Schizophrenia Research Research Articles

The Archive of Gerd Huber (1921-2012) at Bezirkskrankenhaus Günzburg

Gerd Huber (1921-2012) was an influential West German psychiatrist and neurologist of the postwar period. Especially his studies with imaging techniques on the question of brain atrophy, the long-term course and the basic symptoms of schizophrenic disorders made a significant contribution to the research of schizophrenia and were discussed internationally. The Huber Archive, which was handed over to Bezirkskrankenhaus Günzburg, is currently being catalogued for research purposes. The archive contains Huber's private and professional papers, his writings, and a small partial archive of Kurt Schneider. These archival records not only reflect the development of Gerd Huber's academic career, but also are significant for research on the history of psychiatry in postwar West Germany, the development of concepts in the fields of schizophrenia research and biological psychiatry, the history of universities and everyday life, and other topics.

3-year incidence and predictors of metabolic syndrome in schizophrenia in the national FACE-SZ cohort

AimsMetabolic Syndrome (MetS) is a major health epidemic of Western countries and patients with schizophrenia is a particularly vulnerable population due to lifestyle, mental illness and treatment factors. However, we lack prospective data to guide prevention. The aim of our study is then to determine MetS incidence and predictors in schizophrenia. MethodParticipants were recruited in 10 expert centers at a national level and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Inverse probability weighting methods were used to correct for attrition bias. ResultsAmong the 512 participants followed-up for 3 years, 77.9% had at least one metabolic disturbance. 27.5% were identified with MetS at baseline and excluded from the analyses. Among the rest of participants (N = 371, mean aged 31.2 (SD = 9.1) years, with mean illness duration of 10.0 (SD = 7.6) years and 273 (73.6%) men), MetS incidence was 20.8% at 3 years and raised to 23.6% in tobacco smokers, 29.4% in participants receiving antidepressant prescription at baseline and 42.0% for those with 2 disturbed metabolic disturbances at baseline. Our multivariate analyses confirmed tobacco smoking and antidepressant consumption as independent predictors of MetS onset (adjusted odds ratios (aOR) = 3.82 [1.27–11.45], p = 0.016, and aOR = 3.50 [1.26–9.70], p = 0.0158). Antidepressant prescription predicted more specifically increased lipid disturbances and paroxetine was associated with the highest risk of MetS onset. ConclusionThese results are an alarm call to prioritize MetS prevention and research in schizophrenia. We have listed interventions that should be actively promoted in clinical practice.

Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders

Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers. In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding. Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p<0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated. The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention. Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation.

Dopamine, Psychosis, and Symptom Fluctuation: A Narrative Review.

It has been hypothesized since the 1960s that the etiology of schizophrenia is linked to dopamine. In the intervening 60 years, sophisticated brain imaging techniques, genetic/epigenetic advances, and new experimental animal models of schizophrenia have transformed schizophrenia research. The disease is now conceptualized as a heterogeneous neurodevelopmental disorder expressed phenotypically in four symptom domains: positive, negative, cognitive, and affective. The aim of this paper is threefold: (a) to review recent research into schizophrenia etiology, (b) to review papers that elicited subjective evidence from patients as to triggers and repressors of symptoms such as auditory hallucinations or paranoid thoughts, and (c) to address the potential role of dopamine in schizophrenia in general and, in particular, in the fluctuations in schizophrenia symptoms. The review also includes new discoveries in schizophrenia research, pointing to the involvement of both striatal neurons and glia, signaling pathway convergence, and the role of stress. It also addresses potential therapeutic implications. We conclude with the hope that this paper opens up novel avenues of research and new possibilities for treatment.

WITHDRAWN: Structural impairment in superficial and deep white matter and its association with clinical symptoms in schizophrenia: A harmonized, multisite diffusion MRI study

