Brain morphology in antipsychotic-naïve schizophrenia: A study of multiple brain structures

BackgroundAlthough brain volume changes are found in schizophrenia, only a limited number of structural magnetic resonance imaging studies have exclusively examined antipsychotic-naïve patients.AimsTo comprehensively investigate multiple brain structures in a single sample of patients who were antipsychotic-naïve.MethodTwenty antipsychotic-naïve patients with first-episode schizophrenia and 20 healthy comparison subjects were included. Intracranial, total brain, frontal lobe, grey and white matter, cerebellar, hippocampal, parahippocampal, thalamic, caudate nucleus and lateral and third ventricular volumes were measured. Repeated-measures analyses of (co)variance were conducted with intracranial volume as covariate.ResultsThird ventricle volume enlargement was found in patients compared with the healthy subjects. No differences were found in other brain regions.ConclusionsThese findings suggest that some brain abnormalities are present in the early stages of schizophrenia. Moreover, it suggests that brain abnormalities reported in patients with chronic schizophrenia develop in a later stage of the disease and/or are medication induced.

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Multi-scale analysis of schizophrenia risk genes, brain structure, and clinical symptoms reveals integrative clues for subtyping schizophrenia patients

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjy071 ◽

2018 ◽

Vol 11 (8) ◽

pp. 678-687

Author(s):

Liang Ma ◽

Edmund T Rolls ◽

Xiuqin Liu ◽

Yuting Liu ◽

Zeyu Jiao ◽

...

Keyword(s):

Clinical Symptoms ◽

Brain Structures ◽

Brain Regions ◽

First Episode ◽

Grey Matter Volume ◽

Scale Analysis ◽

Risk Genes ◽

Multi Scale ◽

Scale Scores ◽

Multi Scale Analysis

AbstractAnalysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene expression, grey matter volume (GMV), and the positive and negative syndrome scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development. Among these 108 candidates, 19 distinct genes were found associated with 16 brain regions referred to as hot clusters (HCs), primarily in the frontal cortex, sensory-motor regions and temporal and parietal regions. The patients were subtyped into three groups with distinguishable PANSS scores by the GMV of the identified HCs. Furthermore, we found that HCs with common GMV among patient groups are related to genes that mostly mapped to pathways relevant to neural signaling, which are associated with the risk for schizophrenia. Our results provide an integrated view of how genetic variants may affect brain structures that lead to distinct disease phenotypes. The method of multi-scale analysis that was described in this research, may help to advance the understanding of the etiology of schizophrenia.

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Diffusion tensor imaging (DTI) findings in schizophrenia: A review

European Psychiatry ◽

10.1016/s0924-9338(11)72665-7 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 960-960

Author(s):

J.L. Villegas Martínez ◽

J.A. Blanco Garrote ◽

F. Uribe Ladrón de Cegama ◽

B. Arribas Simón ◽

G. Cabús Piñol

Keyword(s):

