Cognitive Deficits In Schizophrenia Research Articles

International expert perspectives on access, engagement, and implementation of cognitive remediation for schizophrenia: A Delphi study.

Cognitive remediation (CR) for schizophrenia has been extensively studied and has proven effective in improving both cognition and functioning. Yet, implementation into mental health services is poor, with implementation and engagement barriers and facilitators not understood. The present study aimed to assess expert opinions on CR barriers and facilitators that pertain to staff, mental health services, and consumers. Thirty-seven international CR experts (clinicians/researchers) responded to Likert-scale questions on implementation and engagement facilitators, essential CR components, barriers in mental health facilities, barriers for clinicians, and barriers for consumer access and engagement across three rounds of a Delphi survey. The main barriers to CR implementation were (a) lack of staff training, (b) lack of perceived relevance/lack of knowledge about cognitive deficits in schizophrenia and CR usefulness in both clinicians and consumers, as well as (c) lack of staff employed in cognitive rehabilitation roles. The presence of defeatist beliefs and difficulty in accessing the place of delivery were both barriers to consumer engagement and access. The most important facilitators for CR were a good therapeutic alliance, CR delivered as part of integrated rehabilitation services, psychoeducation provided to families and stakeholders, and CR focusing on generalization of learning to everyday life. This study highlights the barriers to CR implementation from experts. A multitude of factors were identified that need attention. It is also apparent that CR cost-effectiveness studies are needed to facilitate organizational change and national guideline recommendations for improving mental health services policy around serious mental illness/schizophrenia health care provisions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Etiology of Cognitive Deficits in Schizophrenia: a Review of Studies Based on Polygenic Risk Scores

Background: cognitive deficits in schizophrenia have long been believed to reflect the influence of genetic predisposition to the disease. Schizophrenia genome-wide association studies of the last decade have made it possible to test this hypothesis. The aim: to analyze studies on the relationship between cognitive impairment in schizophrenia patients and polygenic risk scores for schizophrenia (SZ-PRS). Additionally, the associations of PRS for intelligence with cognitive deficits in patients and the associations of SZ-PRS with cognitive functions in healthy people were considered. Material and methods: the literature search was carried out in the PubMed database using the following terms: (schizophr* OR schizoaffective* OR psychosis) AND (cogn* OR intelligence OR IQ) AND (GWAS OR polygenic). Results and discussion: from papers published between January 2015 and February 2024, 40 publications met the inclusion criteria. Their analysis indicate that in schizophrenia patients, in contrast to healthy people, the correlation of SZ-PRS with cognitive deficits and premorbid cognitive abilities is absent. Cognitive functions of patients are associated with PRS of intelligence, however, the bulk of the variance in cognitive deficits in schizophrenia, except for the group with intellectual disability, appears to be associated with non-genetic causes. It can be assumed that disease process factors play the most important role. Future studies should be aimed at establishing whether they are directly related to the pathophysiology of the disease, to the influence of concomitant exposures (treatment, hospitalization, etc.) or cognitive reserve, which will contribute to the correction of cognitive deficits.

Cognition in Schizophrenia: Exploring the Dynamics of Improvement and the Influencing Determinants

Background: Cognitive impairments are fundamental characteristics of schizophrenia, significantly impacting the overall functioning of individuals with the disorder. However, the trajectory of cognitive deficits and the factors influencing their changes over the course of treatment remain poorly understood. Objectives: The present study aimed to investigate the changes in cognitive status of patients with schizophrenia and the factors that influence these changes following hospitalization and treatment. Methods: The study utilized a longitudinal design, enrolling thirty hospitalized patients (15 males and 15 females) from the psychiatric inpatient unit of a general educational hospital. Cognitive assessments were conducted upon admission and discharge. A Generalized Estimating Equation (GEE) model was used to analyze the data, accounting for demographic and clinical variables such as age, gender, Body Mass Index (BMI), family history, and smoking status. Results: The findings revealed a reduction in cognitive deficits following hospitalization and treatment. Significant improvements were observed in verbal memory, working memory, and executive function. However, older patients showed poorer performance in motor speed, verbal fluency, and symbol coding compared to younger patients. Male patients and smokers demonstrated lower cognitive functioning, particularly in verbal fluency, symbol coding, and executive function. Conclusions: This study highlighted the positive effect of comprehensive inpatient treatment on reducing cognitive impairments in individuals with schizophrenia. While improvements were noted in several cognitive domains, the persistence of certain deficits, particularly in relation to demographic factors (age, gender, and smoking status), underscores the need for further research and tailored cognitive rehabilitation interventions. A personalized, multidimensional approach to managing cognitive deficits in schizophrenia could lead to better functional outcomes and enhance the quality of life for affected individuals.

Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways

Cognitive impairment is a core feature of schizophrenia, playing a pivotal role in the pathogenesis and prognosis of this disorder. Cognitive impairment in schizophrenia encompasses a wide range of domains, including processing speed, episodic memory, working memory, and executive function. These deficits persist throughout the course of the illness and significantly impact functional outcomes and quality of life. Therefore, it is imperative to identify the biological basis of cognitive deficits in schizophrenia and develop effective treatments. The role of N-methyl-D-aspartate (NMDA) receptors in synaptic transmission and plasticity has long been recognized, making them potential targets for schizophrenia treatment. This review will focus on emerging pharmacology targeting NMDA receptors, offering strategies for the prevention and treatment of cognitive deficits in schizophrenia.

Efficacy of a Culturally Adapted Emotion Recognition Training Program in Improving Facial Emotion Recognition in Persons with Schizophrenia

Background: Facial emotion recognition (FER) deficits are being considered as core features of social cognitive deficits in schizophrenia, associated with socio-occupational dysfunction. Social cognition intervention programs have been shown to improve these deficits; however, there are no such intervention strategies in India. In this study, we aim to examine the efficacy of Training of Affect Recognition – Indian Version (TAR-IV) to enhance the FER abilities of people with schizophrenia. Methods: In an open-label experimental design, 36 participants with schizophrenia underwent 12 sessions of TAR-IV as an add-on to treatment as usual (TAU), while 29 participants with schizophrenia continued TAU (pharmacological treatment with or without occupational therapy and vocational rehabilitation services). Clinical and functional assessments were done using the positive and negative syndrome scale (PANSS) and socio-occupational functioning scale. Emotion recognition abilities were assessed on the tool for recognition of emotions in neuropsychiatric disorders at baseline, post-intervention, and follow-up (two to three months post-intervention). Results: The intervention group showed significant improvements in FER ( P = .001) and socio-occupational functioning ( P = .008) after receiving the TAR-IV, which remained significant at two months follow-up. A lower age of onset and poorer neurocognitive function at baseline predicted greater changes in emotion recognition ability following the intervention. Conclusions: This study demonstrated the efficacy of TAR-IV, the Indian adaptation of social cognition intervention, in improving emotion recognition abilities and socio-occupational functioning in patients with schizophrenia. These findings need to be replicated in randomized controlled trials.

GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.

The microcircuitry within superficial layers of the dorsolateral prefrontal cortex (DLPFC), composed of excitatory pyramidal neurons and inhibitory GABAergic interneurons, has been suggested as the neural substrate of working memory performance. In schizophrenia, working memory impairments are thought to result from alterations of microcircuitry within the DLPFC. GABAergic interneurons, in particular, are crucially involved in synchronizing neural activity at gamma frequency, the power of which increases with working memory load. Alterations of GABAergic interneurons, particularly parvalbumin (PV) and somatostatin (SST) subtypes, are frequently observed in schizophrenia. Abnormalities of GABAergic neurotransmission, such as deficiencies in the 67 kDA isoform of GABA synthesis enzyme (GAD67), vesicular GABA transporter (vGAT), and GABA reuptake transporter 1 (GAT1) in presynaptic boutons, as well as postsynaptic alterations in GABA A receptor subunits further contribute to impaired inhibition. This review explores GABAergic abnormalities of the postmortem DLPFC in schizophrenia, with a focus on the roles of interneuron subtypes involved in cognition, and GABAergic neurotransmission within presynaptic boutons and postsynaptic alterations. Where available, comparisons between schizophrenia and affective disorders that share cognitive pathology such as bipolar disorder and major depressive disorder will be made. Challenges in directly measuring GABA levels are addressed, emphasizing the need for innovative techniques. Understanding GABAergic abnormalities and their implications for neural circuit dysfunction in schizophrenia is crucial for developing targeted therapies.

Disrupted cognitive network revealed by task-induced brain entropy in schizophrenia.

