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Background Tuberous Sclerosis Complex (TSC) is associated with a range of neuropsychiatric difficulties, appropriately termed TSC-Associated Neuropsychiatric Disorders (TAND). The objectives of the study were to analyze the rates of TAND symptoms in a cohort of patients seen at the TSC Center of Excellence at Cincinnati Children’s Hospital and to identify clinically meaningful profiles based on TAND symptoms. Methods Data from the TAND Checklist was obtained from participants seen at the TSC Center of Excellence at Cincinnati Children’s Hospital Medical Center from June 2015 to August 2018. Cluster and factor analyses for each TAND symptom were performed. Factor scores were then calculated for participants, and a K-means cluster analysis of these scores was used to empirically identify distinct overall TAND symptom profiles occurring in TSC. Results A total of 1545 checklists was completed for 668 participants (37% adults and 63% children). Approximately 90% of participants reported at least one TAND symptom with an average of 12 symptoms (out of 29). Symptom rates ranged between 5 and 60%. The most common symptoms were neuropsychologic symptoms. A seven-cluster and seven-factor solution were found to be optimal. K-means cluster analysis resulted in a seven-profile solution, ranging from low to high symptom burden. Conclusion This study is the first to identify natural phenotypic profiles of TAND symptoms. Study of specific TAND subpopulations with shared profiles may facilitate better understanding of the underlying biology of TAND and better assessment of more targeted treatments.

Although DSM-5 stipulates that symptoms of attention-deficit hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control. Previous psychometric analyses to evaluate these observations have been limited in ways addressed in the current study, which analyzes the structure of an expanded set of adult ADHD symptoms in three pooled US samples: a national household sample, a sample of health plan members, and a sample of adults referred for evaluation at an adult ADHD clinic. Exploratory factor analysis found four factors representing executive dysfunction/inattention (including, but not limited to, all the DSM-5 inattentive symptoms, with non-DSM symptoms having factor loadings comparable to those of DSM symptoms), hyperactivity, impulsivity, and emotional dyscontrol. Empirically-derived multivariate symptom profiles were broadly consistent with the DSM-5 inattentive-only, hyperactive/impulsive-only, and combined presentations, but with inattention including executive dysfunction/inattention and hyperactivity-only limited to hyperactivity without high symptoms of impulsivity. These results show that executive dysfunction is as central as DSM-5 symptoms to adult ADHD, while emotional dyscontrol is more distinct but nonetheless part of the combined presentation of adult ADHD.

Background: Lisdexamfetamine (LDX) is a prodrug and consists of an active moiety, d-amphetamine, bound to lysine. Clinically, d-amphetamine becomes available postcleavage of the prodrug in the blood stream. Clinical effects of LDX in attention-deficit/hyperactivity disorder (ADHD) have been shown to persist up to 14 hours; however, pharmacokinetic (PK) data of LDX and amphetamine in ADHD adults are not currently available. Objectives: (1) To examine PK data of LDX and d-amphetamine in plasma and (2) to compare such PK data with Time-Sensitive ADHD Symptom Scale (TASS) ratings (PK vs. pharmacodynamic [PD]). Methods: Plasma d-amphetamine/LDX levels and TASS ratings were obtained immediately before morning dosing and then 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdosing in 21 adults with ADHD treated with 5 weeks of single-blind LDX up to 70 mg/day (after 1 week single-blind placebo). ADHD Rating Scale scores were obtained at the beginning of the visit, before morning dosing. Results: LDX levels peaked at 1.5 hours after administration (T max) and then rapidly declined (levels were negligible at 6 hours and area under the plasma concentration versus time curve, AUC = 45.9, C max = 25.0, and half-life [t 1/2] = 0.5 hours). Levels of d-amphetamine peaked at (T max) 4.4 hours and then slowly declined (AUC = 641.6, C max = 67.9, and t 1/2 = 17.0 hours). No statistically significant correlations were seen between d-amphetamine levels and TASS scores. Conclusions: (1) Prodrug LDX levels peaked fairly rapidly and declined, while d-amphetamine levels peaked 3 hours later than LDX levels and persisted throughout the day and (2) the absence of PK/PD correlations between PK data and TASS ratings may be due to the subjects being tested in a controlled nonattention demanding environment.

Objectives: Assess agreement between self-ratings via the adult attention-deficit/hyperactivity disorder (ADHD) Self-Report Scale (ASRS)-v1.1 Symptom Checklist and clinician ratings via the adult ADHD Investigator Symptom Rating Scale (AISRS) expanded version using DSM-5 adult ADHD patients (referred sample) and ADHD controls (recruited from a primary care physician practice). Methods: The ASRS v1.1 Symptom Checklist was administered to measure self-reported ADHD symptoms and impairment, the Adult ADHD Clinical Diagnostic Scale v1.2 was used to establish an adult ADHD diagnosis and the childhood and adult/current sections of the scale were used to provide scores to measure symptoms of childhood ADHD and recent symptoms of adult ADHD, the AISRS to measure ADHD current symptom severity. Results: Participants (n = 299; range 18–58), of which 171 were ADHD+ and 128 ADHD−. ASRS and AISRS total scores and individual subsections examining inattention, hyperactivity, emotional dysfunction (EF), and emotional dyscontrol (EC) were all significantly correlated (Spearman's ρ’s = 0.78–0.89, ps < 0.01). Correlations remained significant when controlling for demographic factors and psychiatric conditions. Conclusions: The ASRS (self) and AISRS (clinician rated) scales have high agreement. This agreement extended not only the to the core 18 DSM symptoms, but also to the additional 13 symptoms that examine EC and EF.

