Family and Developmental History of Individuals With Autism Spectrum Disorder: Importance of the Clinical Diagnostic Interview for Diagnosis in Adolescents. An Explorative Study

Background: Diagnosis of autism spectrum disorder (ASD) can be made early in childhood, but also later in adolescence or adulthood. In the latter cases, concerns about an individual's behavior typically lead to consultation of a mental health professional (MHP). As part of the initial clinical examination by the MHP, a clinical diagnostic interview is performed, in order to obtain the patient's history, and may lead to the hypothesis of ASD. We were here interested to study family and developmental history as key parts of the patient's history. The aim of the study was to investigate empirical differences between adolescents with ASD and adolescent control persons in family and developmental history.Method: Clinical diagnostic interview items addressing family and developmental history were adopted from their regular use at several university hospitals and in leading textbooks. Parents of male adolescents with normal intelligence and an ASD diagnosis (n = 67) and parents of male adolescents without psychiatric diagnosis (n = 51) between the age of 12 and 17 years were investigated. Data were operationalized into three categories: 0 = normal behavior, 1 = minor pathological behavior, and 2 = major pathological behavior. Differences were analyzed by multiple t-test of two-way ANOVA.Results: Adolescents with ASD expressed a profile of items significantly differing from control persons. Comparison of significant items with the empirical ASD literature indicated robust accordance.Conclusions: Our findings support the importance and feasibility of the clinical diagnostic interview of family and developmental history for initiation of the diagnostic process of ASD in adolescents.

Family and Developmental History of Female Versus Male Adolescents With ADHD: Disorder-specific Overlap but Few Gender Differences

Background: Gender differences in the development of children and adolescents are well known in the psychiatric examination including the clinical diagnostic interview technique. Some gender-specific differences in behaviors of patients as assessed in the clinical examination are related to typical development and some are related to disorders. Family and developmental history is an important part of the clinical diagnostic interview. Attention-deficit/hyperactivity disorder (ADHD) is associated with disorder-specific markers in family and development history. However, it is unclear to what extent ADHD-specific signs and narratives differ between female and male adolescents. The aim of this study was to assess and to compare the family and developmental history profiles of female versus male adolescents with ADHD.Methods: Data were collected using the clinical diagnostic interview technique from parents of female and male patients diagnosed with ADHD (ICD-10 F90.0, F90.1 and F98.8) between the ages of 12 and 17 years (n = 92). The two groups were matched in pairs for gender, IQ and ICD-10 diagnosis (F90.0, F90.1 and F98.8). The majority of interview data were non-metric and operationalized in three categories: 0 - normal behavior, 1 - minor pathological behavior, 2 - major pathological behavior. The two groups were compared with two-way ANOVA. Results: Female in comparison to male adolescents were reported by the parents with very few differences in items that are typical for ADHD. However, there were a few differences in items in which gender-specific differences are known regardless of ADHD. Conclusions: Our study suggests that ADHD-related items in family and developmental history, as obtained with the clinical diagnostic interview technique, appear in female compared to male adolescents more similar than different.

Inherited Thyroid Tumors With Oncocytic Change

Familial non-medullary thyroid carcinoma (FNMTC) corresponds to 5-10% of all follicular cell-derived carcinoma (FCDTC). Oncocytic thyroid tumors have an increased incidence in the familial context in comparison with sporadic FCDTC, encompassing benign and malignant tumors in the same family presenting with some extent of cell oxyphilia. This has triggered the interest of our and other groups to clarify the oncocytic change, looking for genetic markers that could explain the emergence of this phenotype in thyroid benign and malignant lesions, focusing on familial aggregation. Despite some advances regarding the identification of the gene associated with retinoic and interferon-induced mortality 19 (GRIM-19), as one of the key candidate genes affected in the “Tumor with Cell Oxyphilia” (TCO) locus, most of the mutations follow a pattern of “private mutations”, almost exclusive to one family. Moreover, no causative genetic alterations were identified so far in most families. The incomplete penetrance of the disease, the diverse benign and malignant phenotypes in the affected familial members and the variable syndromic associations create an additional layer of complexity for studying the genetic alterations in oncocytic tumors. In the present review, we summarized the available evidence supporting genomic-based mechanisms for the oncocytic change, particularly in the context of FNMTC. We have also addressed the challenges and gaps in the aforementioned mechanisms, as well as molecular clues that can explain, at least partially, the phenotype of oncocytic tumors and the respective clinico-pathological behavior. Finally, we pointed to areas of further investigation in the field of oncocytic (F)NMTC with translational potential in terms of therapy.