Brain entropy (BEN), which measures the amount of information in brain activity, provides a novel perspective for evaluating brain function. Recent studies using resting-state functional magnetic resonance imaging (fMRI) have shown that BEN during rest can help characterize brain function alterations in schizophrenia (SCZ). However, there is a lack of research on BEN using task-evoked fMRI to explore task-dependent cognitive deficits in SCZ. In this study, we evaluate whether the reduced working memory (WM) capacity in SCZ is possibly associated with dynamic changes in task BEN during tasks with high cognitive demands. We analyzed data from 15 patients with SCZ and 15 healthy controls (HC), calculating task BEN from their N-back task fMRI scans. We then examined correlations between task BEN values, clinical symptoms, 2-back task performance, and neuropsychological test scores. Patients with SCZ exhibited significantly reduced task BEN in the cerebellum, hippocampus, parahippocampal gyrus, thalamus, and the middle and superior frontal gyrus (MFG and SFG) compared to HC. In HC, significant positive correlations were observed between task BEN and 2-back accuracy in several brain regions, including the MFG and SFG; such correlations were absent in patients with SCZ. Additionally, task BEN was negatively associated with scores for both positive and negative symptoms in areas including the parahippocampal gyrus among patients with SCZ. In conclusion, our findings indicate that a reduction in BEN within prefrontal and hippocampal regions during cognitively demanding tasks may serve as a neuroimaging marker for SCZ.

Frontal brain volume correlates of impaired executive function in schizophrenia

Cognitive impairments affect functional capacity in individuals with schizophrenia (SZH), but their neural basis remains unclear. The Wisconsin Card Sorting Test (WCST), and the Stroop Task (SCWT), are paradigmatic tests which have been used extensively for examining executive function in SZH. However, few studies have explored how deficits on these tasks link to brain volume differences commonly seen in SZH. Here, for the first time, we tested associations between FreeSurfer-derived frontal brain volumes and performance on both WCST and SCWT, in a well-matched sample of 57 SZH and 32 control subjects. We also explored whether these associations were dissociable from links to symptom severity in SZH. Results revealed correlations between volumes and task performance which were unique to SZH. In SZH only, volumes of right middle frontal regions correlated with both WCST and Stroop performance: correlation coefficients were significantly different to those present in the control group, highlighting their specificity to the patient group. In the Stroop task, superior frontal regions also showed associations with Stroop interference scores which were unique to SZH. These findings provide important detail around how deficits on these two paradigmatic executive function tasks link to brain structural differences in SZH. Results align with converging evidence suggesting that neuropathology within right middle frontal regions (BA9 and BA46) might be of particular import in SZH. No volumetric associations with symptom severity were found, supporting the notion that the structural abnormalities underpinning cognitive deficits in SZH differ from those associated with symptomatology.

Is game-based therapy effective for treating cognitive deficits in adults with schizophrenia? Evidence from a randomized controlled trial

Cognitive deficits in schizophrenia are a major contributor to poor functional outcomes and everyday functioning, making them a promising therapeutic target. Recent years have witnessed a dramatic increase in the use of digital interventions, such as game-based therapy, targeting various domains of cognition to treat mental disorders. Game-based digital interventions have been suggested to have therapeutic value in health care for people with schizophrenia. To support this idea, a novel, online training program (Komori Life) that targets cognitive deficits in schizophrenia was tested for feasibility of use and initial efficiency. Inpatients with schizophrenia were randomized to complete 20 sessions of either Komori Life (N = 40 completers) or treatment as usual (N = 40 completers). Cognitive and clinical assessments were performed at enrollment and after completion of the training intervention for all patients. In addition, 32 healthy volunteers were recruited as controls, and an eye-tracking paradigm was employed to assess attentional biases to emotional information before and after game intervention for all subjects. The results showed that there were no group differences in cognitive or clinical assessments at baseline between the two patient groups. After game training, there were still no group × time interactions on cognitive or clinical assessment scores. Regarding eye movement measurements, both patient groups showed increased attention to threatening stimuli compared to healthy controls in terms of attentional maintenance at baseline. After game training, the game training group revealed greater improvement in attentional bias towards threatening scenes (decreased percentage of total duration and percentage of total fixations towards threatening stimuli) relative to the treatment as usual group. Moreover, our results partially indicated that training effectiveness was associated with cognitive improvement and that heightened attentional maintenance to threats was associated with worse cognitive performance. This study provides initial evidence that a remote, online cognitive training program is feasible and effective in improving cognitive function in schizophrenia. This form of training may serve as a complementary therapy to existing psychiatric care. Clinical trial registration: the trial is registered at http://www.chictr.org.cn, identifier ChiCTR2100048403.

