Background and Hypothesis Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment

Background Latinxs are vastly underrepresented in mental health research; one of many contributing factors may be complexities in the research consent process, including language preferences. We examined determinants of comprehension of research consent procedures and tested the effects of a preconsent research schema condition among 180 adults with schizophrenia (60 Latinx-English and 60 Latinx-Spanish

Background and Hypothesis Negative symptoms are very important for the overall loss of functioning observed in patients with schizophrenia. There is a need for valid tools to assess these symptoms. Study Design We used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) systematic review guideline to evaluate the quality of the clinical assessment interview for

Background and Hypothesis Corollary discharge mechanism suppresses the conscious auditory sensory perception of self-generated speech and attenuates electrophysiological markers such as the auditory N1 Event-Related Potential (ERP) during Electroencephalographic (EEG) recordings. This phenomenon contributes to self-identification and seems to be altered in people with schizophrenia. Therefore, its

Current pharmacological treatment of schizophrenia employs drugs that interfere with dopamine neurotransmission, aiming to suppress acute exacerbation of psychosis and maintenance treatment to reduce the risk of psychosis recurrence. According to this treatment scheme, available psychotropic drugs intended to treat negative symptoms, cognitive impairment, or anxiety are administered as add-ons to treatment

Background and Hypothesis Obesity is a common comorbidity in individuals with schizophrenia and is associated with poor clinical outcomes. At present, there are limited effective approaches for addressing this issue. We conducted a double-blind, randomized, sham-controlled clinical trial to investigate the efficacy of noninvasive magnetic stimulation techniques in reducing obesity in individuals with

Background and Hypothesis Type-1 trace amine-associated receptors (TAAR1) modulate dopaminergic and glutamatergic neurotransmission and are targeted by novel antipsychotic drugs. We hypothesized that schizophrenia (SCZ) causes adaptive changes in TAAR1 expression in the prefrontal cortex. Study Design We measured TAAR1 mRNA and protein levels by quantitative PCR and immunoblotting in post-mortem prefrontal

Background and Hypothesis Symptoms that precede a first episode of psychosis (FEP) can ideally be targeted by early intervention services with the aim of preventing or delaying psychosis onset. However, these precursor symptoms emerge in combinations and sequences that do not rest fully within traditional diagnostic categories. To advance our understanding of illness trajectories preceding FEP, we

Background and Hypothesis Reduced social cognition has been reported in individuals who have committed interpersonal violence. It is unclear if individuals with schizophrenia and a history of violence have larger impairments than violent individuals without psychosis and non-violent individuals with schizophrenia. We examined social cognition in two groups with violent offenses, comparing their performance

Background and Hypothesis Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies

Background and Hypothesis Structural brain alterations are well-established features of schizophrenia but they do not effectively predict disease/disease risk. Similar to polygenic risk scores in genetics, we integrated multifactorial aspects of brain structure into a summary “Neuroscore” and examined its potential as a marker of disease. Study Design We extracted measures from T1-weighted scans and

Background There is increasing evidence that people with hallucinations overweight perceptual beliefs relative to incoming sensory evidence. Past work demonstrating prior overweighting has used simple, nonlinguistic stimuli. However, auditory hallucinations in psychosis are often complex and linguistic. There may be an interaction between the type of auditory information being processed and its perceived

Background and Hypothesis Disturbances of the narrative self and personal identity accompany the onset of psychotic disorders in late adolescence and early adulthood (a formative developmental stage for self-concept and personal narratives). However, these issues have primarily been studied retrospectively after illness onset, limiting any inferences about their developmental course. Study Design Youth

There is mounting evidence that the social determinants of psychosis operate via a long and circuitous route. Here, we comment on the striking findings from a recent study by Ku et al., that area-level social environmental factors yield social disability and increased risk for schizophrenia through intervening variables and over a long time course. We discuss the relevance of animal models of social

Background Paranoid beliefs commonly occur in the general adolescent population. Exposure to adverse life events (ALEs) and/or bullying are important environmental risk factors. The extent to which others, especially parents, are available to help a young person cope with stressful situations may offset this risk. Study Design A cross-sectional adolescent-parent dyad design (n = 142 pairs) was used

Background and Hypothesis Hallucinations are characterized by disturbances in perceptual decision-making about environmental stimuli. When integrating across multiple stimuli to form a perceptual decision, typical observers engage in “robust averaging” by down-weighting extreme perceptual evidence, akin to a statistician excluding outlying data. Furthermore, observers adapt to contexts with more unreliable