While the disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, superficial white matter (SWM) has drawn less attention in schizophrenia research than deep white matter (DWM). Using the structural equation model (SEM), we aimed to investigate the structural abnormalities of SWM and DWM in schizophrenia and their association with clinical symptoms. We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 schizophrenia patients. After harmonizing the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fiber clustering of the tractography data, resulting in 8 SWM and 33 DWM tracts. In the patient group, we adopted an SEM for the association with clinical symptoms, using the fractional anisotropy (FA) deviation and the Positive and Negative Syndrome Scale scores. Among the 18 tracts with a lower FA in the patient group, the following structures were included in the SEM: the cingulum bundle, genu, rostral body, and isthmus of the corpus callosum; and striato-frontal, superficial frontal, and superficial temporal tracts. The latent variable white matter impairment , consisting of the FA deviations of the seven white matter tracts, was negatively correlated with the latent variable clinical symptom severity (B=-0.23, p=0.047). The negative symptoms (B=1.12) contributed more to the latent variable clinical symptom severity than did the positive symptoms (B=0.74). The SWM and DWM tract structural abnormalities were identified in schizophrenia patients. The association with clinical symptoms was more prominent in the negative symptoms. • The harmonized diffusion MRI data was analyzed using the whole-brain tractography and fiber clustering. • The patients with schizophrenia had a significantly lower FA in 14 DWM and 4 SWM tracts. • The association of white matter impairments with clinical symptoms was more prominent in the negative symptoms.

Challenges and Strategies for the Recruitment of Patients With Schizophrenia in a Research Setting.

BackgroundWith numerous potentially novel targets and pharmacodynamic biomarkers for schizophrenia entering late-stage testing, the next decade will bring an urgent need for well-conducted clinical trials. A critically important step for the successful execution of clinical research trials is timely and appropriate recruitment of participants. Patients with schizophrenia can be especially challenging to recruit due to the disability inherent in psychotic spectrum disorders. Research on how best to recruit for clinical trials is understudied. Clearly defining a model for recruitment procedures would be valuable for researchers, and, by extension, the patient populations who may benefit from the insight gained by future clinical research.MethodsThis article aims to offer suggestions for recruitment based on years of experience at the Columbia Schizophrenia Research Clinic (CSRC), a hub for clinical trials focusing on the etiology and treatment of various psychotic disorders.ResultsThe present report provides practical, step-by-step recommendations for implementing the highly effective CSRC recruitment model, including the benefits of two recruitment initiatives that were instituted in 2018—hiring a dedicated recruiter and targeted chart reviews at affiliated clinics. Other topics discussed include our umbrella protocol and database, advertising, and tips for collaborating with external sites.ConclusionsDespite ongoing complications due to COVID-19, these strategies have been successful, increasing the rate of both consents and study enrolments by ~40% and allowing the CSRC to conduct multiple studies simultaneously.

A Mini-Review Regarding the Modalities to Study Neurodevelopmental Disorders-Like Impairments in Zebrafish-Focussing on Neurobehavioural and Psychological Responses.

Neurodevelopmental disorders (NDDs) are complex disorders which can be associated with many comorbidities and exhibit multifactorial-dependent phenotypes. An important characteristic is represented by the early onset of the symptoms, during childhood or young adulthood, with a great impact on the socio-cognitive functioning of the affected individuals. Thus, the aim of our review is to describe and to argue the necessity of early developmental stages zebrafish models, focusing on NDDs, especially autism spectrum disorders (ASD) and also on schizophrenia. The utility of the animal models in NDDs or schizophrenia research remains quite controversial. Relevant discussions can be opened regarding the specific characteristics of the animal models and the relationship with the etiologies, physiopathology, and development of these disorders. The zebrafish models behaviors displayed as early as during the pre-hatching embryo stage (locomotor activity prone to repetitive behavior), and post-hatching embryo stage, such as memory, perception, affective-like, and social behaviors can be relevant in ASD and schizophrenia research. The neurophysiological processes impaired in both ASD and schizophrenia are generally highly conserved across all vertebrates. However, the relatively late individual development and conscious social behavior exhibited later in the larval stage are some of the most important limitations of these model animal species.

Schizophrenia: A Narrative Review of Etiopathogenetic, Diagnostic and Treatment Aspects.

Although schizophrenia is currently conceptualized as being characterized as a syndrome that includes a collection of signs and symptoms, there is strong evidence of heterogeneous and complex underpinned etiological, etiopathogenetic, and psychopathological mechanisms, which are still under investigation. Therefore, the present viewpoint review is aimed at providing some insights into the recently investigated schizophrenia research fields in order to discuss the potential future research directions in schizophrenia research. The traditional schizophrenia construct and diagnosis were progressively revised and revisited, based on the recently emerging neurobiological, genetic, and epidemiological research. Moreover, innovative diagnostic and therapeutic approaches are pointed to build a new construct, allowing the development of better clinical and treatment outcomes and characterization for schizophrenic individuals, considering a more patient-centered, personalized, and tailored-based dimensional approach. Further translational studies are needed in order to integrate neurobiological, genetic, and environmental studies into clinical practice and to help clinicians and researchers to understand how to redesign a new schizophrenia construct.