Diffusion Tensor Imaging ◽

Diffusion Tensor ◽

Cochrane Review ◽

Brain Structures ◽

Brain Regions ◽

Parahippocampal Gyrus ◽

First Episode ◽

Chronic Patients ◽

Brain White Matter ◽

Diffusion Tensor Imaging Dti

IntroductionDiffusion tensor imaging (DTI) is a magnetic resonance imaging technique that have increasingly being used for the non-invasive evaluation of brain white matter (WM) abnormalities. Several studies suggest that the normal integration of cerebral function may be compromised in schizophrenia. Abnormalities in WM tracts may be directly relevant for the neuropathology of schizophrenia.ObjetivesThe purpose of this review was to discuss recent DTI findings in schizophrenia and a methodologic analysis.MethodsThe literature search was performed with the search engine PubMed of the U.S. National Library of Medicine. Search strategy used was based on the Cochrane review technique, limited to the period between 1998 (first report on DTI and schizophrenia) and May 2010. And limited to ‘Title/Abstract’. The reference lists of these studies were used to identify additional studies.ResultsThere is a striking amount of heterogeneity in findings, probably by methodologic problems. Brain regions such as the cingulate bundle, corpus callosum, and regions within frontal and temporal WM have a proportionally larger number of positive findings across the studies. In addition, WM tracts as The superior longitudinal fasciculus, fronto-occipital longitudinal fasciculi, uncinate fasciculi, frontal longitudinal fasciculus and the arcuate fasciculus have also positive findings in patients with schizophrenia. Other brain structures as the cerebellar peduncles, the fornix, the hippocampus and parahippocampal gyrus, the thalamic and optic radiations have been evaluated and shown positive findings. However, these findings are not present in all studies. DTI abnormalities in first-episode patients are less robust than in chronic patients.ConclusionsRecent DTI findings further support the hypothesis of structural dysconnectivity in schizophrenia.

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Genetic Overlap Between Alzheimer’s Disease and Depression Mapped Onto the Brain

Frontiers in Neuroscience ◽

10.3389/fnins.2021.653130 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jennifer Monereo-Sánchez ◽

Miranda T. Schram ◽

Oleksandr Frei ◽

Kevin O’Connell ◽

Alexey A. Shadrin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genome Wide Association Study ◽

Third Ventricle ◽

Brain Mri ◽

Genetic Correlations ◽

Gaussian Mixture ◽

Brain Morphology ◽

Genetic Overlap ◽

Ventricle Volume

Background: Alzheimer’s disease (AD) and depression are debilitating brain disorders that are often comorbid. Shared brain mechanisms have been implicated, yet findings are inconsistent, reflecting the complexity of the underlying pathophysiology. As both disorders are (partly) heritable, characterising their genetic overlap may provide aetiological clues. While previous studies have indicated negligible genetic correlations, this study aims to expose the genetic overlap that may remain hidden due to mixed directions of effects.Methods: We applied Gaussian mixture modelling, through MiXeR, and conjunctional false discovery rate (cFDR) analysis, through pleioFDR, to genome-wide association study (GWAS) summary statistics of AD (n = 79,145) and depression (n = 450,619). The effects of identified overlapping loci on AD and depression were tested in 403,029 participants of the UK Biobank (UKB) (mean age 57.21, 52.0% female), and mapped onto brain morphology in 30,699 individuals with brain MRI data.Results: MiXer estimated 98 causal genetic variants overlapping between the 2 disorders, with 0.44 concordant directions of effects. Through pleioFDR, we identified a SNP in the TMEM106B gene, which was significantly associated with AD (B = −0.002, p = 9.1 × 10–4) and depression (B = 0.007, p = 3.2 × 10–9) in the UKB. This SNP was also associated with several regions of the corpus callosum volume anterior (B > 0.024, p < 8.6 × 10–4), third ventricle volume ventricle (B = −0.025, p = 5.0 × 10–6), and inferior temporal gyrus surface area (B = 0.017, p = 5.3 × 10–4).Discussion: Our results indicate there is substantial genetic overlap, with mixed directions of effects, between AD and depression. These findings illustrate the value of biostatistical tools that capture such overlap, providing insight into the genetic architectures of these disorders.

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The Effect of Anxiety on Regional Brain Volumes in the National Alzheimer’s Coordinating Center Uniform Data Set

Innovation in Aging ◽

10.1093/geroni/igaa057.1197 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 371-372

Author(s):

Shanna Burke ◽

Tan Li ◽

Adrienne Grudzien ◽

Christopher Barnes ◽

Kevin Hanson ◽

...

