Is There a Characteristic Autonomic Response During Outbursts of Combative Behavior in Dementia Patients?

We sought to determine whether skin conductance level could warn of outbursts of combative behavior in dementia patients by using a wristband device. Two outbursts were captured and are reported here. Although no physiologic parameter measured by the wristband gave advance warning, there is a common pattern of parasympathetic withdrawal (increased heart rate) followed approximately 30 seconds later by sympathetic activation (increased skin conductance). In the literature, a similar pattern occurs in psychogenic non-epileptic seizures. We hypothesize that similar autonomic responses reflect similarities in pathophysiology and that physical activity may partially account for the time course of skin conductance.

Use of a modified mandibular splint to reduce nocturnal symptoms in persons with post-traumatic stress disorder.

OBJECTIVE: Based on a series of clinical observations that a thicker mandibular splint than that commonly used to treat bruxism and related craniomandibular myofascial pain reduced post-traumatic stress disorder (PTSD) nocturnal symptomatology (sleep disruptions, headaches, and nightmares), this study of 100 PTSD participants was undertaken to systematically establish 'proof of concept' of the therapeutic effectiveness of this modified splinting procedure. METHODS: Following the fabrication of splints thicker than those conventionally used, the effectiveness of this new procedure used by dentists was determined by comparing the self-reported frequency and intensity/severity of PTSD symptomatology during a seven-night pretreatment baseline period without the splint with a second seven-night period in which the modified splint was inserted. The scoring for the three dependent measures (sleep disruptions, headaches, and nightmares) was based on the frequencies on a scale from 0-7 multiplied by the intensity/severity on a scale of 1-10. RESULTS: Compared with the pre-splint baseline period, the insertion of the thickened splint resulted in a highly significant reduction of sleep disruption, nocturnal headaches, and nightmares. A second seven-night control period without the splint was followed by a second seven-night period with the splint, reproducing the effectiveness of the first splinting period. CONCLUSION: The results of this study provide the first systematic, documented proof of concept of the effectiveness of a modified splinting procedure in reducing key nocturnal symptoms in PTSD patients.

Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development.

A copy-number variant (CNV) of 16p11.2 encompassing 30 genes is associated with developmental and psychiatric disorders, head size, and body mass. The genetic mechanisms that underlie these associations are not understood. To determine the influence of 16p11.2 genes on development, we investigated the effects of CNV on craniofacial structure in humans and model organisms. We show that deletion and duplication of 16p11.2 have "mirror" effects on specific craniofacial features that are conserved between human and rodent models of the CNV. By testing dosage effects of individual genes on the shape of the mandible in zebrafish, we identify seven genes with significant effects individually and find evidence for others when genes were tested in combination. The craniofacial phenotypes of 16p11.2 CNVs represent a model for studying the effects of genes on development, and our results suggest that the associated facial gestalts are attributable to the combined effects of multiple genes.

Exposure to Sodium Valproate during Pregnancy: Facial Features and Signs of Autism.

BACKGROUND: Valproic acid (VPA) is the most teratogenic anticonvulsant drug in clinical use today. Children exposed prenatally to VPA have previously been shown to have dysmorphic craniofacial features, identified subjectively but not by anthropometric methods. Exposure to VPA has also been associated with an increased frequency of autism spectrum disorder (ASD). An increased cephalic index (the ratio of the cranial lateral width to the cranial anterior-posterior length) has been observed in children with ASD. METHODS: Forty-seven children exposed to VPA during the first trimester of pregnancy were evaluated for dysmorphic facial features, identified subjectively and by measurements. Each VPA-exposed child was evaluated for ASD using the Social Communication Questionnaire, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. The same physical examination was carried out on an unexposed comparison group of 126 children. The unexposed children also had testing for cognitive performance by the Wechsler Intelligence Scale for Children. RESULTS: Several dysmorphic craniofacial features, including telecanthus, wide philtrum, and increased length of the upper lip were identified subjectively. Anthropometric measurements confirmed the increased intercanthal distance and documented additional findings, including an increased cephalic index and decreased head circumference/height index. There were no differences between the craniofacial features of VPA-exposed children with and without ASD. CONCLUSION: An increased frequency of dysmorphic craniofacial features was identified in children exposed to VPA during the first trimester of pregnancy. The most consistent finding was a larger cephalic index, which indicates a disproportion of increased width of the skull relative to the shortened anterior-posterior length. Birth Defects Research 109:1134-1143, 2017. © 2017 Wiley Periodicals, Inc.