The ability to engineer non-Gaussian quantum resources underlies quantum technologies from communication and metrology to universal computation. However, while a number of canonical works have set no-go limits for attaining such resources from Gaussian operations, it is widely assumed that such resources can be tuned freely by non-Gaussian Hamiltonian dynamics. Here we prove a general no-go theorem for such resource shaping: no smooth Hamiltonian dynamics can modify higher-order statistical moments of a continuous-variable state without simultaneously changing its mean and covariance. This analytic constraint implies a rigidity theorem for Hamiltonian quantum control-only quadratic (symplectic) generators preserve the Gaussian moment hierarchy, while every non-quadratic term necessarily couples the Gaussian and non-Gaussian sectors. The theorem identifies the symplectic algebra as the unique invariant subalgebra whose differential representations terminate at finite (second) order within the otherwise infinite Hamiltonian algebra. It thereby defines the analytic boundary between classically simulable Gaussian dynamics and the fully universal non-Gaussian regime-the continuous-variable analogue of the Gottesman-Knill frontier.

Quantum correlations are the singular, defining resource of quantum information science and metrology, forming the basis of every operational advantage that quantum systems hold over classical ones. Yet exact bounds on these correlations-such as the Lieb-Robinson bound on entanglement propagation and the Heisenberg limit on metrological precision-are known only in special cases and have long appeared to arise from unrelated mechanisms. Here we show that these limits share a common geometric origin. We identify a positivity invariant of the block correlation matrix, denoted \\(\\), that quantifies how far a bipartite state lies from the positivity boundary of quantum state space. For any system with a specified observable algebra and parameter-encoding map, every correlation measure determined solely by the positive correlation matrix obeys a \\(\\)-dependent inequality. For systems with simple symmetry structures these inequalities take closed analytic form, reproducing the structure of the Heisenberg and Cramér-Rao limits and producing new results, including an exact entanglement floor and a universal Fisher-information ceiling even in all-to-all connected quantum networks. We thus demonstrate that positive geometry provides a unified framework for the attainable strength of quantum correlations, linking entanglement, metrological sensitivity, and dynamical causal structure through a single invariant.

The ability to engineer non-Gaussian quantum resources underlies quantum technologies from communication and metrology to universal computation. However, while a number of canonical works have set no-go limits for attaining such resources from Gaussian operations, it is widely assumed that such resources can be tuned freely by non-Gaussian Hamiltonian dynamics. Here we prove a general no-go theorem for such resource shaping: no smooth Hamiltonian dynamics can modify higher-order statistical moments of a continuous-variable state without simultaneously changing its mean and covariance. This analytic constraint implies a rigidity theorem for Hamiltonian quantum control-only quadratic (symplectic) generators preserve the Gaussian moment hierarchy, while every non-quadratic term necessarily couples the Gaussian and non-Gaussian sectors. The theorem identifies the symplectic algebra as the unique invariant subalgebra whose differential representations terminate at finite (second) order within the otherwise infinite Hamiltonian algebra. It thereby defines the analytic boundary between classically simulable Gaussian dynamics and the fully universal non-Gaussian regime-the continuous-variable analogue of the Gottesman-Knill frontier.

We show that the Floquet Hamiltonian of a quantum particle driven by a general time-periodic imaginary potential is exactly equivalent, at stroboscopic times, to the Hamiltonian of a free particle constrained to a curved Riemannian manifold with fixed embedding. We illustrate the construction for a sinusoidal drive and for the torus of revolution, and outline how the framework can guide experimental design of curved-space quantum dynamics. Our results unify non-Hermitian Floquet physics with spectral geometry and provide a general recipe for engineering quantum dynamics on embedded manifolds.

We consider the dynamics of the quantum Rabi model driven parametrically by a periodic modulation of a complex coupling. We show both analytically and numerically that instead of Rabi oscillations, this nonunitary coherent driving leads to a unidirectional instanton solution which mediates the rapid and deterministic one-way tunneling of any initial coherent state to the ground state, making the ground state a strong attractor in the quantum dynamics of the qubit. The timescale of this tunneling is shown to be inversely proportional to the effective resonant coupling, allowing for exceptionally fast, deterministic, and high-fidelity qubit reset through a purely coherent, PT-symmetric drive--without coupling to external dissipative baths, lossy resonators, or employing measurement-based feedback. Finally, we show how the drive can be engineered to place the strong attractor at any arbitrary point on the Bloch sphere.

The driven quantum harmonic oscillator is fundamental to a number of important physical systems. Here, we consider the quantum harmonic oscillator under non-Hermitian, PT-symmetric driving, showing that the resulting set of Wigner-space trajectories of an initial coherent state is identical to the set of real-space trajectories of the classical Foucault pendulum. Remarkably, in the case mapped from the trivial 1D pendulum, the corresponding quantum dynamics are those of an oscillator with periodically evolving momentum but fixed position, a novel type of dynamics which are forbidden in classical systems.