Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

Neural substrates of cue reactivity and craving in gambling disorder.

Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in gambling disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with gambling disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional magnetic resonance imaging (fMRI) scan performed ~2-3 h after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity and associations with block-by-block craving ratings. Craving ratings in the participants with gambling disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the gambling disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with gambling disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial prefrontal cortex. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with gambling disorder (compared with controls), providing support for the incentive sensitization theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions.

Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study.

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

Clomipramine treatment of stereotypic behaviors and self-injury in patients with developmental disabilities.

The authors report an open clinical trial of clomipramine for chronic stereotypic and self-injurious behaviors in 11 consecutive patients with concomitant developmental disorders. Ten patients (91%) had marked decreases in rates of target behaviors. No seizures occurred despite the inclusion of six patients with previous histories of epileptic events, and improvement was evident regardless of level of mental retardation. These findings support both the clinical use of serotonergic medications in this population and the need for further research.

Understanding partial hospitalization through a continuity-of-care model.

This paper discusses the role of a partial hospital program for neurologically impaired children and adolescents on a continuum of service delivery. The effectiveness of a partial program in assisting transitions across treatment and community settings is critical in establishing and maintaining treatment gains. This innovative approach and model are reviewed and discussed within the context of an integrated system of care.

Abuse and neglect in psychiatrically hospitalized multihandicapped children.

Medical charts of 150 consecutive admissions of multihandicapped children to a psychiatric hospital were examined to determine the extent and characteristics of abuse and neglect. Results indicated that 39% of the sample experienced or had a history that warranted suspicion of past and/or current maltreatment. Physical abuse was the most frequent type of maltreatment, followed by neglect and sexual abuse. Maltreated multihandicapped patients admitted to the psychiatric unit were less likely to receive diagnoses of organic brain syndrome or profound mental retardation than nonmaltreated multihandicapped counterparts on the same unit. Moreover, data indicated that less severely impaired patients were more likely to be maltreated than were the more severely impaired. Particularly striking was the severity of maltreatment in this multihandicapped sample and the relatively high percentage (40%) of sexually abused patients who were assaulted by multiple perpetrators.

Behavioral treatment of chronic aerophagia.

Effects of various behavioral interventions on stereotyped aerophagic responding by a profoundly mentally retarded, 5-year-old girl were assessed. Aerophagic responding was defined as air swallowing with extreme stomach protrusion, followed by breath-holding. Observations of air swallowing, as well as physiologic measurements related to heart rate and respiratory patterns, were recorded across both baseline and treatment phases of the study. Multiple behavioral interventions were assessed within a laboratory setting using an alternating treatment design format, with the most effective treatment systematically extended to additional settings. Results indicated that a behavior modification treatment package was effective in suppressing the high frequency of this rare stereotyped act to near-zero rates.

Multiple treatment interference in the alternating treatments design as a function of the intercomponent interval length.

In experimental designs requiring the administration of more than one treatment to the same subject(s), the effect of one treatment may be influenced by the effect of another treatment (Campbell & Stanley, 1963), a phenomenon known as multiple treatment interference. We conducted two studies in which multiple treatment interference in an alternating treatments design was shown to be a function of the length of the intercomponent interval (ICI) separating treatment conditions. In the first study, we evaluated the effects of four different treatments on the mouthing of a severely retarded boy. Under a 1-min ICI no consistent differential responding to treatment was obtained. Differential responding emerged when the ICI was increased from 1 min to 120 min, thus suggesting multiple treatment interference in the lack of differential responding under a 1-min changeover interval. Functional control of the nondifferential and differential responding as a function of the ICI length was replicated in a reversal phase. In the second study, we compared two treatment procedures for the disruptive noncompliant behavior of a moderately retarded boy. Multiple treatment interference (i.e., the lack of differential responding) occurred with the 1-min intercomponent interval. An increase to a 120-min ICI again resulted in differential responding. A replication of multiple treatment interference by a reversal to a short interval phase was not achieved in the second subject. Results of this study support much of the basic literature on discrimination and multiple treatment interference.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual screening: an alternative method for reducing stereotypic behaviors.

Visual screening, a mildly aversive response suppression procedure, was evaluated across two studies for its effectiveness in reducing topographically similar and dissimilar stereotypic behaviors of four developmentally disabled children. In the first study, a multiple baseline design across subjects and behaviors was used to assess the effectiveness of the procedure as a treatment for reducing the visual and auditory self-stimulatory responses of two 9-yr-old mentally retarded and behaviorally disturbed children. A multiple baseline design across subjects was used in the second study to evaluate the effectiveness of visual screening as a treatment for reducing stereotypic fabric pulling and self-mutilative ear bending, respectively, of two 13-yr-old mentally retarded, autisticlike adolescents. Long-term follow-up data for both studies were reported. The results suggested that visual screening was an easily administered, effective, and exceptionally durable treatment procedure for controlling a variety of stereotypic behaviors commonly associated with the developmentally disabled.