Aberrant brain functional connectivity mediates the effects of negative symptoms on cognitive function in schizophrenia: A structural equation model

BackgroundSchizophrenia is a severe psychiatric disorder, characterized by positive symptoms, negative symptoms, and cognitive deficits. Elucidating the mechanism of negative symptom and cognitive deficits could contribute to the treatment and prognosis of schizophrenia. We hypothesized that abnormal functional connectivity would be involved in the indirect effects of negative symptoms on cognitive function. MethodsA total of 150 schizophrenia male patients and 108 healthy controls matched for age, education and gender were enrolled in the study. The scores of Brief Negative Symptom Scale were divided into two factors: motivation and pleasure deficits (MAP) and diminished expression (EXP). Subsequently, a series of classic neurocognitive tests were used to evaluate cognitive functions. Resting-state fMRI data was collected from all participants. The Anatomical Automatic Labeling template was employed to establish regions of interest, thereby constructing the functional connectivity network across the entire brain. Eventually, scores of patients' negative symptoms scale, cognitive function, and strengths of abnormal functional connectivity were incorporated into a structural equation model to explore the interactions among variables. ResultsMAP exhibited a distinctly and significantly negative impact on cognitive function. The functional connectivity between the left insula and left precuneus, along with that between the left precuneus and right angular gyrus, collectively served as intermediaries, contributing to the indirect effects of MAP and EXP on cognitive function. ConclusionsOur findings demonstrated the moderating role of aberrant brain functional connectivity between negative symptoms and cognitive function, providing clues about the neural correlates of negative symptoms and cognitive deficits in schizophrenia.

438. Meta-Regression of Adjunctive Treatment Trials for Cognitive Deficits in Schizophrenia

438. Meta-Regression of Adjunctive Treatment Trials for Cognitive Deficits in Schizophrenia

462. Meta-Analysis of Adjunctive Treatment Trials for Cognitive Deficits in Schizophrenia

462. Meta-Analysis of Adjunctive Treatment Trials for Cognitive Deficits in Schizophrenia

Spontaneous mentalizing in patients with schizophrenia – a meta-analysis

IntroductionMentalizing helps us to understand the behaviour of others in our everyday social interactions. Spontaneous mentalizing without explicit instructions refers to representing mental state attribution. Several studies have described social cognitive deficit in schizophrenia, which largely determines the functional outcome of the disease.ObjectivesTo better understand the involvement of spontaneous mentalizing in schizophrenia, we consider it important to summarize the results of studies that used indirect instruction to measure spontaneous mentalizing performance in schizophrenia.MethodsIn our meta-analysis, we conducted a systematic search of four large databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials [CENTRAL], Web of Science). A total of 14 articles were involved.ResultsBased on our findings, the performance of patients with schizophrenia is significantly weaker than in the average population for both scripts with mentalizing interactions (MD: -0.63; 95%CI (-0.90, -0.35); p=0.0021), and with goal-directed movements (SMD: -0.55; 95%CI (-0.97, -0.13); p=0.02). The intentionality of expressions used by patients with schizophrenia is significantly lower compared to the average population (for both animations with complex social interactions: MD: -0.99; 95% CI (-1.39, -0.59); p=0.0003; and with goal-directed movements: MD: -0.31; 95% CI (-0.53, -0.08); p=0.0218). We have found no significant difference neither in appropriateness nor in intentionality of verbal terms between the two goups in the case of animations with random movements.ConclusionsBased on the meta-analysis, we found poorer performance in schizophrenia in spontaneous mentalizing. We also found poorer performance in tasks with goal-directed movements used as control tasks, suggesting a more pervasive impairment of mentalizing in schizophrenia. These deficits may affect the functional outcome of the disease and could potentially have therapeutic implications.Disclosure of InterestNone Declared

Chronic MK-801 administration provokes persistent deficits in social memory in the prairie vole (Microtus ochrogaster): A potential animal model for social deficits of schizophrenia

