Robin J. Hennessy

3D laser surface scanning and geometric morphometric analysis of craniofacial shape as an index of cerebro-craniofacial morphogenesis: initial application to sexual dimorphism.

BACKGROUND Over early fetal life, when disturbances in schizophrenia have been posited and craniofacial dysmorphogenesis reported, cerebral morphogenesis proceeds in embryological intimacy with craniofacial morphogenesis. Digitization technologies now allow 3D recording of craniofacial surface landmarks and modeling of craniofacial shape differences using geometric morphometrics. METHODS Using normal sexual dimorphism as an exemplar, facial surfaces of 131 Medical School employees [82 females, 49 males] were recorded in 3D using a portable, hand-held laser scanner; 3D coordinate data were then analyzed using geometric morphometrics. RESULTS Males and females differed markedly on an omnibus test of craniofacial shape. Logistic regression analysis of 16 principal components of shape variability, explaining 84.9% of the overall sample variance, generated 8 principal components as significant and independent discriminators. On visualization, the female face is wider and flatter; the eyes are more lateral, anterior and are further apart, and nasal bridge is posterior; the nose is smaller; the lips are fuller and the chin more forward. These findings are complementary to sexual dimorphism in cerebral structures. CONCLUSIONS This technique reliably discriminates geometric features of craniofacial morphology that are associated with aspects of cerebral morphology, and may inform on putative neurodevelopmental disorders characterised by dysmorphogenesis.

Facial surface analysis by 3D laser scanning and geometric morphometrics in relation to sexual dimorphism in cerebral-craniofacial morphogenesis and cognitive function

Over early fetal life the anterior brain, neuroepithelium, neural crest and facial ectoderm constitute a unitary, three‐dimensional (3D) developmental process. This intimate embryological relationship between the face and brain means that facial dysmorphogenesis can serve as an accessible and informative index of brain dysmorphogenesis in neurological and psychiatric disorders of early developmental origin. There are three principal challenges in seeking to increase understanding of disorders of early brain dysmorphogenesis through craniofacial dysmorphogenesis: (i) the first, technical, challenge has been to digitize the facial surface in its inherent three‐dimensionality; (ii) the second, analytical, challenge has been to develop methodologies for extracting biologically meaningful shape covariance from digitized samples, making statistical comparisons between groups and visualizing in 3D the resultant statistical models on a ‘whole face’ basis; (iii) the third, biological, challenge is to demonstrate a relationship between facial morphogenesis and brain morphogenesis not only in anatomical–embryological terms but also at the level of brain function. Here we consider each of these challenges in turn and then illustrate the issues by way of our own findings. These use human sexual dimorphism as an exemplar for 3D laser surface scanning of facial shape, analysis using geometric morphometrics and exploration of cognitive correlates of variation in shape of the ‘whole face’, in the context of studies relating to the early developmental origins of schizophrenia.

3D morphometrics of craniofacial dysmorphology reveals sex-specific asymmetries in schizophrenia

Over early fetal life cerebral and craniofacial morphogenesis proceed in embryological intimacy. Therefore, craniofacial shape differences between schizophrenia patients and controls are informative of developmental disturbance(s) in cerebral-craniofacial morphogenesis. 3D craniofacial coordinates were calculated from interlandmark distances for 169 patients with DSM-III-R schizophrenia and 78 matched normal controls. These were analysed using geometric morphometrics with visualisation of the resultant statistical models. Patients of both sexes were characterised by an intricate topography of 3D shape change involving lengthened lower mid-facial height, shortened upper mid-facial height, nasion located posteriorly and a wider face posteriorly; there was sex-specific rotation of the midface such that the base of the nose is more anterior in female patients but more posterior in male patients. Importantly, there were sex-specific asymmetries: in males, controls evidenced marked directional asymmetry while patients showed reduced directional asymmetry; conversely, in females controls evidenced little directional asymmetry while patients showed marked directional asymmetry. In schizophrenia, the topography of craniofacial dysmorphology appears to reflect subtle disruption to a critical 3D trajectory of embryonic-fetal craniofacial growth, particularly along the midline, with disturbance to the establishment of normal asymmetries in a sex-related manner.

Three-dimensional laser surface imaging and geometric morphometrics resolve frontonasal dysmorphology in schizophrenia.

BACKGROUND Although a role for early developmental disturbance(s) in schizophrenia is postulated, it has proved difficult to identify hard, biological evidence. The brain and face emerge in embryologic intimacy, such that in neurodevelopmental disorders, brain dysmorphogenesis is accompanied by facial dysmorphogenesis. METHODS Three-dimensional (3D) laser surface imaging was used to capture the facial surface of patients and control subjects in 37 male and 32 female patients who satisfied DSM-IV criteria for schizophrenia in comparison with 58 male and 34 female control subjects. Surface images were analyzed using geometric morphometrics and 3D visualizations to identify domains of facial shape that distinguish patients from control subjects. RESULTS Both male and, particularly, female patients evidenced significant facial dysmorphology. There was narrowing and reduction of the mid to lower face and frontonasal prominences, including reduced width and posterior displacement of the mouth, lips, and chin; increased width of the upper face, mandible, and skull base, with lateral displacement of the cheeks, eyes, and orbits; and anterior displacement of the superior margins of the orbits. CONCLUSIONS The frontonasal prominence, which enjoys the most intimate embryologic relationship with the anterior brain and also orchestrates aspects of development in maxillary and mandibular domains, evidences a characteristic topography of dysmorphogenesis in schizophrenia.

