We assessed the feasibility and acceptability of using text messages to monitor and encourage physical activity in the first 21 participants enrolled in an ongoing randomized controlled trial evaluating a 16-week Short Message Service/Multimedia Message Service (SMS/MMS) intervention (iSTEP) designed to increase moderate physical activity and improve neurocognition in persons with HIV-associated neurocognitive disorders (HAND; iSTEP, n = 11; control group, n = 10). Data were collected during the intervention and from interviews conducted at the 16-week postintervention visits. Text message response rates for both iSTEP and control participants were high (89% and 85%, respectively). Pedometer self-monitoring, step count goals, and milestone achievement texts were reported to facilitate physical activity. All iSTEP participants (100%) and 70% of control participants indicated that they would recommend the study to other people living with HIV. The results indicate that it is feasible to administer an SMS/MMS physical activity intervention to persons with HAND.

Increased energy or activity is now an essential feature of the mania of Bipolar Disorder (BD) according to DSM-5. This study examined whether objective measures of increased energy can differentiate manic BD individuals and provide greater diagnostic accuracy compared to rating scales, extending the work of previous studies with smaller samples. We also tested the relationship between objective measures of energy and rating scales. 50 hospitalized manic BD patients were compared to healthy subjects (HCS, n=39) in the human Behavioral Pattern Monitor (hBPM) which quantifies motor activity and goal-directed behavior in an environment containing novel stimuli. Archival hBPM data from 17 schizophrenia patients were used in sensitivity and specificity analyses. Manic BD patients exhibited higher motor activity than HCS and higher novel object interactions. hBPM activity measures were not correlated with observer-rated symptoms, and hBPM activity was more sensitive in accurately classifying hospitalized BD subjects than observer ratings. Although the findings can only be generalized to inpatient populations, they suggest that increased energy, particularly specific and goal-directed exploration, is a distinguishing feature of BD mania and is best quantified by objective measures of motor activity. A better understanding is needed of the biological underpinnings of this cardinal feature.

HIV infection is frequently comorbid with methamphetamine (METH) dependence. Both factors are associated with impairment in inhibitory function that continues even after abstinence from the drug. Deficits in prepulse inhibition (PPI), a measure of sensorimotor gating, are induced by acute stimulant administration, but the combined effect of HIV and chronic METH exposure on PPI is not well characterized. We quantified baseline acoustic startle and PPI in mice expressing the HIV-1 gp120 envelope protein (gp120tg) and in wild-type (WT) littermates; thereafter, we administered a chronic regimen of METH or vehicle and tested startle and PPI after 7 days of drug withdrawal. We hypothesized that METH-treated gp120tg mice would exhibit PPI deficits compared with vehicle-treated WT or gp120tg animals. Before METH administration, drug-naive female gp120tg mice exhibited decreased PPI compared with female WT mice, whereas male gp120tg mice exhibited increased startle compared with other groups. After drug withdrawal, no consistent genotype effect was observed, but METH-treated mice exhibited increased PPI compared with vehicle, in contrast to previous reports of acute METH-induced PPI deficits. In summary, PPI impairment in HIV could depend on factors such as sex, whereas changes in PPI following METH withdrawal may depend on the quantity and duration of drug exposure.

Psychiatric patients with bipolar disorder suffer from states of depression and mania, during which a variety of symptoms are present. Current treatments are limited and neurocognitive deficits in particular often remain untreated. Targeted therapies based on the biological mechanisms of bipolar disorder could fill this gap and benefit patients and their families. Developing targeted therapies would benefit from appropriate animal models which are challenging to establish, but remain a vital tool. In this review, we summarize approaches to create a valid model relevant to bipolar disorder. We focus on studies that use translational tests of multivariate exploratory behavior, sensorimotor gating, decision-making under risk, and attentional functioning to discover profiles that are consistent between patients and rodent models. Using this battery of translational tests, similar behavior profiles in bipolar mania patients and mice with reduced dopamine transporter activity have been identified. Future investigations should combine other animal models that are biologically relevant to the neuropsychiatric disorder with translational behavioral assessment as outlined here. This methodology can be utilized to develop novel targeted therapies that relieve symptoms for more patients without common side effects caused by current treatments.