Background and Hypothesis Antipsychotics are first-line drug treatments for schizophrenia. When antipsychotic monotherapy is ineffective, combining two antipsychotic drugs is common although treatment guidelines warn of possible increases in side effects. Risks of metabolic side effects with antipsychotic polypharmacy have not been fully investigated. This study examined associations between antipsychotic

Background and Hypothesis The cholinergic system is altered in schizophrenia. Particularly, patients’ volumes of basal-forebrain cholinergic nuclei (BFCN) are lower and correlated with attentional deficits. It is unclear, however, if and how BFCN changes and their link to cognitive symptoms extend across the schizophrenia spectrum, including individuals with at-risk mental state for psychosis (ARMS)

Background Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less

Background and Hypothesis Individuals at familial risk for developing schizophrenia (FRSZ) or bipolar disorder (FRBD) have shared and unique genetic risks. Few studies have compared neural activation between these two groups. Therefore, the present meta-analysis investigated functional brain similarities and differences between FRSZ and FRBD individuals. Study Design A systematic literature review

Background Ecological momentary assessment (EMA) involves completing multiple surveys over time in daily life, capturing in-the-moment experiences in real-world contexts. EMA use in psychosis studies has surged over several decades. To critically examine EMA use in psychosis research and assist future researchers in designing new EMA studies, this systematic review aimed to summarize the methodological

Background Individuals with psychotic symptoms experience substantial morbidity and have shortened life expectancies; early treatment may mitigate the worst effects. Understanding care preceding a first psychotic disorder diagnosis is critical to inform early detection and intervention. Study Design In this observational cohort study using comprehensive information from the Massachusetts All-Payer

Background and Hypothesis Schizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia and whether these link to molecular genetics. Study Design We systematically searched Web of Science, PubMed, and BrainMap for the amplitude of

Background and Hypothesis The emergence of psychosis in ultra-high-risk subjects (UHR) is influenced by gene-environment interactions that rely on epigenetic mechanisms such as microRNAs. However, whether they can be relevant pathophysiological biomarkers of psychosis’ onset remains unknown. Study Design We present a longitudinal study of microRNA expression, measured in plasma by high-throughput sequencing

Background and Hypothesis Serious mental illness (SMI) may compromise diabetes self-management. This study assessed the association between SMI and glycemic control, and explored sociodemographic predictors and geographic clustering of this outcome among patients with and without SMI. Study Design We used electronic health record data for adult primary care patients with diabetes from 2 San Francisco

Background and Hypothesis Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications

Background Consistent with postmortem findings in patients, most animal models for schizophrenia (SCZ) present abnormal levels of parvalbumin (PV), a marker of fast-spiking GABAergic interneurons, in the prefrontal cortex (PFC) and hippocampus (HIP). However, there are discrepancies in the literature. PV reductions lead to a functional loss of PV interneurons, which is proposed to underly SCZ symptoms

Background and Hypothesis Low-grade neural and peripheral inflammation are among the proposed pathophysiological mechanisms of schizophrenia. White matter impairment is one of the more consistent findings in schizophrenia but the underlying mechanism remains obscure. Many cerebral white matter components are sensitive to neuroinflammatory conditions that can result in demyelination, altered oligodendrocyte

Background and Hypotheses Social dysfunction in schizophrenia includes symptoms of withdrawal and deficits in social skills, social cognition, and social motivation. Based on the course of illness, with social withdrawal occurring prior to psychosis onset, it is likely that the severity of social withdrawal/isolation contributes to schizophrenia neuropathology. Study Design We review the current literature

Background and Hypothesis The life expectancy of patients diagnosed with schizophrenia is 10–12 years lower than in the general population and the mortality gap seems to be worsening. Many of these deaths might be avoidable. We aimed to determine mortality rates and causes of death after a first-episode psychosis, and to examine if clinical characteristics at baseline or during illness could predict

Background and Hypothesis The neurocomputational framework of predictive processing (PP) provides a promising approach to explaining delusions, a key symptom of psychotic disorders. According to PP, the brain makes inferences about the world by weighing prior beliefs against the available sensory data. Mismatches between prior beliefs and sensory data result in prediction errors that may update the

Background and Hypotheses Poor social functioning is common among individuals at clinical high-risk (CHR) for psychosis and is associated with greater likelihood of conversion. Unfortunately, processes contributing to social impairment are unclear, making social functioning difficult to improve via treatment. The current study examined whether abnormalities in social functioning result from aberrant

