Liquid biopsy in advanced NSCLC: EpCAM+ and EpCAM– circulating tumor cells, tumor derived extracellular vesicles and cell-free circulating tumor DNA.

S. de Wit et al., Liquid biopsy in advanced NSCLC: EpCAM+ and EpCAM– circulating tumor cells, tumor derived extracellular vesicles and cell-free circulating tumor DNA, i

Are Nonclinical Obsessive-Compulsive Symptoms Associated with Bias Toward Habits?

In a sample of student volunteers (N=93), we found that obsessive-compulsive symptoms (although not hoarding) were associated with overreliance on stimulus-response habits at the expense of goal-directed control during instrumental responding. Only checking symptoms were associated with bias toward habits after negative affect was controlled for. Further research is warranted to examine if overreliance on habits represents an aberrant learning process that confers risk for obsessive-compulsive psychopathology

Age differences in routine formation: the role of automatization, motivation, and executive functions

Medication adherence can be vital for one’s health, especially in older adults. However, previous research has demonstrated that medication adherence is negatively affected by age-related cognitive decline. In the current study we investigated whether older adults are able to compensate for this decline by relying more on the formation of efficient, automatized routines. To this end, we directly compared daily (placebo) medication adherence in a healthy sample of 68 younger (18–29  years) and 63 older adults (65–86  years) over a period of 4  weeks. We show that despite an age-related decline in cognitive functions (i.e., poorer working memory, prospective memory, task switching, and goal-directed control), older adults adhered better to a daily pill intake routine than younger adults did and, in line with our hypothesis about increased routine formation, reported higher subjective automaticity of pill intake. Across age groups, automatization of pill intake was related to intake regularity and conscientiousness, but not to individual differences in habit tendency as measured in the lab nor to explicit strategic planning. Crucially, the age-related increase in pill intake adherence was mediated by experienced automatization as well as motivation. These findings demonstrate that intact habitual processes and high motivation aid older adults in successfully forming daily routines

Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans.

BACKGROUND: Optimal behavioral performance results from a balance between goal-directed and habitual systems of behavioral control, which are modulated by ascending monoaminergic projections. While the role of the dopaminergic system in behavioral control has been recently addressed, the extent to which changes in global serotonin neurotransmission could influence these 2 systems is still poorly understood. METHODS: We employed the dietary acute tryptophan depletion procedure to reduce serotonin neurotransmission in 18 healthy volunteers and 18 matched controls. We used a 3-stage instrumental learning paradigm that includes an initial instrumental learning stage, a subsequent outcome-devaluation test, and a slip-of-action stage, which directly tests the balance between hypothetical goal-directed and habitual systems. We also employed a separate response inhibition control test to assess the behavioral specificity of the results. RESULTS: Acute tryptophan depletion produced a shift of behavioral performance towards habitual responding as indexed by performance on the slip-of-action test. Moreover, greater habitual responding in the acute tryptophan depletion group was predicted by a steeper decline in plasma tryptophan levels. In contrast, acute tryptophan depletion left intact the ability to use discriminative stimuli to guide instrumental choice as indexed by the instrumental learning stage and did not impair inhibitory response control. CONCLUSIONS: The major implication of this study is that serotonin modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. Our findings thus imply that diminished serotonin neurotransmission shifts behavioral control towards habitual responding.This work was supported by a Wellcome Trust programme grant to T.W.R. (089589/z/09/z). The Behavioral and Clinical Neuroscience Institute is jointly funded by the MRC and the Wellcome Trust (G00001354).This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/ijnp/pyv01

Dorsomedial prefrontal cortex resolves response conflict in rats

The capacity for goal-directed behavior requires not only the encoding of the response-outcome relationship but also the ability to resolve conflict induced by competing responses. Recent neuroimaging studies have identified the prefrontal cortex as critical for resolving conflict between competing responses. At present, however, much of this evidence is indirect, and the necessity of dorsomedial prefrontal cortex (dmPFC) function for the resolution of conflict in goal-directed behavior has not been assessed. Here, we develop a rodent paradigm to investigate response conflict caused by the concurrent activation of a correct and incorrect response. In this paradigm, the outcome of one response also acts as a discriminative stimulus signaling that the other response is correct. Whereas rats with a functional dmPFC are able to resolve this conflict, inactivation of dmPFC using an infusion of muscimol produced a deficit by selectively interfering with their ability to inhibit the incorrect, competing response

Goal-Directed and Habitual Control in Smokers.

