Neuroanatomical abnormalities in first-episode psychosis across independent samples: a multi-centre mega-analysis

Abstract

Background Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples. Methods Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. Results FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms. Conclusions This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.

Latent clinical-anatomical dimensions of schizophrenia

“…An emerging literature points to a continuous unimodal-transmodal cortical synaptic hierarchy 81,82 , manifesting as smooth topographic gradients of gene transcription 83,84 , intracortical myelin 85,86 , cortical thickness 87 , excitation-inhibition balance 88 , and macroscale structural and functional connectivity 63,89–91 . Our results show that the dominant cognitive-negative dimension originates from the ends or “anchors” of this hierarchy: the visual 15,92 and default mode networks 93–95 . This raises the possibility that multiple pathological processes, originating from opposing ends of the putative sensory-fugal hierarchy, may be involved in the disease.…”

Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 2,952 Individuals Assessed in a Worldwide ENIGMA Study

“…Converging evidence from neuroimaging research also supports a dimensional view of psychosis. Cortical neuroanatomical abnormalities have been reported in individuals with treatment resistant SZ [27], chronic SZ [28], first-episode psychosis [29], CHR [30,31], schizotypal personality disorders [32], and individuals with non-clinical psychotic symptoms [33]. Recently, the SZ Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust abnormalities in subcortical volumes [34], cortical thickness (CT), and surface area (SA) in SZ [28], while also indicating that these abnormalities may be influenced by illness severity and antipsychotic medication [28,34].…”

Magnetic resonance imaging for early detection schizophrenia

“…Since the seminal findings of enlarged lateral ventricles in patients with schizophrenia described by Johnstone and colleagues in the mid-1970s [8], neuroimaging has advanced our understanding of brain abnormalities and pathophysiological mechanisms of schizophrenia. Localised and large-scale morphometric and functional alterations of multiple brain systems can be found across all stages of the disease including clinical high-risk individuals [9][10][11], early psychosis [12][13][14] and chronic schizophrenia [15][16][17]. MRI-based biomarkers predicting the transition from unspecific prodromal symptoms to psychosis [18][19][20][21], as well as distinguishing different subpopulations [22][23][24] and symptom dimensions [25][26][27][28], have been frequently reported.…”