Publications by authors named "Stephen Lawrie"

Background: The choroid plexus is an important structure within the ventricular system. Schizophrenia has been associated with morphological changes to the choroid plexus but the presence and extent of alterations at different illness stages is unclear.

Methods: We examined choroid plexus volumes in participants at clinical high-risk for psychosis (N = 110), participants with first-episode psychosis (N = 37), participants with schizophrenia (N = 28), clinical (N = 38) and non-clinical controls (N = 75).

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Clinical high-risk for psychosis (CHR-P) individuals are typically recruited from clinical services but the clinical and functional outcomes of community-recruited CHR-P individuals remain largely unclear. The Youth Mental Health Risk and Resilience Study (YouR-Study) obtained a community sample of CHR-P individuals through an online-screening approach and followed-up these individuals for a period of up to 3 years to determine transition rates, persistence of attenuated psychotic symptoms (APS) and functional outcomes. Baseline data were obtained from  = 144 CHR-P participants,  = 51 participants who met online cutoff criteria but not CHR-P criteria (CHR-Ns), and  = 58 healthy controls.

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Background And Hypotheses: In the past 2 decades, substantial effort has been put into research on therapeutic options for people at ultra-high risk (UHR) for developing a first episode of psychosis (FEP), focusing on omega-3 polyunsaturated fatty acids (PUFAs) in preventing transition to psychosis. Despite an initial positive finding, subsequent studies failed to find a beneficial effect. The current study aimed to further investigate the effect of omega-3 PUFAs in UHR, to determine whether this line of research is worth pursuing.

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Article Synopsis
  • Subcortical brain structures play a crucial role in various developmental and psychiatric disorders, and a study analyzed brain volumes in 74,898 individuals, identifying 254 genetic loci linked to these volumes, which accounted for up to 35% of variation.
  • The research included exploring gene expression in specific neural cell types, focusing on genes involved in intracellular signaling and processes related to brain aging.
  • The findings suggest that certain genetic variants not only influence brain volume but also have potential causal links to conditions like Parkinson’s disease and ADHD, highlighting the genetic basis for risks associated with neuropsychiatric disorders.
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Article Synopsis
  • The editorial explores what makes academic psychiatry unique and what qualities define psychiatrists as academics.
  • It highlights the importance of academic psychiatry in enhancing clinical services and patient care.
  • The piece emphasizes the need to inspire and encourage the upcoming generation to pursue careers in academic psychiatry.
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Article Synopsis
  • Researchers tried to create models to predict how well people with first episode psychosis (FEP) would do after treatment, but it was hard to tell if these predictions worked for different groups of patients.
  • They tested these models using patients from two big studies in Europe and found out that while the models were somewhat accurate, they didn't work as well when applied to patients from a different study.
  • The results showed that it’s really important to check and improve these prediction models with independent samples of patients to make them better and more reliable in the future.
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Article Synopsis
  • Subcortical brain structures play a crucial role in various disorders, and a study analyzed the genetic basis of brain volumes in nearly 75,000 individuals of European ancestry, revealing 254 loci linked to these volumes.
  • The research identified significant gene expression in neural cells, relating to brain aging and signaling, and found that polygenic scores could predict brain volumes across different ancestries.
  • The study highlights genetic connections between brain volumes and conditions like Parkinson's disease and ADHD, suggesting specific gene expression patterns could be involved in neuropsychiatric disorders.
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Bipolar disorder (BD) involves autonomic nervous system dysfunction, detectable through heart rate variability (HRV). HRV is a promising biomarker, but its dynamics during acute mania or depression episodes are poorly understood. Using a Bayesian approach, we developed a probabilistic model of HRV changes in BD, measured by the natural logarithm of the Root Mean Square of Successive RR interval Differences (lnRMSSD).

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Background: Personal sensing, leveraging data passively and near-continuously collected with wearables from patients in their ecological environment, is a promising paradigm to monitor mood disorders (MDs), a major determinant of the worldwide disease burden. However, collecting and annotating wearable data is resource intensive. Studies of this kind can thus typically afford to recruit only a few dozen patients.

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Despite the functional impact of cognitive deficit in people with psychosis, objective cognitive assessment is not typically part of routine clinical care. This is partly due to the length of traditional assessments and the need for a highly trained administrator. Brief, automated computerised assessments could help to address this issue.

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Background: The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes.

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Background: We examined the course of illness over a 12-month period in a large, international multi-center cohort of people with a first-episode schizophrenia spectrum disorder (FES) in a naturalistic, prospective study (PSYSCAN).

Method: Patients with a first episode of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder were recruited at 16 institutions in Europe, Israel and Australia. Participants (N = 304) received clinical treatment as usual throughout the study.

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Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK).

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Background: Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N<50). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions.

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The non-reporting of negative studies results in a scientific record that is incomplete, one-sided and misleading. The consequences of this range from inappropriate initiation of further studies that might put participants at unnecessary risk to treatment guidelines that may be in error, thus compromising day-to-day clinical practice.

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Major depressive disorder often originates in adolescence and is associated with long-term functional impairment. Mechanistically characterizing this heterogeneous illness could provide important leads for optimizing treatment. Importantly, reward learning is known to be disrupted in depression.

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Malawi has a population of around 20 million people and is one of the world's most economically deprived nations. Severe mental illness (largely comprising psychoses and severe mood disorders) is managed by a very small number of staff in four tertiary facilities, aided by clinical officers and nurses in general hospitals and clinics. Given these constraints, psychosis is largely undetected and untreated, with a median duration of untreated psychosis (DUP) of around six years.

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People with psychosis in Malawi have very limited access to timely assessment and evidence-based care, leading to a long duration of untreated psychosis and persistent disability. Most people with psychosis in the country consult traditional or religious healers. Stigmatising attitudes are common and services have limited capacity, particularly in rural areas.

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Background: Schizophrenia is a heritable psychiatric disorder with a polygenic architecture. Genome-wide association studies have reported that an increasing number of risk-associated variants and polygenic risk scores (PRSs) explain 17% of the variance in the disorder. Substantial heterogeneity exists in the effect of these variants, and aggregating them based on biologically relevant functions may provide mechanistic insight into the disorder.

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Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals.

Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder.

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Background: This study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps.

Methods: Magnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl's gyri and bilateral superior temporal gyri.

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Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms.

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Dysfunction of glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia and may be particularly relevant in severe, treatment-resistant symptoms. The underlying mechanism may involve hypofunction of the NMDA receptor. We investigated whether schizophrenia-related pathway polygenic scores, composed of genetic variants within NMDA receptor encoding genes, are associated with cortical glutamate in schizophrenia.

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