Evaluation of Phosphatidylethanol Elimination in Alcohol Use Disorder Patients Undergoing Withdrawal Treatment.

AIMS: Phosphatidylethanol (PEth) is used to monitor alcohol consumption in alcohol use disorder (AUD). In this study, we aim to evaluate the elimination time of PEth with regard to the clinically established 200 and 20 ng/ml cutoffs for PEth 16:0/18:1. METHODS: Data from 49 patients undergoing treatment for AUD were evaluated. PEth concentrations were measured at the beginning and repeatedly during the treatment period of up to 12 weeks to monitor the elimination of PEth. We evaluated the time in weeks until the cutoff concentrations of <200 and <20 ng/ml were achieved. The correlation between the initial PEth concentration and the number of days until the PEth concentration had dropped below 200 and 20 ng/ml was assessed by calculating Pearson's correlation coefficients. RESULTS: The initial PEth concentrations ranged from <20 to >2500 ng/ml. In 31 patients, the time until the cutoff values were reached could be documented. Even after 6 weeks of abstinence, PEth concentrations above the cutoff of 200 ng/ml could still be detected in two patients. A strong significant positive correlation was found between the initial PEth concentration and the time required to drop below the two cutoffs. CONCLUSION: A waiting period of more than 6 weeks after declared abstinence should be granted for individuals with AUD before using only one single PEth concentration to assess the consumption behavior. However, we recommend to always use at least two PEth concentrations for the evaluation of alcohol-drinking behaviors in AUD patients.

The Neurophysiology of Implicit Alcohol Associations in Recently Abstinent Patients With Alcohol Use Disorder: An Event-Related Potential Study Considering Gender Effects.

BACKGROUND: Neuroscientific models of alcohol use disorders (AUDs) postulate an imbalance between automatic, implicit, and controlled (conscious) processes. Implicit associations towards alcohol indicate the automatically attributed appeal of alcohol-related stimuli. First, behavioral studies indicate that negative alcohol associations are less pronounced in patients compared to controls, but potential neurophysiological differences remain unexplored. This study investigates neurophysiological correlates of implicit alcohol associations in recently abstinent patients with AUD for the first time, including possible gender effects. METHODS: A total of 62 patients (40 males and 22 females) and 21 controls performed an alcohol valence Implicit Association Test, combining alcohol-related pictures with positive (incongruent condition) or negative (congruent condition) words, while brain activity was recorded using 64-channel electroencephalography. Event-related potentials (ERPs) for alcohol-negative and alcohol-positive trials were computed. Microstate analyses investigated the effects of group (patients, controls) and condition (incongruent, congruent); furthermore, possible gender effects in patients were analyzed. Significant effects were localized with standardized low-resolution brain electromagnetic topography analysis. RESULTS: Although no behavioral group differences were found, ERPs of patients and controls were characterized by distinct microstates from 320 ms onwards. ERPs between conditions differed only in patients with higher signal strength during incongruent trials. Around 600 ms, controls displayed higher signal strength than patients. A gender effect mirrored this pattern with enhanced signal strength in females as opposed to male patients. Around 690 ms, a group-by-valence interaction indicated enhanced signal strength in congruent compared to incongruent trials, which was more pronounced in controls. CONCLUSIONS: For patients with AUD, the pattern, timing, and source localization of effects suggest greater effort regarding semantic and self-relevant integration around 400 ms during incongruent trials and attenuated emotional processing during the late positive potential timeframe. Interestingly, this emotional attenuation seemed reduced in female patients, thus corroborating the importance of gender-sensitive research and potential treatment of AUD.

Screened Attention Deficit/Hyperactivity Disorder as a Predictor of Substance Use Initiation and Escalation in Early Adulthood and the Role of Self-Reported Conduct Disorder and Sensation Seeking: A 5-Year Longitudinal Study with Young Adult Swiss Men.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and sensation seeking (SS) have been consistently related to a higher risk of substance use (SU) and substance use disorder (SUD). OBJECTIVES: To investigate the relationship between ADHD and prevalence rates in males at age 20 and age 25, the initiation of SU and SUD after age 20, and the escalation of SU from age 20 to age 25, and to explore the role of CD and SS in the relation of ADHD with SU and SUD initiation and escalation. METHOD: Data were obtained as part of the Cohort Study on Substance Use Risk Factors (C-SURF), which focused on young Swiss men aged 20 years at baseline and 25 years at follow-up. RESULTS: Participants who screened positive for ADHD at baseline exhibited a higher rate of SU and SUD than participants who screened negative. The presence of ADHD symptoms at age 20 predicted initiation of all SU between age 20 and age 25, except for alcohol and smoking. After controlling for self-reported CD and SS, ADHD still predicted this late initiation of use of hallucinogens, meth-/amphetamines, and ecstasy/MDMA; non-medical use of ADHD medication and sedatives, and alcohol use disorder (AUD). No escalation of weekly drinking and smoking or annual cannabis use was observed from age 20 to age 25. CONCLUSION: Screened-positive ADHD is an independent predictor of late SU and AUD, along with self-reported CD and SS. From a public health perspective, identifying ADHD is not only important in childhood and adolescence but also in early adulthood to guide specific interventions to lower risks of drug use initiation and the development of AUD in early adulthood.

Glucocorticoid administration restores salience network activity in patients with spider phobia.

BACKGROUND: Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli. METHODS: We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20 mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points. RESULTS: Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo-treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol- versus placebo-treated patients to a level that was similar to that observed in healthy controls. CONCLUSIONS: Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.

Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis.

BACKGROUND: White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. METHODS: Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). RESULTS: CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. CONCLUSION: The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study.

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.