AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises were present in 97% of patients aged 2 to 12 years, occurred in the majority of patients in all age groups, and tended to be most severe during early childhood. Prominent non-motor symptoms were sleep disturbance, irritable mood, and feeding difficulties. The majority of subjects (70%) had profound motor impairment characterized by absent head control and minimal voluntary movement, while 17% had mild motor impairment and were able to walk independently. Dopamine agonists were the medications most likely to produce some symptomatic benefit, but were associated with dose-limiting side effects (dyskinesia, insomnia, irritability, vomiting) that led to discontinuation 25% of the time. The age distribution of our cohort (70% of subjects under age 13 years) and the observation of a greater proportion of patients with a more severe disease phenotype in the younger compared to the older patients, both suggest a significant mortality risk during childhood for patients with severe disease.

Associations between somatomotor-putamen resting state connectivity and obsessive-compulsive symptoms vary as a function of stress during early adolescence: Data from the ABCD study.

Obsessive-compulsive symptoms (OCS) are relatively common during adolescence although most individuals do not meet diagnostic criteria for obsessive-compulsive disorder (OCD). Nonetheless, OCS during adolescence are associated with comorbid psychopathologies and behavioral problems. Heightened levels of environmental stress and greater functional connectivity between the somatomotor network and putamen have been previously associated with elevated OCS in OCD patients relative to healthy controls. However, the interaction of these factors within the same sample of individuals has been understudied. This study examined somatomotor-putamen resting state connectivity, stress, and their interaction on OCS in adolescents from 9-12 years of age. Participants (n = 6386) were drawn from the ABCD Study 4.0 release. Multilevel modeling was used to account for nesting in the data and to assess changes in OCS in this age range. Stress moderated the association between somatomotor-putamen connectivity and OCS (ß = 0.35, S.E. = 0.13, p = 0.006). Participants who reported more stress than their average and had greater somatomotor-left putamen connectivity reported more OCS, whereas participants who reported less stress than their average and had greater somatomotor-left putamen connectivity reported less OCS. These data suggest that stress differentially affects the direction of association between somatomotor-putamen connectivity and OCS. Individual differences in the experience or perception of stress may contribute to more OCS in adolescents with greater somatomotor-putamen connectivity.

Somatostatin neurons in the bed nucleus of the stria terminalis play a sex-dependent role in binge Drinking.

Alcohol use disorder (AUD) is characterized by alcohol use coupled with chronic relapse and involves brain regions including the bed nucleus of the stria terminalis (BNST). Here, we explore whether a subpopulation of BNST neurons, somatostatin (SST) expressing GABAergic neurons, play a role in an animal model of binge-like alcohol consumption, the Drinking in the Dark (DID) model. Chemogenetic activation of BNST SST neurons reduced binge alcohol consumption in female but not male SST-Cre mice, while inhibition of these neurons in the same mice had no effect. In addition, chemogenetic activation of these neurons did not cause apparent changes in models of anxiety-like behavior in either sex. Basal SST cell counts and intrinsic excitability of SST neurons were compared to attempt to understand sex differences in DREADD-induced changes in drinking, and while males had a greater number of BNST SST neurons, this effect went away when normalizing for total BNST volume. Together, these results suggest SST neurons in the BNST should be further explored as a potential neuronal subtype modulated by AUD, and for their therapeutic potential.

Coprophenomena Associated With Worse Individual and Family Function for Youth With Tourette Syndrome: A Cross-Sectional Study.

Background and Objectives: Tourette syndrome (TS) is defined by multiple motor tics and one or more phonic tics with a symptom duration of >1 year. Coprophenomena are uncommon tics characterized by obscene sounds, words, or gestures. Youth with TS commonly have psychiatric co-occurring conditions such as attention-deficit hyperactivity disorder or obsessive-compulsive disorder and have reported lower scores on measures of individual and family functioning than youth without TS. This study aimed to determine associations among co-occurring condition symptoms, tic severity, and function in youth with TS and coprophenomena compared with those with TS without coprophenomena. Methods: Data were collected through a multicenter, cross-sectional study. Youth with TS were recruited from 2 referral centers, and data were collected from youth and their parents or caregivers. Tic severity was assessed using the Yale Global Tic Severity Scale, and individual function was measured with the Children's Global Assessment Scale. Family impact was measured using the Family Impact Module in domains of parent health-related quality of life (HRQOL), family functioning, and total family impact. We compared individual and family function in youth with TS with coprophenomena (TS+copro) and without coprophenomena (TS-copro). Wilcoxon rank-sum tests were used to compare scores on individual function and family function measures. Results: Of 169 participants, 17 (10.1%) reported coprophenomena. Participants with TS and coprophenomena had higher tic severity scores than those without coprophenomena (TS+copro mean = 36.9, TS-copro = 20.8). Youth with coprophenomena had lower scores for global function (TS+copro median = 51, TS-copro = 60), family functioning (TS+copro = 43.8, TS-copro = 59.4), parent HRQOL (TS+copro = 57, TS-copro = 72), and total family QOL (TS+copro = 50.7, TS-copro = 65.3). Discussion: Youth with TS and coprophenomena had lower individual function, family function, and parent HRQOL than youth without coprophenomena. Coprophenomena presence may indicate that youth have a more severe phenotype of TS, and youth with copropheneomena may benefit from additional caregiver or family supports.