Sex-dependent correlates of arterial stiffness in Tanzanian adults.

OBJECTIVE: Arterial stiffness is a known indicator for cardiovascular disease. However, the factors that lead to arterial stiffening have primarily been studied in participants from high-income countries. Here, we examine clinical and lifestyle metrics in relation to arterial stiffness in Tanzanian adults. METHODS: We performed pulse wave velocity (PWV), the gold standard measure of arterial stiffness, on 808 Tanzanian adults (ages 18-65) enrolled in a longitudinal cohort studying trends in blood pressure. RESULTS: As expected, PWV was strongly associated with age, blood pressure and sex. We controlled for these factors in our statistical analysis. Lifestyle metrics were compared across multiple PWV quantiles. We found that determinants of PWV varied by sex: in female participants, PWV was associated with common obesity metrics and menopause, while in male participants, PWV was associated with HIV status and duration of anti-retroviral therapy (ART). Further clinical and lifestyle factors such as marriage status and type of occupation were also significantly associated with PWV and moderated by sex. CONCLUSION: Together, our data demonstrate the importance of studying sex-specific causal pathways for arterial stiffness and of including under-represented populations in these studies.

Verbal Learning and Memory Enhancement Strategies in Schizophrenia: A Randomized, Controlled Investigation.

OBJECTIVES: Verbal episodic memory is a key domain of impairment in people with schizophrenia with close ties to a variety of aspects of functioning and therapeutic treatment response. A randomized, blinded trial of two mnemonic strategies for verbal episodic memory deficits for people with schizophrenia was conducted. METHODS: Sixty-one people with schizophrenia were assigned to one of three experimental conditions: training in a mnemonic strategy that included both visualization and narrative structure (Story Method), a condition in which participants were trained to visualize words interacting with one another (Imagery), or a non-trained control condition in which participants received equivalent exposure to training word lists and other verbal memory assessments administered in the other two conditions, but without provision of any compensatory mnemonic strategy. Participants were assessed on improvements in recall of the word list used as part of training, as well as two, standardized verbal memory assessments which included stimuli not used as part of strategy training. RESULTS: The Story Method produced improvements on a trained word list that generalized to a non-trained, prose memory task at a 1-week follow-up. In contrast, provision of a mnemonic strategy of simple visualization of words produced little improvement on word recall of trained words or on measures of generalization relative to the performance of participants in the control condition. CONCLUSIONS: These findings support the inclusion of enriched mnemonic strategies consisting of both visualization and narrative structure in sustained and comprehensive programs of CR for enhancement of verbal episodic memory in schizophrenia. (JINS, 2017, 23, 352-357).

Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis.

Importance: The clinical high-risk state in psychosis is most often characterized by subthreshold psychotic symptoms (STPS) and represents a target for psychosis prevention. However, evidence suggests that between 30% and 50% of patients with a first episode of psychosis (FEP) report no prior history of STPS, indicating that not all patients with FEP experience a previous clinical high-risk phase. As with other early characteristics of illness onset, this diversity in the early course of symptoms may offer prognostic value for subsequent clinical trajectories. Objective: To determine whether a history of pre-onset STPS is associated with differential 1-year treatment outcomes in an early intervention service for FEP. Design, Setting, and Participants: Data on 195 patients 15 to 35 years of age who were recruited between January 17, 2003, and October 17, 2013, were collected from a catchment-based specialized early intervention service for FEP. Patients who reported experiencing at least 1 STPS prior to the onset of FEP were identified as STPS present (STPSp; n = 135); those who reported no such history were identified as STPS absent (STPSa; n = 60). Statistical analysis was conducted from December 15, 2016, to February 15, 2018. Main Outcomes and Measures: Summary scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Hamilton Anxiety Rating Scale, Global Assessment of Functioning scores, and Social and Occupational Functioning Assessment Scale scores at baseline and after 1 year of treatment were analyzed to evaluate 1-year outcomes. Results: Individuals in the STPSp group (39 female and 96 male participants; mean [SD] age, 23.4 [4.2] years) and the STPSa group (20 female and 40 male participants; mean [SD] age, 23.9 [5.1] years) did not differ in symptom severity or functioning at baseline. Although both groups improved by 1 year of treatment, mixed analyses of covariance (controlling for duration of untreated psychosis) revealed group-by-time interactions for scores on the Scale for the Assessment of Negative Symptoms (F1,192 = 6.17; P = .01), the Global Assessment of Functioning (F1,188 = 7.54; P = .006), and the Social and Occupational Functioning Assessment Scale (F1,192 = 3.79; P = .05). Mixed analyses of covariance also revealed a group effect for scores on the Scale for the Assessment of Positive Symptoms (F1,192 = 5.31; P = .02). After controlling for multiple comparisons, all significant results indicate poorer 1-year outcomes for patients with STPSp compared with patients with STPSa. Conclusions and Relevance: A history of pre-onset STPS consistent with a prior clinical high-risk state is associated with poorer outcomes in psychotic symptoms and global functioning for patients after 1 year of treatment for FEP. The presence or absence of pre-onset STPS therefore has prognostic value for treatment outcomes, even during a later stage of psychotic illness.

