Impairment of the GABAergic system in the anterior insular cortex of heroin-addicted males.

Opioid addiction is a global problem, causing the greatest health burden among drug use disorders, with opioid overdose deaths topping the statistics of fatal overdoses. The multifunctional anterior insular cortex (AIC) is involved in inhibitory control, which is severely impaired in opioid addiction. GABAergic interneurons shape the output of the AIC, where abnormalities have been reported in individuals addicted to opioids. In these neurons, glutamate decarboxylase (GAD) with its isoforms GAD 65 and 67 is a key enzyme in the synthesis of GABA, and research data point to a dysregulation of GABAergic activity in the AIC in opioid addiction. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of the AIC in opioid addiction by densitometric evaluation of GAD 65/67-immunostained neuropil. The study showed bilaterally increased neuropil density in layers III and V in 13 male heroin-addicted males compared to 12 healthy controls, with significant U-test P values for layer V bilaterally. Analysis of confounding variables showed that age, brain volume and duration of formalin fixation did not confound the results. Our findings suggest a dysregulation of GABAergic activity in the AIC in opioid addiction, which is consistent with experimental data from animal models and human neuroimaging studies.

Inverse pattern of GABAergic system impairment in the external versus internal globus pallidus in male heroin addicts.

Opioid addiction is a global problem that has been exacerbated in the USA and Europe by the COVID-19 pandemic. The globus pallidus (GP) plays a prominent neurobiological role in the regulation of behaviour as an output station of the striato-pallidal system. GABAergic large projection neurons are the main neuronal type in the external (EGP) and internal (IGP) parts of the GP, where addiction-specific molecular and functional abnormalities occur. In these neurons, glutamate decarboxylase (GAD) with isoforms GAD 65 and 67 is a key enzyme in GABA synthesis, and experimental studies suggest GAD dysregulation in the GP of heroin addicts. Our study, which was performed on paraffin-embedded brains from the Magdeburg Brain Bank, aimed to investigate abnormalities in the GABAergic function of large GP neurons by densitometric evaluation of their GAD 65/67-immunostained thick dendrites. The study revealed a bilaterally decreased fibres density in the EGP paralleled by the increase in the IGP in 11 male heroin addicts versus 11 healthy controls (significant U-test P values). The analysis of confounding variables found no interference of age, brain volume, and duration of formalin fixation with the results. Our findings suggest a dysregulation of GABAergic activity in the GP of heroin addicts, which is consistent with experimental data from animal models and plays potentially a role in the disturbed function of basal ganglia circuit in opioid addiction.

Peritraumatic distress in mothers of severely ill children: a cross-sectional study.

INTRODUCTION: Peritraumatic distress is a syndrome that involves negative emotions, such as anxiety, helplessness and horror, experienced during and shortly after a traumatic event. The intensity of peritraumatic distress is significantly linked to the intensity of post-traumatic stress syndrome (PTSD) symptoms. The aim of the study was to study the intensity of peritraumatic distress symptoms in the mothers of severely ill children and the relationship between peritraumatic distress and psychological, socio-demographic and medical coefficients in the mothers. MATERIAL AND METHODS: An anonymous survey was performed in a group of 135 mothers of children with a perinatal medical history and mothers of children hospitalized in an intensive care unit and an oncology unit. The demographic questionnaire was compiled by the authors along with several standardized research tools. RESULTS: Intensity of peritraumatic distress correlates strongly positively with anxiety, ρ = 0.50; P < 0.001, and moderately positively with intrusion ρ = 0.39; P < 0.00, arousal, ρ = 0.38; P < 0.001, PTSD intensification, ρ = 0.40; P < 0.001, depression, ρ = 0.49; P < 0.001. Significant predictors of peritraumatic distress include the use of such coping strategies as acceptance, ß = -0.44; P = 0.001, denial, ß = 0.20; P = 0.019, planning, ß = -0.26; P = 0.012 and humour, ß = -0.29; P = 0.048, as well as the possibility to obtain self-worth support, ß = -0.07; P = 0.029 (R2 corrected = 0,32; F(5.33) = 9.43; P < 0.001). CONCLUSIONS: Coping strategies are a potentially modifiable factor, thus, implementing prevention programmes concerning the strategies should be considered.

Paternal deprivation affects the functional maturation of corticotropin-releasing hormone (CRH)- and calbindin-D28k-expressing neurons in the bed nucleus of the stria terminalis (BNST) of the biparental Octodon degus.

While the critical role of maternal care on the development of brain and behavior of the offspring has been extensively studied, our knowledge about the importance of paternal care for brain development of his offspring is still comparatively scarce. The aim of this study in the biparental caviomorph rodent Octodon degus was to analyze the impact of paternal care on the development of corticotropin-releasing hormone (CRH)-expressing neurons in the bed nucleus of the stria terminalis (BNST) and hypothalamic paraventricular nucleus (PVN). Both brain areas are key players in neuronal circuits that regulate hypothalamic-pituitary-adrenal axis (HPA) activity. At the age of postnatal day (PND) 21, we found that paternal deprivation resulted in a decreased density of CRH-containing neurons in the medial, but not in the lateral BNST, whereas no changes were observed in the PVN. These deprivation-induced changes were still prominent in adulthood. At PND 21, the density of Ca-binding protein calbindin D28K (CaBP-D28K)-expressing neurons was specifically increased in the medial, but not lateral BNST of father-deprived animals. In contrast, adult father-deprived animals show significantly decreased density of CaBP-D28K-expressing neurons in the lateral, but not medial BNST. Taken together, these results may have important implications for our understanding of the experience-driven development of neural circuits that regulate HPA activity mediating acute responses to stress and chronic anxiety.