Neural correlates of drinking reduction during a clinical trial of cognitive behavioral therapy for alcohol use disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a region implicated in cognitive control and goal-directed behavior, plays a role in behavior change during CBT by facilitating the regulation of craving (ROC). METHODS: Treatment-seeking participants with AUD (N = 22) underwent functional magnetic resonance imaging (fMRI) scanning both before and after a 12-week, single-arm trial of CBT, using an ROC task that was previously shown to engage the DLPFC. RESULTS: We found that both the percentage of heavy drinking days (PHDD) and the overall self-reported alcohol craving measured during the ROC task were significantly reduced from pre- to post-CBT. However, we did not find significant changes over time in either the ability to regulate craving or regulation-related activity in any brain region. We found a significant 3-way interaction between the effects of cue-induced craving, cue-induced brain activity and timepoint of assessment (pre- or post-CBT) on PHDD in the left DLPFC. Follow-up analysis showed that cue-induced craving was associated with cue-induced activity in the left DLPFC among participants who ceased heavy drinking during CBT, both at pre-CBT and post-CBT timepoints. No such associations were present at either timepoint among participants who continued to drink heavily. CONCLUSIONS: These results suggest that patients in whom DLPFC functioning is more strongly related to cue-induced craving may preferentially respond to CBT.

Neural correlates of drinking reduction during cognitive behavioral therapy for alcohol use disorder.

Cognitive behavioral therapy (CBT) is an effective treatment for alcohol use disorder (AUD). We hypothesized that the dorsolateral prefrontal cortex (DLPFC), a brain region implicated in cognitive control and goal-directed behavior, plays a role behavior change during CBT by facilitating regulation of craving. To examine this, treatment-seeking participants with AUD (N=22) underwent functional MRI scanning both before and after a 12-week single-arm trial of CBT, using a regulation of craving (ROC) fMRI task designed to measure an individual's ability to control alcohol craving and previously shown to engage the DLPFC. We found that both the number of heavy drinking days (NHDD, the primary clinical outcome) and the self-reported alcohol craving measured during the ROC paradigm were significantly reduced from pre- to post-CBT [NHDD: t=15.69, p<0.0001; alcohol craving: (F(1,21)=16.16; p=0.0006)]. Contrary to our hypothesis, there was no change in regulation effects on self-reported craving over time (F(1,21)=0.072; p=0.79), nor was there was a significant change in regulation effects over time on activity in any parcel. Searching the whole brain for neural correlates of reductions in drinking and craving after CBT, we found a significant 3-way interaction between the effects of cue-induced alcohol craving, cue-induced brain activity and timepoint of assessment (pre- or post-CBT) on NHDD in a parcel corresponding to area 46 of the right DLPFC (ß=-0.37, p=0.046, FDR corrected). Follow-up analyses showed that reductions in cue-induced alcohol craving from pre- to post-CBT were linearly related to reductions in alcohol cue-induced activity in area 46 only among participants who ceased heavy drinking during CBT (r=0.81, p=0.005) but not among those who continued to drink heavily (r=0.28, p=0.38). These results are consistent with a model in which CBT impacts heavy drinking by increasing the engagement of the DLPFC during cue-induced craving.

Retrospectively assessed subjective effects of initial opioid use differ between opioid misusers with opioid use disorder (OUD) and those who never progressed to OUD: Data from a pilot and a replication sample.

Attempts to identify opioid users with increased risk of escalating to opioid use disorder (OUD) have had limited success. Retrospectively assessed subjective effects of initial opioid misuse were compared in a pilot sample of opioid misusers (nonmedical use ≤60 times lifetime) who had never met criteria for OUD (N = 14) and heroin-addicted individuals in treatment for OUD (N = 15). Relative to opioid misusers without a lifetime OUD diagnosis, individuals with OUD reported greater euphoria and other positive emotions, activation, pruritus, and internalizing symptoms. Consistent with these findings, proxy Addiction Research Center Inventory (ARCI) Amphetamine Group, and Morphine Benzedrine Group scale mean item scores were significantly higher in those with OUD. Replication was attempted in opioid misusers with (N = 25) and without OUD (N = 25) who were assessed as part of an ongoing genetic study. We observed similar significant between-group differences in individual subjective effect items and ARCI scale mean item scores in the replication sample. We, thus confirm findings from prior reports that retrospectively assessed subjective responses to initial opioid exposure differ significantly between opioid users who do, and do not, progress to OUD. Our report extends these findings in comparisons limited to opioid misusers. Additional research will be necessary to examine prospectively whether the assessment of subjective effects after initial use has predictive utility in the identification of individuals more likely to progress to OUD.

