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Substance use disorders (SUD) are complex biopsychosocial processes involving proximal risk factors (e.g., anxiety, depression, life stressors), a pattern of losing control over substance intake, craving, as well as detrimental consequences. A large and consistent literature has tied spirituality and religion (S/R) to lower incidence and severity of SUD in the general population, and clinical research among substance users has substantiated clear benefits of S/R engagement on short- and long-term course of SUD. This chapter reviews the extant literature on S/R and SUD, and outlines clinical methods to facilitate the application and integration of S/R coping into treatment, including 12-step programs. More broadly, we describe now S/R can be integrated by mental health clinicians into the SBIRT (Screening, Brief Intervention, and Referral to Treatment) approach to SUD, an evidence-based framework that is widely-utilized in a variety of service settings. In sum, integration of S/R practices should be considered as part of a menu of options for care, when treating individuals with SUD.

The term stimulant refers to a diverse array of natural and synthetic compounds whose use results in varying degrees of euphoria, as well as heightened attention, wakefulness, and libido, in addition to sympathomimetic effects. Certain stimulants are FDA approved for various medical and psychiatric conditions and are therefore available via prescription. While some stimulants have relatively benign physiological profiles, such as caffeine, use of other stimulants such as amphetamines or cocaine can result in significant negative physiological and/or psychiatric consequences such as stroke or myocardial infarction, psychosis, and movement disorders, and also carry a high risk for physiological dependence and the development of use disorders (addiction). As a result of their non-medical and abuse potential, a robust illicit stimulant trade remains active worldwide. There are no pharmacotherapies that are FDA approved for the treatment of any stimulant use disorder, but several behavioral therapies, such as contingency management, have demonstrated promise. This chapter reviews the mechanisms of action of various stimulants, diagnostic features of different stimulant intoxication/withdrawal/use disorders, and evidence-based treatment modalities for these diagnostic entities. The stimulants of particular focus in this chapter will be caffeine, cocaine, as well as amphetamine and amphetamine-type (AAT) stimulants.

Alcohol use disorders (AUDs) are less prevalent in pregnant women than in nonpregnant women, but these disorders can create a host of clinical challenges when encountered. Unfortunately, little evidence is available to guide clinical decision making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but it remains controversial as to the volume of alcohol consumption that correlates with these consequences. Likewise, little evidence is available to support the use of particular pharmacologic interventions for AUDs during pregnancy or to guide the management of alcohol detoxification in pregnant women. The use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Nevertheless, despite the lack of robust data to guide management of AUDs in pregnancy, clinicians need to make management decisions when confronted with these challenging situations. In that context, this article reviews the epidemiology of AUDs in pregnancy and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, with the goal of informing clinicians about what is known about managing these co-occurring conditions.

In older populations, substance use disorders are highly prevalent, often underdiagnosed and undertreated, and are associated with significant systemic medical and psychiatric comorbidity. Diagnostic criteria for substance use disorders have changed with the publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, and these updated criteria are reviewed here. Furthermore, the epidemiology and proposed etiology of substance use disorders in late life are discussed. A particular focus is placed on reviewing the role of the psychiatrist in the evaluation and management of older adults with substance use disorders, especially when chronic pain is part of the clinical picture. Recommendations for evaluation and management of older adults with (or suspected to have) substance use disorders are outlined, and two case examples are provided to further solidify these concepts.

Background Generalized social phobia (GSP) and generalized anxiety disorder (GAD) are both associated with emotion dysregulation. Research implicates dorsal anterior cingulate cortex in both explicit emotion regulation (EER) and top-down attentional control (TAC). Although studies have examined these processes in GSP or GAD, no work compares findings across the two disorders or examines functioning in cases comorbid for both disorders (GSP/GAD). Here we compare the neural correlates of EER and TAC in GSP, GAD, and GSP/GAD. Methods Medication-free adults with GSP (EER n = 19; TAC n = 18), GAD (EER n = 17; TAC n = 17), GSP/GAD (EER n = 17; TAC n = 15), and no psychopathology (EER n = 18; TAC n = 18) participated. During EER, individuals alternatively viewed and upregulated and downregulated responses to emotional pictures. During TAC, they performed an emotional Stroop task. Results For both tasks, significant group × condition interactions emerged in dorsal anterior cingulate cortex and parietal cortices. Healthy adults showed significantly increased recruitment during emotion regulation, relative to emotion-picture viewing. GAD, GSP, and GSP/GAD subjects showed no such increases, with all groups differing from healthy adults but not from each other. Evidence of emotion-related disorder-specificity emerged in medial prefrontal cortex and amygdala. This disorder-specific responding varied as a function of emotion content but not emotion-regulatory demands. Conclusions GSP and GAD both involve reduced capacity for engaging emotion-regulation brain networks, whether explicitly or via TAC. A reduced ability to recruit regions implicated in top-down attention might represent a general risk factor for anxiety disorders.

The RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences. This process, known as V(D)J recombination, assembles the vastly diverse antigen receptor genes from numerous V, D, and J coding segments. In vitro biochemical and cellular transfection studies suggest that RAG1/2 may also play postcleavage roles by forming complexes with the recombining ends to facilitate DNA end processing and ligation. In the current study, we examine the in vivo consequences of a mutant form of RAG1, RAG1-S723C, that is proficient for DNA cleavage, yet exhibits defects in postcleavage complex formation and end joining in vitro. We generated a knockin mouse model harboring the RAG1-S723C hypomorphic mutation and examined the immune system in this fully in vivo setting. RAG1-S723C homozygous mice exhibit impaired lymphocyte development and decreased V(D)J rearrangements. Distinct from RAG nullizygosity, the RAG1-S723C hypomorph results in aberrant DNA double-strand breaks within rearranging loci. RAG1-S723C also predisposes to thymic lymphomas associated with chromosomal translocations in a p53 mutant background, and heterozygosity for the mutant allele accelerates age-associated immune system dysfunction. Thus, our study provides in vivo evidence that implicates aberrant RAG1/2 activity in lymphoid tumor development and premature immunosenescence.

Many hospitals do not have regular access to psychiatry consult services. This is well understood as a common shortage at nonacademic community hospitals (especially in rural environments, and may also be a problem at noncontiguously located smaller hospitals that are affiliated with academic medical centers in urban settings. The authors sought to deliver timely inpatient psychiatric consultation-liaison services via telemedicine to a local but physically separated hospital affiliated with an academic medical center.The authors collaborated with an office dedicated to the advancement of telemedicine technology at their academic medical center. They developed a telemedicine-based care model to deliver inpatient consultation-liaison psychiatry consultations to an affiliated (but physically separate) small academic hospital that did not have its own on-site consultation-liaison psychiatry team.The authors were able to successfully complete 30 consultations, each within 24 h. Only 1 patient was ultimately unwilling to participate in the telemedicine interview. As consultations were accomplished on same day as request, patient length of stay was unaffected.This pilot study suggests that telemedicine is a viable model for inpatient consultation-liaison psychiatry services to hospitals without on-site psychiatry resources and represents a viable alternative model of service delivery.

Background: Rates of opioid overdose deaths are increasing in the United States, leading to intensified efforts to provide medication-assisted treatments for opioid use disorders. It is not clear what effect opioid agonist treatments (ie, the μ-opioid receptor full agonist methadone and the partial agonist buprenorphine) may have on respiratory function. However, sleep-disordered breathing has been documented in methadone maintenance pharmacotherapy, and there is emerging evidence for similar sleep-disordered breathing in buprenorphine and buprenorphine-naloxone maintenance treatment . Objective: To provide further clinical evidence of sleep-disordered breathing emerging in the context of buprenorphine-naloxone maintenance pharmacotherapy . Methods: The authors report two additional cases of sleep-disordered breathing that developed in patients with severe opioid use disorders, treated successfully as outpatients with buprenorphine-naloxone maintenance. Both patients provided written consent for their clinical information to be included in this case report, and elements of their identities have been masked to provide confidentiality . Results: Two adult female patients, who were stable in buprenorphine-naloxone maintenance treatment developed daytime sleepiness, were referred for evaluation and found to have sleep-disordered breathing. One patient's daytime sleepiness improved with reduction in both buprenorphine-naloxone and other sedating medications as well as initiation of a constant positive airway pressure (CPAP) device. However, the other patient could not tolerate decreases in buprenorphinenaloxone and/or CPAP initiation and her daytime sleepiness persisted . Conclusion: Buprenorphine-naloxone maintenance treatment can be associated with sleep-disordered breathing. It can be difficult to differentiate the cause(s) of sleep-disordered breathing among the effects of buprenorphine-naloxone treatment itself, co-occurring conditions, such as obesity and cigarette smoking or other medications, or some combination thereof. Regardless of etiology, sleep-disordered breathing and its consequences present unique challenges to the patient in recovery from an opioid use disorder and therefore warrants careful evaluation and management .