Three-Dimensional Analysis of Nasal Symmetry Following Primary Correction of Unilateral Cleft Lip Nasal Deformity.

OBJECTIVE: To evaluate nasal symmetry using three-dimensional photogrammetry following primary tip rhinoplasty with or without an internal splint in patients with unilateral complete cleft lip/palate. DESIGN: We captured three-dimensional images of patients with unilateral complete cleft lip/palate who underwent nasolabial repair by rotation-advancement of the lip and primary tip rhinoplasty, either with or without an internal resorbable splint, and normal control subjects. We assessed nasal symmetry by identifying the plane of maximum symmetry and the root-mean-square deviation between native and reflected surfaces. PATIENTS/PARTICIPANTS: We imaged 38 controls and 38 subjects with repaired unilateral complete cleft lip/palate (20 with, 18 without an internal splint). RESULTS: Nasal asymmetry root-mean-square deviation clustered between 0.19 and 0.50 mm (median = 0.24 ± 0.08 mm) for controls; whereas, those with repaired unilateral complete cleft lip/palate ranged from 0.4 to 1.5 mm (median = 0.75 ± 0.40 mm). Although root-mean-square deviation ranges overlapped, patients with repaired unilateral complete cleft lip/palate had significantly greater asymmetry than controls (P < .001). We found no difference in asymmetry between patients with or without an internal splint (P = .5). CONCLUSIONS: Three-dimensional photogrammetry was used to successfully compare symmetry among different patient and control groups. Although "normal" nasal symmetry was attained in some patients following cleft lip/nasal repair, most had persistent asymmetry compared with normal controls. Placement of a resorbable internal splint did not improve symmetry in patients with unilateral complete cleft lip/palate.

The Changing Nasolabial Dimensions following Repair of Unilateral Cleft Lip: An Anthropometric Study in Late Childhood.

BACKGROUND: Repair of unilateral cleft lip and nasal deformity in three dimensions requires anticipation of changes in the fourth dimension that can be determined by periodic and objective assessment. METHODS: Fifty patients with unilateral cleft lip with or without cleft palate underwent primary repair from 1999 to 2004 and were followed through 2014. Anthropometry was performed immediately postoperatively and at a first and second follow-up interval, occurring at an average age of 6.6 and 11.5 years, respectively. Measured differences between cleft and noncleft sides included heminasal width (subnasale-alare), cutaneous labial height (subnasale-crista philtri inferior, subalare-crista philtri inferior), and transverse labial width at the cutaneous-vermilion border (crista philtri inferior-chelion). Contrasts for the rates of growth were assessed with t tests for correlated measures. Using the same method, the difference between growth on cleft and noncleft sides in the second period was compared to that in the first period. RESULTS: Heminasal width remained narrower on the cleft side, but this difference decreased over time. Subnasale-crista philtri inferior remained longer on the cleft side; there was no difference between the rate of growth on the cleft and noncleft sides in the second period. Subalare-crista philtri inferior remained shorter on the cleft side by a consistent difference at both times of follow-up measurements. Transverse labial width at the cutaneous-vermilion border remained shorter on the cleft side, but this difference decreased in the second period. CONCLUSION: Understanding how nasolabial features change with growth is critical to crafting the initial repair of unilateral cleft lip and nasal deformity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Stimulus Overselectivity in Autism, Down Syndrome, and Typical Development.

