Symptoms Of Schizophrenia Spectrum Disorders Research Articles

Antipsychotic Drugs and Cognitive Function

Cognitive deficits are a substantial part of the symptoms of schizophrenia spectrum disorders (SSDs) and contribute heavily to the burden of disease. Antipsychotic drugs are not cognitive enhancers, but due to their different receptor-binding profiles, they could differ in their effects on cognition. No previous network meta-analysis compared antipsychotics to placebo, which is important to determine whether use of these drugs is associated with cognitive performance in SSDs at all. To determine the association of treatment with various antipsychotics and cognition in patients with SSDs. Cochrane Schizophrenia Trials Register through June 25, 2023. Randomized clinical trials examining the effects on cognition of antipsychotic drugs or placebo in participants with SSD. A systematic review and random-effects frequentist network meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses-Network Meta-analysis reporting guideline. The primary outcome was change in overall cognition score calculated for each study. Secondary outcomes included cognitive domains, quality of life, and functioning. This study included 68 studies involving 9525 participants (mean [SD] age, 35.1 [8.9] years; 5878 male [70%] and 2890 [30%] female; some studies did not provide this information). There were few clear differences between antipsychotics, but first-generation dopamine antagonists haloperidol (standardized mean difference [SMD], 0.04; 95% CI, -0.25 to 0.33) and fluphenazine (SMD, 0.15; 95% CI, -0.39 to 0.69) as well as clozapine (SMD, 0.12; 95% CI, -0.23 to 0.48) ranked low. No individual antipsychotic was associated with a clearly better outcome than placebo, but antipsychotics as a group were, with small effect sizes (mean SMDs: adrenergic/low dopamine, 0.21; serotonergic/dopaminergic, 0.26; muscarinic, 0.28; dopaminergic, 0.40). Although data are relatively sparse, those reviewed in this study suggest that first-generation dopamine antagonists and clozapine should be avoided when cognitive deficits are a concern. Antipsychotics are not procognitive drugs. The overall small superior outcomes compared to placebo may be explained by less disordered thought patterns associated with fewer positive symptoms rather than cognitive deficits in the proper sense. The findings also suggest that harmonizing measurement of cognitive function in randomized clinical trials would be beneficial.

Neural Circuitry and Therapeutic Targeting of Depressive Symptoms in Schizophrenia Spectrum Disorders.

Conceptual similarities between depressive and negative symptoms complicate biomarker and intervention development. This study employed a data-driven approach to delineate the neural circuitry underlying depressive and negative symptoms in schizophrenia spectrum disorders (SSDs). Data from three studies were analyzed (157 participants with SSDs) to assess brain-behavior relationships: two neuroimaging studies and a randomized trial of repetitive transcranial magnetic stimulation (rTMS). Partial least squares correlation (PLSC) was used to investigate associations between resting-state functional connectivity and depressive and negative symptoms. Secondary analyses of rTMS trial data (active, N=37; sham, N=33) were used to assess relationships between PLSC-derived symptom profiles and treatment outcomes. PLSC identified three latent variables (LVs) relating functional brain circuitry with symptom profiles. LV1 related a general depressive symptom factor with positive associations between and within the default mode network (DMN), the frontoparietal network (FPN), and the cingulo-opercular network (CON). LV2 related negative symptoms (no depressive symptoms) via negative associations, especially between the FPN and the CON, but also between the DMN and the FPN and the CON. LV3 related a guilt and early wakening depression factor via negative rather than positive associations with the DMN, FPN, and CON. The secondary visual network had a positive association with general depressive symptoms and negative associations with guilt and negative symptoms. Active (but not sham) rTMS applied bilaterally to the dorsolateral prefrontal cortex (DLPFC) reduced general depressive but not guilt-related or negative symptoms. The results clearly differentiate the neural circuitry underlying depressive and negative symptoms, and segregated across the two-factor structure of depression in SSDs. These findings support divergent neurobiological pathways of depressive symptoms and negative symptoms in people with SSDs. As treatment options are currently limited, bilateral rTMS to the DLPFC is worth exploring further for general depressive symptoms in people with SSDs.

