Distinguishing Neuroimaging Features in Patients Presenting with Visual Hallucinations

ABSTRACT SUMMARY: Visual hallucinations are relatively uncommon presentations in medical and psychiatric clinics, where they are generally regarded as a marker of possible underlying "organic" brain disease. Thus, patients with visual hallucinations are often referred for imaging of the brain. This article presents a pragmatic approach for the radiologist reviewing such imaging. Because conditions that can present with visual hallucinations are legion, a familiarity with the features of the hallucinations themselves, which can serve as clues to the underlying cause, can be helpful in interpreting such cases. We consider the nature of visual hallucinations and the mechanisms underlying their formation. We then provide a framework to guide the search for their cause, first in terms of focal lesions along the visual pathway and then global conditions affecting Ͼ1 region. ABBREVIATIONS: CJD ϭ Creutzfeldt-Jakob disease; VH ϭ visual hallucinatio

Widespread white matter microstructural differences in schizophrenia across 4322 individuals:Results from the ENIGMA Schizophrenia DTI Working Group

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Molecular Psychiatry advance online publication, 17 October 2017; doi:10.1038/mp.2017.170

Synaptic Dysbindin-1 Reductions in Schizophrenia Occur in an Isoform-Specific Manner Indicating Their Subsynaptic Location

Background: An increasing number of studies report associations between variation in DTNBP1, a top candidate gene in schizophrenia, and both the clinical symptoms of the disorder and its cognitive deficits. DTNBP1 encodes dysbindin-1, reduced levels of which have been found in synaptic fields of schizophrenia cases. This study determined whether such synaptic reductions are isoform-specific. Methodology/Principal Findings: Using Western blotting of tissue fractions, we first determined the synaptic localization of the three major dysbindin-1 isoforms (A, B, and C). All three were concentrated in synaptosomes of multiple brain areas, including auditory association cortices in the posterior half of the superior temporal gyrus (pSTG) and the hippocampal formation (HF). Tests on the subsynaptic tissue fractions revealed that each isoform is predominantly, if not exclusively, associated with synaptic vesicles (dysbindin-1B) or with postsynaptic densities (dysbindin-1A and -1C). Using Western blotting on pSTG (n = 15) and HF (n = 15) synaptosomal fractions from schizophrenia cases and their matched controls, we discovered that synaptic dysbindin-1 is reduced in an isoform-specific manner in schizophrenia without changes in levels of synaptophysin or PSD-95. In pSTG, about 92% of the schizophrenia cases displayed synaptic dysbindin-1A reductions averaging 48% (p = 0.0007) without alterations in other dysbindin-1 isoforms. In the HF, by contrast, schizophrenia cases displayed normal levels of synaptic dysbindin-1A, but 67% showed synaptic reductions in dysbindin-1B averaging 33% (p = 0.0256), while 80% showed synaptic reductions in dysbindin-1C averaging 35% (p = 0.0171). Conclusions/Significance: Given the distinctive subsynaptic localization of dysbindin-1A, -1B, and -1C across brain regions, the observed pSTG reductions in dysbindin-1A are postsynaptic and may promote dendritic spine loss with consequent disruption of auditory information processing, while the noted HF reductions in dysbindin-1B and -1C are both presynaptic and postsynaptic and could promote deficits in spatial working memory

Volumetric abnormalities predating the onset of schizophrenia and affective psychoses: an MRI study in subjects at ultra-high risk of psychosis

Fulltext embargoed for: 12 months post date of publicationIt remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder

Volumetric abnormalities predating the onset of schizophrenia and affective psychoses: An MRI study in subjects at ultrahigh risk of psychosis

It remains unclear whether brain structural abnormalities observed before the onset of psychosis are specific to schizophrenia or are common to all psychotic disorders. This study aimed to measure regional gray matter volume prior to the onset of schizophreniform and of affective psychoses. We investigated 102 subjects at ultrahigh risk (UHR) of developing psychosis recruited from the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia. Twenty-eight of these subjects developed psychosis subsequent to scanning: 19 schizophrenia, 7 affective psychoses, and 2 other psychoses. We examined regional gray matter volume using 1.5 mm thick, coronal, 1.5 Tesla magnetic resonance imaging and voxel-based morphometry methods of image analysis. Subjects were scanned at presentation and were followed up clinically for a minimum of 12 months, to detect later transition to psychosis. We found that both groups of subjects who subsequently developed psychosis (schizophrenia and affective psychosis) showed reductions in the frontal cortex relative to UHR subjects who did not develop psychosis. The subgroup that subsequently developed schizophrenia also showed smaller volumes in the parietal cortex and, at trend level, in the temporal cortex, whereas those who developed an affective psychosis had significantly smaller subgenual cingulate volumes. These preliminary findings suggest that volumetric abnormalities in UHR individuals developing schizophrenia vs affective psychoses comprise a combination of features that predate both disorders and others that may be specific to the nature of the subsequent disorder. © 2012 The Author

Human amygdala volume is predicted by common DNA variation in the stathmin and serotonin transporter genes

Despite the relevance of changes in amygdala volume to psychiatric illnesses and its heritability in both health and disease, the influence of common genetic variation on amygdala morphology remains largely unexplored. In the present study, we investigated the influence of a number of novel genetic variants on amygdala volume in 139 neurologically healthy individuals of European descent. Amygdala volume was significantly associated with allelic variation in the stathmin (STMN1) and serotonin transporter (SLC6A4) genes, which have been linked to healthy and disordered affective processing. These results were replicated across both manual and automated methods of amygdala parcellation, although manual tracing showed stronger effects, providing a cautionary note to studies relying on automated parcellation methods. Future studies will need to determine whether amygdala volume mediates the impact of stathmin and serotonin transporter gene variants on normal and dysfunctional emotion processing

A comparative study of segmentation techniques for the quantification of brain subcortical volume.

Manual tracing of magnetic resonance imaging (MRI) represents the gold standard for segmentation in clinical neuropsychiatric research studies, however automated approaches are increasingly used due to its time limitations. The accuracy of segmentation techniques for subcortical structures has not been systematically investigated in large samples. We compared the accuracy of fully automated [(i) model-based: FSL-FIRST; (ii) patch-based: volBrain], semi-automated (FreeSurfer) and stereological (Measure®) segmentation techniques with manual tracing (ITK-SNAP) for delineating volumes of the caudate (easy-to-segment) and the hippocampus (difficult-to-segment). High resolution 1.5 T T1-weighted MR images were obtained from 177 patients with major psychiatric disorders and 104 healthy participants. The relative consistency (partial correlation), absolute agreement (intraclass correlation coefficient, ICC) and potential technique bias (Bland-Altman plots) of each technique was compared with manual segmentation. Each technique yielded high correlations (0.77-0.87, p < 0.0001) and moderate ICC's (0.28-0.49) relative to manual segmentation for the caudate. For the hippocampus, stereology yielded good consistency (0.52-0.55, p < 0.0001) and ICC (0.47-0.49), whereas automated and semi-automated techniques yielded poor ICC (0.07-0.10) and moderate consistency (0.35-0.62, p < 0.0001). Bias was least using stereology for segmentation of the hippocampus and using FreeSurfer for segmentation of the caudate. In a typical neuropsychiatric MRI dataset, automated segmentation techniques provide good accuracy for an easy-to-segment structure such as the caudate, whereas for the hippocampus, a reasonable correlation with volume but poor absolute agreement was demonstrated. This indicates manual or stereological volume estimation should be considered for studies that require high levels of precision such as those with small sample size