Stimulus overselectivity refers to maladaptive narrow attending that is a common learning problem among children with intellectual disabilities and frequently associated with autism. The present study contrasted overselectivity among groups of children with autism, Down syndrome, and typical development. The groups with autism and Down syndrome were matched for intellectual level, and all three groups were matched for developmental levels on tests of nonverbal reasoning and receptive vocabulary. Delayed matching-to-sample tests presented color/form compounds, printed words, photographs of faces, Mayer-Johnson Picture Communication Symbols, and unfamiliar black forms. No significant differences among groups emerged for test accuracy scores. Overselectivity was not statistically overrepresented among individuals with autism in contrast to those with Down syndrome or typically developing children.

Quantitative Measures of Craniofacial Dysmorphology in a Family Study of Schizophrenia and Bipolar Illness.

Several laboratories, including ours, have reported an overrepresentation of craniofacial (CF) anomalies in schizophrenia (SZ). How might this dysmorphology arise in a brain-based disorder? Because the brain and face derive from shared embryologic primordia and morphogenetic forces, maldevelopmental processes may result in both CF and brain dysmorphology.Our approach is 2-pronged. First, we have employed, for the first time in the study of psychiatric disorders, objective measures of CF morphology that utilize an extensive normative database, permitting computation of standardized scores for each subject. Second, we have rendered these findings biologically interpretable by adopting principles of embryology in the analysis of dysmorphology.Dependent measures in this investigation focused on derivatives of specific embryonic primordia and were contrasted among probands with psychotic disorders, their first-degree relatives, and normal controls (NC). Subject groups included patients with a diagnosis of SZ (N = 39) or bipolar (BP) disorder with psychotic features (N = 32), their clinically unaffected relatives (N = 82 and N = 41, respectively), and NC (N = 95) subjects.Anomalies involving derivatives of frontonasal and mandibular embryonic primordia showed a clear association with psychotic illness, as well as familial aggregation in relatives in both diagnostic groups. In contrast, one class of CF anomalies emerged only among SZ probands and their first-degree relatives: dysmorphology arising along the junction of the frontonasal and maxillary prominence derivatives, manifested as marked asymmetries. This class was not overrepresented among the BP patients nor among their relatives, indicating that this dysmorphology appears to be specific to SZ and not a generalized feature of psychosis. We discuss these findings in light of embryologic models that relate brain regions to specific CF areas.

Laser light scan analysis of the "anticonvulsant face".

BACKGROUND: The "anticonvulsant face," with a short nose, broad nasal bridge, epicanthal folds, and wide mouth, was described in the 1970s in children who had been exposed during pregnancy to the anticonvulsant drugs phenytoin and phenobarbital. The laser light scan makes it possible to establish three-dimensional positions of physical features and to determine more objectively the changes in the size and shape of the affected soft tissues of the faces of children exposed to these anticonvulsant drugs during pregnancy. METHODS: Thirteen individuals, exposed throughout pregnancy to phenytoin as either monotherapy or polytherapy, were identified in a previous analysis as having significant changes in their craniofacial features based on measurements of cephalometric radiographs. Those changes were associated with midface hypoplasia and a short nose, features of the "anticonvulsant face." The soft tissues of their faces have been evaluated with laser light scans. RESULTS: The notable changes in soft tissues identified by laser light scans were a wide philtrum (cph-cph), narrow mouth (ch-ch), short nasal bridge (n-prn), shortened nose height (n-sn), and flattened orbits (orbital protrusion index). CONCLUSION: This analysis of the facial features of phenytoin-exposed individuals, selected because of changes in their craniofacial bony structures, showed that there were several significant changes, two of which, widening of the philtrum and a small mouth, have not been described previously as part of this phenotype.

Genome-wide association study of proneness to anger.