A Perceptual Inference Mechanism for Hallucinations Linked to Striatal Dopamine.

Hallucinations, a cardinal feature of psychotic disorders such as schizophrenia, are known to depend on excessive striatal dopamine. However, an underlying cognitive mechanism linking dopamine dysregulation and the experience of hallucinatory percepts remains elusive. Bayesian models explain perception as an optimal combination of prior expectations and new sensory evidence, where perceptual distortions such as illusions and hallucinations may occur if prior expectations are afforded excessive weight. Such excessive weight of prior expectations, in turn, could stem from a gain-control process controlled by neuromodulators such as dopamine. To test for such a dopamine-dependent gain-control mechanism of hallucinations, we studied unmedicated patients with schizophrenia with varying degrees of hallucination severity and healthy individuals using molecular imaging with a pharmacological manipulation of dopamine, structural imaging, and a novel task designed to measure illusory changes in the perceived duration of auditory stimuli under different levels of uncertainty. Hallucinations correlated with a perceptual bias, reflecting disproportional gain on expectations under uncertainty. This bias could be pharmacologically induced by amphetamine, strongly correlated with striatal dopamine release, and related to cortical volume of the dorsal anterior cingulate, a brain region involved in tracking environmental uncertainty. These findings outline a novel dopamine-dependent mechanism for perceptual modulation in physiological conditions and further suggest that this mechanism may confer vulnerability to hallucinations in hyper-dopaminergic states underlying psychosis.

Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder.

BACKGROUND: We used positron emission tomography imaging with [11C]raclopride to examine the effects of consumption of alcohol or placebo beverage by participants with alcohol use disorder (AUD) compared with healthy participants with and without family history of AUD. We sought to assess dopamine release following alcohol exposure in relation to AUD risk. METHODS: Three groups were enrolled: participants with AUD (n = 15) and healthy participants with family history negative (n = 34) or positive (n = 16) for AUD. Participants consumed a placebo (n = 65) or alcohol (n = 63) beverage in counterbalanced order before positron emission tomography scanning (128 scans). Binding potential (BPND) in the two drink conditions and the percent change in BPND between conditions were evaluated across striatal subregions. Subjective effects of beverage consumption were rated. Effects of group, drink order, and sex were evaluated. RESULTS: Alcohol resulted in greater dopamine release than did placebo in the ventral striatum (p < .001). There were no main effects of group, drink order, or sex on ventral striatum BPND or percent change in BPND. However, there was a drink order-by-group interaction (p = .02) whereby family history-positive participants who received placebo first had both lower placebo BPND and less difference between placebo and alcohol BPND than all other groups, consistent with expectation of alcohol powerfully evoking dopamine release in this group. Subjective responses showed the same order-by-group interaction. CONCLUSIONS: Hyper-responsivity of the dopaminergic system in family history-positive participants to expectation of alcohol may contribute to the expression of familial risk for AUD.