Background and Hypothesis While the phenotypic association between schizophrenia and breast cancer has been observed, the underlying intrinsic link is not adequately understood. We aim to conduct a comprehensive interrogation on both phenotypic and genetic relationships between schizophrenia and breast cancer. Study Design We first used data from UK Biobank to evaluate a phenotypic association and

Background and Hypotheses Several biological markers are believed to reflect accelerated aging in schizophrenia spectrum disorders; however, retinal neural changes have not yet been explored as potential CNS biomarkers of accelerated aging in this population. The aim of this study was to determine whether retinal neural layer thinning is more strongly related to age in schizophrenia and schizoaffective

Background and Hypothesis To clarify whether the familial liability to psychosis associated with bipolar disorder (BD) is nonspecific or has a greater effect on risk for psychosis in cases with prominent mood symptoms and/or a remitting course. Study Design We examined, in 984 809 offspring raised in intact families in Sweden, born 1980–1996 and followed-up through 2018, by multivariable Cox proportional

Background and Hypothesis Some of the most debilitating aspects of schizophrenia and other serious mental illnesses (SMI) are the impairments in social perception, motivation, and behavior that frequently accompany these conditions. These impairments may ultimately lead to chronic social disconnection (ie, social withdrawal, objective isolation, and perceived social isolation or loneliness), which

Background and hypothesis Psychiatric disorders impose a huge health and economic burden on modern society. However, there is currently no proven completely effective treatment available, partly owing to the inefficiency of drug target identification and validation. We aim to identify therapeutic targets relevant to psychiatric disorders by conducting Mendelian randomization (MR) analysis. Study design

Social motivation impairments, or “asociality,” have long been considered a core clinical feature of schizophrenia. Although the prevalence and pervasive negative impact of poor social motivation is well-documented, our understanding is limited regarding causal mechanisms. Advances in definition, conceptualization, and characterization are needed to inform research aimed at understanding these mechanisms

Background and Hypothesis Impairments in function (ie, the ability to independently accomplish daily tasks) have been established in psychotic disorders. Identifying factors that contribute to these deficits is essential to developing effective interventions. The current study had several goals: examine potential differential relationships across domains of neurocognition, assess whether reinforcement

Background and Hypothesis Individuals with schizophrenia or bipolar disorder have attenuated auditory mismatch negativity (MMN) responses, indicating impaired sensory information processing. Computational models of effective connectivity between brain areas underlying MMN responses show reduced connectivity between fronto-temporal areas in individuals with schizophrenia. Here we ask whether children

Background and Hypothesis Schizophrenia is associated with altered energy metabolism, but the cause and potential impact of these metabolic changes remain unknown. 22q11.2 deletion syndrome (22q11.2DS) represents a genetic risk factor for schizophrenia, which is associated with the loss of several genes involved in mitochondrial physiology. Here we examine how the haploinsufficiency of these genes

Background and Hypothesis Diminished social motivation is a negative symptom of schizophrenia and leads to severe functional consequences for many patients suffering from the illness. However, there are no effective medications available to treat this symptom. Despite the lack of approved treatments for patients, there is a growing body of literature on the effects of several classes of drugs on social

Background and Hypothesis Although studies have identified social fragmentation as an important risk factor for schizophrenia and other psychotic disorders, it is unknown whether it may impact social functioning. This study investigates whether social fragmentation during childhood predicts maladaptation to school as well as social functioning during childhood and adulthood. Study Design Data were

Background and Hypothesis The hippocampus is a heterogenous brain structure that differs between the sexes and has been implicated in the pathophysiology of psychiatric illnesses. Here, we explored sex and diagnostic group differences in hippocampal subfield volumes, in individuals with schizophrenia spectrum disorder (SZ), bipolar disorders (BD), and healthy controls (CTL). Study Design One thousand

Background and hypothesis Schizophrenia is highly heritable, with a polygenic effect of many genes conferring risk. Evidence on whether cumulative risk also predicts alterations in brain morphology and function is inconsistent. This systematic review examined evidence for schizophrenia polygenic risk score (sczPRS) associations with commonly used magnetic resonance imaging (MRI) measures. We expected

Background and Hypothesis Social motivation, defined as the fundamental human desire to seek out, engage in, and maintain interpersonal bonds, has become a growing area of research in schizophrenia. The major focus has been on understanding the impact of social reward-related processes. An obvious but rarely acknowledged fact is that social interactions, much like other goal-directed acts, require