Radiosensitive severe combined immune deficiency in humans results from mutations in Artemis, a protein which, when coupled with DNA-dependent protein kinase catalytic subunit (DNA-PKcs), possesses DNA hairpin-opening activity in vitro. Here, we report that Artemis-deficient mice have an overall phenotype similar to that of DNA-PKcs-deficient mice-including severe combined immunodeficiency associated with defects in opening and joining V(D)J coding hairpin ends and increased cellular ionizing radiation sensitivity. While these findings strongly support the notion that Artemis functions with DNA-PKcs in a subset of NHEJ functions, differences between Artemis- and DNA-PKcs-deficient phenotypes, most notably decreased fidelity of V(D)J signal sequence joining in DNA-PKcs-deficient but not Artemis-deficient fibroblasts, suggest additional functions for DNA-PKcs. Finally, Artemis deficiency leads to chromosomal instability in fibroblasts, demonstrating that Artemis functions as a genomic caretaker.

Opioid dependent patients are hospitalized frequently. We aimed to determine if initiation of buprenorphine treatment during hospitalization facilitates entry into treatment following discharge.Retrospective case series (n = 47).Twenty-two (46.8%) patients successfully initiated buprenorphine treatment within 2 months of discharge. Those patients obtaining a referral to a specific program were more successful in continuing treatment, but this difference did not reach statistical significance (59.1% vs 39.1%, p = 0.18).Hospitalization may be an important opportunity to engage opioid dependent patients to initiate buprenorphine treatment.This study provides provisional support for utilizing buprenorphine for hospitalized patients.

Received July 8, 2014; revised August 9, 2014; accepted August 11, 2014. FromSchool ofMedicine, University of California San Francisco, San Francisco, CA (WBF); Department of Psychiatry, University of California San Francisco, San Francisco, CA (ADB, JJD, JAB); Department of Radiology andBiomedical Imaging, University of California San Francisco, San Francisco, CA (J-PJY). Send correspondence and reprint requests to William B. Feldman, D.Phil., School of Medicine, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143; e-mail: william.feldman@ucsf.edu & 2015 The Academy of PsychosomaticMedicine. Published by Elsevier Inc. All rights reserved. Introduction

Alcohol use disorders (AUDs) and depressive illnesses are highly prevalent, frequently co-occur, and are associated with worse outcomes when paired. The assessment and treatment of patients with co-occurring alcohol use disorders and depressive illnesses is wrought with many significant challenges. When it comes to advocating treatment guidelines for this dually-diagnosed population, the data are limited, but, nonetheless, do suggest that an integrated approach to patients presenting with co-occurring AUD and depressive symptoms can be efficacious. In this approach, ongoing evaluation and treatment are provided under one roof according to the evolving needs of each patient. Utilizing antidepressant medications in conjunction with psychosocial therapies may augment overall treatment efficacy; data also suggest that combining and tailoring psychosocial therapies, such as motivational enhancement therapies, cognitive therapies, and twelve-step facilitation may further improve treatment outcomes for patients with co-occurring depressive and alcohol use disorders.

Little is known about the neural underpinnings of generalized social phobia, which is defined by a persistent heightened fear of social disapproval. Using event-related functional MRI (fMRI), the authors examined whether the intent of an event, which mediates the neural response to social disapproval in healthy individuals, differentially affects response in generalized social phobia.Sixteen patients with generalized social phobia and 16 healthy comparison subjects group-matched on age, gender, and IQ underwent fMRI scans while reading stories that involved neutral social events, unintentional social transgressions (e.g., choking on food at a party and coughing it up), or intentional social transgressions (e.g., disliking food at a party and spitting it out).Significant group-by-transgression interactions were observed in ventral regions of the medial prefrontal cortex. Healthy individuals tended to show increased blood-oxygen-level-dependent responses to intentional relative to unintentional transgressions. Patients with generalized social phobia, however, showed significantly increased responses to the unintentional transgressions. They also rated the unintentional transgressions as significantly more embarrassing than did the comparison subjects. Results also revealed significant group main effects in the amygdala and insula bilaterally, reflecting elevated generalized social phobia responses in these regions to all event types.These results further implicate the medial prefrontal cortex in the pathophysiology of generalized social phobia, specifically through its involvement in distorted self-referential processing. These results also further underscore the extended role of the amygdala and insula in the processing of social stimuli more generally in generalized social phobia.