A randomized controlled trial is being conducted in the United States to test the efficacy of a personalized interactive mobile health intervention (iSTEP) designed to increase physical activity (PA) and improve neurocognitive functioning among HIV-positive persons. This article describes an initial qualitative study performed to develop iSTEP for the HIV-positive population, including assessment of PA barriers and facilitators. Two focus groups, with 9 and 12 unique HIV-positive individuals, respectively, were administered to evaluate barriers limiting PA and potential iSTEP content created to encourage greater PA. Group discussions revealed prominent PA barriers, including HIV symptoms (neuropathy, lipoatrophy), antiretroviral medication effects, and fatigue; significant PA facilitators included self-monitoring and family support. Participants provided feedback on strategies to increase PA and expressed positive support for a mobile intervention adapted to personal priorities. These findings will assist the development of novel PA interventions focused on treating the epidemic of HIV-associated neurocognitive disorders.

Rationale

Cross-species quantification of physiological behavior enables a better understanding of the biological systems underlying neuropsychiatric diseases such as bipolar disorder (BD). Cardinal symptoms of manic BD include increased motor activity and goal-directed behavior, thought to be related to increased catecholamine activity, potentially selective to dopamine homeostatic dysregulation.

Objectives

The objective of this study was to test whether acute administration of amphetamine, a norepinephrine/dopamine transporter inhibitor and dopamine releaser, would replicate the profile of activity and exploration observed in both humans with manic BD and mouse models of mania.

Methods

Healthy volunteers with no psychiatric history were randomized to a one-time dose of placebo (n = 25), 10 mg d-amphetamine (n = 18), or 20 mg amphetamine (n = 23). Eighty mice were administered one of four doses of d-amphetamine or vehicle. Humans and mice were tested in the behavioral pattern monitor (BPM), which quantifies motor activity, exploratory behavior, and spatial patterns of behavior.

Results

In humans, the 20-mg dose of amphetamine increased motor activity as measured by acceleration without marked effects on exploration or spatial patterns of activity. In mice, amphetamine increased activity, decreased specific exploration, and caused straighter, one-dimensional movements in a dose-dependent manner.

Conclusions

Consistent with mice, amphetamine increased motoric activity in humans without increasing exploration. Given that BD patients exhibit heightened exploration, these data further emphasize the limitation of amphetamine-induced hyperactivity as a suitable model for BD. Further, these studies highlight the utility of cross-species physiological paradigms in validating biological mechanisms of psychiatric diseases.

OBJECTIVES:Amphetamine improves vigilance as assessed by continuous performance tests (CPT) in children and adults with attention deficit hyperactivity disorder (ADHD). Less is known, however, regarding amphetamine effects on vigilance in healthy adults. Thus, it remains unclear whether amphetamine produces general enhancement of vigilance or if these effects are constrained to the remediation of deficits in patients with ADHD. METHODS:We tested 69 healthy adults (35 female) on a standardized CPT (Conner's CPT-2) after receiving 10- or 20-mg d-amphetamine or placebo. To evaluate potential effects on learning, impulsivity, and perseveration, participants were additionally tested on the Iowa Gambling Task (IGT) and Wisconsin Card Sorting Task (WCST). RESULTS:Participants receiving placebo exhibited the classic vigilance decrement, demonstrated by a significant reduction in attention (D') across the task. This vigilance decrement was not observed, however, after either dose of amphetamine. Consistent with enhanced vigilance, the 20-mg dose also reduced reaction time variability across the task and the ADHD confidence index. The effects of amphetamine appeared to be selective to vigilance since no effects were observed on the IGT, WCST, or response inhibition/perseveration measures from the CPT. CONCLUSIONS:The present data support the premise that amphetamine improves vigilance irrespective of disease state. Given that amphetamine is a norepinephrine/dopamine transporter inhibitor and releaser, these effects are informative regarding the neurobiological substrates of attentional control. (JINS, 2018, 24, 283-293).

