruited 78 patients with SMI consecutively hospitalized in the Psychiatry Clinic of the Ospedali Riuniti of Ancona, Italy. We administered a checklist for socio-demographic and clinical features (diagnosis, age of onset, illness duration, number of episodes, number of episodes per year, suicidal attempts and comorbidities), and evaluated the following metabolic parameters: weight, height, BMI, abdominal circumference, blood pressure, total cholesterol, HDL, triglycerides, glycemia and insulinemia. We determined insulin-resistance according to the HOMA-IR model. We performed bivariate Pearson correlations to compare metabolic and socio-demographic/clinical parameters.ResultsThe analyses showed positive correlations between BMI and disease duration (P = 0.003), and BMI and the number of episodes (P = 0.022). Furthermore, a positive correlation was found between HOMA-IR and the number of episodes per year (P = 0.008). The associations remained statistically significant after controlling for age through partial correlations.ConclusionsWeight gain and insulin-resistance in severe mental illness are associated with a more severe SMI, as suggested by the greater number of acute episodes.DisclosureNo significant relationships.

Gender Differences in Clinical and Psychosocial Features Among Persons With Schizophrenia: A Mini Review

An extensive literature regarding gender differences relevant to several aspects of schizophrenia is nowadays available. It includes some robust findings as well as some inconsistencies. In the present review, we summarize the literature on gender differences in schizophrenia relevant to clinical and social outcome as well as their determinants, focusing on clinical variables, while gender differences on biological factors which may have an impact on the outcome of the disorder were not included herewith. Consistent findings include, in male with respect to female patients, an earlier age of illness onset limited to early- and middle-onset schizophrenia, a worse premorbid functioning, a greater severity of negative symptoms, a lower severity of affective symptoms and a higher rate of comorbid alcohol/substance abuse. Discrepant findings have been reported on gender differences in positive symptoms and in social and non-social cognition, as well as in functional outcome and rates of recovery. In fact, despite the overall finding of a more severe clinical picture in males, this does not seem to translate into a worse outcome. From the recent literature emerges that, although some findings on gender differences in schizophrenia are consistent, there are still aspects of clinical and functional outcome which need clarification by means of further studies taking into account several methodological issues.

Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci.

The study explored whether schizophrenia risk alleles of the DRD2 rs2514218 and ZNF804A rs1344706 polymorphisms also influenced the risk and severity of childhood-onset schizophrenia (COS) and differentiated it from autism spectrum disorders (ASD). We compared 75 children with COS to 75 children with ASD, 150 patients with adult-onset schizophrenia and 150 healthy individuals. Frequency of the DRD2 T-allele, assumed to be protective against schizophrenia overall, was higher in COS compared to adult-onset schizophrenia and healthy controls. The risk allele A of ZNF804A was associated with greater severity of negative symptoms in COS. The latter result is consistent with the involvement of ZNF804A in the development of severe forms of schizophrenia. The findings regarding DRD2 suggest that the same genetic variants may play different roles in schizophrenia with childhood and adult onset. This warrants further research, since D2 receptor blockade is a general pharmacodynamic property of antipsychotics.

Elevated emotion reactivity and emotion regulation in individuals at clinical high risk for developing psychosis and those diagnosed with a psychotic disorder.

Disrupted affective processes are core features of psychosis; yet emotion reactivity and emotion regulation impairments have not been fully characterized in individuals at clinical high-risk for developing psychosis (CHR) or adolescents diagnosed with a psychotic disorder (AOP). Characterizing these impairments may provide a fuller understanding of factors contributing to psychosis risk and psychosis onset. Using cross-sectional and longitudinal data, we evaluated (1) group-level effects of emotion reactivity and regulation, (2) stability of group-level effects over time and age, (3) relationships between emotion reactivity and regulation, and (4) associations between these measures and psychosocial functioning and clinical symptomatology. Eighty-seven participants (CHR=32, TD=42, AOP=13; 12-25 years, 1-5 visits) completed the Emotion Reactivity Scale, Difficulties in Emotion Regulation Scale, and Emotion Regulation Questionnaire. We assessed psychotic symptoms with the Structured Interview for Prodromal Syndromes and measured real-world functioning with the Global Functioning: Social and Role Scales. We used analysis of variance to assess Aim 1 and linear mixed models to address Aims 2-4. CHR and AOP endorsed experiencing heightened levels of emotion reactivity and greater difficulty utilizing emotion regulation strategies compared to TD. These impairments were stable across time and adolescent development. Greater levels of emotion reactivity were associated with greater emotion regulation impairments. Greater impairments in emotion regulation were associated with lower social functioning and greater negative symptom severity. Therapeutic interventions designed to reduce emotion reactivity and improve one's ability to utilize emotion regulation strategies may be effective in reducing clinical symptomatology and improving real-world functioning in CHR and AOP.

