Recovery of Decreased Metabotropic Glutamate Receptor 5 Availability in Abstinent Alcohol-Dependent Patients.

Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular, cerebral metabotropic glutamate receptor 5 (mGluR5). 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET has revealed that chronic alcohol use leads to decreased limbic mGluR5 availability, which was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2 and 6 mo of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse. Methods:18F-FPEB scans were performed for 16 recently detoxified alcohol-dependent patients (baseline condition), 2 mo after detoxification (n = 10), and 6 mo after detoxification (n = 8); 32 age- and sex-matched controls were included for comparison. mGluR5 availability was quantified by the 18F-FPEB total distribution volume using both voxel-by-voxel and volume-of-interest analyses. During follow-up, craving was assessed using the Desire for Alcohol Questionnaire, and alcohol consumption was assessed using the timeline follow-back method and monitored by hair ethyl glucuronide analysis. Results: During abstinence, alcohol-dependent patients showed sustained recovered mGluR5 availability in cortical and subcortical regions compared with the baseline, up to the levels observed in controls, after 6 mo in most areas except for the hippocampus, nucleus accumbens, and thalamus. Higher striatopallidal mGluR5 availability was observed at the baseline in patients who had a relapse during the 6-mo follow-up period (+25.1%). Also, normalization of striatal mGluR5 to control levels was associated with reduced craving ("desire and intention to drink" and "negative reinforcement"; r = 0.72-0.94). Conclusion: Reduced cerebral mGluR5 availability in alcohol-dependent patients recovers during abstinence and is associated with reduced craving. Higher striatal mGluR5 availability in alcohol-dependent users may be associated with long-term relapse.

Early maladaptive schemas: Similarities and differences between female patients with eating versus substance use disorders.

Personality features are considered to be important factors in the pathogenesis of both eating disorder (ED) and substance use disorder (SUD). This study investigates similarities and differences between these early maladaptive schemas (EMSs) (a) between female patients with ED (N = 179) or SUD (N = 169) and (b) between ED subtypes of the restrictive (N = 52), bulimic type (N = 127), or SUD. In total, 348 female patients (Mage  = 29.95; SDage  = 8.40) completed the Young Schema Questionnaire. Multivariate analyses of covariance with EMS scales as dependent variables and (a) ED versus SUD and (b) ED subtypes versus SUD as independent variables and age and psychopathology as control variables revealed that ED patients scored significantly higher on Unrelenting Standards, Defectiveness, Social Undesirability, and Failure than did SUD patients. Additionally, when comparing ED subtypes and SUD, bulimic and SUD patients scored significantly higher on Insufficient Self-Control than did restrictive patients. These results confirm the role of EMSs in ED (subtypes) and SUD.

Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol Dependence.

Animal studies suggest an important role for the metabotropic glutamate receptor subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human evidence is lacking. The goal of this study was to investigate cerebral mGlu5 availability in alcohol-dependent subjects versus controls using 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET. Methods: Dynamic 90-min 18F-FPEB scans combined with arterial blood sampling were acquired for 16 recently abstinent alcohol-dependent subjects and 32 age-matched controls. Regional mGlu5 availability was quantified by the 18F-FPEB total distribution volume using both a voxel-by-voxel and a volume-of-interest analysis with partial-volume effect correction. Alcohol consumption within the last 3 mo was assessed by questionnaires and by hair ethyl glucuronide analysis. Craving was assessed using the Desire for Alcohol Questionnaire. Results: mGlu5 availability was lower in mainly limbic regions of alcohol-dependent subjects than in controls (P < 0.05, familywise error-corrected), ranging from 14% in the posterior cingulate cortex to 36% in the caudate nucleus. Lower mGlu5 availability was associated with higher hair ethyl glucuronide levels for most regions and was related to a lower level of craving specifically in the middle frontal gyrus, cingulate cortex, and inferolateral temporal lobe. Conclusion: These findings provide human in vivo evidence that limbic mGlu5 has a role in the pathophysiology of alcohol dependence, possibly involved in a compensatory mechanism helping to reduce craving during abstinence.

