Evaluation of the Capacity to Marry.

Clinical and forensic evaluators are often faced with the task of answering unique questions about capacity and competency. One seldom-discussed question is that of an individual's capacity to marry. This article uses a case example as a framework for discussing the challenges of evaluating an individual's capacity to marry. We will set the background with legal history and then provide guidance for making this type of assessment.

Telepsychiatry for Inpatient Consultations at a Separate Campus of an Academic Medical Center.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series.

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 buprenorphine-naloxone 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.

Initiating buprenorphine treatment for hospitalized patients with opioid dependence: A case series.

BACKGROUND AND OBJECTIVES: Opioid dependent patients are hospitalized frequently. We aimed to determine if initiation of buprenorphine treatment during hospitalization facilitates entry into treatment following discharge. METHODS: Retrospective case series (n = 47). RESULTS: 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). DISCUSSION AND CONCLUSIONS: Hospitalization may be an important opportunity to engage opioid dependent patients to initiate buprenorphine treatment. SCIENTIFIC SIGNIFICANCE: This study provides provisional support for utilizing buprenorphine for hospitalized patients.

Alcohol use disorders in pregnancy.

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.

Treatment of the depressed alcoholic patient.

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.

Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder.

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.

Social norm processing in adult social phobia: atypically increased ventromedial frontal cortex responsiveness to unintentional (embarrassing) transgressions.

OBJECTIVE: 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. METHOD: 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). RESULTS: 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. CONCLUSIONS: 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.

Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation.

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.

Neural response to self- and other referential praise and criticism in generalized social phobia.

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 x valence x 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.

Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing mice.

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.