Reduced willingness to expend effort for rewards is associated with risk for conversion and negative symptom severity in youth at clinical high-risk for psychosis.

Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and predictive of conversion to illness. Mechanisms underlying negative symptoms are unclear in the CHR population. The current study evaluated whether CHR participants demonstrated deficits in the willingness to expend effort for rewards and whether these impairments are associated with negative symptoms and greater risk for conversion. Participants included 44 CHR participants and 32 healthy controls (CN) who completed the Effort Expenditure for Reward Task (EEfRT). Compared to CN, CHR participants displayed reduced likelihood of exerting high effort for high probability and magnitude rewards. Among CHR participants, reduced effort expenditure was associated with greater negative symptom severity and greater probability of conversion to a psychotic disorder on a cross-sectional risk calculator. Findings suggest that effort-cost computation is a marker of illness liability and a transphasic mechanism underlying negative symptoms in the SZ spectrum.

Reinforcement learning abnormalities in the attenuated psychosis syndrome and first episode psychosis

Prior studies indicate that chronic schizophrenia (SZ) is associated with a specific profile of reinforcement learning abnormalities. These impairments are characterized by: 1) reductions in learning rate, and 2) impaired Go learning and intact NoGo learning. Furthermore, each of these deficits are associated with greater severity of negative symptoms, consistent with theoretical perspectives positing that avolition and anhedonia are associated with impaired value representation. However, it is unclear whether these deficits extend to earlier phases of psychotic illness and when individuals are unmedicated. Two studies were conducted to examine reinforcement learning deficits in earlier phases of psychosis and in high risk patients. In study 1, participants included 35 participants with first episode psychosis (FEP) with limited antipsychotic medication exposure and 25 healthy controls (HC). Study 2 included 17 antipsychotic naïve individuals who were at clinical high-risk for psychosis (CHR) (i.e., attenuated psychosis syndrome) and 18 matched healthy controls (HC). In both studies, participants completed the Temporal Utility Integration Task, a measure of probabilistic reinforcement learning that contained Go and NoGo learning blocks. FEP displayed impaired Go and NoGo learning. In contrast, CHR did not display impairments in Go or NoGo learning. Impaired Go learning was not significantly associated with clinical outcomes in the CHR or FEP samples. Findings provide new evidence for areas of spared and impaired reinforcement learning in early phases of psychosis.

Clinical and pathopsychological features of youth depression with attenuated schizophrenic symptoms

To determine the clinical and pathopsychological features of youth depressions with attenuated schizophrenic symptoms (ASS), and their significance for early differential diagnostic and nosological assessment. Twenty young patients (19.7±3.7 years) with the first depressive episode with attenuated schizophrenic symptoms (ASS) (ICD-10 items F32.1, F32.2, F32.3) (basic group) were divided into subgroup 1 with attenuated positive symptoms - APS (19.3%) and subgroup 2 with attenuated negative symptoms - ANS (45.1%). Eleven young patients (19.4±2.9 years) with the classic depressive episode without ASS (ICD-10 items F32.1, F32.2) were included in a control group. Psychometric scales HDRS, SOPS, SANS, pathopsychological methods and Adult Personality Traits Questionnaire (APTQ) were used. Statistically significant differences in the severity of depression were not found. A higher SOPS total score (p=0.006) and a greater severity of negative symptoms on SANS (p=0.006) were detected in patients of clinical groups compared with the comparison group. Distortion of the generalization process was detected in 60% of cases, impairments of immediate memorization were found in 30%, and the non-constructive nature of associations in 10%. Indirect data on greater emotional integrity of patients from the comparison group was obtained. The presence of similar clinical and psychological abnormalities in the youth depressions with ASS allows us to attribute these phenomena to the possible risk factors for the development of schizophrenia.