BACKGROUND: Community samples suggest that approximately 1 in 20 children and adults exhibit clinically significant anger, hostility, and aggression. Individuals with dysregulated emotional control have a greater lifetime burden of psychiatric morbidity, severe impairment in role functioning, and premature mortality due to cardiovascular disease. METHODS: With publically available data secured from dbGaP, we conducted a genome-wide association study of proneness to anger using the Spielberger State-Trait Anger Scale in the Atherosclerosis Risk in Communities (ARIC) study (n = 8,747). RESULTS: Subjects were, on average, 54 (range 45-64) years old at baseline enrollment, 47% (n = 4,117) were male, and all were of European descent by self-report. The mean Angry Temperament and Angry Reaction scores were 5.8 ± 1.8 and 7.6 ± 2.2. We observed a nominally significant finding (p = 2.9E-08, λ = 1.027 - corrected pgc = 2.2E-07, λ = 1.0015) on chromosome 6q21 in the gene coding for the non-receptor protein-tyrosine kinase, Fyn. CONCLUSIONS: Fyn interacts with NDMA receptors and inositol-1,4,5-trisphosphate (IP3)-gated channels to regulate calcium influx and intracellular release in the post-synaptic density. These results suggest that signaling pathways regulating intracellular calcium homeostasis, which are relevant to memory, learning, and neuronal survival, may in part underlie the expression of Angry Temperament.

Nasal Morphology of the Chinese: Three-Dimensional Reference Values for Rhinoplasty.

OBJECTIVE: To determine normative nasal measurements for Chinese young adults, conditioned on demographics. STUDY DESIGN: A cross-sectional descriptive study. SETTING: A university hospital. SUBJECTS AND METHODS: Three-dimensional (3D) photographs were captured from 103 Chinese subjects between 18 and 35 years of age using a commercial stereophotographic system. Anthropometric landmarks were identified on these 3D surface images, and measurements suitable for nasal analysis were performed and contrasted against established Caucasian norms. Gender differences in anthropometric dimensions were also analyzed. RESULTS: Normative data for these measurements are made available. Linear nasal measurements, except those for mid-columella length, were significantly larger in men than in women; further, the nasal tip angle and nasofrontal angle were significantly larger in Chinese women. Contrasts of these new data against published Caucasian norms revealed dimensions that differ for these 2 groups. The Chinese normative mean values for morphological nose width, nasal tip angle, nasofrontal angle, and alar slope angle exceeded those reported for North American Caucasians. CONCLUSIONS: Gender-specific normative data for the Chinese nose were established in this study to provide a useful tool for surgeons in dealing with rhinoplasty. Moreover, the Chinese nasal anthropometric measurements in this study are broader and flatter than those reported for North American Caucasians.

Stereophotogrammetry-based facial depth measurements: a novel method for quantifying facial projection.

BACKGROUND: Orthognathic surgery leads to alteration of the spatial relationship of the mandible and maxilla resulting changes in the degree of facial projection. Traditional 2-dimensional cephalometry and photographic techniques do not provide data on facial depth. Though stereophotogrammetry can be used as a noninvasive method for evaluating facial depth, the unavailability of ethnicity-specific norms hinder its routine use in clinical practice. The objectives of this study were to (a) generate an analytic scheme suitable for evaluating facial depth using stereophotogrammetry and (b) create normative data for the facial depth measurements for young Hong Kong Chinese adults. METHODS: Stereophotographic images from 41 male and 45 female ethnic Chinese young adults without facial deformities were analyzed. Facial depth measurements were performed based on standard anthropometric landmarks, with the aid of 3dMDVultus software. RESULTS: All facial depth measurements were found in absolute terms to be significantly higher in males. In contrast, the upper face, maxillary, and sublabial depth indices were significantly higher in females, whereas no significant gender differences emerged for lower facial and maxillomandibular indices. CONCLUSIONS: A novel method of using stereophotographic images for quantifying facial depth was evaluated. Normative facial depth measurements for young Hong Kong Chinese adults were established. This gender-specific database can be used as a reference in the diagnosis, treatment planning, or evaluation of outcomes after surgical correction of facial deformities.

A 3D anthropometric analysis of the orolabial region in Chinese young adults.