Strategies for Achieving Better Cognitive Health in Individuals with Schizophrenia Spectrum: A Focus on the Canadian Landscape: Stratégies pour atteindre une meilleure santé cognitive chez les personnes souffrant du spectre de la schizophrénie : un regard sur le paysage canadien.

Schizophrenia spectrum disorders (SSDs) are a group of psychiatric disorders characterized by positive and negative symptoms as well as cognitive impairment that can significantly affect daily functioning. We reviewed evidence-based strategies for improving cognitive function in patients with SSDs, focusing on the Canadian landscape. Although antipsychotic medications can address the positive symptoms of SSDs, cognitive symptoms often persist, causing functional impairment and reduced quality of life. Moreover, cognitive function in patients with SSDs is infrequently assessed in clinical practice, and evidence-based recommendations for addressing cognitive impairment in people living with schizophrenia are limited. While cognitive remediation (CR) can improve several domains of cognitive function, most individuals with SSDs are currently not offered such an intervention. While the development of implementation strategies for CR is underway, available and emerging pharmacological treatments may help overcome the limited capacity for psychosocial approaches. Furthermore, combining pharmacological with non-pharmacological interventions may improve outcomes compared to pharmacotherapy or CR alone. This review highlights the challenges and discusses the potential solutions related to the assessment and management of cognitive impairment to help mental health-care practitioners better manage cognitive impairment and improve daily functioning in individuals with SSDs.

Overlap between individual differences in cognition and symptoms of schizophrenia

BackgroundNeurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified. Study designWe used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). ResultsWe found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment. ConclusionsThe iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.

Placebo effects of repetitive transcranial magnetic stimulation on negative symptoms and cognition in patients with schizophrenia spectrum disorders: a systematic review and meta-analysis.

Negative symptoms and cognitive impairments are highly frequent in schizophrenia spectrum disorders (SSD), associated with adverse functional outcomes and quality of life. Repetitive transcranial magnetic stimulation (rTMS) has been considered a promising therapeutic option in SSD. However, placebo effects of rTMS on these symptoms remained unclear. To investigate placebo effects of rTMS on alleviating negative symptoms and cognitive impairment in patients with SSD and to explore potential moderators. We systematically searched five electronic databases up to 15 July 2023. Randomized, double-blind, sham-controlled trials investigating effects of rTMS on negative symptoms or cognition in patients with SSD were included. The pooled placebo effect sizes, represented by Hedges' g, were estimated using the random-effects model. Potential moderators were explored through subgroup analysis and meta-regression. Forty-four randomized controlled trials with 961 patients (mean age 37.53 years; 28.1% female) in the sham group were included. Significant low-to-moderate pooled placebo effect sizes were observed for negative symptoms (g=0.44, p<0.001), memory (g=0.31, p=0.010), executive function (g=0.35, p<0.001), working memory (g=0.26, p=0.004), and processing speed (g=0.36, p=0.004). Subgroup analysis indicated that placebo effects were affected by sham stimulation methods, rTMS targeting approaches, and stimulation frequency. Placebo effects of rTMS on negative symptoms and cognition in patients with SSD are significant in a small-to-moderate magnitude, which might be mediated by rTMS parameters. Our findings will provide new insights for practitioners to further optimize and establish standardized rTMS protocols for future RCTs tackling cardinal symptoms in SSD. https://www.crd.york.ac.uk/prospero/, identifier CRD42023390138.