Affinity scores: An individual-centric fingerprinting framework for neuropsychiatric disorders

Population-centric frameworks of biomarker identification for psychiatric disorders focus primarily on comparing averages between groups and assume that diagnostic groups are (1) mutually-exclusive, and (2) homogeneous. There is a paucity of individual-centric approaches capable of identifying individual-specific ‘fingerprints’ across multiple domains. To address this, we propose a novel framework, combining a range of biopsychosocial markers, including brain structure, cognition, and clinical markers, into higher-level ‘fingerprints’, capable of capturing intra-illness heterogeneity and inter-illness overlap. A multivariate framework was implemented to identify individualised patterns of brain structure, cognition and clinical markers based on affinity to other participants in the database. First, individual-level affinity scores defined each participant’s “neighbourhood” across each measure based on variable-specific hop sizes. Next, diagnostic verification and classification algorithms were implemented based on multivariate affinity score profiles. To perform affinity-based classification, data were divided into training and test samples, and 5-fold nested cross-validation was performed on the training data. Affinity-based classification was compared to weighted K-nearest neighbours (KNN) classification. The framework was applied to the Australian Schizophrenia Research Bank (ASRB) dataset, which included data from individuals with chronic and treatment resistant schizophrenia and healthy controls. Individualised affinity scores provided a ‘fingerprint’ of brain structure, cognition, and clinical markers, which described the affinity of an individual to the representative groups in the dataset. Diagnostic verification capability was moderate to high depending on the choice of multivariate affinity metric. Affinity score-based classification achieved a high degree of accuracy in the training, nested cross-validation and prediction steps, and outperformed KNN classification in the training and test datasets. Affinity scores demonstrate utility in two keys ways: (1) Early and accurate diagnosis of neuropsychiatric disorders, whereby an individual can be grouped within a diagnostic category/ies that best matches their fingerprint, and (2) identification of biopsychosocial factors that most strongly characterise individuals/disorders, and which may be most amenable to intervention.

Magnetic Resonance Imaging throughout the Clinical Course of Schizophrenia: Neurobiological Underpinnings and Clinical Implications.

As a non-invasive detection method and an advanced imaging method, magnetic resonance imaging (MRI) has been widely used in the research of schizophrenia. Although a large number of neuroimaging studies have confirmed that MRI can display abnormal brain phenotypes in patients with schizophrenia, no valid uniform standard has been established for its clinical application. On the basis of previous evidence, we argue that MRI is an important tool throughout the whole clinical course of schizophrenia. The purpose of this commentary is to systematically describe the role of MRI in schizophrenia and to provide references for its clinical application.

The effect of ketamine on delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb

Respiratory rhythm plays an important role in cognitive functions in rodents, as well as in humans. Respiratory related oscillation (RRO), generated in the olfactory bulb (OB), is an extrinsic rhythm imposed on brain networks. In rats, RRO can couple with intrinsic brain oscillations at theta frequency during sniffing and in the delta range outside of such episodes. Disruption of gamma synchronization in cortical networks by ketamine is well established whereas its effects on slow rhythms are poorly understood. We found in this study, that RRO in prefrontal cortex (PFC) and hippocampus (HC) remains present after ketamine injection, even on the background of highly unstable respiratory rate, co-incident with “psychotic-like” behavior and abnormal cortical gamma activity. Guided by the timing of ketamine-induced gamma reaction, pairwise coherences between structures exhibiting RRO and their correlation structure was statistically tested in 5-min segments post-injection (0–25 min) and during recovery (1, 5, 10 h). As in control, RRO in the OB was firmly followed by cortical-bound OB exits directed toward PFC but not to HC. RRO between these structures, however, significantly correlated with OB-HC but not with OB-PFC. The only exception to this general observation was observed during a short transitional period, immediately after injection. Ketamine has a remarkable history in psychiatric research. Modeling chronic NMDA-hypofunction using acute NMDA-receptor blockade shifted the primary focus of schizophrenia research to dysfunctional cortical microcircuitry and the recent discovery of ketamine’s antidepressant actions extended investigations to neurophysiology of anxiety and depression. Cortical oscillations are relevant for understanding their pathomechanism.

