Exploring the Interactions between Non-Medical Methamphetamine Use and Prescribed Buprenorphine or Naltrexone in Opioid Use Disorder Treatment Retention.

OBJECTIVES: Our objectives were to examine the impact of methamphetamine use on opioid use disorder (OUD) treatment retention in patients prescribed either buprenorphine/buprenorphine-naloxone (BUP-NX) or naltrexone/extended-release naltrexone (XR-NTX), while also exploring the role of other risk factors that may modify the impact of methamphetamine use. METHODS: We conducted an exploratory retrospective study examining OUD treatment retention in 127 patients in Ohio (USA). Patients were prescribed either BUP-NX or naltrexone/XR-NTX. Cox proportional hazard regression was used to compare time to dropout of treatment between patients positive and negative on screening for methamphetamines at intake, estimate the association between other risk factors and time to dropout, and test interactions between risk factors and methamphetamine status. RESULTS: Among patients prescribed naltrexone/XR-NTX, those positive for methamphetamines had almost three times the risk of treatment dropout (AHR = 2.89, 95% CI =1.11, 7.07), significantly greater (interaction p = .039) than the methamphetamine effect among those prescribed BUP-NX (AHR = 0.94, 95% CI = 0.51, 1.65). Early in treatment, being prescribed BUP-NX was strongly associated with a greater risk of treatment dropout (at baseline: AHR = 2.90, 95% CI = 1.33, 7.15), regardless of baseline methamphetamine use status. However, this effect decreased with time and shifted to greater risk of dropout among those prescribed naltrexone/XR-NTX (non-proportional hazard; interaction with time AHR = 0.66, 95% CI = 0.49, 0.86), with the shift occurring sooner among those positive for methamphetamine at baseline. CONCLUSIONS: Additional support should be provided to patients who use methamphetamines prior to starting OUD treatment.

Visuospatial and Sensory Integration Tasks in Patients With Schizophrenia or Schizoaffective Disorder: Relationship to Body Mass Index and Smoking.

Neurological soft signs (NSSs) are highly prevalent among patients with schizophrenia, but their pathophysiological significance remains unclear. The present study employed perceptual-motor and visuospatial processing tests that have not yet been attempted in this patient population. Patients with schizophrenia or schizoaffective disorder (n = 42) and mentally healthy subjects (n = 10) were administered Copy Figure Test, Detection and Recognition of an Object Test and Road Map Test. As compared to controls, schizophrenic and schizoaffective patients displayed significantly poorer ability to copy three-dimensional figures (namely, Necker- and hidden line elimination cubes) and to orient in space on a road-map test; group differences in copying two-dimensional figures and on objects' recognition against a background noise were not apparent. In the schizophrenia/schizoaffective group, more mistakes on the hidden line elimination cube was associated with greater body mass index and greater severity of nicotine dependence measured via the Fagerstrom Test of Nicotine Dependence. The above findings replicate those of prior reports and extend them to the tasks that do not involve motivational and attentional confounds. Furthermore, the present data support the hypothesis that subtle cerebral cortical abnormalities detected with specific NSSs tests may be related to some aspects of metabolic and motivational function in patients with schizophrenia/schizoaffective disorder.

Aromatized testosterone attenuates contextual generalization of fear in male rats.

Generalization is a common symptom of many anxiety disorders, and females are 60% more likely to suffer from an anxiety disorder than males. We have previously demonstrated that female rats display significantly accelerated rates of contextual fear generalization compared to male rats; a process driven, in part, by activation of ERß. The current study was designed to determine the impact of estrogens on contextual fear generalization in male rats. For experiment 1, adult male rats were gonadectomized (GDX) and implanted with a capsule containing testosterone proprionate, estradiol, dihydrotestosterone proprionate (DHT), or an empty capsule. Treatment with testosterone or estradiol maintained memory precision when rats were tested in a different (neutral) context 1day after training. However, male rats treated with DHT or empty capsules displayed significant levels of fear generalization, exhibiting high levels of fear in the neutral context. In Experiment 2, we used acute injections of gonadal hormones at a time known to elicit fear generalization in female rats (e.g. 24h before testing). Injection treatment followed the same pattern of results seen in Experiment 1. Finally, animals given daily injections of the aromatase inhibitor, Fadrozole, displayed significant fear generalization. These data suggest that testosterone attenuates fear generalization likely through the aromatization testosterone into estradiol as animals treated with the non-aromatizable androgen, DHT, or animals treated with Fadrozole, displayed significant generalized fear. Overall, these results demonstrate a sex-dependent effect of estradiol on the generalization of contextual fear.

Hippocampal cytosolic estrogen receptors regulate fear generalization in females.

Generalization of fear responses is a symptom of many anxiety disorders and we have previously demonstrated that female rats generalize fear to a neutral context at a faster rate compared to males. This effect is due in part, to activation of ER and modulation of memory retrieval mechanisms resulting in fear generalization. Given that the effects of estradiol on fear generalization required approximately 24h, our data suggested possible genomic actions on fear generalization. To determine whether these actions were due to cytosolic versus membrane bound receptors, female rats were given infusions of ICI 182,780, a cytosolic estrogen receptor antagonist, into the lateral ventricle or dorsal hippocampus simultaneously with estradiol treatment or with an ER agonist (DPN). Infusions of ICI into the lateral ventricle or the dorsal hippocampus blocked fear generalization induced by peripheral or central treatment with estradiol or DPN, suggesting that estradiol acts through cytosolic ERß receptors. In further support of these findings, intracerebroventricular or intra-hippocampal infusions of bovine serum conjugated estradiol (E2-BSA), activating membrane-bound estrogen receptors only, did not induce fear generalization. Moreover, rats receiving intra-hippocampal infusions of the ERK/MAPK inhibitor, U0126, continued to display estradiol-induced generalization, again suggesting that membrane-bound estrogen receptors do not contribute to fear generalization. Overall, these data suggest that estradiol-induced enhancements in fear generalization are mediated through activation of cytosolic/nuclear ER within the dorsal hippocampus. This region seems to be an important locus for the effects of estradiol on fear generalization although additional neuroanatomical regions have yet to be identified.