Predictors of medication adherence in a large 1-year prospective cohort of individuals with schizophrenia: insights from the multicentric FACE-SZ dataset.

Schizophrenia is characterized by the most salient medication adherence problems among severe mental disorders, but limited prospective data are available to predict and improve adherence in this population. This investigation aims to identify predictors of medication adherence over a 1-year period in a large national cohort using clustering analysis. Outpatients were recruited from ten Schizophrenia Expert Centers and were evaluated with a day-long standardized battery including clinician and patient-rated medication adherence measures. A two-step cluster analysis and multivariate logistic regression were conducted to identify medication adherence profiles based on the Medication Adherence rating Scale (MARS) and baseline predictors. A total of 485 participants were included in the study and medication adherence was significantly improved at the 1-year follow-up. Higher depressive scores, lower insight, history of suicide attempt, younger age and alcohol use disorder were all associated with poorer adherence at 1 year. Among the 203 patients with initially poor adherence, 86 (42%) switched to good adherence at the 1-year follow-up, whereas 117 patients (58%) remained poorly adherent. Targeting younger patients with low insight, history of suicide, alcohol use disorder and depressive disorders should be prioritized through literacy and educational therapy programs. Adherence is a construct that can vary considerably from year to year in schizophrenia, and therefore may be amenable to interventions for its improvement. However, caution is also warranted as nearly one in five patients with initially good adherence experienced worsened adherence 1 year later.

Craving dynamics and related cerebral substrates predict timing of use in alcohol, tobacco, and cannabis use disorders.

Background: Patients treated for Substance Use Disorders exhibit highly fluctuating patterns of craving that could reveal novel prognostic markers of use. Accordingly, we 1) measured fluctuations within intensively repeated measures of craving and 2) linked fluctuations of craving to connectivity indices within resting-state (rs) brain regions to assess their relation to use among patients undergoing treatment for Alcohol, Tobacco and Cannabis Use Disorders. Method: Participants -64 individuals with SUD for tobacco, alcohol, or cannabis and 35 healthy controls-completed a week of Ecological Momentary Assessment (EMA) during which they reported craving intensity and substance use five times daily. Before EMA, a subsample of 50 patients, and 34 healthy controls also completed resting-state (rs)-MRI acquisitions. Craving temporal dynamics within each day were characterized using Standard Deviation (SD), Auto-Correlation Factor (ACF), and Mean Successive Square Difference (MSSD). Absolute Difference (AD) in craving between assessments was a prospective prediction measure. Results: Within-day, higher MSSD predicted greater substance use while controlling for mean craving. Prospectively higher AD predicted later increased substance use independently of previous use or craving level. Moreover, MSSD was linked to strength in five functional neural connections, most involving frontotemporal systems. Cerebello-thalamic and thalamo-frontal connectivity were also linked to substance use and distinguished the SUD from the controls. Conclusion: To the best of our knowledge, this is the first study to indicate that instability in craving may be a trigger for use in several SUD types, beyond the known effect of craving intensity.

The Executive Functioning Paradox in Substance Use Disorders.

Deficits in neurocognitive functioning are trait-like vulnerabilities that have been widely studied in persons with substance use disorders (SUD), but their role in the craving-use association and relapse vulnerability remains poorly understood. The main objectives of this study were to examine whether executive capacities moderate the magnitude of the craving-substance use relationship, and if this influence is correlated with the functional connectivity of cerebral networks, combining rsfMRI examinations and ecological momentary assessment (EMA). Eighty-six patients beginning outpatient treatment for alcohol, tobacco or cannabis addiction and 40 healthy controls completed neuropsychological tests followed by EMA to collect real-time data on craving. Fifty-four patients and 30 healthy controls also completed a resting-state fMRI before the EMA. Among the patients with SUD, better verbal fluency and resistance to interference capacities were associated with a greater propensity to use substances when the individual was experiencing craving. Preliminary rsfMRI results identified specific networks that interacted with executive performance capacities to influence the magnitude of the craving-use association. Individuals with better executive functioning may be more prone to relapse after craving episodes. Specifically, better resistance to interference and cognitive flexibility skills may reduce attention to distracting stimuli, leading to a greater awareness of craving and susceptibility to use substances.