Background

A personalized mobile health intervention (iSTEP) aims to promote a Mediterranean diet and increase physical activity, thereby improving neurocognitive functioning among persons living with HIV (PLWH). This article describes a qualitative study conducted to develop iSTEP for PLWH, including assessment of diet habits and preferences for tracking physical activity.

Method

Two focus groups, with seven and 13 PLWH respectively, discussed barriers and facilitators of a healthy diet and provided feedback to refine iSTEP components, including the feasibility of using a Fitbit and the content of text messages designed to encourage improved diet and physical activity.

Results

Focus group discussions revealed several healthy diet barriers, including housing instability, time required for food preparation, cost of healthy food, depression, gastrointestinal issues, physical disability, and changes in appetite since HIV diagnosis. Participant-identified healthy diet facilitators included affordable price options for healthy food, a structured food plan, desire to modify appearance or weight, access to medical professionals, motivation for disease prevention, and social support. Participants endorsed wearing a Fitbit on the wrist and receiving text messages as useful methods to monitor and encourage a better diet and greater physical activity.

Conclusions

These findings assisted the expansion of a mobile health intervention that promotes health behaviors in order to improve neurocognitive outcomes among PLWH.

Trial registration

NCT03123731 , prospectively registered on ClinicalTrials.gov, April 21, 2017.

Current literature on the effect of cannabis use on sleep quality is mixed, and few studies have used objectively-measured sleep measures or real-time sampling of cannabis use to examine this relationship. The prevalence of cannabis use among older adults and persons living with HIV has increased in recent years, and poor sleep quality is elevated in these populations as well. However, research examining cannabis-sleep relationships in these populations is lacking. Thus, we aimed to examine the relationship between daily cannabis use and subsequent objectively-measured sleep quality in middle-aged and older adults with and without HIV. In this pilot study, seventeen (11 HIV+, 6 HIV-) adults aged 50-70 who consumed cannabis completed four daily smartphone-based surveys for 14 days, in which they reported their cannabis use (yes/no) since the last survey. Participants also wore actigraphy watches during the 14-day period to objectively assess sleep quality (i.e., efficiency, total sleep time, and sleep fragmentation). In linear mixed-effects models, cannabis use was significantly associated with greater subsequent total sleep time (β=0.56; p=0.046). Cannabis use was not related to a change in sleep efficiency (β=1.50; p=0.46) nor sleep fragmentation (β=0.846, p=0.756) on days with cannabis use versus days without cannabis use. These preliminary results indicate cannabis use may have a positive effect on sleep duration in middle-aged and older adults. However, future studies with larger sample sizes that assess cannabis use in more detail (e.g., route of administration, dose, reason for use) are needed to further understand this relationship.

Individuals with bipolar disorder (BD) exhibit deleterious decision making, negatively impacting their lives. Such aberrant decision making can be quantified using the Iowa Gambling Task (IGT), which requires choosing between advantageous and disadvantageous options based on different reward/punishment schedules. The mechanisms underlying this behavioral deficit are unknown, but may include the reduced dopamine transporter (DAT) functioning reported in BD patients. Using both human and mouse IGTs, we tested whether reduced DAT functioning would recreate patterns of deficient decision making of BD patients. We assessed the IGT performance of 16 BD subjects (7 female) and 17 healthy control (HC) subjects (12 female). We recorded standard IGT performance measures and novel post-reward and post-punishment decision-making strategies. We characterized a novel single-session mouse IGT using C57BL/6J mice (n = 44). The BD and HC IGT performances were compared with the effects of chronic (genetic knockdown (KD; n = 31) and wild-type (n = 28) mice) and acute (C57BL/6J mice (n = 89) treated with the DAT inhibitor GBR12909) reductions of DAT functioning in mice performing this novel IGT. BD patients exhibited impaired decision making compared with HC subjects. Both the good-performing DAT KD and GBR12909-treated mice exhibited poor decision making in the mouse IGT. The deficit of each population was driven by high-reward sensitivity. The single-session mouse IGT measures dynamic risk-based decision making similar to humans. Chronic and acute reductions of DAT functioning in mice impaired decision-making consistent with poor IGT performance of BD patients. Hyperdopaminergia caused by reduced DAT may impact poor decision making in BD patients, which should be confirmed in future studies.