Addiction specialist's role in liver transplantation procedures for alcoholic liver disease.

Although liver transplantation (LT) is performed increasingly for patients with end-stage alcoholic liver disease (ALD), the topic remains controversial. Traditionally, the role of an addiction specialist focused on the screening and identification of patients with a high risk on relapse in heavy alcohol use. These patients were in many cases subsequently excluded from a further LT procedure. Recently, awareness is growing that not only screening of patients but also offering treatment, helping patients regain and maintain abstinence is essential, opening up a broader role for the addiction specialist (team) within the whole of the transplant procedure. Within this context, high-risk assessment is proposed to be an indication of increasing addiction treatment intensity, instead of being an exclusion criterion. In this review we present an overview regarding the state of the art on alcohol relapse assessment and treatment in patients with alcohol use disorders, both with and without ALD. Screening, treatment and monitoring is suggested as central roles for the addiction specialist (team) integrated within transplant centers.

Age Neutrality of Categorically and Dimensionally Measured DSM-5 Section II Personality Disorder Symptoms.

Studies on the face validity of DSM-5 Section II categorical personality disorder (PD) symptoms indicate a bias against older adults. To extend these results, this article explores whether categorically and dimensionally scored PD symptoms of DSM-5 Section II, as measured in the Assessment of DSM-IV Personality Disorders (ADP-IV; Schotte & de Doncker, 1994), corroborate potential age bias across younger (aged 18-34), middle-aged (35-59 years), and older adults (aged 60-75). Differential item functioning (DIF) analyses, following a classical test theory approach, showed that 2 of the 79 symptoms were measured differently across 3 age groups when categorically assessed, and 4 when dimensionally measured. Nevertheless, subsequent differential test functioning analyses supported a low aggregated impact of DIF on the dimensional scales, justifying mean-level comparisons across age groups. Generalizability of the results is discussed in light of methodological issues concerning the research of age neutrality of PD symptoms, including the employed measurement instrument, PD symptom measurement approach, and sample and age range used to describe older adults.

Age neutrality of the young schema questionnaire in patients with a substance use disorder.

BACKGROUND: Young's Schema Focused Therapy (SFT) is gaining popularity in the treatment of older adults. In the context of this therapy, the Young Schema Questionnaire (YSQ) was developed to assess the early maladaptive schemas (EMS). EMS are considered to be relatively stable over time, but research shows that questionnaires often lack face validity in older adults, which makes it difficult to investigate EMS in older adults and their stability across the lifespan. METHODS: In the present cross-sectional study, we investigated the age neutrality of the Young Schema Questionnaire--Long Form in young (aged 18-34 years), middle-aged (aged 35-59 years), and older (aged 60-75 years) adults in a clinical sample of substance use disorders (N = 321) by examining potential differential item functioning (DIF). While investigating the stability of the schemas, we controlled for substance dependency and clinical symptoms by means of, respectively, the Drug Use Screening Inventory - Revised and the Symptom Checklist-90-R. RESULTS: The Bonferroni-adjusted Liu-Agresti Cumulative Common Log-Odds Ratio confirmed large DIF for six items, divided across five schema scales (Mistrust/Abuse, Subjugation, Entitlement, Enmeshment and Self-sacrifice). Of the six items that presented DIF, only one item showed differential test functioning (Entitlement). Overall results show only 3% DIF, implying age neutrality of the questionnaire. CONCLUSIONS: Current results corroborate that most EMS scales are equally measured across age, and reliable comparisons can be made across the lifespan, allowing for good clinical practice and further research on SFT in older adults. Only for Entitlement, Enmeshment, and Insufficient Self-control, caution is needed when comparing mean scores across the age groups.

Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence.

Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB1R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB1R availability, 20 healthy social drinkers underwent [(18)F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB1R PET after chronic heavy drinking (ALC CHR) and after 1 month of abstinence (ALC ABST). Seventeen healthy subjects served as controls. Compared with baseline, ALC ACU resulted in a global increase of CB1R availability (+15.8%). In contrast, a global decreased CB1R availability was found in ALC CHR patients (-16.1%) compared with controls, which remained unaltered after abstinence (-17.0%). Voxel-based analysis showed that ALC CHR patients had reduced CB1R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB1R availability extended also to other areas such as the ventral striatum and mesotemporal lobe. In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature. An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction.

Oral glucose tolerance tests in treated patients with schizophrenia. Data to support an adaptation of the proposed guidelines for monitoring of patients on second generation antipsychotics?

OBJECTIVE: A recent consensus conference has proposed guidelines for the monitoring for diabetes in patients with schizophrenia and also identifies the need of long-term prospective studies. METHOD: A large scale prospective study on metabolic risks of antipsychotic medication is currently ongoing. At baseline, patients get a full laboratory screening, ECG and an oral glucose tolerance test (OGTT). Baseline data on 100 non-diabetic patients at study inclusion and stable on medication for at least 6 months are presented. RESULTS: Glucose abnormalities are found in 22% of patients at baseline. A monitoring protocol based only on fasting glucose would not have detected 63.6% of these patients with classifiable glucose abnormalities in our sample. Fasting insulin and measures for insulin resistance have a high predictive value for abnormalities late in the OGTT. CONCLUSION: Already at baseline, metabolic problems are frequently present in patients with schizophrenia treated with antipsychotics. Adding assessment of fasting insulin in a monitoring protocol improves detection of glucose abnormalities late in an OGTT.

Attention to 3-D shape, 3-D motion, and texture in 3-D structure from motion displays.

We used fMRI to directly compare the neural substrates of three-dimensional (3-D) shape and motion processing for realistic textured objects rotating in depth. Subjects made judgments about several different attributes of these objects, including 3-D shape, the 3-D motion, and the scale of surface texture. For all of these tasks, we equated visual input, motor output, and task difficulty, and we controlled for differences in spatial attention. Judgments about 3-D shape from motion involve both parietal and occipito-temporal regions. The processing of 3-D shape is associated with the analysis of 3-D motion in parietal regions and the analysis of surface texture in occipito-temporal regions, which is consistent with the different behavioral roles that are typically attributed to the dorsal and ventral processing streams.

The processing of visual shape in the cerebral cortex of human and nonhuman primates: a functional magnetic resonance imaging study.

We compared neural substrates of two-dimensional shape processing in human and nonhuman primates using functional magnetic resonance (MR) imaging in awake subjects. The comparison of MR activity evoked by viewing intact and scrambled images of objects revealed shape-sensitive regions in occipital, temporal, and parietal cortex of both humans and macaques. Intraparietal cortex in monkeys was relatively more two-dimensional shape sensitive than that of humans. In both species, there was an interaction between scrambling and type of stimuli (grayscale images and drawings), but the effect of stimulus type was much stronger in monkeys than in humans. Shape- and motion-sensitive regions overlapped to some degree. However, this overlap was much more marked in humans than in monkeys. The shape-sensitive regions can be used to constrain the warping of monkey to human cortex and suggest a large expansion of lateral parietal and superior temporal cortex in humans compared with monkeys.

Similarities and differences in motion processing between the human and macaque brain: evidence from fMRI.

The present report reviews a series of functional magnetic resonance imaging (fMRI) activation studies conducted in parallel in awake monkeys and humans using the same motion stimuli in both species. These studies reveal that motion stimuli engage largely similar cortical regions in the two species. These common regions include MT/V5 and its satellites, of which FST contributes more to the human motion complex than is generally assumed in human imaging. These results also establish a direct link between selectivity of MT/V5 neurons for speed gradients and functional activation of human MT/V5 by three-dimensional (3D) structure from motion stimuli. On the other hand, striking functional differences also emerged: in humans V3A and several regions in the intraparietal sulcus (IPS) are much more motion sensitive than their simian counterparts.