Keyword(s):

Parietal Lobe ◽

Secondary Analysis ◽

Occipital Lobe ◽

Ventricular Volume ◽

Brain Regions ◽

Brain Morphology ◽

Intracranial Volume ◽

Data Set ◽

Brain Volumes ◽

Regional Brain

Abstract Anxiety has been associated with greater risk of Alzheimer’s disease (AD) and existing research has identified structural differences in regional brain tissue in anxious compared to healthy samples, but results have been variable and somewhat inconsistent. We sought to determine the effect of anxiety on regional brain volumes by cognitive and apolipoprotein e (APOE) e4 status using data from a large, national dataset. A secondary analysis of the National Alzheimer’s Coordinating Center Uniform (NACC) Data Set was conducted using complete MRI data from 1,371 participants (mean age: 70.5; SD: 11.7). Multiple linear regression was used to estimate the adjusted effect of anxiety (via the Neuropsychiatric Inventory Questionnaire) on regional brain volumes through measurement of 30 structural MRI biomarkers. Anxiety was associated with lower total brain and total cortical gray matter volumes and increased lateral ventricular volume (p<.05). Lower mean volumes were also observed in all hippocampal, frontal lobe, parietal lobe, temporal lobe, and right occipital lobe volumes among participants who reported anxiety. Conversely, greater ventricular volumes were also correlated with anxiety. Findings suggest that anxiety is associated with significant atrophy in multiple brain regions and ventricular enlargement, even after controlling for intracranial volume and demographic covariates. Anxiety-related changes to brain morphology may contribute to greater AD risk.

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Grey matter abnormalities in first-episode schizophrenia and affective psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.191.51.s111 ◽

2007 ◽

Vol 191 (S51) ◽

pp. s111-s116 ◽

Cited By ~ 41

Author(s):

Kevin D. Morgan ◽

Paola Dazzan ◽

Kenneth G. Orr ◽

Gerard Hutchinson ◽

Xavier Chitnis ◽

...

Keyword(s):

Grey Matter ◽

Third Ventricle ◽

Magnetic Resonance Images ◽

Anterior Cingulate ◽

First Episode ◽

Proton Density ◽

Brain Abnormalities ◽

Affective Psychosis ◽

Cortical Grey Matter ◽

First Onset

BackgroundGrey matter and other structural brain abnormalities are consistently reported in first-onset schizophrenia, but less is known about the extent of neuroanatomical changes in first-onset affective psychosisAimsTo determine which brain abnormalities are specific to (a) schizophrenia and (b) affective psychosisMethodWe obtained dual-echo (proton density/T2-weighted) magnetic resonance images and carried out voxel-based analysis on the images of 73 patients with first-episode psychosis (schizophrenia n=44, affective psychosis n=29) and 58 healthy controlsResultsBoth patients with schizophrenia and patients with affective psychosis had enlarged lateral and third ventricle volumes. Regional cortical grey matter reductions (including bilateral anterior cingulate gyrus, left insula and left fusiform gyrus) were evident in affective psychosis but not in schizophrenia, although patients with schizophrenia displayed decreased hippocampal grey matter and increased striatal grey matter at a more liberal statistical thresholdConclusionsBoth schizophrenia and affective psychosis are associated with volumetric abnormalities at the onset of frank psychosis, with some of these evident in common brain areas

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Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Scientific Reports ◽

10.1038/s41598-020-75616-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

João V. Nani ◽

Richard S. Lee ◽

Camila M. Yonamine ◽

Osvaldo A. Sant’Anna ◽

Maria A. Juliano ◽

...

Keyword(s):

Animal Model ◽

Enzyme Activity ◽

Chronic Schizophrenia ◽

Brain Regions ◽

Term Treatment ◽

First Episode ◽

Acute Administration ◽

Long Term Treatment ◽

Healthy Control ◽

Normal Rat

Abstract Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.

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Lifetime antipsychotic use and brain structures in schizophrenia and other psychoses – 43-year study of the Northern Finland Birth Cohort 1966

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.077 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S100-S101

Author(s):

S. Huhtaniska ◽

I. Korkala ◽

T. Heikka ◽

J. Tohka ◽

J. Manjon ◽

...