Frontonasal dysmorphology in bipolar disorder by 3D laser surface imaging and geometric morphometrics: Comparisons with schizophrenia

Any developmental relationship between bipolar disorder and schizophrenia engenders continuing debate. As the brain and face emerge in embryological intimacy, brain dysmorphogenesis is accompanied by facial dysmorphogenesis. 3D laser surface imaging was used to capture the facial surface of 13 male and 14 female patients with bipolar disorder in comparison with 61 male and 75 female control subjects and with 37 male and 32 female patients with schizophrenia. Surface images were analysed using geometric morphometrics and 3D visualisations to identify domains of facial shape that distinguish bipolar patients from controls and bipolar patients from those with schizophrenia. Both male and female bipolar patients evidenced significant facial dysmorphology: common to male and female patients was overall facial widening, increased width of nose, narrowing of mouth and upward displacement of the chin; dysmorphology differed between male and female patients for nose length, lip thickness and tragion height. There were few morphological differences in comparison with schizophrenia patients. That dysmorphology of the frontonasal prominences and related facial regions in bipolar disorder is more similar to than different from that found in schizophrenia indicates some common dysmorphogenesis. Bipolar disorder and schizophrenia might reflect similar insult(s) acting over slightly differing time-frames or slightly differing insult(s) acting over a similar time-frame.

Automatic symmetry plane estimation of bilateral objects in point clouds

In this paper, the problem of estimating automatically the symmetry plane of bilateral objects (having perfect or imperfect mirror symmetry) in point clouds is reexamined. Classical methods, mostly based on the ICP algorithm, are shown to be limited and complicated by an inappropriate parameterization of the problem. First, we show how an adequate parameterization, used in an ICP-like scheme, can lead to a simpler, more accurate and faster algorithm. Then, using this parameterization, we reinterpret the problem in a probabilistic framework, and use the maximum likelihood principle to define the optimal symmetry plane. This problem can be solved efficiently using an EM algorithm. The resulting iterative scheme can be seen as an ICP-like algorithm with multiple matches between the two sides of the object. This new algorithm, implemented using a multiscale, multiresolution approach, is evaluated in terms of accuracy, robustness and speed on ground truth data, and some results on real data are presented.

Craniofacial Dysmorphology in 22q11.2 Deletion Syndrome by 3D Laser Surface Imaging and Geometric Morphometrics: Illuminating the Developmental Relationship to Risk for Psychosis

Persons with 22q11.2 deletion syndrome (22q11.2DS) are characterized inter alia by facial dysmorphology and greatly increased risk for psychotic illness. Recent studies indicate facial dysmorphology in adults with schizophrenia. This study evaluates the extent to which the facial dysmorphology of 22q11.2DS is similar to or different from that evident in schizophrenia. Twenty‐one 22q11.2DS‐sibling control pairs were assessed using 3D laser surface imaging. Geometric morphometrics was applied to 30 anatomical landmarks, 480 geometrically homologous semi‐landmarks on curves and 1720 semi‐landmarks interpolated on each 3D facial surface. Principal component (PC) analysis of overall shape space indicated PC2 to strongly distinguish 22q11.2DS from controls. Visualization of PC2 indicated 22q11.2DS and schizophrenia to be similar in terms of overall widening of the upper face, lateral displacement of the eyes/orbits, prominence of the cheeks, narrowing of the lower face, narrowing of nasal prominences and posterior displacement of the chin; they differed in terms of facial length (increased in 22q11.2DS, decreased in schizophrenia), mid‐face and nasal prominences (displaced upwards and outwards in 22q11.2DS, less prominent in schizophrenia); lips (more prominent in 22q11.2DS; less prominent in schizophrenia) and mouth (open mouth posture in 22q11.2DS; closed mouth posture in schizophrenia). These findings directly implicate dysmorphogenesis in a cerebral‐craniofacial domain that is common to 22q11.2DS and schizophrenia and which may repay further clinical and genetic interrogation in relation to the developmental origins of psychotic illness.

Controversies in schizophrenia research: the ‘continuum’ challenge, heterogeneity vs homogeneity, and lifetime developmental-‘neuroprogressive’ trajectory

In reviewing the extent to which our understanding has advanced between the 4thand 5thsymposia on Search for the Causes of Schizophrenia, the conclusion is salutary: a committed and expanding research community, able to apply an increasing armamentarium of molecular genetic, neuropathological, neuroimaging and additional techniques, has made only modest gains over this five-year period. In the face of such a slow (though not negligible) rate of progress, it is necessary to give further consideration to some of the premises which guide current thinking, as they may be impeding rather than facilitating these endeavours.

An algorithm to map asymmetries of bilateral objects in point clouds

We present a method to automatically quantify the local asymmetries of bilateral structures in point clouds. The method relies on the robust computation of the approximate symmetry plane of the object under study. This plane is defined as the minimiser of a criterion, based on a M-estimator and devised to reduce the influence of asymmetrical features of the object. An algorithm is then proposed to minimise this criterion. Once the algorithm has converged, the residual distances between the points and their symmetrical counterparts quantify the local asymmetries, yielding a 3D asymmetry map. We show the algorithm to be accurate, with a high capture range, on an ideal, perfectly symmetrical dataset. We investigate its robustness and accuracy properties on highly corrupted datasets. We also evaluate the accuracy of the obtained 3D maps using ground truth datasets where the asymmetries are known. Finally, we propose several original applications of this method on real data.

The 'Totality' of Psychosis: Epidemiology and Developmental Pathobiology

Among numerous impediments to further advancement between the fifth and sixth symposia on Search for the Causes of Schizophrenia, several uncertainties endure: (i) What are the boundaries of psychotic illness? (ii) Where do we position what we currently conceptualise and diagnose as schizophrenia within the much broader reality of psychotic disorder among those with serious mental illness and, indeed, of psychotic phenomena among the general population? (iii) To what extent are those components of psychotic illness that we resolve into separate diagnostic categories actually distinct in any fundamental way in terms of their epidemiological, clinical and pathobiological ‘signature’?