Recent Advances and Future Directions in Brain MR Imaging Studies in Schizophrenia: Toward Elucidating Brain Pathology and Developing Clinical Tools

Abstract

Schizophrenia is a common severe psychiatric disorder that affects approximately 1% of general population through the life course. Historically, in Kraepelin's time, schizophrenia was a disease unit conceptualized as dementia praecox; however, since then, the disease concept has changed. Recent MRI studies had shown that the neuropathology of the brain in this disorder was characterized by mild progression before and after the onset of the disease, and that the brain alterations were relatively smaller than assumed. Although genetic factors contribute to the brain alterations in schizophrenia, which are thought to be trait differences, other changes include factors that are common in psychiatric diseases. Furthermore, it has been shown that the brain differences specific to schizophrenia were relatively small compared to other changes, such as those caused by brain development, aging, and gender. In addition, compared to the disease and participant factors, machine and imaging protocol differences could affect MRI signals, which should be addressed in multi-site studies. Recent advances in MRI modalities, such as multi-shell diffusion-weighted imaging, magnetic resonance spectroscopy, and multimodal brain imaging analysis, may be candidates to sharpen the characterization of schizophrenia-specific factors and provide new insights. The Brain/MINDS Beyond Human Brain MRI (BMB-HBM) project has been launched considering the differences and noises irrespective of the disease pathologies and includes the future perspectives of MRI studies for various psychiatric and neurological disorders. The sites use restricted MRI machines and harmonized multi-modal protocols, standardized image preprocessing, and traveling subject harmonization. Data sharing to the public will be planned in FY 2024. In the future, we believe that combining a high-quality human MRI dataset with genetic data, randomized controlled trials, and MRI for non-human primates and animal models will enable us to understand schizophrenia, elucidate its neural bases and therapeutic targets, and provide tools for clinical application at bedside.

Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study

“…In line with previous studies of volumetric alterations in the schizophrenia spectrum, 1–6 , 13 we found that a pattern of morphological features, including the IFG pars triangularis, putamen, and pallidum contributed to the identification of ChSZ patients. Using a manual tracing method within the IFG, we previously found that the volume reduction in the IFG pars triangularis is a disease-specific feature in the schizophrenia spectrum, such as UHR, 21 FEP, 21 and ChSZ, 23 and the extent of structural alteration was associated with brain activity during a verbal fluency test in FEP.…”

Human Brain Magnetic Resonance Imaging Studies for Psychiatric Disorders: The Current Progress and Future Directions

“…This limitation needs to be considered when demographic variables are known to affect biological markers, such as brain measurements. In this case, large samples with a wide age range (e.g., more than 1,000 HCs from those aged 15-60 years) are needed to determine the deviation from normative healthy development and aging (18) , (29) , (30) , (31) . These complications do not discourage the use of the cross-disorder study approach, but instead, they emphasize the need for better qualitative controls capable of considering both clinical disorder progression and additional confounding demographics.…”

“…Magnetic resonance imaging (MRI) has been used as a candidate research tool in elucidating the pathological characteristics of these disorders and applying the biological markers to clinical settings in the future (18) . In this review, we intend to introduce a selection of recent and relevant MRI studies to highlight the current progress and limitations of MRI research in psychiatry.…”

Alterations in subcortical magnetic susceptibility and disease-specific relationship with brain volume in major depressive disorder and schizophrenia

“…In fact, previous studies reported altered subcortical volumes in various psychiatric disorders, including MDD and schizophrenia (7)(8)(9)(10)(11)(12). Subcortical regions, including the caudate [7,8], thalamus, and hippocampus [8], are found to be smaller in MDD patients compared to healthy controls (HCs); however, the study conducted using MRI of 8,590 samples from the UK Biobank did not observe any statistically signi cant differences between individuals with depressive symptoms and HCs in any of the subcortical volumes [9].…”

“…Subcortical regions, including the caudate [7,8], thalamus, and hippocampus [8], are found to be smaller in MDD patients compared to healthy controls (HCs); however, the study conducted using MRI of 8,590 samples from the UK Biobank did not observe any statistically signi cant differences between individuals with depressive symptoms and HCs in any of the subcortical volumes [9]. In contrast, in schizophrenia several consistent changes in subcortical volume have been reported [10,11]. The Enhancing Neuroimaging Genetics through Mega-Analysis (ENIGMA) Consortium Schizophrenia Working Group conducted a multicenter meta-analysis and found that patients with schizophrenia had smaller volumes in the hippocampus, amygdala, thalamus, and accumbens and larger volumes in the pallidum compared to HCs [12].…”