Cortical changes in patients with schizophrenia across two ethnic backgrounds

While it is known that cultural background influences the healthy brain, less is known about how it affects cortical changes in schizophrenia. Here, we tested whether schizophrenia differentially affected the brain in Japanese and German patients. In a sample of 155 patients with a diagnosis of schizophrenia and 191 healthy controls from Japan and Germany, we acquired 3 T-MRI of the brain. We subsequently compared cortical thickness and cortical surface area to identify whether differences between healthy controls and patients might be influenced by ethnicity. Additional analyses were performed to account for effects of duration of illness and medication. We found pronounced interactions between schizophrenia and cultural background in the cortical thickness of several areas, including the left inferior and middle temporal gyrus, as well as the right lateral occipital cortex. Regarding cortical surface area, interaction effects appeared in the insula and the occipital cortex, among others. Some of these brain areas are related to the expression of psychotic symptoms, which are known to differ across cultures. Our results indicate that cultural background impacts cortical structures in different ways, probably resulting in varying clinical manifestations, and call for the inclusion of more diverse samples in schizophrenia research.

Neural Correlates of Facial Emotion Recognition in Non-help-seeking University Students With Ultra-High Risk for Psychosis.

BackgroundSince the introduction of the neurodevelopmental perspective of schizophrenia research on individuals at ultra-high risk for psychosis (UHR) has gained increasing interest, aiming at early detection and intervention. Results from fMRI studies investigating behavioral and brain functional changes in UHR during facial emotion recognition, an essential component of social cognition, showed heterogenous results, probably due clinical diversity across these investigations. This fMRI study investigated emotion recognition in a sub-group of the UHR spectrum, namely non-help-seeking, drug-naïve UHR with high cognitive functioning to reveal the neurofunctional underpinnings of their social functioning in comparison to healthy controls.MethodsTwo large cohorts of students from an elite University (n1 = 4,040, n2 = 4,364) were screened firstly with the Prodromal Questionnaires and by surpassing predefined cut-offs then interviewed with the semi-structured Interview for Psychosis-Risk Syndromes to verify their UHR status. Twenty-one identified non-help-seeking UHR and 23 non-UHR control subjects were scanned with functional magnetic resonance imaging while classifying emotions (i.e., neutral, happy, disgust and fear) in a facial emotion recognition task.ResultsBehaviorally, no group differences were found concerning accuracy, reaction times, sensitivity or specificity, except that non-help-seeking UHR showed higher specificity when recognizing neutral facial expressions. In comparison to healthy non-UHR controls, non-help-seeking UHR showed generally higher activation in the superior temporal and left Heschl's gyrus as well as in the somatosensory, insular and midcingulate cortex than the control subjects during the entire recognition task regardless of the emotion categories. In an exploratory analysis, in the non-help-seeking UHR group, functional activity in the left superior temporal gyrus was significantly correlated with deficits in the ability to experience emotions at uncorrected statistical thresholds.ConclusionsCompared to healthy controls, non-help-seeking UHR show no behavioral deficits during facial emotion recognition, but functional hyperactivities in brain regions associated with this cognitive process. Our study may inspire future early intervention and provide loci for treatment using neural stimulation.

A family study on first episode of psychosis patients: exploring neuropsychological performance as an endophenotype

IntroductionFamily studies provide the opportunity to investigate endophenotypes as a powerful neurobiological platform to better understand the underlying neurobiological mechanisms of schizophrenia spectrum disorders. Shared features between the patients and their first-degree relatives may shed some light on the path to identify potential causes of psychosis, and to implement preventive and therapeutic interventions.ObjectivesThis study aimed to explore and compare neuropsychological measures in first episodes of psychosis (FEP) patients, their first-degree relatives and healthy controls (HC), participants on the PAFIP-FAMILIES project.Methods Statistical analyses were performed using one-way ANOVA, followed by multiple comparisons test where appropriate. Age, sex and years of education were introduced as covariates.Results From 387 eligible FEP patients enrolled in a previous cohort, 133 were included. In addition, 244 of their first-degree relatives (146 parents and 98 siblings) and 202 HC participated in this study (see Figure 1). In general, relatives showed an intermediate neuropsychological performance between the HC and the FEP patients (see Figure 2). Specifically, siblings performed similar to HC in the domains verbal memory, visual memory, working memory, motor dexterity and theory of mind, since their values practically overlap those of HC. The parents presented significant deficits, similar to that of the affected individuals, in executive functions and attention domains.ConclusionsThese findings suggest that executive and attention dysfunction might have a greater family aggregation and could be a relevant cognitive endophenotype for psychotic disorders. The study shows the potential of exploring intra-family neuropsychological performance supporting neurobiological and genetic research in schizophrenia.DisclosureNo significant relationships.

