Mapping anhedonia onto reinforcement learning: A behavioural meta-analysis

BACKGROUND: Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. METHODS: Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. RESULTS: MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. CONCLUSION: Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior

Using pharmacological insights to inform real-life decision making − part 2

2siPart of special issue: Papers of the 23rd ECNP CongressreservedmixedFAGIOLINI, A.; PITCHOT, W.Fagiolini, A.; Pitchot, W

Serotonin, personality and borderline personality disorder

Serotonin is one of the neurotransmitters implicated in normal personality Many psychobiological models of personality include,some dimensions related to serotonin. For instance, the harm avoidance dimension of the blosocial model developed by Cloninger is related to serotonergic activity Higher scores on the harm avoidance dimension should theoretically reflect increased serotonergic activity However, correlation studies related serotonin activity to harm avoidance dimension have not yielded consistent findings. These controversial results are probably related to the complexity of the neurotransmitter systems, and the different assessment techniques used in these studies. Finally, recent genetic studies have examined the association between personality dimensions and serotonergic receptor polymorphisms with mixed results. Serotonin is not only related to some dimensions of normal personality Several psychopathological disorders are associated with serotonergic dysfunction. More particularly, borderline personality disorder (BPD) can be defined by many of the symptoms associated with serotonergic dysregulation, including affective lability, suicidal behaviours, impulsivity and loss of impulse control. Indeed, several reports have demonstrated the efficacy of selective serotonin re-uptake drugs in treating the depressive and impulsive symptoms of patients with BPD. Moreover, some challenge studies have reported a lower serotonergic activity in BPD. Because these challenges are not specific, we have assessed the serotonergic activity in BPD with the flesinoxan challenge. Preliminary results showed that the prolactine responses to flesinoxan were significantly lower in BPD patients compared to those observed in controls

Growth hormone response to apomorphine in obsessive-compulsive disorder.

Several lines of evidence suggest that dopamine plays a role in the pathophysiology of obsessive-compulsive disorder (OCD). Indeed, some trials have shown the efficacy of neuroleptic addition in the treatment of OCD patients. In this study, we assessed the growth hormone (GH) response to 0.5 mg apomorphine(sc) in 8 drug-free inpatients (6 male, 2 female; mean age +/- SD = 34.7 +/- 12.6) meeting DSM-III-R criteria for OCD without major depression and compared their responses with those of 8 healthy male volunteers (mean age = 27.1 +/- 8.5). The groups did not differ in their mean GH peak response: 12.4 +/- 9.7 ng/mL in OCD patients versus 21.1 +/- 14.2 ng/mL in normal controls (F = 0.9, df1, 14, P = 0.37). These results do not support the hypothesis of dopaminergic overactivity in OCD. In fact, the completely blunted GH response to apomorphine in 2 OCD patients suggests the biological heterogeneity of OCD. Some dopaminergic disturbances could be observed in patients with comorbid diagnoses or patients unresponsive to serotonin reuptake inhibitors, but the results of this study require confirmation from a larger sample with a precise assessment of comorbidity

GROWTH HORMONE RESPONSE TO APOMORPHINE TEST IN RETARDED VS AGITATED DEPRESSED PATIENTS

peer reviewe

Streven naar remissie van depressie door een betere en bredere aanpak van de symptomen

The first part of this paper outlines the scale, impact and current management of major depressive disorder. Major depressive disorder is a huge public health problem, and despite the availability of a range of effective antidepressants and approaches to therapy, many patients fail to achieve remission, or if they do, they go on to suffer relapse or recurrence. Partial remission leaves patients experiencing residual symptoms, with a greater risk of relapse, more severe, chronic disease, impaired psychosocial functioning, a lower health-related quality of life, and an increased risk of mortality. This background provides the context for exploration of the traditional definition of remission, and it is suggested that a broader definition of remission would be a better guide to therapy. The main point of this paper is the proposal for an alternative definition of remission that incorporates positive therapeutic outcomes in four perspectives; psychodynamic, cognitive, biological and functional. Barriers to the application of a broader definition of remission in the clinic are explored briefly, and the need for specific, practical multi-axial instruments for use in MDD is acknowledged. Broad remission is more likely to be achieved using antidepressants that address a wider range of symptoms. It is also important to continue therapy beyond the acute stage into continuation, and possibly maintenance therapy, if complete remission is to be achieved and maintained in the long term