Abnormal Effective Connectivity Underlying Auditory Mismatch Negativity Impairments in Schizophrenia

BackgroundAuditory mismatch negativity (MMN) is a translatable event-related potential biomarker, and its reduction in schizophrenia is associated with the severity of clinical symptoms. While MMN recorded at the scalp is generated by a distributed network of temporofrontal neural sources, the primary contributing sources and the dynamic interactions among sources underlying MMN impairments in schizophrenia have not been previously characterized. MethodsA novel data-driven analytic framework was applied to large cohorts of healthy comparison subjects (n = 449) and patients with schizophrenia (n = 589) to identify the independent contributing sources of MMN, characterize the patterns of effective connectivity underlying reduced MMN in patients, and explore the clinical significance of these abnormal source dynamics in schizophrenia. ResultsA network of 11 independent contributing sources underlying MMN distributed across temporofrontal cortices was identified. Orderly shifts in peak source activity were detected in a steplike manner, starting at temporal structures and progressing across frontal brain regions. MMN reduction in patients was predominantly associated with reduced contributions from 3 frontal midline sources: orbitofrontal, anterior cingulate, and middle cingulate cortices. Patients showed increased connectivity from temporal to prefrontal regions in conjunction with decreased cross-hemispheric connectivity to prefrontal regions. The decreased connectivity strength of precentral to prefrontal regions in patients with schizophrenia was associated with greater severity of negative symptoms. ConclusionsAlterations in the dynamic interactions among temporofrontal sources underlie MMN abnormalities in schizophrenia. These results advance our understanding of the neural substrates and temporal dynamics of normal and impaired information processing with novel applications for translatable biomarkers of neuropsychiatric disorders.

S79. REINFORCEMENT LEARNING ABNORMALITIES IN INDIVIDUALS AT CLINICAL HIGH RISK AND IN THE FIRST EPISODE OF PSYCHOSIS

BackgroundPrior studies indicate that chronic schizophrenia (SZ) is associated with a specific profile of reinforcement learning abnormalities. These impairments are characterized by: 1) reductions in learning rate, and 2) impaired Go learning and intact NoGo learning. Furthermore, each of these deficits are associated with greater severity of negative symptoms, consistent with theoretical perspectives positing that avolition and anhedonia are associated with deficits in generating, updating, and maintaining mental representations of reward value hat are needed to guide decision-making. However, it is unclear whether these deficits extend to earlier phases of psychotic illness and when individuals are unmedicated.MethodsTwo studies were conducted to examine reinforcement learning deficits in earlier phases of psychosis. In study 1, participants included 35 participants with first episode psychosis (FEP) and 25 healthy controls (HC). Study 2 included 17 antipsychotic naïve individuals who met criteria for attenuated psychosis syndrome (APS) (i.e., those with a prodromal syndrome) and 18 matched healthy controls (HC). In both studies, participants completed the Temporal Utility Integration Task, a measure of probabilistic reinforcement learning that contained Go and NoGo learning blocks. Participants in the clinical groups also completed neuropsychological testing and standard clinical interviews designed to determine symptom severity and diagnosis.ResultsFEP displayed impaired Go learning and intact NoGo learning. In contrast, APS did not display impairments in Go or NoGo learning at the group level. Negative symptoms were not significantly associated with reinforcement learning in APS participants. However, greater impairments in Go learning were associated with increased cross-sectional risk for conversion on the NAPLS risk calculator score in the APS group.DiscussionFindings provide new evidence for areas of spared and impaired reinforcement learning in early phases of psychosis. Similar to chronic SZ, FEP was associated with impaired Go learning, and intact NoGo learning. Reinforcement learning is more spared in those at clinical high-risk, except those at greatest risk for conversion, where Go learning deficits are more pronounced. These findings suggest that reinforcement learning deficits may emerge early among those who are at clinical high risk for developing psychosis and that they are already pronounced by illness onset in the first episode. Importantly, these reinforcement learning deficits do not appear to be a byproduct of illness chronicity or antipsychotic medication use, but rather a consequence of the illness itself.

Actigraphy studies and clinical and biobehavioural correlates in schizophrenia: a systematic review.

Actigraphy is a non-invasive method of monitoring circadian rhythms and motor activity. We systematically reviewed extant evidence until September 2018 pertaining to actigraphy use in schizophrenia, its clinical/biological correlates and posit future research directions. Within 38 included studies involving 2700 subjects, patients with schizophrenia generally have lower motor activity levels, poorer sleep quality and efficiency, increased sleep fragmentation and duration compared with healthy controls. Lowered motor activity and longer sleep duration in patients were associated with greater severity of negative symptoms. Less structured motor activity and decreased sleep quality were associated with greater severity of positive symptoms, worse cognitive functioning involving attention and processing speed, illness chronicity, higher antipsychotic dose, and poorer quality of life. Correlations of actigraphic measures with biological factors are sparse with inconclusive results. Future studies with larger sample sets may adopt a multimodal, longitudinal approach which examines both motor and sleep activity, triangulates clinical, actigraphic and biological measures to clarify their inter-relationships and inform risk prediction of illness onset, course, and treatment response over time.

Is It Possible to Predict the Future in First-Episode Psychosis?

The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features—like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis—are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognostic markers in FEP. Combination of different markers in ML models with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.

