Gillinder Bedi

Automated analysis of free speech predicts psychosis onset in high-risk youths.

Background/Objectives:Psychiatry lacks the objective clinical tests routinely used in other specializations. Novel computerized methods to characterize complex behaviors such as speech could be used to identify and predict psychiatric illness in individuals.AIMS:In this proof-of-principle study, our aim was to test automated speech analyses combined with Machine Learning to predict later psychosis onset in youths at clinical high-risk (CHR) for psychosis.Methods:Thirty-four CHR youths (11 females) had baseline interviews and were assessed quarterly for up to 2.5 years; five transitioned to psychosis. Using automated analysis, transcripts of interviews were evaluated for semantic and syntactic features predicting later psychosis onset. Speech features were fed into a convex hull classification algorithm with leave-one-subject-out cross-validation to assess their predictive value for psychosis outcome. The canonical correlation between the speech features and prodromal symptom ratings was computed.Results:Derived speech features included a Latent Semantic Analysis measure of semantic coherence and two syntactic markers of speech complexity: maximum phrase length and use of determiners (e.g., which). These speech features predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews. Speech features were significantly correlated with prodromal symptoms.Conclusions:Findings support the utility of automated speech analysis to measure subtle, clinically relevant mental state changes in emergent psychosis. Recent developments in computer science, including natural language processing, could provide the foundation for future development of objective clinical tests for psychiatry.

Intimate partner violence: What are the impacts on children?

Abstract Evidence suggests that children who live with intimate partner violence between their parents or caregivers are at risk for psychological and behavioural problems. This paper presents an overview of the substantial body of literature now existing in this field. It reports on the prevalence of intimate partner abuse in developed countries and the potentially large population of children who experience conflict of this nature. Rates of co-occurrence of intimate partner violence and directly targeted physical child abuse are reviewed, as well as possible reasons for this overlap. Impacts of living with intimate partner violence during childhood are summarised. Heightened prevalence of posttraumatic symptomatology, mood difficulties, and behavioural problems have been reported in this population of children, and there are indications that difficulties may persist. Possible mediators and mechanisms of these associations are reviewed. The difficulty of separating the effects of directly targeted child assault from those of living with violence is discussed, as is the apparent similarity in outcomes associated with each type of violence. The paper is concluded with comments on implications and recommendations for future research.

Nabilone Decreases Marijuana Withdrawal and a Laboratory Measure of Marijuana Relapse

Few individuals seeking treatment for marijuana use achieve sustained abstinence. The cannabinoid receptor agonist, Δ9-tetrahydrocannabinol (THC; dronabinol), decreases marijuana withdrawal symptoms, yet does not decrease marijuana use in the laboratory or clinic. Dronabinol has poor bioavailability, which may contribute to its poor efficacy. The FDA-approved synthetic analog of THC, nabilone, has higher bioavailability and clearer dose-linearity than dronabinol. This study tested whether nabilone administration would decrease marijuana withdrawal symptoms and a laboratory measure of marijuana relapse relative to placebo. Daily, nontreatment-seeking marijuana smokers (8 men and 3 women), who reported smoking 8.3±3.1 marijuana cigarettes/day completed this within-subject study comprising three, 8-day inpatient phases; each phase tested a different nabilone dose (0, 6, 8 mg/day, administered in counter-balanced order on days 2–8). On the first inpatient day, participants took placebo capsules and smoked active marijuana (5.6% THC) at six timepoints. For the next 3 days, they had the opportunity to self-administer placebo marijuana (0.0% THC; withdrawal), followed by 4 days in which active marijuana was available for self-administration (5.6% THC; relapse). Both nabilone dose conditions decreased marijuana relapse and reversed withdrawal-related irritability and disruptions in sleep and food intake (p<0.05). Nabilone (8 mg/day) modestly worsened psychomotor task performance. Neither dose condition increased ratings of capsule ‘liking’ or desire to take the capsules relative to placebo. Thus, nabilone maintenance produced a robust attenuation of marijuana withdrawal symptoms and a laboratory measure of relapse even with once per day dosing. These data support testing of nabilone for patients seeking marijuana treatment.

Ecstasy use and higher-level cognitive functions: weak effects of ecstasy after control for potential confounds.