Real-time cognitive performance and positive symptom expression in schizophrenia.

Deficits in cognitive functions are frequent in schizophrenia and are often conceptualized as stable characteristics of this disorder. However, cognitive capacities may fluctuate over the course of a day and it is unknown if such variation may be linked to the dynamic expression of psychotic symptoms. This investigation used Ecological Momentary Assessment (EMA) to provide mobile tests of cognitive functions and positive symptoms in real time. Thirty-three individuals with schizophrenia completed five EMA assessments per day for a one-week period that included real-time assessments of cognitive performance and psychotic symptoms. A subsample of patients and 31 healthy controls also completed a functional MRI examination. Relative to each individual's average score, moments of worsened cognitive performance on the mobile tests were associated with an increased probability of positive symptom occurrence over subsequent hours of the day (coef = 0.06, p < 0.05), adjusting for the presence of psychotic symptoms at the moment of mobile test administration. These prospective associations varied as a function of graph theory indices in MRI analyses. These findings demonstrate that cognitive performance is prospectively linked to psychotic symptom expression in daily life, and that underlying brain markers may be observed in the Executive Control Network. While the potential causal nature of this association remains to be investigated, our results offer promising prospects for a better understanding of the underlying mechanisms of symptom expression in schizophrenia.

Brief interventions for improving adherence in schizophrenia: A pilot study using electronic medication event monitoring.

Poor medication adherence remains frequent in schizophrenia. The present study examined the efficacy of two month-long pilot interventions using the Medication Event Monitoring System (MEMS®). Thirty-three outpatients at high risk for relapse were randomized to receive a smartphone-based intervention, a nurse-based intervention, or treatment as usual. All patients then used the MEMS® to objectively measure medication adherence over six months. No differences were observed in adherence measures or relapse rates across the three groups. When using electronic medication monitoring as an objective measure of adherence, easily-implemented interventions may not significantly improve adherence in patients at high risk for relapse.

Learning-driven cerebellar intrinsic functional connectivity changes in men.

Learning involves distributed but coordinated activity among the widespread connected brain areas. Increase in areas connections' strength may be established offline, that is, aside from the task itself, in a resting-state. The resulting functional connectivity may hence constitute a neural trace of the learning episode. The present study examined whether a conditional visuomotor learning task previously shown to activate the cerebellum would modify cerebellar intrinsic connectivity in groups of young and older male subjects. In the group of young subjects, resting-state connectivity within several cerebellar networks (fronto-cerebellar, temporo-cerebellar, cerebello-cerebellar) was modified following the task. In most cases, modulation resulted in increased anticorrelations between cerebellar and cortical areas and the amplitude of changes was correlated with learning efficacy. The group of older subjects drastically differed, with sparser modifications of resting-state functional connectivity and no cerebellar networks involved. The findings of this exploratory study indicate that associative learning modifies the strength of intrinsic connectivity in young subjects but to a lesser degree in older subjects. They further suggest that functional connectivity within cerebellar networks may play an operative role in this kind of learning.

Feasibility and validity of mobile cognitive testing in patients with substance use disorders and healthy controls.

BACKGROUND AND OBJECTIVES: Mobile testing of executive deficits in substance-related addictions is highly novel but requires validation. METHODS: Sixty-one individuals (34 patients, 27 healthy controls) completed Ecological Momentary Assessments with mobile executive tests. RESULTS: Compliance with the tests was high (78% to 91%) in both the patient and control groups. No fatigue effects were detected, practice effects were observed for controls only, and convergent validity was found relative to neuropsychological assessments. Conclusions The use of mobile cognitive testing is feasible and valid in this population. Scientific Significance Mobile cognitive tests provide new opportunities for both research and clinical intervention. (Am J Addict 2018;27:553-556).