The prairie vole (Microtus ochrogaster) is a rodent species that has been used extensively to study biological aspects of human social bonding. Nevertheless, this species has not been studied in the context of modeling social deficits characteristic of schizophrenia. Building on studies in rodents that show that sub-chronic administration of an NMDA receptor antagonist induces persistent behavioral and neurological characteristics of schizophrenia, we administered MK-801 (0.2 mg/kg, daily, for 7 days) or physiological saline to young adult (45 days old) virgin male voles. At 69 days of age, we paired these males with virgin females. 24 h later, we assessed the males’ social investigation of each female across the first 5 min of a three-hour preference test, and side-by-side contact with each female during the last hour of the test. Unlike saline-treated males, MK-801-treated males did not preferentially investigate the unfamiliar female, indicating a deficit in social memory. Although males of both groups preferentially spent time with their female partner, regression analysis revealed that deficits in social memory predicted lower partner preference in MK-801-treated males. We interpret these results in the context of recent studies of the natural history of the prairie vole as well as in the context of cognitive deficits in schizophrenia and propose that the social component of episodic memory might influence an individual’s capacity to form and maintain long-term social bonds.

Elevations in the Mitochondrial Matrix Protein Cyclophilin D Correlate With Reduced Parvalbumin Expression in the Prefrontal Cortex of Patients With Schizophrenia.

Cognitive deficits in schizophrenia are linked to dysfunctions of the dorsolateral prefrontal cortex (DLPFC), including alterations in parvalbumin (PV)-expressing interneurons (PVIs). Redox dysregulation and oxidative stress may represent convergence points in the pathology of schizophrenia, causing dysfunction of GABAergic interneurons and loss of PV. Here, we show that the mitochondrial matrix protein cyclophilin D (CypD), a critical initiator of the mitochondrial permeability transition pore (mPTP) and modulator of the intracellular redox state, is altered in PVIs in schizophrenia. Western blotting was used to measure CypD protein levels in postmortem DLPFC specimens of schizophrenic patients (n = 27) and matched comparison subjects with no known history of psychiatric or neurological disorders (n = 26). In a subset of this cohort, multilabel immunofluorescent confocal microscopy with unbiased stereological sampling methods were used to quantify (1) numbers of PVI across the cortical mantle (20 unaffected comparison, 14 schizophrenia) and (2) PV and CypD protein levels from PVIs in the cortical layers 2-4 (23 unaffected comparison, 18 schizophrenia). In schizophrenic patients, the overall number of PVIs in the DLPFC was not significantly altered, but in individual PVIs of layers 2-4 PV protein levels decreased along a superficial-to-deep gradient when compared to unaffected comparison subjects. These laminar-specific PVI alterations were reciprocally linked to significant CypD elevations both in PVIs and total DLPFC gray matter. Our findings support previously reported PVI anomalies in schizophrenia and suggest that CypD-mediated mPTP formation could be a potential contributor to PVI dysfunction in schizophrenia.

Functional Connectivity of Language-Related Cerebellar Regions Is Reduced in Schizophrenia Patients.

Schizophrenia (SZ) is a widespread psychiatric disorder that is traditionally characterized by positive and negative symptoms. However, recent focus has shifted to cognitive deficits as a crucial aspect. The cerebellum, conventionally tied to motor coordination, is now recognized as pivotal in the pathophysiology of SZ cognitive impairments. Proposed disruptions in the cortico-cerebellar-thalamic-cortico circuit contribute to these deficits. Despite evidence of cerebellar abnormalities, within-cerebellum functional connectivity is often overlooked. This study explores spontaneous functional interactions within the cerebellum and their link to cognitive deficits in SZ. Using a multi-domain task battery (MDTB) parcellation, fMRI data from SZ patients and healthy controls were analyzed. Significant differences in cerebellar connectivity emerged, particularly in regions related to attention, language, and memory processing. Correlations between connectivity values and SZ symptomatology were identified. A post hoc analysis, considering the patients' hallucination vulnerability, revealed distinct connectivity patterns. Non-hallucinating and low-hallucinating SZ patients exhibited higher cerebellar connectivity than high-hallucinating patients, especially in language and motor control regions. These findings suggest a gradient of cerebellar connectivity alterations corresponding to hallucination vulnerability in SZ patients. This study offers novel insights into cerebellar impairments in SZ, highlighting the role of within-cerebellum connectivity in cognitive deficits. The observed connectivity patterns in language-related regions contribute to understanding language development and auditory verbal hallucinations in SZ.