Schizo - obsessive disorder - separate clinical entity or elusive comorbidity? - a systematic review

IntroductionIn some clinical scenarios obsessive and delusive symptoms exhibit several similarities, making it challenging to differentiate between schizophrenia spectrum disorder (SSD) and obsessive-compulsive disorder (OCD). There are numerous reports of patients suffering from those disorders and manifesting both psychotic and obsession-like features, which makes accurate distinction even more complicated. We found several conflicting theories attempting to elucidate this overlap, one being the existence of the separate clinical entity - schizo-obsessive disorder.ObjectivesThe aim of this study is to consolidate current knowledge, synthesize existing theories and explore diagnostic implications.MethodsWe conducted a systematic literature review following the PRISMA protocol, we scrutinized studies addressing obsession-like symptoms in SSD, psychotic symptoms in OCD, and comorbidity of those disorders. We included peer-reviewed non-interventional studies published in English and Polish from 2013 onwards. The search was performed in the following medical databases: PubMed, Science Direct, Scopus, and Web of Science. Synthesis utilized a narrative approach due to diverse study designs, outcomes and observational nature of the collected data.ResultsWe identified several dozen articles, which revealed a range of diverse findings, often inconclusive, and occasionally conflicting, Although, the collected data indicate the schizo-obsessive spectrum exhibits clinical relevance.ConclusionsThe ambiguity in results emphasizes the necessity for further investigations into pathomechanism of schizophrenia and OCD. Future research, particularly involving children and adolescents, should strive for a comprehensive understanding of the nuanced manifestations of obsessive-like and psychotic symptoms in both disorders, aiding in refining diagnostic criteria and developing effective intervention strategies.Disclosure of InterestNone Declared

Methods and models for investigating anomalous experiences in schizophrenia spectrum disorders

ABSTRACT The self-disorder model provides a phenomenological framework for understanding how the core symptoms of Schizophrenia Spectrum Disorders (SSDs) are rooted in an instability of minimal selfhood. This instability involves a range of “anomalous experiences”: transformations in an individual’s perceptual field and sense of being an agent of action. The explanatory value of this theoretical model can be summarized in two claims about the role of anomalous experiences in self-disorders: (1) anomalous experiences express a common trait-like disturbance that is characteristic of SSDs, and (2) anomalous experiences contribute to explanations regarding how self-disorders progress into SSDs. While hypotheses consistent with the first claim have been substantiated in several studies, hypotheses consistent with the second claim remain underexamined. We argue that attending to this gap in the literature requires considering which methodological strategies are best suited for investigating if and how anomalous experiences contribute to the development of self-disorders into SSDs and psychotic states. Network modeling is discussed as one such strategy suitable for examining the role of anomalies of lived-world in the maintenance of paranoid delusions in SSDs.

The combination of oxytocin and mindfulness-based group therapy for empathy and negative symptoms in schizophrenia spectrum disorders – A double-blinded, randomized, placebo-controlled pilot study

Treatment options for social cognition and negative symptoms in schizophrenia spectrum disorders (SSD) remain limited. Oxytocin could be a promising augmentation approach, but the social context influences the effect in humans. This pilot study hypothesized that oxytocin in a positive social setting through mindfulness-based group therapy (MBGT) would positively affect empathy and negative symptoms as well as affect and stress in an exploratory approach in SSD. An experimental, randomized, double-blinded (participants, psychotherapists), placebo-controlled pilot study with 41 individuals with SSD was conducted at the Charité – Universitätsmedizin Berlin. Oxytocin or placebo (24 I.U.) was administered intranasally 45 min before two sessions of MBGT each. A 2 × 2 mixed model ANCOVA design was calculated to assess empathy by the Interpersonal Reactivity Index and the Multifaceted Empathy Test and negative symptoms by the Self-Evaluation of Negative Symptoms. No benefit of oxytocin compared to placebo on empathy was observed, but significant between-group differences favoring oxytocin were found regarding the negative symptoms Diminished emotional range and Avolition. Negative affect and stress were significantly reduced compared to baseline. Mindfulness increased in both groups. Results indicated protocol adherence and retention rate of 91.1%, a drop-out rate of 8.9 % and a completion of 96 % of all sessions by the participants. No severe adverse events or side effects were reported. Our findings indicate proof-of-concept and suggest a potential role of oxytocin on negative symptoms and related variables in SSD in combination with MBGT. Future research should examine the stability of these effects with larger sample sizes.