BACKGROUND Although there have been several reports linking ecstasy use with lowered cognitive function, much previous research suffers from substantial methodological limitations. The present study aimed to examine associations between ecstasy use and higher-level cognitive functions, using a larger sample size than most previous research and better controlling for a range of potential confounds. METHOD A cross-sectional cohort design assessed 45 currently abstinent ecstasy polydrug users (EP), 48 cannabis polydrug users (CP) and 40 legal drug users (LD). Standardized neuropsychological tests were used to measure attention, verbal, visual and working memory and executive function. Prospective memory function was also assessed. RESULTS It was not possible to discriminate between groups on the basis of the cognitive functions assessed. Regression analyses showed an inverse association between lifetime dose of ecstasy and verbal memory performance. A combination of drug-use variables, including measures of ecstasy use, contributed to prediction of attention/working memory. However, individual associations were small, explaining 1-6% of variance in cognitive scores. CONCLUSIONS Although the results suggest that heavy use of ecstasy is associated with some lowering of higher-level cognitive functions, they do not indicate a clinical picture of substantial cognitive dysfunction.

Optimism, coping style and emotional well-being in cardiac patients.

OBJECTIVE Optimism is associated with superior emotional well-being in people with chronic and acute health problems, possibly because optimists are more likely to implement problem-focused coping. Another interpretation posits that optimism can be a defensive response designed to diminish affective reactions to health problems. The study objective is to investigate this possibility. DESIGN A cross-sectional examination of relationships between dispositional and relative optimism, threat avoidance and emotional well-being in 85 cardiac patients. RESULTS Blunting, a measure of threat avoidance, was found to be associated with both optimism and emotional well-being, and the common variance was predictive of positive affect. As expected, this link was stronger in people with low self-efficacy for problem-focused coping. CONCLUSION These findings support a defensive interpretation of optimism amongst patients with recently-experienced cardiac disease, particularly as the effect was more pronounced in the low self-efficacy subsample. We discuss possible explanations for these findings and implications for the study of coping with serious illness.

Impact of Social Status and Antidepressant Treatment on Neurogenesis in the Baboon Hippocampus

Adult hippocampal neurogenesis is critically implicated in rodent models of stress and anxiety as well as behavioral effects of antidepressants. Whereas similar factors such as psychiatric disorder and antidepressant administration are correlated with hippocampal volume in humans, the relationship between these factors and adult neurogenesis is less well understood. To better bridge the gap between rodent and human physiology, we examined the numbers of proliferating neural precursors and immature cells in the hippocampal dentate gyrus (DG) as well as in vivo magnetic resonance imaging (MRI)-estimated whole hippocampal volume in eight socially dominant- or subordinate-like (SL) baboons administered the antidepressant fluoxetine or vehicle. SL baboons had lower numbers of proliferating cells and immature neurons than socially dominant-like baboons. Fluoxetine treatment was associated with a larger whole hippocampal volume but surprisingly resulted in lower numbers of immature neurons. These findings are the first to indicate that adult neurogenesis in the baboon hippocampal DG may be functionally relevant in the context of social stress and mechanisms of antidepressant action.

A window into the intoxicated mind? Speech as an index of psychoactive drug effects.

Abused drugs can profoundly alter mental states in ways that may motivate drug use. These effects are usually assessed with self-report, an approach that is vulnerable to biases. Analyzing speech during intoxication may present a more direct, objective measure, offering a unique ‘window’ into the mind. Here, we employed computational analyses of speech semantic and topological structure after ±3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) and methamphetamine in 13 ecstasy users. In 4 sessions, participants completed a 10-min speech task after MDMA (0.75 and 1.5 mg/kg), methamphetamine (20 mg), or placebo. Latent Semantic Analyses identified the semantic proximity between speech content and concepts relevant to drug effects. Graph-based analyses identified topological speech characteristics. Group-level drug effects on semantic distances and topology were assessed. Machine-learning analyses (with leave-one-out cross-validation) assessed whether speech characteristics could predict drug condition in the individual subject. Speech after MDMA (1.5 mg/kg) had greater semantic proximity than placebo to the concepts friend, support, intimacy, and rapport. Speech on MDMA (0.75 mg/kg) had greater proximity to empathy than placebo. Conversely, speech on methamphetamine was further from compassion than placebo. Classifiers discriminated between MDMA (1.5 mg/kg) and placebo with 88% accuracy, and MDMA (1.5 mg/kg) and methamphetamine with 84% accuracy. For the two MDMA doses, the classifier performed at chance. These data suggest that automated semantic speech analyses can capture subtle alterations in mental state, accurately discriminating between drugs. The findings also illustrate the potential for automated speech-based approaches to characterize clinically relevant alterations to mental state, including those occurring in psychiatric illness.

