Cold-induced expression of a truncated adenylyl cyclase 3 acts as rheostat to brown fat function.

Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducible promoter that generates a 5' truncated AC3 mRNA isoform (Adcy3-at), whose expression is driven by a cold-induced, truncated isoform of PPARGC1A (PPARGC1A-AT). Male mice lacking Adcy3-at display increased energy expenditure and are resistant to obesity and ensuing metabolic imbalances. Mouse and human AC3-AT are retained in the endoplasmic reticulum, unable to translocate to the plasma membrane and lack enzymatic activity. AC3-AT interacts with AC3 and sequesters it in the endoplasmic reticulum, reducing the pool of adenylyl cyclases available for G-protein-mediated cAMP synthesis. Thus, AC3-AT acts as a cold-induced rheostat in BAT, limiting adverse consequences of cAMP activity during chronic BAT activation.

Detecting feigned symptoms of depression, anxiety, and ADHD, in college students with the structured inventory of malingered symptomatology.

OBJECTIVE: Research consistently shows how easily students can feign symptoms of ADHD on self-report checklists to determine eligibility for curricular and standardized testing accommodations. However, it is unclear how easily students can feign psychological symptoms to accesses academic accommodations, making the assessment of symptom validity important in both populations. METHOD: Using a between-subjects design, 75 college students were randomly assigned to one of three groups: (1) coached feigning of ADHD, (2) coached feigning of depression and anxiety (DA), and (3) honest responding (HR). Participants completed the Depression, Anxiety, and Stress Scale (DASS-21) and the Structured Inventory of Malingered Symptomatology (SIMS). RESULTS: The SIMS showed 100% specificity, but low sensitivity (36-52%) for detecting feigned symptoms with different cutoffs. Differences on SIMS subtests were apparent by group with elevated scores for the DA group on the Affective Disorders subscale and elevation for the ADHD group on the Low Intelligence and Amnestic subscales. Participants identified as feigning by the SIMS typically reported more severe symptoms than participants not identified on the DASS-21. CONCLUSIONS: The SIMS equally classified the feigned ADHD and DA participants for both cutoff scores utilized. Potential reasons for low sensitivity rates are discussed and future research recommendations are made.

Detecting noncredible performance with the neuropsychological assessment battery, screening module: A simulation study.

OBJECTIVE: While the Neuropsychological Assessment Battery, Screening Module (S-NAB) is a commonly used cognitive screening measure, no composite embedded performance validity test (PVT) formula has yet been described within it. This study sought to empirically derive PVT formulas within the S-NAB using an analog simulation paradigm. METHOD: Seventy-two university students (M age = 18.92) were randomly assigned to either an Asymptomatic (AS) or simulated mild traumatic brain injury (S-mTBI) group and were administered a neuropsychological test battery that included the S-NAB and standalone and embedded PVTs. The AS group was instructed to perform optimally, and the S-mTBI group received symptom and test coaching to help simulate mTBI-related impairment. Both groups received warnings regarding the presence of PVTs throughout the test battery. RESULTS: Groups showed significant differences (all ps < .001) on all S-NAB domain scores and PVTs. In the S-NAB, the Attention (S-ATT) and Executive Function (S-EXE) domains showed the largest effect sizes (Cohen's ds = 2.02 and 1.79, respectively). Seven raw scores from S-ATT and S-EXE subtests were entered as predictor variables in a direct logistic regression (LR). The model accurately classified 90.3% of cases. Two PVT formulas were described: (1) an exponentiated equation from LR results and (2) an arithmetic formula using four individually meaningful variables. Both formulas demonstrated outstanding discriminability between groups (AUCs = .96-.97) and yielded good classification statistics compared to other PVTs. CONCLUSIONS: This study is the first to describe composite, embedded PVT formulas within the S-NAB. Implications, limitations, and appropriate future directions of inquiry are discussed.

Changes in Neuropsychological Status during the Initial Phase of Abstinence in Alcohol Use Disorder: Neurocognitive Impairment and Implications for Clinical Care.

BACKGROUND: Neuropsychological deficits are common in individuals with alcohol use disorder (AUD) and impact daily functioning and AUD treatment outcomes. Longitudinal studies demonstrate that extended abstinence improves neuropsychological functioning. The effects of short-term abstinence are less clear. OBJECTIVES: This study examined changes in neuropsychological functioning after acute detoxification over a 10-day period at the beginning of residential AUD treatment. Notably, this study evaluated cognitive functioning according to diagnostic classifications for neurocognitive disorder according to DSM-5. METHODS: Using a within-subjects design, neuropsychological functioning of participants (N = 28) undergoing a 14-day residential AUD treatment program was assessed at two time points over 10 days (i.e., treatment entry, prior to treatment discharge). Tests of immediate memory, visuospatial abilities, attention, language abilities, delayed memory, and executive functioning were administered. RESULTS: After completing acute detoxification, almost all participants (93%) were clinically impaired in at least one of the five cognitive domains at residential treatment entry, with one third of the sample impaired on ≥3 domains. Ten days later, 71% remained clinically impaired in at least one of five cognitive domains, with 29% of the sample impaired on ≥3 domains. Significant improvement over the 10-day period was observed for immediate memory, visuospatial abilities, and overall cognitive functioning. Clinical significance of these changes is also reported. Conclusions/Importance: The results from this study help to characterize cognitive functioning in terms of neurocognitive impairment. A brief period of abstinence begins to ameliorate neuropsychological deficits, but many individuals remain cognitively impaired throughout treatment. Implications for treatment are discussed.

Neuropsychological assessment in a case of adult-onset hemophagocytic lymphohistiocytosis (HLH).

We present a case of an individual diagnosed with hemophagocytic lymphohistiocytosis (HLH), an extremely rare and commonly fatal disorder characterized by rapid dysregulation of immune system processes. Typical age of onset is in childhood, with adult-onset occurring less frequently. The pathophysiology of this condition is characterized by a hyperinflammatory response with infiltration of visceral organs, lymph nodes, bone marrow, and the central nervous system. The clinical presentation has been documented in the extant medical literature. However, there appear to be no published reports of neuropsychological functioning in HLH patients. The patient we present here is a 28-year-old woman with 16 years of education who developed HLH subsequent to systemic lupus erythematosus flare-up. She was initially comatose for 3 weeks. Acute MRI reported multiple subcortical abnormalities, including the brainstem. The patient underwent chemotherapy, immunosuppresant, and steroid treatments. She underwent a neuropsychological evaluation at 2.5 and 7 months post initial presentation. Preliminary neuropsychological evaluation found impairments in motor abilities and aspects of executive functions. Subsequent evaluation showed improved executive function and relative sparing of higher-order cognitive abilities, but continued impairment on motor tests. To our knowledge this is the first study to report neuropsychological data for an adult diagnosed with HLH.