Trajectories and predictors of response to social cognition training in people with schizophrenia: A proof-of-concept machine learning study

BackgroundSocial cognition training (SCT) can improve social cognition deficits in schizophrenia. However, little is known about patterns of response to SCT or individual characteristics that predict response. Methods76 adults with schizophrenia randomized to receive 8–12 weeks of remotely-delivered SCT were included in this analysis. Social cognition was measured with a composite of six assessments. Latent class growth analyses identified trajectories of social cognitive response to SCT. Random forest and logistic regression models were trained to predict membership in the trajectory group that showed improvement from baseline measures including symptoms, functioning, motivation, and cognition. ResultsFive trajectory groups were identified: Group 1 (29 %) began with slightly above average social cognition, and this ability significantly improved with SCT. Group 2 (9 %) had baseline social cognition approximately one standard deviation above the sample mean and did not improve with training. Groups 3 (18 %) and 4 (36 %) began with average to slightly below-average social cognition and showed non-significant trends toward improvement. Group 5 (8 %) began with social cognition approximately one standard deviation below the sample mean, and experienced significant deterioration in social cognition. The random forest model had the best performance, predicting Group 1 membership with an area under the curve of 0.73 (SD 0.24; 95 % CI [0.51–0.87]). ConclusionsFindings suggest that there are distinct patterns of response to SCT in schizophrenia and that those with slightly above average social cognition at baseline may be most likely to experience gains. Results may inform future research seeking to individualize SCT treatment for schizophrenia.

Cannabidiol, cognition and schizophrenia: a narrative review

Schizophrenia is a serious mental disorder affecting about 1% of the population. It is characterised by multiple symptoms which are mostly responsive to treatment with antipsychotic medications. Cognitive impairment is regarded as a core feature of illness which is mostly poorly responsive to treatment with the current antipsychotic medications. Improving cognitive function is an important treatment goal as it is associated with better outcomes in employment and quality of life. Adjunctive pharmacological treatments have been examined to improve measures of cognition but with limited success. Cannabidiol (CBD), has shown promise in preclinical models of cognitive deficits of schizophrenia. On the other hand, limited studies in small groups of patients with schizophrenia have shown no significant clinical benefits for cognitive function as an adjunct to ongoing treatment with antipsychotics. A single trial, in which CBD as a standalone treatment was compared to the antipsychotic medication amisulpride, showed significant changes in cognitive measures for both agents, with no statistically significant difference between them. It might therefore be concluded that the preclinical findings have failed to translate to the clinic. However, the preclinical findings themselves are based on a circumscribed set of studies in multiple cognitive models and have used varying doses and routes of drug administration. The same general methodological issues are present in the suite of clinical studies. Issues such as patient heterogeneity in terms of illness duration, formulation and dose of CBD employed, and length of cannabinoid treatment might militate positive findings. The limited clinical database available makes the benefits (or lack thereof) of CBD for the cognitive effects of schizophrenia uncertain. Continued research in much larger patient populations than have so far been investigated as well as a consideration of dose ranging studies are required to fully assess the potential risks against the benefits of CBD treatment for cognitive deficits in schizophrenia.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally. We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation. Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups. The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Imaging the Vesicular Acetylcholine Transporter in Schizophrenia: A Positron Emission Tomography Study Using [18F]-VAT

BackgroundDespite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [18F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition. MethodsA total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [18F]-VAT. Distribution volume (VT) for [18F]-VAT was derived for each region of interest, and group differences in VT were assessed with 2-sample t tests. Functional significance was explored through correlations between VT and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB). ResultsNo group differences in [18F]-VAT VT were observed. However, within the SCZ group, psychosis symptom severity was positively associated with VT in multiple regions of interest, with the strongest effects in the hippocampus, thalamus, midbrain, cerebellum, and cortex. In addition, in the SCZ group, working memory performance was negatively associated with VT in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex. ConclusionsIn this initial study, the severity of 2 important features of SCZ—psychosis and working memory deficit—was strongly associated with [18F]-VAT VT in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in SCZ and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in SCZ and the development of therapeutic targets.