Interactions between physical exercise, associative memory, and genetic risk for Alzheimer's disease.

The ε4 allele of the APOE gene heightens the risk of late onset Alzheimer's disease. ε4 carriers, may exhibit cognitive and neural changes early on. Given the known memory-enhancing effects of physical exercise, particularly through hippocampal plasticity via endocannabinoid signaling, here we aimed to test whether a single session of physical exercise may benefit memory and underlying neurophysiological processes in young ε3 carriers (ε3/ε4 heterozygotes, risk group) compared with a matched control group (homozygotes for ε3). Participants underwent fMRI while learning picture sequences, followed by cycling or rest before a memory test. Blood samples measured endocannabinoid levels. At the behavioral level, the risk group exhibited poorer associative memory performance, regardless of the exercising condition. At the brain level, the risk group showed increased medial temporal lobe activity during memory retrieval irrespective of exercise (suggesting neural compensatory effects even at baseline), whereas, in the control group, such increase was only detectable after physical exercise. Critically, an exercise-related endocannabinoid increase correlated with task-related hippocampal activation in the control group only. In conclusion, healthy young individuals carrying the ε4 allele may present suboptimal associative memory performance (when compared with homozygote ε3 carriers), together with reduced plasticity (and functional over-compensation) within medial temporal structures.

Striatal Response to Reward Anticipation as a Biomarker for Schizophrenia and Negative Symptoms: Effects, Test-Retest Reliability, and Stability Across Sites.

BACKGROUND: Ventral striatal hypoactivation during reward anticipation has consistently been observed in patients with schizophrenia. In addition, that hypoactivation has been shown to correlate negatively with negative symptoms, and in particular with apathy. However, little is known about the stability of these results over time and their reliability across different centers. METHODS: In total, 67 patients with schizophrenia (15 females) and 55 healthy controls (13 females) were recruited in 2 centers in Switzerland and Germany. To assess the neural bases of reward anticipation, all participants performed a variant of the Monetary Incentive Delay task while undergoing event-related functional magnetic resonance imaging at baseline and after 3 months. Stability over time was measured using intra-class correlation (ICC(A,1)) and stability between centers was measured with mixed models. RESULTS: Results showed the expected ventral striatal hypoactivation in patients compared to controls during reward anticipation. We showed that these results were stable across centers. The primary analysis did not reveal an effect of time. Test-retest reliability was moderate for controls, and poor for patients. We did not find an association between ventral striatal hypoactivation and negative symptoms in patients. CONCLUSIONS: Our results align with the hypothesis that ventral striatal activation is related to modulation of motivational saliency during reward anticipation. They also confirm that patients with schizophrenia show impaired reward anticipation. However, the poor test-retest reliability and the absence of an association with symptoms suggests that further research is needed before ventral striatal activity can be used as a biomarker on the individual patient level.

Adaptive coding of reward in schizophrenia, its change over time and relation to apathy.

Adaptive coding of reward is the process by which neurons adapt their response to the context of available compensations. Higher rewards lead to a stronger brain response, but the increase of the response depends on the range of available rewards. A steeper increase is observed in a narrow range, and a more gradual slope in a wider range. In schizophrenia, adaptive coding appears affected in different domains, and in the reward domain in particular. Here we tested adaptive coding of reward in a large group of patients with schizophrenia (N = 86) and controls (N = 66). We assessed 1) the association between adaptive coding deficits and symptoms; 2) the longitudinal stability of deficits (the same task was performed three months apart); 3) the stability of results between two experimental sites. We used fMRI and the Monetary Incentive Delay task to assess participant' adaptation to two different reward ranges: a narrow and a wide range. We used a region of interest analysis, evaluating adaptation within striatal and visual regions. Patients and controls underwent a full demographic and clinical assessment. We found reduced adaptive coding in patients, due to a decreased slope in the narrow reward range, with respect to that of control participants in striatal but not visual regions. This pattern was observed at both research sites. Upon re-test, patients increased their narrow range slopes, showing improved adaptive coding, whereas controls slightly reduced them. At re-test, patients with overly steep slopes in the narrow range also showed higher levels of negative symptoms. Our data confirm deficits in reward adaptation in schizophrenia and reveal a practice effect in patients, leading to improvement, with steeper slopes upon retest. However, in some patients, an overly steep slope may result in poor discriminability of larger rewards, due to early saturation of the brain response. Together, the loss of precision of reward representation in new (first exposure, underadaptation) and more familiar (re-test, overadaptation) situations may contribute to the multiple motivational symptoms in schizophrenia.

Experience of violence and attitudes of staff members towards coercion in psychiatric settings: observational study.

BACKGROUND: Among important dimensions related to the use of coercive measures, professionals' attitude towards coercion is of particular interest. Little is known about how experiences of violence in the workplace might influence these attitudes. AIMS: The present study aimed to investigate potential correlates of attitudes towards coercion, especially experiences of violence in the workplace. METHOD: Mental health professionals were contacted through an online survey to assess their attitudes towards coercion using the Staff Attitude to Coercion Scale (SACS). The three subscales of the SACS (critical, pragmatic and positive attitudes) were analysed in a multivariate multiple linear regression, using a set of covariates including experiences of violence in the workplace. We hypothesised that experience of violence in the workplace would correlate with less critical attitudes of staff members towards coercion. RESULTS: A total of 423 professionals were included in the regression analysis. Age, professional category, feeling of insecurity, having witnessed or used coercion, and the emotional burden associated with coercive measures had a joint significant effect on the three SACS subscales. A feeling of insecurity, but not the experience of violence, was associated with a less critical, more positive appraisal of coercive measures. The emotional burden related to the use of coercion was associated with a more critical attitude. CONCLUSIONS: The present results highlight the importance of considering staff members' training and well-being regarding their feelings of insecurity when addressing attitudes towards coercion. The experience of patients should be integrated into staff training and coercion reduction programmes.