Sex differences in hedonic judgement of odors in schizophrenia cases and healthy controls

The neurocircuitries subserving affective and olfactory processes overlap, are sexually dimorphic, and show disruptions in schizophrenia, suggesting their intersection may be a window on the core process producing psychosis. This study investigated diagnostic and sex differences in hedonic judgments of odors and smell identification in 26 schizophrenia cases and 27 healthy controls. Associations between olfaction measures and psychiatric symptoms were also examined. Cases and controls had similar identification accuracy of unpleasant odors, but cases were significantly less accurate in naming pleasant odors. In cases, greater negative symptom severity was related to abnormal hedonic judgments; specifically, higher pleasantness ratings for unpleasant odors and higher unpleasantness ratings for pleasant odors. Greater positive symptom severity was associated with lower pleasantness ratings for neutral odors. Regarding sex differences, male cases and female controls rated pleasant odors as significantly more unpleasant than male controls. Correlations between depression severity and pleasantness ratings of neutral odors were in opposite directions in male and female cases. These results suggest that a normal sexual dimorphism in the circuitry for hedonic odor judgments may interact with schizophrenia pathology, supporting the utility of olfactory hedonics as a sex-specific biomarker of this pathology.

T17. OXIDATIVE STRESS BIOMARKERS AND NEGATIVE DIMENSION IN THE FIRST TEN YEARS OF SCHIZOPHRENIA: A 1-YEAR FOLLOW-UP STUDY

BackgroundSeveral studies have documented changes in oxidative parameters and antioxidant enzymes in patients with schizophrenia (1, 2). However, their relation to negative symptoms and the longitudinal clinical course is still unclear.The objectives of the present study are to: 1) analyze the association between oxidative stress biomarkers and negative dimension; 2) identify if these biomarkers could predict clinical outcomes in stable patients with schizophrenia at 1-year follow-up.MethodsA 1-year follow-up study of 57 stable outpatients with schizophrenia (≤10 years of illness) (mean age=31.5 ± 6.5; 63.2% males).AssessmentPANSS, Clinical Assessment Interview of Negative Symptoms (CAINS) -Motivation/Pleasure (MAP) & Expression (EXP) domains-, Brief Negative Symptom Scale (BNSS). Oxidative stress biomarkers: homocysteine, hemolysis test (% hemolysis), lipid peroxidation subproducts (LPO), catalase activity in erythrocytes (CAT).Pearson correlations were performed to determine associations between biomarkers and clinical scores at baseline, and they were included in stepwise multiple linear regression analyses, considering potential confounding factors.The clinical course for each psychopathological domain was determined using the formula: [follow-up-baseline scores]. Positive values were interpreted as worsening, while negative improvement. Pearson correlation and multiple linear regression analyses were performed to determine if baseline levels of oxidative stress parameters were predictors of clinical changes at follow-up.Results1) Baseline associations: Final regression models identified that LPO level was a significant predictor of lower scores in PANSS-N, BNSS total, Avolition and Blunted Affect subscale of BNSS and CAINS-EXP (β= -0.408; -0.290, -0.254, -0.296, -0.247, respectively).2) Longitudinal course: At 1-year follow-up, patients only improved significantly (p<0.05) in PANSS-Total [59.4 ± 16.4 - 54.5 ± 16.0 (t=3.362)], PANSS-General [29.7 ± 8.9 - 26.9 ± 7.9 (t=3.362)], Blunted Affect subscale [6.9 ± 5.0 - 5.9 ± 4.7 (t=2.489)], and almost significant (p<0.069) in CAINS-EXP and BNSS total score. No significant changes in BMI, waist circumference, smoking or antipsychotic equivalent doses were detected, but they were also considered in regression analyses. A higher percentage of hemolysis at baseline, with a decrease in equivalent doses of antipsychotics, both significantly predict an improvement in scores of PANSS-N (R2=0.140, F=7.166), BNSS (R2=0.246, F=6.193) and CAINS-EXP (R2=0.186, F=5.259).DiscussionLower concentrations of LPO were related to greater severity of negative symptoms as avolition and blunted affect (inner world). Longitudinal analyses showed that higher % of hemolysis at baseline predict an improvement of negative dimension at 1-year follow-up. From our results, we hypothesize that there is an inverse relationship between oxidative stress and negative dimension in stable patients with schizophrenia during the first ten years of illness.