The Evidence Base For Psychiatric Support For Living Independently And Being Included In The Community

Functional recovery of subjects with schizophrenia remains an unmet need despite the availability of effective pharmacological and psychosocial treatments. The focus of recovery-oriented approaches is on fostering hope and resilience, fighting self-stigma, supporting self-determination and promoting social inclusion. The implementation of recovery-oriented plans requires an in depth understanding of key factors influencing real-life functioning, health status and quality of life. Recently published data from the Italian Network for Research on Psychoses have provided evidence that baseline variables associated with functional outcome at follow-up included domains not routinely assessed and targeted by intervention programs in community mental health services. As pointed out by experts in schizophrenia research and care, the management of subjects with schizophrenia has not significantly improved and only a minority of them receives integrated and personalized treatments. Shared decision-making and integrated pharmacological and psychosocial treatments, tailored on subjects’ needs, might significantly improve the outcome of subjects with schizophrenia, supporting independent living and inclusion in the community.DisclosureHonoraria, advisory board, or consulting fees from Angelini, Astra Zeneca, Bristol-Myers Squibb, Gedeon Richter Bulgaria, Innova-Pharma, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer, and Pierre Fabre, for services not related to this abstract

Treatment and Qualitative Research of Schizophrenia

IntroductionThe author demonstrates the psychodynamic understanding of schizophrenia and describes the ensuing personality-structural psychotherapy. Schizophrenia from a psychodynamic understanding is a disease in the core of the identity with disturbances of the personality functions of identity, ego-demarcation, aggression, fear, narcissism, perception, cognitive abilities and the body- ego. It is the concern of the author to investigate how schizophrenically structured patients and their family members experience the group dynamic field in which the patients grew up and its relations to the illness. The following five topics: contact and experiences within the family of childhood, body care and physical contact, kindergarden and school life, puberty, and contacts outside the family have been investigated.ObjectivesThe aim is to show how the family settings and backgrounds are conducive to developing schizophreniaMethodsThe author chosed for her investigation the method of biographical interviews, introduced by Witzel (1985). This method of interviewing is problem centered, object and process oriented. The analysis of the exhaustive tape-recorded interviews was made by using the method of qualitative analysis based on the grounded theory.ResultsSchizophrenia from psychodynamic understanding is a disease in the core of the identity with disturbances of the personality functions of identity, ego-demarcation, aggression, fear, narcissism, perception, cognitive abilities and the body- ego.ConclusionsIt is the concern of the author to investigate how schizophrenically structured patients and their family members experience the group dynamic social energetic field in which the patients grew up and its relations to the illnessDisclosureNo significant relationships.

The Potential Relationship Between The Environmental Risk Factors And Social Cognition in Psychosis

IntroductionIn schizophrenia research, little is known about the relationship of environmental exposures with social cognition deficits.ObjectivesWe aimed to investigate the relationship between social cognitive performance and well-defined environmental risk factors (childhood adversities, birth season, paternal age, obstetric complications, urban living i.e.) in schizophrenia.Methods54 schizophrenia patients and 37 healthy controls (HCs) were included in our study. Participants in both groups were of similar age, gender, and educational level. Two theory of mind (ToM) tests (DEZIKÖ and RMET), and the Childhood Trauma Questionnaire (CTQ) were applied. ToM test scores among groups (patients with/ without risk factors, and HC) were compared using analysis of variance.ResultsOverall, the schizophrenia group scored higher on the CTQ and performed worse on ToM tests than the HCs. Patients were more likely to report obstetric complications, advanced paternal age, winter and rural birth. Both the patients having high and low CTQ scores performed poorer on the RMET and false belief test than HCs. However, there was no significant difference in DEZİKÖ-total scores of patients with low CTQ scores and HCs. Patients with advanced paternal age at birth achieved lower faux pas sub-scores. Urban birth and RMET scores were positively correlated in patients.ConclusionsOur findings suggest the environmental factors such as childhood traumas, advanced paternal age, and rural birth seem to negatively affect the social cognitive performance of schizophrenia patients.DisclosureNo significant relationships.