A Conceptual Analysis of Post-psychotic Depression

"The conundrum of post-psychotic depression (PPD) is still present in the psychiatric literature, for more than a century since it was first described by Mayer-Gross. After a short existence in the DSM-IV and ICD-10, this nosological construct was excluded from newer versions of the mental disorders classifications. Therefore, an exploratory analysis of the PPD concept was considered useful both from clinical and theoretical perspectives. There is a high prevalence of depressive symptoms in patients with schizophrenia spectrum disorders (SSD) and, although not all of them represent cases of PPD, they are considered risk factors for suicide. The arguments and contra-arguments for/against PPD were reviewed, and the potential pharmacological interventions for this disorder were analyzed. The explored evidence indicates that PPD is worth further investigation, and in order to differentiate it from schizoaffective disorder, negative symptoms of SSD, or depressive manifestations within the acute psychotic episodes, clearly defined criteria should be found. The use of validated scales, like the Calgary Depression Scale for Schizophrenia and the InterSePT Scale for Suicidal Thinking, is recommended for the initial assessment of depression and suicidal risk in patients with SSD, but also for their monitoring during the acute and maintenance phases. Besides the administration of combined, antidepressant and antipsychotic treatment, the use of clozapine, and the recommendation to initiate treatment for SSD with atypical antipsychotics whenever possible, there is a dearth of studies exploring specific interventions for PPD. Future studies are expected to address the validity of the nosological construct of PPD and the most adequate therapeutic and prophylactic interventions in patients with SSD."

Do deficits in subjective stress recovery predict subsequent stress sensitivity and symptoms in schizophrenia spectrum disorders?

High levels of stress play a crucial role in the development of psychotic symptoms, such as paranoia, and may stem in part from recovery deficits after stress exposure. However, it remains unclear whether deficient recovery causes a build-up of heightened stress levels that increases stress sensitivity and symptoms when exposed to another stressor. To test this, we investigated the effect of subjective stress recovery on the response to a subsequent stressor and paranoia.We applied two consecutive runs of the same combined physical and cognitive stressor separated by a recovery phase of 60 min in individuals with schizophrenia spectrum disorders (n = 49). We repeatedly assessed self-reported stress, negative affect, heart rate, heart rate variability, salivary cortisol, and paranoia. Recovery of self-reported stress was defined as the geometric mean of the percentage changes of self-reported stress during recovery after the first stressor, and was regressed on the response to the second stressor controlling for self-reported stress during the first stressor.Lower subjective stress recovery predicted higher levels of self-reported stress, negative affect, and paranoia in response to the second stressor. The subjective stress recovery was not predictive of the physiological stress response (heart rate, heart rate variability, or salivary cortisol).Taken together, the findings indicate that recovery deficits could contribute to high levels of self-reported stress, negative affect, and paranoia in schizophrenia spectrum disorders and that the improvement of stress recovery could be a promising approach for interventions.

The relationship between sleep and suicidality in schizophrenia spectrum and other psychotic disorders: A systematic review.