Subjective, cognitive and cardiovascular dose-effect profile of nabilone and dronabinol in marijuana smokers.

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. The synthetic THC analogue, nabilone, has better bioavailability than dronabinol. We therefore aimed to characterize nabilones behavioral and physiological effects across a range of acute doses in current marijuana smokers and compare these with dronabinols effects. Participants (4 female; 10 male) smoking marijuana 6.6 (standard deviation = 0.7) days/week completed this outpatient, within‐subjects, double‐blind, randomized protocol. Over seven sessions, the time‐dependent subjective, cognitive and cardiovascular effects of nabilone (2, 4, 6, 8 mg), dronabinol (10, 20 mg) and placebo were assessed. Nabilone (4, 6, 8 mg) and dronabinol (10, 20 mg) increased ratings of feeling a good effect, a strong effect and/or ‘high’ relative to placebo; nabilone had a slower onset of peak subjective effects than dronabinol. Nabilone (6, 8 mg) modestly lowered psychomotor speed relative to placebo and dronabinol. There were dose‐dependent increases in heart rate after nabilone, and nabilone (2 mg) and dronabinol (10 mg) decreased systolic blood pressure. Thus, nabilone produced sustained, dose‐related increases in positive mood, few cognitive decrements and lawful cardiovascular alterations. It had a longer time to peak effects than dronabinol, and effects were more dose‐related, suggesting improved bioavailability. Nabilone was well tolerated by marijuana smokers, supporting further testing as a potential medication for marijuana dependence.

Oral Cannabidiol does not Alter the Subjective, Reinforcing or Cardiovascular Effects of Smoked Cannabis

Cannabidiol (CBD), a constituent of cannabis with few psychoactive effects, has been reported in some studies to attenuate certain aspects of Δ9-tetrahydrocannabinol (THC) intoxication. However, most studies have tested only one dose of CBD in combination with one dose of oral THC, making it difficult to assess the nature of this interaction. Further, the effect of oral CBD on smoked cannabis administration is unknown. The objective of this multi-site, randomized, double-blind, within-subject laboratory study was to assess the influence of CBD (0, 200, 400, 800 mg, p.o.) pretreatment on the reinforcing, subjective, cognitive, and physiological effects of smoked cannabis (0.01 (inactive), 5.30–5.80% THC). Non-treatment-seeking, healthy cannabis smokers (n=31; 17M, 14 F) completed eight outpatient sessions. CBD was administered 90 min prior to cannabis administration. The behavioral and cardiovascular effects of cannabis were measured at baseline and repeatedly throughout the session. A subset of participants (n=8) completed an additional session to measure plasma CBD concentrations after administration of the highest CBD dose (800 mg). Under placebo CBD conditions, active cannabis (1) was self-administered by significantly more participants than placebo cannabis and (2) produced significant, time-dependent increases in ratings of ‘High’, ‘Good Effect’, ratings of the cannabis cigarette (eg, strength, liking), and heart rate relative to inactive cannabis. CBD, which alone produced no significant psychoactive or cardiovascular effects, did not significantly alter any of these outcomes. Cannabis self-administration, subjective effects, and cannabis ratings did not vary as a function of CBD dose relative to placebo capsules. These findings suggest that oral CBD does not reduce the reinforcing, physiological, or positive subjective effects of smoked cannabis.

Self-reported ecstasy use: the impact of assessment method on dosage estimates in recreational users.

While research has associated recreational ecstasy use with negative outcomes, there remain a number of methodological limitations of human studies. The present study examined the impact of self-report methodology on lifetime ecstasy dosage figures using three estimation methods: a single question estimation, a context-based timeline method and a quantity–frequency method. We used a repeated measures design, testing 38 participants aged over 18 years who reported using ecstasy on ten or more occasions. Methodology was found to impact on estimations made, with the timeline method producing higher figures than the single question. While single question and timeline estimations were positively correlated, there was no relationship between either of these methods and the quantity–frequency method. The present findings are in keeping with indications in the alcohol and other drug literature that the use of contextual memory cues increases accuracy of recall as indicated by higher estimations, and that quantity–frequency methods may not adequately assess variability in lifetime drug-use patterns.