Background. Generalized social phobia (GSP) involves the fear/avoidance of social situations whereas generalized anxiety disorder (GAD) involves an intrusive worry about everyday life circumstances. It remains unclear whether these, highly co-morbid, conditions represent distinct disorders or alternative presentations of a single underlying pathology. In this study, we examined stimulus-reinforcement-based decision making in GSP and GAD. Method. Twenty unmedicated patients with GSP, 16 unmedicated patients with GAD and 19 age-, IQ- and gender-matched healthy comparison (HC) individuals completed the Differential Reward/Punishment Learning Task (DRPLT). In this task, the subject chooses between two objects associated with different levels of reward or punishment. Thus, response choice indexes not only reward/punishment sensitivity but also sensitivity to reward/ punishment level according to between-object reinforcement distance. Results. We found that patients with GAD committed a significantly greater number of errors than both the patients with GSP and the HC individuals. By contrast, the patients with GSP and the HC individuals did not differ in performance on this task. Conclusions. These results link GAD with anomalous non-affective-based decision making. They also indicate that GSP and GAD are associated with distinct pathophysiologies.

RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated "core" RAG proteins. To identify potential functions for noncore regions and assess functionality of core RAG1 in vivo, we generated core RAG1 knockin (RAG1(c/c)) mice. Significant B and T cell numbers are generated in RAG1(c/c) mice, showing that core RAG1, despite missing approximately 40% of the RAG1 sequence, retains significant in vivo function. However, lymphocyte development and the overall level of V(D)J recombination are impaired at the progenitor stage in RAG1(c/c) mice. Correspondingly, there are reduced numbers of peripheral RAG1(c/c) B and T lymphocytes. Whereas normal B lymphocytes undergo rearrangement of both JH loci, substantial levels of germline JH loci persist in mature B cells of RAG1(c/c) mice, demonstrating that DJH rearrangement on both IgH alleles is not required for developmental progression to the stage of VH to DJH recombination. Whereas VH to DJH rearrangements occur, albeit at reduced levels, on the nonselected alleles of RAG1(c/c) B cells that have undergone D to JH rearrangements, we do not detect VH to DH rearrangements in RAG1(c/c) B cells that retain germline JH alleles. We discuss the potential implications of these findings for noncore RAG1 functions and for the ordered assembly of VH, DH, and JH segments.

Context Generalized social phobia (GSP) is characterized by fear/avoidance of social situations. Previous studies have examined the neural responses in GSP to one class of social stimuli, facial expressions. However, studies have not examined the neural response in GSP to another equally important class of social stimuli, the communication of praise or criticism. Objective To examine the neural response to receipt of praise or criticism in GSP; specifically, to determine whether patients with GSP show an increased response to the receipt of both praise and criticism and whether self-relevance modulates this relationship. Design Case-control study. Setting Government clinical research institute. Participants Unmedicated individuals with GSP (n = 17) and age-, IQ-, and sex-matched healthy comparison individuals (n = 17). Main Outcome Measure Blood oxygenation level–dependent signal, as measured via functional magnetic resonance imaging. During functional magnetic resonance imaging scans, individuals read positive (eg, You are beautiful), negative (eg, You are ugly), and neutral (eg, You are human) comments that could be either about the self or about somebody else (eg, He is beautiful). Results Hypothesized significant group × valence × referent interactions were observed within regions of the medial prefrontal cortex and bilateral amygdala. In these regions, the patients with GSP showed significantly increased blood oxygenation level–dependent responses, relative to comparison individuals, to negative comments (criticism) referring to themselves. However, in contrast, there were no significant group differences with respect to negative comments referring to others or neutral or positive comments referring to self or others. Conclusions These results implicate the medial prefrontal cortex, involved in the representation of the self, together with the amygdala, in the pathophysiology of GSP. Further, findings demonstrate a meaningful effect of psychological context on neural-circuitry hyperactivity in GSP.