Keyword(s):

Birth Cohort ◽

Antipsychotic Medication ◽

Lateral Ventricle ◽

Brain Structures ◽

Brain Morphology ◽

Psychotic Symptoms ◽

Intracranial Volume ◽

Brain Volumes ◽

Left Lateral Ventricle ◽

Brain Changes

IntroductionThe effects of long-term antipsychotic medication use on structural brain changes in psychoses are still unknown. Severity and duration of illness are key confounders when evaluating antipsychotic effects on brain morphology.ObjectivesUnderstanding the role of antipsychotic medication on brain morphology in psychoses.AimsTo analyze whether cumulative lifetime or current antipsychotic medication dose relates to brain morphology in schizophrenia and other psychoses at age of 43 years.MethodsForty-four schizophrenia cases and 35 with other psychoses from the Northern Finland Birth Cohort 1966 were scanned on a 1.5T GE Signa scanner and brain structures were extracted using volBrain automated volumetry system (http://volbrain.upv.es). Data of antipsychotic medication were collected from medical records and interviews. We used linear regression model to analyze the effect of antipsychotic medication on brain volumes and used intracranial volume and onset age as covariates. We also performed additional analyses adding psychotic symptoms (PANSS Total score) as a covariate.ResultsHigher lifetime and current dose associated to left lateral ventricle increase (b = 0.33, P = 0.033; b = 0.307, P = 0.042, respectively) and right and left accumbens decrease (b = −0.405, P = 0.013, b = −0.404, P = 0.010; b = −0.302, P = 0.027, b = −0.282, P = 0.036, respectively) in schizophrenia but not in other psychoses. When PANSS was added to the model, the findings remained regarding right and left accumbens, but not regarding left lateral ventricle.ConclusionsIt seems that antipsychotic medication affects the brain in schizophrenia, but not in the heterogeneous group of other psychoses. In schizophrenia, brain changes associated to antipsychotic medication cannot be explained by illness duration or symptom severity.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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FC07-03 - Neurological soft signs and morphological changes of basal ganglia and thalamus in patients with first-episode psychosis

European Psychiatry ◽

10.1016/s0924-9338(11)73552-0 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1848-1848

Author(s):

D. Hirjak ◽

B. Stieltjes ◽

K.H. Fritzsche ◽

T. Wüstenberg ◽

U. Seidl ◽

...

Keyword(s):

Basal Ganglia ◽

Morphological Changes ◽

Brain Regions ◽

First Episode Psychosis ◽

First Episode ◽

Intracranial Volume ◽

Neurological Soft Signs ◽

Episode Psychosis ◽

Gender Education ◽

Magnetic Resonance Imaging Mri

ObjectivesMinor motor and sensory deficits or neurological soft signs (NSS) are frequently found in individuals suffering from schizophrenia at any stage of their illness. The basal ganglia and the thalamus are accepted as being important for both motor control and integration of sensory input. However, whether NSS are related to structural alterations of these brain regions remains controversial.Method20 patients with a first-episode psychosis were investigated using high-resolution magnetic resonance imaging (MRI) at 3 Tesla. NSS were examined on the Heidelberg Scale after remission of acute symptoms and correlated with volume and shape of striatum, pallidum and thalamus by using sophisticated MRI analyses, namely VBM-DARTEL (volume) and FSL-FIRST (shape).Results NSS scores in patients with schizophrenia were significantly associated with volumetric changes and surface alterations in all investigated areas. Associations remained significant when controlling for age, gender, education, medication and intracranial volume.ConclusionOur findings lend further support for an involvement of the basal ganglia and the thalamus in NSS.

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Multi-Racial Normative Data for Lobar and Subcortical Brain Volumes in Old Age: Korean and Caucasian Norms May Be Incompatible With Each Other†

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.675016 ◽

2021 ◽

Vol 13 ◽

Author(s):

Yu Yong Choi ◽

Jang Jae Lee ◽

Kyu Yeong Choi ◽

Uk-Su Choi ◽

Eun Hyun Seo ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Normative Data ◽