Schizophrenia in Translation: Why the Eye?

Schizophrenia is increasingly recognized as a systemic disease, characterized by dysregulation in multiple physiological systems (eg, neural, cardiovascular, endocrine). Many of these changes are observed as early as the first psychotic episode, and in people at high risk for the disorder. Expanding the search for biomarkers of schizophrenia beyond genes, blood, and brain may allow for inexpensive, noninvasive, and objective markers of diagnosis, phenotype, treatment response, and prognosis. Several anatomic and physiologic aspects of the eye have shown promise as biomarkers of brain health in a range of neurological disorders, and of heart, kidney, endocrine, and other impairments in other medical conditions. In schizophrenia, thinning and volume loss in retinal neural layers have been observed, and are associated with illness progression, brain volume loss, and cognitive impairment. Retinal microvascular changes have also been observed. Abnormal pupil responses and corneal nerve disintegration are related to aspects of brain function and structure in schizophrenia. In addition, studying the eye can inform about emerging cardiovascular, neuroinflammatory, and metabolic diseases in people with early psychosis, and about the causes of several of the visual changes observed in the disorder. Application of the methods of oculomics, or eye-based biomarkers of non-ophthalmological pathology, to the treatment and study of schizophrenia has the potential to provide tools for patient monitoring and data-driven prediction, as well as for clarifying pathophysiology and course of illness. Given their demonstrated utility in neuropsychiatry, we recommend greater adoption of these tools for schizophrenia research and patient care.

Perceptions of causal attribution and attitudes to genetic testing among people with schizophrenia and their first-degree relatives

Rapid advances in the genetics of psychiatric disorders mean that diagnostic and predictive genetic testing for schizophrenia risk may one day be a reality. This study examined how causal attributions for schizophrenia contribute to interest in a hypothetical genetic test. People with schizophrenia and first-degree relatives of people with schizophrenia were recruited through a schizophrenia research bank and mental health organisation. Semi-structured telephone interviews were conducted with 13 individuals with schizophrenia and 8 first-degree relatives. Transcripts were subjected to a qualitative analysis using the thematic analysis framework. Five themes were developed: (i) “It is like a cocktail”, with most participants aware that both genetic and environmental factors contributed to causation, and many mentioning the positive impact of genetic causal explanations; (ii) “Knowledge is power” (i.e., in favour of genetic testing); (iii) Genetic testing provides opportunities for early intervention and avoiding triggers, with participants citing a wide range of perceived benefits of genetic testing but few risks; (iv) Views on reproductive genetic testing for schizophrenia risk with a few participants viewing it as “playing God” but not necessarily being against it; and (v) “It snowballs”, whereby participants’ understanding of genetics was sophisticated with most believing that multiple rather than single genes contributed to schizophrenia. In conclusion, many individuals had a sound understanding of the role of genetic testing if it were to become available, with evidence of insight into the role of multiple genes and the contribution of other risk factors that may interact with any inherited genetic risk.

Startle Latency as a Potential Marker for Amygdala-Mediated Hyperarousal

BackgroundFear-related disorders are characterized by hyperexcitability in reflexive circuits and maladaptive associative learning mechanisms. The startle reflex is suited to investigate both processes, either by probing it under baseline conditions or by deriving it in fear conditioning studies. In anxiety research, the amplitude of the fear-potentiated startle has been shown to be influenced by amygdalar circuits and has typically been the readout of interest. In schizophrenia research, prolonged startle peak latency under neutral conditions is an established readout, thought to reflect impaired processing speed. We therefore explored whether startle latency is an informative readout for human anxiety research. MethodsWe investigated potential similarities and differences of startle peak latency and amplitude derived from a classical fear conditioning task in a sample of 206 participants with varying severity levels of anxiety disorders and healthy control subjects. We first reduced startle response to stable components and regressed individual amygdala gray matter volumes onto the resulting startle measures. We then probed time, stimulus, and group effects of startle latency. ResultsWe showed that startle latency and startle amplitude were 2 largely uncorrelated measures; startle latency, but not amplitude, showed a sex-specific association with gray matter volume of the amygdala; startle latencies showed a fear-dependent task modulation; and patients with fear-related disorders displayed shorter startle latencies throughout the fear learning task. ConclusionsThese data provide support for the notion that probing startle latencies under threat may engage amygdala-modulated threat processing, making them a complementary marker for human anxiety research.