Individuals with Schizophrenia Spectrum Disorders (SSDs) have significantly higher rates of suicidal thoughts, attempts, and death by suicide in comparison to the general population. Sleep disturbances (reduced duration, timing and quality of sleep) are risk factors for suicidality in the general population, with research indicating the relationship is both immediate and accumulative. Sleep disturbances are also considered to be implicated in the onset and exacerbation of psychotic symptoms in SSDs. Reducing the risk of suicidality in SSDs remains an important public health priority, thus exploration of contributing risk factors is warranted. Sleep monitoring may also offer an adjunct risk monitoring method to suicidality assessments in SSDs, and a potential treatment target for psychotic symptoms. This review aimed to explore proximal and longitudinal relationships between self-reported and objectively measured sleep and suicidality in SSDs and other psychotic disorders. A comprehensive search of four databases was conducted. Eleven studies met the inclusion criteria (10 cross sectional and 1 longitudinal). Narrative synthesis indicated that self-reported sleep disturbances and sleep disorders (e.g. insomnia) were associated with increased risk of suicidal ideation and attempt. However, one study employing polysomnography did not find sleep to be associated with suicidality. Methodological limitations of the evidence base include: i) little experimental or longitudinal evidence, (ii) self-report and/or single item assessment of sleep disturbance, (iii) limited use of validated measures of suicidality, (iv) considerable research in long-term schizophrenia but sparse evidence in early psychosis. Future research should explore (i) cross-sectional and longitudinal relationships between specific aspects of suicidality and objective sleep parameters, (ii) use qualitative or mixed-methods designs to disentangle the nuances and bidirectionality in the sleep-suicide relationship, (iii) explore the psychological processes underpinning or mediating the sleep-suicide relationship in SSDs.

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals

The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD=0.34, 95% Confidence Interval, CI=[0.03; 0.66]; 5-factor: aMD=0.38, 95% CI=[0.08; 0.63]), lower severity of negative dimension (3-factor: aMD=-0.49, 95% CI [-0.90;-0.09]; 5-factor: aMD=-0.50, 95% CI=[-0.91;-0.08]), higher severity of excitement dimension (aMD=0.16, 95% CI=[0.03; 0.28]). No association was found between cannabis use and disorganization (aMD=-0.13, 95% CI=[-0.42; 0.17]) or depression (aMD=-0.14, 95% CI=[-0.34; 0.06]). No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Cognitive correlates of auditory hallucinations in schizophrenia spectrum disorders

Auditory hallucinations (AHs) are one of the central symptoms of schizophrenia spectrum disorders (SSD). Current cognitive models of AH implicate source monitoring, top-down processes, and inhibitory control. However, research combining these processes is limited. Our study aimed to examine how source monitoring bias, top-down processes, and inhibitory control contribute to AHs in individuals with SSD. Eighty seven patients (aged 18–45 years) with SSD were included in the analyses. Participants completed cognitive tasks assessing source monitoring (Action Memory Task), top-down processes (False Perception Task; FPT), and inhibitory control (Auditory Go/NoGo task). AH was positively associated with response bias on the FPT. Correlations between AH and the other cognitive tasks were nonsignificant. Source monitoring errors correlated positively with response bias measures and negatively with Hits on the FPT. PANSS total score was positively correlated with source monitoring bias and False Alarms on the Go/NoGo task. The severity of disorganized symptoms was related to Source Monitoring Errors and False Alarms in the Go/NoGo task. Negative symptoms were associated with Hits and False Alarms in the Go/NoGo task.Future studies are necessary to further elucidate the relationships between different cognitive processes that may be related to clinical symptoms of psychosis.

Effect of a group-based acceptance and commitment therapy (ACT) intervention on self-esteem and psychological flexibility in patients with schizophrenia in remission.

The present study explored whether acceptance and commitment therapy (ACT), a cognitive behavioral therapy approach, could improve the symptoms of schizophrenia spectrum disorders among patients with schizophrenia in remission. A pre- and post-treatment design with two evaluation time points was employed. Sixty outpatients with schizophrenia in remission were randomly divided into two groups: the ACT plus treatment as usual (ACT+TAU) and treatment as usual (TAU) groups. The ACT+TAU group participated in 10 group-based ACT interventions and TAU in the hospital, and the TAU group only received TAU interventions. General psycho-pathological symptoms, self-esteem, and psychological flexibility were assessed before intervention (baseline; pre-test) and after intervention (five weeks; post-test). Results indicated that, compared to the TAU group, the ACT+TAU group exhibited a more significant improvement in general psychopathological symptoms, self-esteem, cognitive fusion, and acceptance and action at post-test. ACT intervention could effectively decrease the general psycho-pathological symptoms and increase self-esteem level and psychological flexibility in people with schizophrenia in remission.

