Treatment of 22q11.2 deletion syndrome-associated schizophrenia with comorbid anxiety and panic disorder

22q11.2 deletion syndrome (22q11DS) is a risk factor for psychiatric illnesses, including schizophrenia and anxiety. Small studies have shown that several neuroleptic medications are effective in treating psychosis in this population, but are also associated with an increased risk of adverse effects - particularly, seizures. In this case, we discuss a 34-year-old patient presenting with late onset schizophrenia, which ultimately led to her diagnosis of 22q11DS. Subsequent management of the patient’s psychosis with asenapine was complicated by concurrent anxiety and panic disorder; thus, we examine the role of anxiolytic therapy in conjunction with antipsychotics in this patient population

Treatment of 22q11.2 deletion syndrome-associated schizophrenia with comorbid anxiety and panic disorder.

22q11.2 deletion syndrome (22q11DS) is a risk factor for psychiatric illnesses, including schizophrenia and anxiety. Small studies have shown that several neuroleptic medications are effective in treating psychosis in this population, but are also associated with an increased risk of adverse effects - particularly, seizures. In this case, we discuss a 34-year-old patient presenting with late onset schizophrenia, which ultimately led to her diagnosis of 22q11DS. Subsequent management of the patient’s psychosis with asenapine was complicated by concurrent anxiety and panic disorder; thus, we examine the role of anxiolytic therapy in conjunction with antipsychotics in this patient population

Propionate Increases Hepatic Pyruvate Cycling and Anaplerosis and Alters Mitochondrial Metabolism

In mammals, pyruvate kinase (PK) plays a key role in regulating the balance between glycolysis and gluconeogenesis; however, in vivo regulation of PK flux by gluconeogenic hormones and substrates is poorly understood. To this end, we developed a novel NMR-liquid chromatography/tandem-mass spectrometry (LC-MS/MS) method to directly assess pyruvate cycling relative to mitochondrial pyruvate metabolism (V(Pyr-Cyc)/V(Mito)) in vivo using [3-(13)C]lactate as a tracer. Using this approach, V(Pyr-Cyc)/V(Mito) was only 6% in overnight fasted rats. In contrast, when propionate was infused simultaneously at doses previously used as a tracer, it increased V(Pyr-Cyc)/V(Mito) by 20–30-fold, increased hepatic TCA metabolite concentrations 2–3-fold, and increased endogenous glucose production rates by 20–100%. The physiologic stimuli, glucagon and epinephrine, both increased hepatic glucose production, but only glucagon suppressed V(Pyr-Cyc)/V(Mito). These data show that under fasting conditions, when hepatic gluconeogenesis is stimulated, pyruvate recycling is relatively low in liver compared with V(Mito) flux and that liver metabolism, in particular pyruvate cycling, is sensitive to propionate making it an unsuitable tracer to assess hepatic glycolytic, gluconeogenic, and mitochondrial metabolism in vivo