The orolabial region undergoes considerable changes after orthognathic surgery or orthodontic treatment. Ethnicity, age, and sex-specific norms are needed during the planning of interventions in this region. In 2008 the Br J Oral Maxillofac Surg published anthropometric measurements of the lips of Chinese children, but to our knowledge such reference data for young Chinese adults are not currently available. We therefore used digital anthropometry on 3-dimensional craniofacial images acquired from 103 healthy young Chinese adults with Class I skeletal pattern. Anthropometric landmarks were identified, which provided linear and angular measurements. All orolabial measurements were significantly larger in men than women, with the exception of the labiomental angle. In contrast, there were no sex differences in the anthropometric proportions. We therefore provide what we think are the first cross-sectional norms available for young Chinese adults. These norms can be used to evaluate the morphology of the lips objectively for preoperative diagnosis, planning of treatment, and assessment of postoperative outcomes.

Normative findings for periocular anthropometric measurements among Chinese young adults in Hong Kong.

Measurement of periocular structures is of value in several clinical specialties including ophthalmology, optometry, medical and clinical genetics, oculoplastic surgery, and traumatology. Therefore we aimed to determine the periocular anthropometric norms for Chinese young adults using a noninvasive 3D stereophotography system. Craniofacial images using the 3dMDface system were acquired for 103 Chinese subjects (51 males and 52 females) between the ages of 18 and 35 years. Anthropometric landmarks were identified on these digital images according to standard definitions, and linear distances between these landmarks were calculated. It was found that ocular measurements were significantly larger in Chinese males than females for intercanthal width, biocular width, and eye fissure lengths. No gender differences were found in the eye fissure height and the canthal index which ranged between 43 and 44. Both right and left eye fissure height-length ratios were significantly larger in females. This is the first study to employ 3D stereophotogrammetry to create a database of anthropometric normative data for periocular measurements. These data would be useful for clinical interpretation of periocular pathology and serve as reference values when planning aesthetic and posttraumatic surgical interventions.

Quantitative assessment of craniofacial morphology in Johanson-Blizzard syndrome.

BACKGROUND: Here we apply objective, reliable methods of dysmorphology diagnosis to a patient with Johanson-Blizzard syndrome (MIM #243800). Using an extensive normative database, we computed standardized scores on a graded continuum for operational definitions of nasal alar hypoplasia, a commonly observed feature of this condition. CASE: Most of these measurements in this case were greater than 2 standard deviations below the mean, adjusted for age, gender, and ethnicity. CONCLUSION: This report provides a worked example of quantitative anthropometric assessment in the context of a case report, using tools that may find general application in clinical genetics.

Non-Mendelian etiologic factors in neuropsychiatric illness: pleiotropy, epigenetics, and convergence.

The target article by Charney on behavior genetics/genomics discusses how numerous molecular factors can inform heritability estimations and genetic association studies. These factors find application in the search for genes for behavioral phenotypes, including neuropsychiatric disorders. We elaborate upon how single causal factors can generate multiple phenotypes, and discuss how multiple causal factors may converge on common neurodevelopmental mechanisms.

Genetic association of GABA-A receptor alpha-2 and mu opioid receptor with cocaine cue-reactivity: evidence for inhibitory synaptic neurotransmission involvement in cocaine dependence.

BACKGROUND: This pilot feasibility study examined the role of genetics in laboratory-induced cocaine craving. METHODS: Thirty-four African American, cocaine-depend- ent male subjects underwent a baseline assessment, cue-exposure session, and genetic analysis. Subjects were classified as either cue-reactive or nonreactive. RESULTS: Among single nucleotide polymorphism markers in 13 candidate genes examined for association with cocaine cue-reactivity, two were statistically significant: GABRA2 (coding for GABA-A receptor alpha-2 subunit; rs11503014, nominal p= .001) and OPRM1 (coding for mu opioid receptor; rs2236256, nominal p= .03). CONCLUSIONS: These pilot results suggest that cocaine craving shows variability among cocaine-dependent subjects, and that GABRA2 and OPRM1 polymorphisms have differential influences on cocaine cue-reactivity, warranting studies in future research.