Whole Tumor Capsule is Prognostic of a Very Good Outcome in the Classical Variant of Papillary Thyroid Cancer

Context Tumour capsule integrity is becoming a relevant issue to predict the biological behaviour of human tumours, including thyroid cancer. Aim To verify if a whole tumour capsule in the classical variant of PTC (CVPTC) could have a predictive role of a good outcome as for follicular variant (FVPTC). Methods FVPTC (n=600) and CVPTC (n=554) cases, were analysed. We distinguished encapsulated-FVPTC (E-FVPTC) and encapsulated-CVPTC (E-CVPTC) and, thereafter, invasive (Ei-FVPTC and Ei-CVPTC) and non-invasive (En-FVPTC and En-CVPTC) tumours, according to the invasion or integrity of tumour capsule, respectively. Cases without tumour capsule were indicated as invasive-FVPTC (I-FVPTC) and invasive-CVPTC (I-CVPTC). Sub-group of each variant was evaluated for BRAF mutations. Results E-FVPTC was more frequent than E-CVPTC (p<0.0001). No differences were found between En-FVPTC and En-CVPTC or between Ei-FVPTC and Ei-CVPTC. After 18 years of follow-up, a greater number of not-cured cases were observed in Ei-CVPTC with respect to Ei-FVPTC, but not in En-CVPTC to En-FVPTC. Multivariate clustering analysis showed that En-FVPTC, En-CVPTC, and Ei-FVPTC have similar features but different from I-FVPTC and I-CVPTC and, to a lesser extent, from Ei-CVPTC. 177/614 (28.8%) cases were BRAF V600E-mutated and 10/614(1.6%) carried BRAF-rare alterations. Significantly higher rate of En-CVPTC (22/49,44.9%) than En-FVPTC (15/195,7.7%) (p<0.0001) were BRAF V600E-mutated. Conclusions En-CVPTC is less prevalent than En-FVPTC. However, they have a good clinical/ pathological behavior comparable to En-FVPTC. This finding confirms the good prognostic role of a whole tumour capsule also in CVPTC. New nomenclature for En-CVPTC, similar to that introduced for En-FVPTC (i.e, NIFTP) could be envisaged.

Spherically symmetric analytic solutions and naked singularities in Einstein–Aether theory

We analyze all the possible spherically symmetric exterior vacuum solutions allowed by the Einstein–Aether theory with static aether. We show that there are three classes of solutions corresponding to different values of a combination of the free parameters, $$c_{14}=c_1+c_4$$ c 14 = c 1 + c 4 , which are: $$ 0< c_{14}<2$$ 0 < c 14 < 2 , $$c_{14} < 0$$ c 14 < 0 , and $$c_{14}=0$$ c 14 = 0 . We present explicit analytical solutions for $$c_{14}=3/2, 16/9, 48/25, -16$$ c 14 = 3 / 2 , 16 / 9 , 48 / 25 , - 16 and 0. The first case has some pathological behavior, while the rest have all singularities at $$r=0$$ r = 0 and are asymptotically flat spacetimes. For the solutions $$c_{14}=16/9, 48/25\, \mathrm {\, and \,}\, -16$$ c 14 = 16 / 9 , 48 / 25 and - 16 we show that there exist no horizons, neither Killing horizon nor universal horizon, thus we have naked singularities. This characteristic is completely different from general relativity. We briefly discuss the thermodynamics for the case $$c_{14}=0$$ c 14 = 0 where the horizon exists.