Background and Hypotheses Auditory verbal hallucinations (AVH) are central features of schizophrenia (SZ). However, AVH also occur in a small percentage of the general population who do not have a need for care, termed nonclinical voice hearers (NCVH). We sought to determine the degree to which the experience of AVH was similar in NCVH and in people with schizophrenia (PSZ) and evaluate the degree

Background and Hypothesis Long-acting injectable antipsychotic drugs (LAIs) are mainly used for relapse prevention but could also be advantageous for acutely ill patients with schizophrenia. Study Design We conducted a systematic review and meta-analysis of randomized-controlled-trials (RCTs) comparing the second-generation long-acting injectable antipsychotics (SGA-LAIs) olanzapine, risperidone, paliperidone

Background and hypothesis Previous studies show that people with severe mental illness (SMI) are at higher risk of COVID-19 mortality, however limited evidence exists regarding risk post-vaccination. We investigated COVID-19 mortality among people with schizophrenia and other SMIs before, during and after the UK vaccine roll-out. Study Design Using the Greater Manchester (GM) Care Record to access

Background Immune mechanisms are indicated in schizophrenia (SCZ). Recent genome-wide association studies (GWAS) have identified genetic variants associated with SCZ and immune-related phenotypes. Here, we use cutting edge statistical tools to identify shared genetic variants between SCZ and white blood cell (WBC) counts and further understand the role of the immune system in SCZ. Study Design GWAS

While the evolution of our modern concepts of mania and melancholia over the 19th century is relatively well-understood, no such clear narrative exists for the nonaffective psychotic syndromes that culminated in Kraepelin’s concept of dementia praecox in 1899. These narratives were relatively distinct in Germany and France. An important milestone in the French literature is the 1852 essay by the alienist

Background and Hypothesis Māori, the indigenous peoples of New Zealand, experience increased rates of psychotic disorders and first-episode psychosis. However, it is unclear whether they also present with increased psychosis risk symptoms, such as subclinical psychotic-like experiences (PLEs). Measurement of risk symptoms is key for early intervention. Further, it is unclear if systemic factors such

Background and Hypothesis Childhood adversity is associated with a myriad of psychiatric symptoms, including psychotic experiences (PEs), and with multiple psychological processes that may all mediate these associations. Study Design Using a network approach, the present study examined the complex interactions between childhood adversity, PEs, other psychiatric symptoms, and multiple psychological

Background and Hypothesis Trauma is a robust risk factor for delusional ideation. However, the specificity and processes underlying this relationship are unclear. Qualitatively, interpersonal traumas (i.e., trauma caused by another person) appear to have a specific relationship with delusional ideation, particularly paranoia, given the commonality of social threat. However, this has not been empirically

Background and Hypothesis There is uncertainty about the relationship between the family intelligence quotient (IQ) deviation and the risk for schizophrenia spectrum disorders (SSD). This study tested the hypothesis that IQ is familial in first episode psychosis (FEP) patients and that their degree of familial resemblance is associated with different profiles. Study Design The participants of the PAFIP-FAMILIAS

Background Neuropsychiatric disorders are highly heritable and have overlapping genetic underpinnings. Single nucleotide polymorphisms (SNPs) in the gene CACNA1C have been associated with several neuropsychiatric disorders, across multiple genome-wide association studies. Method A total of 70,711 subjects from 37 independent cohorts with 13 different neuropsychiatric disorders were meta-analyzed to

Background and Hypothesis Around 5%–7% of the adult population are estimated to have lifetime psychotic experiences (PEs), which are associated with psychosis risk. PEs assessed with Community Assessment of Psychic Experiences (CAPE) are associated with psychosis but also non-psychotic disorders, which could be partly explained by CAPE indirectly capturing emotional symptoms. We investigated the psychometric

Background Digital interventions have potential applications in promoting long-term recovery and improving outcomes in first-episode psychosis (FEP). This study aimed to evaluate the cost-effectiveness of Horyzons, a novel online social therapy to support young people aged 16–27 years following discharge from FEP services, compared with treatment as usual (TAU) from a healthcare sector and a societal

Background Impaired social functioning is a major, but under-elucidated area of schizophrenia. It’s typically understood as consequential to, eg, negative symptoms, but meta-analyses on the subject have not examined psychopathology in a broader perspective and there’s severe heterogeneity in outcome measures. To enhance functional recovery from schizophrenia, a more comprehensive understanding of the

Background and Hypothesis Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz).