Distinguishing bipolar and major depressive disorders by brain structural morphometry: a pilot study.

BACKGROUND: The clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions. METHODS: For our sample of 16 BD patients, 19 MDD patients and 29 healthy volunteers, we adopted vertex-wise cortical based brain imaging techniques to examine cortical thickness and surface area, two components of cortical volume with distinct genetic determinants. Based on specific characteristics of neuroanatomical features, we then used support vector machine (SVM) algorithm to discriminate between patients with BD and MDD. RESULTS: Compared to MDD patients, BD patients showed significantly larger cortical surface area in the left bankssts, precuneus, precentral, inferior parietal, superior parietal and the right middle temporal gyri. In addition, larger volumes of subcortical regions were found in BD patients. In SVM discriminative analyses, the overall accuracy was 74.3 %, with a sensitivity of 62.5 % and a specificity of 84.2 % (p = 0.028). Compared to controls, larger surface area in the temporo-parietal regions were observed in BD patients, and thinner cortices in fronto-temporal regions were observed in MDD patients, especially in the medial orbito-frontal area. CONCLUSIONS: These findings have demonstrated distinct spatially distributed variations in cortical thickness and surface area in patients with BD and MDD, suggesting potentially varying etiological and neuropathological processes in these two conditions. The employment of multimodal classification on disorder-specific biological features has shed light to the development of potential classification tools that could aid diagnostic decisions.

Distinct structural neural patterns of trait physical and social anhedonia: evidence from cortical thickness, subcortical volumes and inter-regional correlations.

Anhedonia is an enduring trait accounting for the reduced capacity to experience pleasure. Few studies have investigated the brain structural features associated with trait anhedonia. In this study, the relationships between cortical thickness, volume of subcortical structures and scores on the Chapman physical and social anhedonia scales were examined in a non-clinical sample (n=72, 35 males). FreeSurfer was used to examine the cortical thickness and the volume of six identified subcortical structures related to trait anhedonia. We found that the cortical thickness of the superior frontal gyrus and the volume of the pallidum in the left hemisphere were correlated with anhedonia scores in both physical and social aspects. Specifically, positive correlations were found between levels of social anhedonia and the thickness of the postcentral and the inferior parietal gyri. Cortico-subcortical inter-correlations between these clusters were also observed. Our findings revealed distinct correlation patterns of neural substrates with trait physical and social anhedonia in a non-clinical sample. These findings contribute to the understanding of the pathologies underlying the anhedonia phenotype in schizophrenia and other psychiatric disorders.

MRI predicts remission at 1 year in first-episode schizophrenia in females with larger striato-thalamic volumes.

BACKGROUND/AIMS: The Remission in Schizophrenia Working Group has defined remission as 'a low-mild symptom intensity level, maintained for a minimum of 6 months, where such symptoms do not affect an individual's behaviour' [Andreasen et al.: Am J Psychiatry 2005;162:441-449]. Since brain morphology relates to symptomatology, treatment and illness progression, MRI may assist in predicting remission. METHODS: Thirty-nine patients newly diagnosed with DSM-IV schizophrenia underwent MRI brain scan prior to antipsychotic exposure. The Global Assessment of Functioning (GAF) score was entered into a voxel-based analysis to evaluate its relationship with cerebral grey matter volume from the baseline MRI. We entered age, total intracranial volume and intake GAF score as co-variates. Males and females were analysed separately because gender is a potent determinant of outcome. RESULTS: Males had lower GAF scores than females, both at intake and at 1 year. Males comprised only 40% (12 out of 39) of the early remission group. For females only, early remission was strongly and positively correlated with bilateral lentiform and striatal volumes. For males, there was no such relationship. CONCLUSION: Larger striato-thalamic volume correlated with early remission in females only. These baseline MRI findings were unlikely to be confounded by antipsychotic treatment and chronicity. These brain morphological markers show gender dimorphism and may assist in the prediction of early remission in newly diagnosed schizophrenia.

MRI study of minor physical anomaly in childhood autism implicates aberrant neurodevelopment in infancy.

BACKGROUND: MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism. METHODS: We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates. RESULTS: Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles. CONCLUSIONS: Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism.

Possible retrogenesis observed with fiber tracking: an anteroposterior pattern of white matter disintegrity in normal aging and Alzheimer's disease.

Retrogenesis refers to the phenomenon by which degenerative processes in aging reverse the sequence of acquisition in development. Although there has been some evidence for brain retrogenesis in abnormal aging, e.g., Alzheimer's disease (AD), it has not been explicitly addressed in the normal aging. Using diffusion tensor imaging and tractography, we explored the effects of normal and abnormal aging on the integrity of white matter (WM) in fifty participants, including 18 AD patients, 17 normal elderly, and 15 normal young adults. Compared with young adults, the traditional voxel-based analysis, and the quantitative fiber tracking methods revealed lower fractional anisotrophy (FA) for both normal elderly and AD patients, indicating WM disintegrity in the anterior part of the brain with developmentally late-myelinating fiber bundles. Furthermore, AD patients showed lower FA in the posterior part of the brain with relatively early-myelinating fiber bundles. Additional analysis on axial diffusion and radial diffusion measures suggest that demyelination may be the main mechanism underlying the observed microstructural impairments. Consistent with a proposal of retrogenesis, our results demonstrate an anteroposterior pattern of white matter disintegrity in both normal aging and AD, with the pattern being more salient in the latter than in the former.

Autistic disorders and schizophrenia: related or remote? An anatomical likelihood estimation.

Shared genetic and environmental risk factors have been identified for autistic spectrum disorders (ASD) and schizophrenia. Social interaction, communication, emotion processing, sensorimotor gating and executive function are disrupted in both, stimulating debate about whether these are related conditions. Brain imaging studies constitute an informative and expanding resource to determine whether brain structural phenotype of these disorders is distinct or overlapping. We aimed to synthesize existing datasets characterizing ASD and schizophrenia within a common framework, to quantify their structural similarities. In a novel modification of Anatomical Likelihood Estimation (ALE), 313 foci were extracted from 25 voxel-based studies comprising 660 participants (308 ASD, 352 first-episode schizophrenia) and 801 controls. The results revealed that, compared to controls, lower grey matter volumes within limbic-striato-thalamic circuitry were common to ASD and schizophrenia. Unique features of each disorder included lower grey matter volume in amygdala, caudate, frontal and medial gyrus for schizophrenia and putamen for autism. Thus, in terms of brain volumetrics, ASD and schizophrenia have a clear degree of overlap that may reflect shared etiological mechanisms. However, the distinctive neuroanatomy also mapped in each condition raises the question about how this is arrived in the context of common etiological pressures.