Drinking reduction during cognitive behavioral therapy for alcohol use disorder is associated with a reduction in anterior insula-bed nucleus of the stria terminalis resting-state functional connectivity.

BACKGROUND: Connectivity between the anterior insula (AI) and the bed nucleus of the stria terminalis (BNST) may play a role in negative emotions that drive compulsive drinking in patients with alcohol use disorder (AUD). We hypothesized that reductions in drinking during cognitive behavioral therapy (CBT), an effective treatment that teaches regulation (coping) skills for managing negative emotions during abstinence, would be associated with reductions in resting-state functional connectivity (RSFC) between the AI and the BNST. METHODS: We included 18 patients with a Diagnostic and Statistical Manual of Mental Disorders, fifth edition diagnosis of AUD who were (1) seeking treatment and (2) drinking heavily at baseline. We measured RSFC as Pearson's correlation between the BNST and multiple regions of interest in the insula at baseline and after completion of 12 weeks of a single-arm clinical trial of outpatient CBT. We also assessed the number of heavy drinking days over the previous 28 days (NHDD) at both time points. We used 1-sample t-tests to evaluate AI-BNST RSFC at baseline, paired t-tests to evaluate changes in AI-BNST RSFC from pre-CBT to post-CBT, and linear regression to evaluate the relationship between changes in AI-BNST RSFC and NHDD. RESULTS: We found a significant positive RSFC between the AI and the BNST at baseline (p = 0.0015). While there were no significant changes in AI-BNST RSFC from pre- to post-CBT at the group level (p = 0.42), we found that individual differences in reductions in AI-BNST RSFC from pre- to post-CBT were directly related to reductions in NHDD from pre- to post-CBT (r = 0.73, p = 0.0008). CONCLUSIONS: These findings provide preliminary evidence that reduced AI-BNST RSFC may be a mechanism of drinking reduction in AUD and that AI-BNST RSFC may be a target for CBT and possibly other treatments.

New directions in the treatment of opioid withdrawal.

The treatment of opioid withdrawal is an important area of clinical concern when treating patients with chronic, non-cancer pain, patients with active opioid use disorder, and patients receiving medication for opioid use disorder. Current standards of care for medically supervised withdrawal include treatment with µ-opioid receptor agonists, (eg, methadone), partial agonists (eg, buprenorphine), and α2-adrenergic receptor agonists (eg, clonidine and lofexidine). Newer agents likewise exploit these pharmacological mechanisms, including tramadol (µ-opioid receptor agonism) and tizanidine (α2 agonism). Areas for future research include managing withdrawal in the context of stabilising patients with opioid use disorder to extended-release naltrexone, transitioning patients with opioid use disorder from methadone to buprenorphine, and tapering opioids in patients with chronic, non-cancer pain.

Individual-specific functional connectivity of the amygdala: A substrate for precision psychiatry.

The amygdala is central to the pathophysiology of many psychiatric illnesses. An imprecise understanding of how the amygdala fits into the larger network organization of the human brain, however, limits our ability to create models of dysfunction in individual patients to guide personalized treatment. Therefore, we investigated the position of the amygdala and its functional subdivisions within the network organization of the brain in 10 highly sampled individuals (5 h of fMRI data per person). We characterized three functional subdivisions within the amygdala of each individual. We discovered that one subdivision is preferentially correlated with the default mode network; a second is preferentially correlated with the dorsal attention and fronto-parietal networks; and third subdivision does not have any networks to which it is preferentially correlated relative to the other two subdivisions. All three subdivisions are positively correlated with ventral attention and somatomotor networks and negatively correlated with salience and cingulo-opercular networks. These observations were replicated in an independent group dataset of 120 individuals. We also found substantial across-subject variation in the distribution and magnitude of amygdala functional connectivity with the cerebral cortex that related to individual differences in the stereotactic locations both of amygdala subdivisions and of cortical functional brain networks. Finally, using lag analyses, we found consistent temporal ordering of fMRI signals in the cortex relative to amygdala subdivisions. Altogether, this work provides a detailed framework of amygdala-cortical interactions that can be used as a foundation for models relating aberrations in amygdala connectivity to psychiatric symptoms in individual patients.

Correction to: Qualitative vs. Quantitative Methods in Psychiatric Research: Updated.

Chapter 2 was published with incorrect family name of the chapter author as Kobiessy.

Qualitative vs. Quantitative Methods in Psychiatric Research: Updated.

