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Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats.

ABSTRACT: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients would be reflected in affective biases and decision making behaviour in rodents. The diffusion model was also used to investigate the underlying decision making processes. Positive biases were induced in this task over timeframes that mirror the rapid versus delayed antidepressant efficacy of the drugs in clinical populations. Diffusion modelling revealed that the antidepressants tested also have different effects on decision making processes, suggesting they may act through different neurobiological substrates. This combination of behaviour and computational modelling may provide a useful approach to further investigate the mechanisms underlying rapid antidepressant effect and assess potential new treatments.

SUBMITTER: Hales CA

PROVIDER: S-EPMC5720479 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats.

Hales Claire A CA Houghton Conor J CJ Robinson Emma S J ESJ

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 20171031 12

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders. Until the recent discovery of the rapid onset antidepressant action of ketamine, pharmacological treatments for MDD were limited to conventional antidepressant drugs with delayed clinical efficacy. Using a judgement bias task, this study has investigated whether the temporal differences observed in patients would be reflected in affective biases and decision making behaviour in rodents. The diffusion model was al ...[more]

PMID: 29100819

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Project description:IMPORTANCE:For antidepressants, the translation of evidence of comparative effectiveness into practice is suboptimal. This deficit directly affects outcomes and quality of care for patients with depression. To overcome this problem, we developed the Depression Medication Choice (DMC) encounter decision aid, designed to help patients and clinicians consider the available antidepressants and the extent to which they improved depression and other issues important to patients. OBJECTIVE:Estimate the effect of DMC on quality of the decision-making process and depression outcomes. DESIGN, SETTING, AND PARTICIPANTS:We conducted a cluster randomized trial of adults with moderate to severe depression considering treatment with an antidepressant. Primary care practices in 10 rural, suburban, and urban primary care practices across Minnesota and Wisconsin were randomly allocated to treatment of depression with or without use of the DMC decision aid. INTERVENTION:Depression Medication Choice, a series of cards, each highlighting the effect of the available options on an issue of importance to patients for use during face-to-face consultations. MAIN OUTCOMES AND MEASURES:Decision-making quality as judged by patient knowledge and involvement in decision making, patient and clinician decisional comfort (Decisional Conflict Scale) and satisfaction, encounter duration, medication adherence, depression symptoms, and the Patient Health Questionnaire for depression (PHQ-9). RESULTS:We enrolled 117 clinicians and 301 patients (67% women; mean [SD] age, 44 [15] years; mean [SD] PHQ-9 score, 15 [4]) into the trial. Compared with usual care (UC), use of DMC significantly improved patients' decisional comfort (DMC, 80% vs UC, 75%; P = .02), knowledge (DMC, 65% vs UC, 56%; P =?.03), satisfaction (risk ratio [RR], from 1.25 [P =?.81] to RR, 2.4 [P =?.002] depending on satisfaction domain), and involvement (DMC, 47% vs UC, 33%; P<.001). It also improved clinicians' decisional comfort (DMC, 80% vs UC, 68%; P <?.001) and satisfaction (RR, 1.64; P =?.02). There were no differences in encounter duration, medication adherence, or improvement of depression control between arms. CONCLUSIONS AND RELEVANCE:The DMC decision aid helped primary care clinicians and patients with moderate to severe depression select antidepressants together, improving the decision-making process without extending the visit. On the other hand, DMC had no discernible effect on medication adherence or depression outcomes. By translating comparative effectiveness into patient-centered care, use of DMC improved the quality of primary care for patients with depression. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01502891.

Project description:ObjectiveNumerous studies have identified impaired decision making (DM) under both ambiguity and risk in adult patients with schizophrenia. However, the assessment of DM in patients with adolescent-onset schizophrenia (AOS) has been challenging as a result of the instability and heterogeneity of manifestations. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT), which are frequently used to evaluate DM respectively under ambiguity and risk, are sensitive to adolescents and neuropsychiatric patients. Our research intended to examine the performance of DM in a relatively large sample of patients with AOS using the above-mentioned two tasks. We also aimed to take a closer look at the relationship between DM and symptom severity of schizophrenia.MethodsWe compared the performance of DM in 71 patients with AOS and 53 well-matched healthy controls using IGT for DM under ambiguity and GDT for DM under risk through net scores, total scores and feedback ration. Neuropsychological tests were conducted in all participants. Clinical symptoms were evaluated by using Positive and Negative Syndrome Scale (PANSS) in 71 patients with AOS. Pearson's correlation revealed the relationship among total score of DM and clinical and neuropsychological data.ResultsCompared to healthy controls, patients with AOS failed to show learning effect and had a significant difference on the 5th block in IGT and conducted more disadvantageous choices as well as exhibited worse negative feedback rate in GDT. Apart from DM impairment under risk, diminished DM abilities under ambiguity were found related to poor executive function in AOS in the present study.ConclusionsOur findings unveiled the abnormal pattern of DM in AOS, mainly reflected under the risky condition, extending the knowledge on the performance of DM under ambiguity and risk in AOS. Inefficient DM under risk may account for the lagging impulse control and the combined effects of developmental disease. In addition, our study demonstrated that the performance on IGT was related to executive function in AOS.

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Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats.

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Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats.

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