Autism Spectrum Disorder and Schizophrenia Spectrum Disorders

Autism spectrum disorder (ASD) and schizophrenia spectrum disorders (SSD) are currently conceptualized as distinct illnesses. However, there has been considerable debate over the association between these two disorders. Research findings over the last decade suggest a number of overlapping domains between ASD and SSD: shared environmental risk factors, genetics, neurobiological features, brain imaging, clinical features, and comorbidities. These commonalities lead to significant challenges in differentiating between the core symptoms of ASD and SSD. Misinterpretation of symptoms is common in clinical practice, particularly while working with young people at the early stage of these neurodevelopmental conditions, such as first-episode psychosis or clinical high risk. It is essential for mental health professionals to know about research-informed clinical guidelines on how to differentiate ASD and SSD in the clinical setting. [ Psychiatr Ann . 2023;53(5):209–215.]

Gender-specific anatomical correlations of schizotypy in healthy individuals

IntroductionSchizotypy refers to a continuum of symptoms from subclinical manifestations in the general population to severe symptoms in schizophrenia spectrum disorders. Neuroimaging studies revealed significant relationships between schizotypy and cortical anatomy in the general population. However, it remains unclear whether these structural associations has a gender specificity.ObjectivesThe present study used structural MRI data to investigate the relationship between subclinical schizotypy symptoms and cortical and subcortical morphometric measures in male and female samples of healthy individuals.Methods164 right-handed healthy unmedicated individuals (18.0-34.9 years, 57% females) underwent structural MRI at 3T Philips scanner. T1-weighted images were processed via FreeSurfer 6.0 to quantify cortical thickness for 34 regions-of-interest (ROIs) according to Desikan atlas and volumes for 7 subcortical structures at each hemisphere. Schizotypy levels were assessed using self-report Schizotypal Personality Questionnaire, total schizotypy score and 4 factors scores (Cognitive-perceptual, negative, disorganized and paranoid factors as per Stefanis et al. Schizophr Bull. 2004; 30 335-350) were calculated. Partial correlation analysis (ppcor version 1.1, R version 4.2.1) was used to assess the associations between ROIs cortical thickness and total schizotypy or 4 factors scores including age and sex as covariates. The same analysis was performed for subcortical volumes including intracranial volume as additional covariate.ResultsIn male group we revealed a positive correlation between greater thickness of the left caudal middle frontal gyrus and higher total schizotypy (r=0.42, punc=0.0003, 95% CI [0.21–0.60]) and negative factor of schizotypy (r=0.49, punc&lt;0.0001, 95% CI [0.28–0.65]) (Image). No correlations survived correction for multiple comparisons in female sample. There were no differences in age, caudal middle frontal gyrus thickness, total schizotypy or negative factor of schizotypy scores between male and female subgroups.Image:ConclusionsThe results suggest that the association of dorsolateral prefrontal cortex (DLPFC) and levels of schizotypy is gender specific. We showed that total and negative schizotypy positively correlated with thicker DLPFC in male but not in female sample. The present data are inverse to findings of prefrontal cortical thinning observed in schizophrenia. Such correlations suggest that thicker cortex could be a potential compensatory mechanism or could reflect alterations in trajectory of cortical thickness reductions across the lifespan.The work was supported by RFBR grant 20-013-00748Disclosure of InterestNone Declared

Lower fractional anisotropy without evidence for neuro-inflammation in patients with early-phase schizophrenia spectrum disorders