Since the incipiency of psychiatry as a medical specialty, the "holy grail" has been neuroscience-based diagnostic system and treatment strategies, but this lofty, yet necessary, goal has eluded the greatest minds for centuries. Now, with advances in molecular genetics and resting-state neuroimaging, neuroscience-based diagnosis and treatment are now more possible than ever. However, clinical symptomatology, longitudinal course, and delimitation of illnesses (i.e., phenotypic classification) remain indispensable for responsible, reproducible, and meaningful use of these new methodologies.

Tobacco Use Prevalence and Smoking Cessation Pharmacotherapy Prescription Patterns Among Hospitalized Patients by Medical Specialty.

INTRODUCTION: Effective smoking cessation medications are readily available but may be underutilized in hospital settings. In our large, tertiary care hospital, we aimed to (1) characterize patient tobacco use prevalence across medical specialties, (2) determine smoking cessation pharmacotherapy prescription variation across specialties, and (3) identify opportunities for improvement in practice. METHODS: Using electronic health records at Barnes Jewish Hospital, we gathered demographic data, admitting service, admission route, length of stay, self-reported tobacco use, and smoking cessation prescriptions over a 6-year period, from 2010 to 2016. We then compared tobacco use prevalence and smoking cessation prescriptions across medical specialties using a cross-sectional, retrospective design. RESULTS: Past 12-month tobacco use was reported by patients in 27.9% of inpatient admissions; prescriptions for smoking cessation pharmacotherapy were provided during 21.5% of these hospitalizations. The proportion of patients reporting tobacco use was highest in psychiatry (55.3%) and lowest in orthopedic surgery (17.1%). Psychiatric patients who reported tobacco use were most likely to receive pharmacotherapy (71.8% of admissions), and plastic surgery patients were least likely (4.7% of admissions). Compared with Caucasian tobacco users, African American patients who used tobacco products were less likely to receive smoking cessation medications (adjusted odds ratio [aOR] = 0.65; 95% confidence interval [CI] = 0.62 to 0.68). CONCLUSIONS: Among hospitalized tobacco users, safe and cost-effective pharmacotherapies are under-prescribed. We identified substantial variation in prescribing practices across different medical specialties and demographic groups, suggesting the need for an electronic medical record protocol that facilitates consistent tobacco use cessation pharmacotherapy treatment. IMPLICATIONS: Tobacco use cessation pharmacotherapy is underutilized during hospitalization, and prescription rates vary greatly across medical specialties and patient characteristics. Hospitals may benefit from implementing policies and practices that standardize and automate the offer of smoking pharmacotherapy for all hospitalized patients who use tobacco.

From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation.

Smoking cessation treatment outcomes may be heavily influenced by genetic variations among smokers. Therefore, identifying specific variants that affect response to different pharmacotherapies is of major interest to the field. In the current study, we systematically review all studies published in or after the year 1990 which examined one or more gene-drug interactions for smoking cessation treatment. Out of 644 citations, 46 articles met the inclusion criteria for the systematic review. We summarize evidence on several genetic polymorphisms (CHRNA5-A3-B4, CYP2A6, DBH, CHRNA4, COMT, DRD2, DRD4 and CYP2B6) and their potential moderating pharamacotherarpy effects on patient cessation efficacy rates. These findings are promising and call for further research to demonstrate the effectiveness of genetic testing in personalizing treatment decision-making and improving outcome.

Naltrexone: A History and Future Directions.

Trying to kick drug addiction without medicines is said to be like relying on willpower to overcome diabetes or asthma. Enter naltrexone, which has been around since 1984 and reduces the cravings for drugs and alcohol by fine-tuning the brain's chemical reward system. Why has it recently increased in popularity? How does it compare to similar strategies? Has it made a difference? Our authors, who have long studied addiction and the brain, confront a drug and alcohol addiction problem that today kills more Americans each day than gun violence or car accidents.

Vertical line quadrisection: "what" it represents and who gets the upper hand.

BACKGROUND: Normal adults demonstrate a slight upward bias (vertical pseudoneglect) when attempting vertical line bisection. The mechanism for this bias is unknown. Activation of the allocentric (object-centered) ventral visual system during attempted bisection may induce this bias. This object-centered ventral stream may also mediate focal attention. As compared to bisection, when normal participants perform a vertical line quadrisection task that requires more focal attention, they may have a greater upward bias. METHODS: Sixteen participants bisected and quadrisected vertical lines. RESULTS: The mean upward bias (deviation error) for the quadrisection tasks was significantly higher than the mean error for the line bisections. CONCLUSIONS: These results are consistent with the hypothesis that activation of the ventral stream by a task that requires focal allocentric attention can induce an upward vertical bias that is greater than the upward bias observed with allocentric line bisection, a task that requires more global attention.