Characterization of different subtypes of schizophrenia: Premorbid functioning, neurophysiological differences, functional outcomes

Introduction Although not included in current diagnostic systems, deficit versus non-deficit and resistant versus non-resistant schizophrenia subtypes look more promising than traditional schizophrenia subtypes in terms of stability across time, clinical utility and interest for research. Aims To critically analyze evidence supporting the validity of two schizophrenia subtypes: Deficit Schizophrenia (DS) and Treatment Resistant Schizophrenia (TRS). Methods Empirical data supporting the validity of DS and TRS subtypes will be critically reviewed. Results DS, in comparison with non-deficit schizophrenia, is characterized by poorer premorbid functioning, more insidious onset, lower prevalence of dysphoria, hostility, suicidal ideation, depressive symptoms and substance abuse, different neurobiological abnormalities, and poorer response to treatment. The diagnosis of DS shows high reliability and stability across time. However, research based on this approach has proven difficult, especially in first-episode schizophrenia, and findings have not been as homogeneous as expected. TRS patients, as compared to non-TRS ones, show persisting psychotic symptoms, greater severity of negative symptoms, more severe cognitive dysfunctions, poorer premorbid functioning, longer duration of untreated psychosis, more frequent co-morbidity with personality disorders, earlier illness onset and poorer social functioning. Conclusions Future research should consider a) refining diagnostic criteria for DS and identifying valid DS endophenotypes; b) dissecting TRS based on psychopathological characteristics (e.g. presence of primary and persistent negative symptoms or persistently severe positive symptoms), and underlying neurobiological mechanisms (e.g. dopamine synthesis capacity and glutamatergic transmission).

Diabetes Knowledge Among Adults with Serious Mental Illness and Comorbid Diabetes Mellitus

This study examined the association between psychiatric symptoms and diabetes knowledge (DK) among 90 adults with serious mental illness (SMI) and type 2 diabetes. The relationship between DK and glucose control (i.e., A1C) was also examined. In a hierarchical linear regression, greater negative symptom severity and lower cognitive functioning both predicted lower DK, though cognitive functioning superseded negative symptom severity when analyzed simultaneously. A Pearson correlation showed no significant relationship between DK and A1C. Although symptom severity and cognitive functioning are both related to DK among this population, cognitive functioning maybe particularly important.

Psychopathological characteristics and social functioning of the schizophrenic patients with the T allele of the MTHFR677C>T polymorphism

To compare the severity of psychopathological symptoms and characteristics of personal and social functioning in patients with schizophrenia, carriers of different alleles of the MTHFR677C>T polymorphism. One hundred and fifty patients diagnosed with schizophrenia were genotyped for the MTHFR677C>T polymorphism, some of them were examined using psychometric scales and tests (PANSS, SANS, PSP, CDSS, a battery of cognitive tests etc). Patients with the MTHFR677T variant had greater severity of negative symptoms regardless of psychometric instruments used in the study, greater severity of schizophrenia disorder in whole measured with the PANSS General psychopathological symptoms subscale, higher scores on the PANSS cognitive cluster and lower levels of personal and social functioning measured with the PSP compared to the patients with the MTHFR677CС genotype. The results of psychometric testing are in line with significant differences of MTHFR677T allele carriers from those with the MTHFR677CС genotype in the number of disable patients and the use of different types of psychiatric services. The differences were not related to sex, age, illness duration and depressive symptoms measured with CDSS and PANSS «depression/anxiety» factor.

Cross diagnostic comparisons of quality of life deficits in remitted and unremitted patients with schizophrenia and bipolar disorder

BackgroundPatients with schizophrenia (SCZ) and bipolar disorder (BD) have been found to report lower quality of life (QOL) compared to healthy controls separately. However, data are wanting on cross diagnostic comparisons of QOL within psychotic spectrum conditions. This study examined QOL differences and clinical predictors between schizophrenia (SCZ) and bipolar disorder (BD). Based on extant data, we hypothesized that patients with remitted SCZ and BD had comparable QOL levels, and that more severe symptoms and poorer psychosocial functioning predicted poorer QOL in our patients. MethodsTwo hundred and twenty-two sex and age-matched subjects (44 BD, 122 SCZ, 56 healthy controls) were assessed on their QOL, psychosocial functioning, symptomatology, and state of remission. ResultsOverall, SCZ patients had worse QOL in the environment domain (p=0.008) and overall QOL (p=0.007) compared with BD patients. Both patient groups in remission had similar QOL, while unremitted SCZ patients reported poorer QOL in all domains compared to unremitted BD patients (p<0.01). Within patients, greater severity of negative symptoms and poorer psychosocial functioning were associated with poorer QOL (p<0.05). DiscussionRemission status affected QOL in both patient groups. The association of worse QOL with greater negative psychotic psychopathology and poorer psychosocial functioning highlighted potential clinical markers of QOL, which can aid in the management of psychotic spectrum disorders.