Various lines of research suggest immune dysregulation as a potential therapeutic target for negative and cognitive symptoms in schizophrenia spectrum disorders (SSD). Immune dysregulation would lead to higher extracellular free-water (EFW) in cerebral white matter (WM), which may partially underlie the frequently reported lower fractional anisotropy (FA) in SSD. We aim to investigate differences in EFW concentrations – a presumed proxy for neuro-inflammation – between early-phase SSD patients (n = 55) and healthy controls (HC; n = 37), and to explore immunological and cognitive correlates. To increase specificity for EFW, we study several complementary magnetic resonance imaging contrasts that are sensitive to EFW. FA, mean diffusivity (MD), magnetization transfer ratio (MTR), myelin water fraction (MWF) and quantitative T1 and T2 were calculated from diffusion-weighted imaging (DWI), magnetization transfer imaging (MTI) and multicomponent driven equilibrium single-pulse observation of T1/T2 (mcDESPOT). For each measure, WM skeletons were constructed with tract-based spatial statistics. Multivariate SSD-HC comparisons with WM skeletons and their average values (i.e. global WM) were not statistically significant. In voxel-wise analyses, FA was significantly lower in SSD in the genu of the corpus callosum and in the left superior longitudinal fasciculus (p < 0.04). Global WM measures did not correlate with immunological markers (i.e. IL1-RA, IL-6, IL-8, IL-10 and CRP) or cognition in HC and SSD after corrections for multiple comparisons. We confirmed lower FA in early-phase SSD patients. However, nonFA measures did not provide additional evidence for immune dysregulation or for higher EFW as the primary mechanism underlying the reported lower FA values in SSD.

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders.

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses.

Challenges and Considerations in Treating Negative and Cognitive Symptoms of Schizophrenia Spectrum Disorders

The prototypical patient with schizophrenia spectrum disorders (SSDs) is often thought to possess positive symptoms. However, patients with SSDs can present with predominantly negative and cognitive symptoms, which can create diagnostic and treatment challenges. A 33-year-old female veteran presented to the emergency department with diminished speech output, markedly blunted affect, tangential speech, was not oriented to situation, and appeared to be responding to internal stimuli. Following inpatient admission, the veteran was diagnosed with schizoaffective disorder, which was misdiagnosed as major depressive disorder and borderline personality disorder during her military service. She was initially treated with olanzapine injections and psychotherapy but continued to experience worsening symptoms, resulting in multiple hospitalizations. After starting clozapine, she demonstrated marked improvement and continued with outpatient mental health care. Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for the patient. Clozapine is a promising treatment for addressing these symptoms. This case demonstrates how careful multidisciplinary evaluations, review of health records, collateral information from family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.

Disentangling the Relationships Between the Clinical Symptoms of Schizophrenia Spectrum Disorders and Theory of Mind: A Meta-analysis.

Previous studies have suggested links between clinical symptoms and theory of mind (ToM) impairments in schizophrenia spectrum disorders (SSD), but it remains unclear whether some symptoms are more strongly linked to ToM than others. A meta-analysis (Prospero; CRD42021259723) was conducted to quantify and compare the strength of the associations between ToM and the clinical symptoms of SSD (Positive, Negative, Cognitive/Disorganization, Depression/Anxiety, Excitability/Hostility). Studies (N = 130, 137 samples) including people with SSD and reporting a correlation between clinical symptoms and ToM were retrieved from Pubmed, PsycNet, Embase, Cochrane Library, Science Direct, Proquest, WorldCat, and Open Gray. Correlations for each dimension and each symptom were entered into a random-effect model using a Fisher's r-to-z transformation and were compared using focused-tests. Publication bias was assessed with the Rosenthal failsafe and by inspecting the funnel plot and the standardized residual histogram. The Cognitive/Disorganization (Zr = 0.28) and Negative (Zr = 0.24) dimensions revealed a small to moderate association with ToM, which was significantly stronger than the other dimensions. Within the Cognitive/Disorganization dimension, Difficulty in abstract thinking (Zr = 0.36) and Conceptual disorganization (Zr = 0.39) showed the strongest associations with ToM. The association with the Positive dimension (Zr = 0.16) was small and significantly stronger than the relationship with Depression/Anxiety (Zr = 0.09). Stronger associations were observed between ToM and clinical symptoms in younger patients, those with an earlier age at onset of illness and for tasks assessing a combination of different mental states. The relationships between Cognitive/Disorganization, Negative symptoms, and ToM should be considered in treating individuals with SSD.