INTRODUCTION: Harmful behavior such as smoking may reflect a disturbance in the balance of goal-directed and habitual control. Animal models suggest that habitual control develops after prolonged substance use. In this study, we investigated whether smokers (N = 49) differ from controls (N = 46) in the regulation of goal-directed and habitual behavior. It was also investigated whether individual differences in nicotine dependence levels were associated with habitual responding. METHODS: We used two different multistage instrumental learning tasks that consist of an instrumental learning phase, subsequent outcome devaluation, and a testing phase to measure the balance between goal-directed and habitual responding. The testing phases of these tasks occurred after either appetitive versus avoidance instrumental learning. The appetitive versus aversive instrumental learning stages in the two different tasks modeled positive versus negative reinforcement, respectively. RESULTS: Smokers and nonsmoking controls did not differ on habitual versus goal-directed control in either task. Individual differences in nicotine dependence within the group of smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. CONCLUSIONS: The current finding highlights the importance of individual differences within smokers. For future research, neuroimaging studies are suggested to further unravel the nature of the imbalance between goal-directed versus habitual control in severely dependent smokers by directly measuring activity in the corresponding brain systems. IMPLICATIONS: Goal-directed versus habitual behavior in substance use and addiction is highly debated. This study investigated goal-directed versus habitual control in smokers. The findings suggest that smokers do not differ from controls in goal-directed versus habitual control. Individual differences in nicotine dependence within smokers, however, were positively associated with habitual responding after appetitive instrumental learning. This effect seems to be due to impaired stimulus-outcome learning, thereby hampering goal-directed task performance and tipping the balance to habitual responding. These findings add to the ongoing debate on habitual versus goal-directed control in addiction and emphasize the importance of individual differences within smokers

Association of Use of Oral Contraceptives With Depressive Symptoms Among Adolescents and Young Women

Importance: Oral contraceptives have been associated with an increased risk of subsequent clinical depression in adolescents. However, the association of oral contraceptive use with concurrent depressive symptoms remains unclear. Objectives: To investigate the association between oral contraceptive use and depressive symptoms and to examine whether this association is affected by age and which specific symptoms are associated with oral contraceptive use. Design, Setting, and Participants: Data from the third to sixth wave of the prospective cohort study Tracking Adolescents' Individual Lives Survey (TRAILS), conducted from September 1, 2005, to December 31, 2016, among females aged 16 to 25 years who had filled out at least 1 and up to 4 assessments of oral contraceptive use, were used. Data analysis was performed from March 1, 2017, to May 31, 2019. Exposure: Oral contraceptive use at 16, 19, 22, and 25 years of age. Main Outcomes and Measures: Depressive symptoms were assessed by the DSM-IV-oriented affective problems scale of the Youth (aged 16 years) and Adult Self-Report (aged 19, 22, and 25 years). Results: Data from a total of 1010 girls (743-903 girls, depending on the wave) were analyzed (mean [SD] age at the first assessment of oral contraceptive use, 16.3 [0.7]; (mean [SD] age at the final assessment of oral contraceptive use, 25.6 [0.6] years). Oral contraceptive users particularly differed from nonusers at age 16 years, with nonusers having a higher mean (SD) socioeconomic status (0.17 [0.78] vs-0.15 [0.71]) and more often being virgins (424 of 533 [79.5%] vs 74 of 303 [24.4%]). Although all users combined (mean [SD] ages, 16.3 [0.7] to 25.6 [0.6] years) did not show higher depressive symptom scores compared with nonusers, adolescent users (mean [SD] age, 16.5 [0.7] years) reported higher depressive symptom scores compared with their nonusing counterparts (mean [SD] age, 16.1 [0.6] years) (mean [SD] score, 0.40 [0.30] vs 0.33 [0.30]), which persisted after adjustment for age, socioeconomic status and ethnicity (β coefficient for interaction with age,-0.021; 95% CI,-0.038 to-0.005; P =.0096). Adolescent contraceptive users particularly reported more crying (odds ratio, 1.89; 95% CI, 1.38-2.58; P <.001), hypersomnia (odds ratio, 1.68; 95% CI, 1.14-2.48; P =.006), and more eating problems (odds ratio, 1.54; 95% CI, 1.13-2.10; P =.009) than nonusers. Conclusions and Relevance: Although oral contraceptive use showed no association with depressive symptoms when all age groups were combined, 16-year-old girls reported higher depressive symptom scores when using oral contraceptives. Monitoring depressive symptoms in adolescents who are using oral contraceptives is important, as the use of oral contraceptives may affect their quality of life and put them at risk for nonadherence