The Placement of Obsessive-Compulsive Symptoms Within a Five-Factor Model of Maladaptive Personality

Dimensional models of obsessive-compulsive (OC) symptoms, as seen in obsessive-compulsive disorder (OCD), are instrumental in explaining the heterogeneity observed in this condition and have received considerable empirical support. Normative models of personality partially align with OC symptoms; however, maladaptive personality models present a more compelling approach because of their direct relevance to pathological behavior. Prior efforts to map OC symptoms to maladaptive personality space, as operationalized by the DSM-5 Alternative Model of Personality Disorder (AMPD), find these symptoms cross-load under both Negative Affectivity and Psychoticism traits. However, tests of OC symptoms in conjunction with the full AMPD structure, and its 25 lower-level facets, are lacking. We applied joint exploratory factor analysis to an AMPD instrument, the Personality Inventory for DSM-5 (PID-5), and OC symptom data from two separate samples (total N=1506) to locate OC symptoms within AMPD space. As expected, OC symptoms cross-loaded on Negative Affectivity, Psychoticism and on the low-end of Disinhibition. OC symptoms more strongly loaded on Psychoticism across samples, suggesting structural relations between OCD and psychotic experiences are stronger than DSM models imply. Facet loadings largely resembled the canonical PID-5 structure. A notable exception was that two Psychoticism facets (Perceptual Dysregulation and Unusual Beliefs/Experiences) more closely tracked OC symptom loadings. We also report exploratory analyses of OC symptom subscales (e.g., obsessing, ordering, checking) with PID-5 variables. Results are discussed in the context of the placement of OC symptoms/OCD in PID-5 space and within the Hierarchical Taxonomy of Psychopathology, an ongoing effort to improve psychopathology classification.

Consolidating the Circuit Model for Addiction

Addiction is a disease characterized by compulsive drug seeking and consumption observed in 20–30% of users. An addicted individual will favor drug reward over natural rewards, despite major negative consequences. Mechanistic research on rodents modeling core components of the disease has identified altered synaptic transmission as the functional substrate of pathological behavior. While the initial version of a circuit model for addiction focused on early drug adaptive behaviors observed in all individuals, it fell short of accounting for the stochastic nature of the transition to compulsion. The model builds on the initial pharmacological effect common to all addictive drugs—an increase in dopamine levels in the mesolimbic system. Here, we consolidate this early model by integrating circuits underlying compulsion and negative reinforcement. We discuss the genetic and epigenetic correlates of individual vulnerability. Many recent data converge on a gain-of-function explanation for circuit remodeling, revealing blueprints for novel addiction therapies. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Geometric Justification of the Fundamental Interaction Fields for the Classical Long-Range Forces

Based on the principle of reparametrization invariance, the general structure of physically relevant classical matter systems is illuminated within the Lagrangian framework. In a straightforward way, the matter Lagrangian contains background interaction fields, such as a 1-form field analogous to the electromagnetic vector potential and symmetric tensor for gravity. The geometric justification of the interaction field Lagrangians for the electromagnetic and gravitational interactions are emphasized. The generalization to E-dimensional extended objects (p-branes) embedded in a bulk space M is also discussed within the light of some familiar examples. The concept of fictitious accelerations due to un-proper time parametrization is introduced, and its implications are discussed. The framework naturally suggests new classical interaction fields beyond electromagnetism and gravity. The simplest model with such fields is analyzed and its relevance to dark matter and dark energy phenomena on large/cosmological scales is inferred. Unusual pathological behavior in the Newtonian limit is suggested to be a precursor of quantum effects and of inflation-like processes at microscopic scales.