Synaptic and Intrinsic Activation of GABAergic Neurons in the Cardiorespiratory Brainstem Network

GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in close apposition to cardioinhibitory parasympathetic cardiac neurons in the nucleus ambiguus (NA). These neurons fire in synchronization with inspiratory activity. Although they receive excitatory glutamatergic synaptic inputs during inspiration, this excitatory neurotransmission was not altered by blocking nicotinic receptors, and many of these GABAergic neurons continue to fire after synaptic blockade. The spontaneous firing in these GABAergic neurons was not altered by the voltage-gated calcium channel blocker cadmium chloride that blocks both neurotransmission to these neurons and voltage-gated Ca2+ currents, but spontaneous firing was diminished by riluzole, demonstrating a role of persistent sodium channels in the spontaneous firing in these cardiorespiratory GABAergic neurons that possess a pacemaker phenotype. The spontaneously firing GABAergic neurons identified in this study that increase their activity during inspiration would support respiratory rhythm generation if they acted primarily to inhibit post-inspiratory neurons and thereby release inspiration neurons to increase their activity. This population of inspiratory-modulated GABAergic neurons could also play a role in inhibiting neurons that are most active during expiration and provide a framework for respiratory sinus arrhythmia as there is an increase in heart rate during inspiration that occurs via inhibition of premotor parasympathetic cardioinhibitory neurons in the NA during inspiration

The italian version of the 92-item prodromal questionnaire: Concurrent validity with the SIPS and factor analysis in a sample of 258 outpatients aged 11-36years

BACKGROUND: Current early screeners for psychosis-risk states have still to prove ability in identifying at-risk individuals. Among screeners, the 92-item Prodromal Questionnaire (PQ-92) is often used. We aimed to assess the validity of its Italian translation in a large Italian adolescent and young adult help-seeking sample. METHODS: We included all individuals aged 12-36years seeking help at psychiatric mental health services in a large semirural Roman area (534,600 population) who accepted to participate. Participants completed the Italian version of the PQ-92 and were subsequently assessed with the Structured Interview of Prodromal/Psychosis-Risk Syndromes (SIPS). We examined diagnostic accuracy (sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios) and content, concurrent, and convergent validity between PQ-92 and SIPS using Cronbach's alpha, Cohen's kappa, and Spearman's rho, respectively. We tested the validity of adopted cut-offs through Receiver Operating Characteristic (ROC) curves plotted against SIPS diagnoses and the instrument's factor-structure through Principal Component Analysis. RESULTS: PQ-92 showed high internal consistency, acceptable diagnostic accuracy and concurrent validity, and excellent convergent validity. ROC analyses pointed to scores of 18 on the Positive subscale and 36 on the total PQ-92 as best cut-offs. The Scree-test identified a four-factor solution as fitting best. CONCLUSIONS: Psychometric properties of Italian PQ-92 were satisfactory. Optimal cut-offs were confirmed at ≥18 on the positive subscale, but at ≥36 on the total scale was able to identify more SIPS-positive case

The italian version of the 92-item prodromal questionnaire: Concurrent validity with the SIPS and factor analysis in a sample of 258 outpatients aged 11-36years

BACKGROUND: Current early screeners for psychosis-risk states have still to prove ability in identifying at-risk individuals. Among screeners, the 92-item Prodromal Questionnaire (PQ-92) is often used. We aimed to assess the validity of its Italian translation in a large Italian adolescent and young adult help-seeking sample. METHODS: We included all individuals aged 12-36years seeking help at psychiatric mental health services in a large semirural Roman area (534,600 population) who accepted to participate. Participants completed the Italian version of the PQ-92 and were subsequently assessed with the Structured Interview of Prodromal/Psychosis-Risk Syndromes (SIPS). We examined diagnostic accuracy (sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios) and content, concurrent, and convergent validity between PQ-92 and SIPS using Cronbach's alpha, Cohen's kappa, and Spearman's rho, respectively. We tested the validity of adopted cut-offs through Receiver Operating Characteristic (ROC) curves plotted against SIPS diagnoses and the instrument's factor-structure through Principal Component Analysis. RESULTS: PQ-92 showed high internal consistency, acceptable diagnostic accuracy and concurrent validity, and excellent convergent validity. ROC analyses pointed to scores of 18 on the Positive subscale and 36 on the total PQ-92 as best cut-offs. The Scree-test identified a four-factor solution as fitting best. CONCLUSIONS: Psychometric properties of Italian PQ-92 were satisfactory. Optimal cut-offs were confirmed at ≥18 on the positive subscale, but at ≥36 on the total scale was able to identify more SIPS-positive case