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Background: Despite extensive research in the past decades, the influence of genetics on cognitive functions in schizophrenia remains unclear. Dystrobrevin-binding protein 1 (DTNBP1) is one of the most promising candidate genes in schizophrenia. An association of DTNBP1 with cognitive dysfunction, particularly memory impairment, has been reported in a number of studies. However, the results remain inconsistent. The aim of this study was to measure the association between DTNBP1 polymorphisms and cognitive domains in a well-characterized sample. Methods: Ninety-one clinically stable schizophrenia outpatients underwent a battery of cognitive tests. Six single nucleotide polymorphisms (SNPs) of DTNBP1 were genotyped in all participants. Statistical and multivariate analyses were performed. Results: Factor analysis revealed 4 factors corresponding to distinct cognitive domains, namely sustained attention, set-shifting, executive functioning, and memory. We found a significant association of the rs909706 polymorphism with attention (p = 0.030) and a nonsignificant trend for set-shifting (p = 0.060). The other SNPs and haplotypes were not associated with cognitive function. Discussion: Replication of this finding in a larger sample is needed in order to confirm the importance of this particular polymorphism in the genetics of schizophrenia, particularly the distinct cognitive domains. In conclusion, the present study supports the involvement of DTNBP1 in the regulation of cognitive processes and demonstrates association in particular with sustained attention and set-shifting in schizophrenia patients. (C) 2016 S. Karger AG, Basel
Persistence with antidepressant drugs in patients with dementia: a retrospective database analysis
(2016)
Background: The aims of the present study are to determine what proportion of patients with dementia receives antidepressants, how long the treatment is administered, and what factors increase the risk of discontinuation. Methods: The study was based on Disease Analyzer database and included 1,203 general practitioners (GP) and 209 neurologists/psychiatrists (NP). 12,281 patients with a diagnosis of dementia and an initial prescription of an antidepressant drug between January 2004 and December 2013 were included. The main outcome measure was antidepressant discontinuation rates within 6 months of the index date. Results: After 6 months of follow-up, 52.7% of dementia patients treated with antidepressants had stopped medication intake. There was a significantly decreased risk for treatment discontinuation for patients using selective serotonin reuptake inhibitors (SSRRIs) or serotonin and norepinephrine reuptake inhibitors (SSNRIs) compared to tricyclic antidepressants. There was a significantly increased risk of treatment discontinuation for older patients and patients treated in NP practice. Comorbidity of diabetes or history of stroke was associated with a decreased risk of treatment discontinuation. Conclusion: The study results show insufficient persistence in antidepressant treatment in dementia patients in a real world setting. The improvement must be achieved to ensure the treatment recommended in the guidelines.
Different systems for habitual versus goal-directed control are thought to underlie human decision-making. Working memory is known to shape these decision-making systems and
their interplay, and is known to support goal-directed decision making even under stress. Here, we investigated if and how decision systems are differentially influenced by breaks filled with diverse everyday life activities known to modulate working memory performance. We used a within-subject design where young adults listened to music and played a video game during breaks interleaved with trials of a sequential two-step Markov decision task, designed to assess habitual as well as goal-directed decision making. Based on a neurocomputational model of task performance, we observed that for individuals with a rather limited
working memory capacity video gaming as compared to music reduced reliance on the goal-directed decision-making system, while a rather large working memory capacity prevented such a decline. Our findings suggest differential effects of everyday activities on key decision-making processes.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Behavioral choice can be characterized along two axes. One axis distinguishes reflexive, model-free systems that slowly accumulate values through experience and a model-based system that uses knowledge to reason prospectively. The second axis distinguishes Pavlovian valuation of stimuli from instrumental valuation of actions or stimulus–action pairs. This results in four values and many possible interactions between them, with important consequences for accounts of individual variation. We here explored whether individual variation along one axis was related to individual variation along the other. Specifically, we asked whether individuals' balance between model-based and model-free learning was related to their tendency to show Pavlovian interferences with instrumental decisions. In two independent samples with a total of 243 participants, Pavlovian–instrumental transfer effects were negatively correlated with the strength of model-based reasoning in a two-step task. This suggests a potential common underlying substrate predisposing individuals to both have strong Pavlovian interference and be less model-based and provides a framework within which to interpret the observation of both effects in addiction.