Brain Aging ◽

Brain Structures ◽

Brain Regions ◽

Normative Values ◽

Aging Brain ◽

Intracranial Volume ◽

Brain Volumes ◽

Subcortical Volumes

Brain aging is becoming an increasingly important topic, and the norms of brain structures are essential for diagnosing neurodegenerative diseases. However, previous studies of the aging brain have mostly focused on Caucasians, not East Asians. The aim of this paper was to examine ethnic differences in the aging process of brain structures or to determine to what extent ethnicity affects the normative values of lobar and subcortical volumes in clinically normal elderly and the diagnosis in multi-racial patients with Alzheimer's disease (AD). Lobar and subcortical volumes were measured using FreeSurfer from MRI data of 1,686 normal Koreans (age range 59–89) and 851 Caucasian, non-Hispanic subjects in the ADNI and OASIS datasets. The regression models were designed to predict brain volumes, including ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and MRI scanner manufacturers as independent variables. Ethnicity had a significant effect for all lobar (|β| > 0.20, p < 0.001) and subcortical regions (|β| > 0.08, p < 0.001) except left pallidus and bilateral ventricles. To demonstrate the validity of the z-score for AD diagnosis, 420 patients and 420 normal controls were selected evenly from the Korean and Caucasian datasets. The four validation groups divided by race and diagnosis were matched on age and sex using a propensity score matching. We analyzed whether and to what extent the ethnicity adjustment improved the diagnostic power of the logistic regression model that was built using the only z-scores of six regions: bilateral temporal cortices, hippocampi, and amygdalae. The performance of the classifier after ethnicity adjustment was significantly improved compared with the classifier before ethnicity adjustment (ΔAUC = 0.10, D = 7.80, p < 0.001; AUC comparison test using bootstrap). Korean AD dementia patients may not be classified by Caucasian norms of brain volumes because the brain regions vulnerable to AD dementia are bigger in normal Korean elderly peoples. Therefore, ethnicity is an essential factor in establishing normative data for regional volumes in brain aging and applying it to the diagnosis of neurodegenerative diseases.

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Choroid Plexus Enlargement and Allostatic Load in Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbz100 ◽

2019 ◽

Vol 46 (3) ◽

pp. 722-731 ◽

Cited By ~ 1

Author(s):

Yan-Fang Zhou ◽

Jun-Chao Huang ◽

Ping Zhang ◽

Feng-Mei Fan ◽

Song Chen ◽

...

Keyword(s):

Choroid Plexus ◽

Sex Education ◽

Allostatic Load ◽

Early Stage ◽

Brain Structures ◽

First Episode ◽

Intracranial Volume ◽

Brain Disorder ◽

Treatment And Prevention ◽

Treatment Naïve

Abstract Although schizophrenia is a brain disorder, increasing evidence suggests that there may be body-wide involvement in this illness. However, direct evidence of brain structures involved in the presumed peripheral-central interaction in schizophrenia is still unclear. Seventy-nine previously treatment-naïve first-episode schizophrenia patients who were within 2-week antipsychotics initial stabilization, and 41 age- and sex-matched healthy controls were enrolled in the study. Group differences in subcortical brain regional structures measured by MRI and the subclinical cardiovascular, metabolic, immune, and neuroendocrine biomarkers as indexed by allostatic load, and their associations were explored. Compared with controls, patients with schizophrenia had significantly higher allostatic load (P = .001). Lateral ventricle (P < .001), choroid plexus (P < .001), and thalamus volumes (P < .001) were significantly larger, whereas amygdala volume (P = .001) was significantly smaller in patients. The choroid plexus alone was significantly correlated with higher allostatic load after age, sex, education level, and the total intracranial volume were taken into account (t = 3.60, P < .001). Allostatic load was also significantly correlated with PANSS positive (r = 0.28, P = .016) and negative (r = −0.31, P = .008) symptoms, but in opposite directions. The peripheral multisystemic and central nervous system abnormalities in schizophrenia may interact through the choroid plexus during the early stage of the illness. The choroid plexus might provide a sensitive structural biomarker to study the treatment and prevention of brain-periphery interaction abnormalities in schizophrenia.

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