Three perspectives on learning in a simulated patient scenario: a qualitative interview study with student, simulated patient, and teacher.

INTRODUCTION: Patient simulation can be useful for medical students in developing communication skills for vulnerable situations. Three participants are primarily involved in the patient simulation activities: the student, the simulated patient (SP), and the teacher. We here aimed to explore these participants' perceptions of learning in a patient simulation scenario. METHODS: We conducted individual interviews with eight students, three teachers, and one SP at a psychiatry placement of a Medical Doctor Program (5th year). During the interviews we asked the participants to watch a video of their participation in a patient simulation session. Thus, we obtained three perspectives on each of the eight recordings. We analysed our data with qualitative content analysis. RESULTS: Three themes were generated: identity formation, collaborative learning, and learning intentions. This highly emotional scenario forced students out of their comfort zone, to the intersection of their roles as private person and professional. The SP perceived the collaborative creation of the scenario as significant learning. The teacher took a professional position and perceived the learning in the perspective of a future colleague. CONCLUSIONS: The mutually created emotionally loaded scenario was found to be important from all three perspectives, forcing the students to identify unexpected ways of communicating. This possibly enhanced their professional identity development. Implications for future research can be to explore the process of skills transfer.

Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT).

BACKGROUND: Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression. METHODS: Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session. RESULTS: In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52). CONCLUSION: Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

Size of basal ganglia in suicide attempters, and its association with temperament and serotonin transporter density.

Magnetic resonance imaging was used to compare subcortical volumes of seven suicide attempters with those of six healthy controls. Suicide attempters had 10% smaller right caudate nucleus and 19% bilaterally smaller globus pallidus. In suicide attempters, volumes of the globus pallidus correlated negatively with previously reported measures of solidity (non-impulsive temperament) and serotonin transporter binding potential.

Life-time adversities, reported thirteen years after a suicide attempt: relationship to recovery, 5HTTLPR genotype, and past and present morbidity.

In this study, we investigated how adversities related to past and present morbidity, and genotype. Forty-two, suicide attempters and 22 matched control patients were followed-up after 13 years. Life-time adversities were explored in an interview, and the patients were reassessed psychiatrically. The serotonin-transporter-linked promotor region (5-HTTLPR) was typed. More adversities were reported by suicide attempters than controls, and by still-ill than recovered suicide attempters. Adversities reported at follow-up were related to psychiatric morbidity at follow-up, but not to morbidity 13 years earlier. The 5-HTTLPR, genotype was associated with reported adversities, but not chances of recovery. Adversities potentially affected chronic morbidity. 5-HTTLPR genotype did not affect long-term recovery.

Genetic variation in brain-derived neurotrophic factor is associated with serotonin transporter but not serotonin-1A receptor availability in men.

BACKGROUND: The serotonergic system, including the serotonin transporter (5-HTT), which is the target of many antidepressants, seems to be influenced by brain-derived neurotrophic factor (BDNF). METHODS: Positron emission tomography (PET) was used to address, in 25 and 53 healthy volunteers, respectively, the possible association between six polymorphisms in the gene encoding BDNF and the availability of two proteins expressed by serotonergic neurons: the 5-HTT, measured with the radioligand [(11)C]MADAM, and the serotonin-1A (5-HT1A) receptor, measured with [(11)C]WAY-100635. RESULTS: Several single nucleotide polymorphisms were associated with [(11)C]MADAM binding potential (BP) in most brain regions, male carriers of the valine/valine genotype of the Val66Met polymorphism displaying higher availability. Effect sizes ranged from a 50% to a threefold increase. In contrast, there was no association for [(11)C]WAY-100635 BP. The observation that BDNF polymorphisms were associated with 5-HTT availability could be partly replicated in an independent population comprising nine male suicide attempters and nine matched control subjects, in which transporter availability had been measured with single photon emission computed tomography with (123)I-beta-CIT as ligand. CONCLUSIONS: Our results suggest that genetic variation in BDNF influences 5-HTT but not 5-HT1A receptor density in the human brain.

The role of dopamine and serotonin in suicidal behaviour and aggression.

Serotonin and dopamine are two monoamines which are known to interact with each other. Their role for suicidal behaviour, aggression and mood are reviewed in this chapter. We found a substantial amount of evidence for the relevance of a serotonin and dopamine model of aggression, and for aggression as a major risk factor for suicide. Evidence was found that serotonin and dopamine also may be involved in depressed mood, and possibly the individual's ability to cope with imminent suicidality.

Serotonin transporter gene polymorphisms: effect on serotonin transporter availability in the brain of suicide attempters.

The efficacy of serotonin reuptake inhibitors in depression and anxiety disorders suggests the gene coding for the serotonin transporter (5-HTT), SLC6A4, as a candidate of importance for these conditions. Positive findings regarding associations between polymorphisms in SLC6A4 have been reported, indicating that these polymorphisms may influence anxiety-related personality traits, as well as the risk of developing depression and suicidality. Serotonin 5-HTT availability was assessed with single photon emission computed tomography (SPECT), using (123)I-beta-CIT as ligand, in a population of unmedicated male suicide attempters (n=9) and in matched controls (n=9). Two polymorphisms in SLC6A4 were assessed, including the 5-HTTLPR located in the promoter region and a variable number of tandem repeats (VNTR) polymorphism in intron 2 (STin2). In suicide attempters, but not in controls, low 5-HTT availability was associated with the S allele of 5-HTTLPR and with the 12 repeat allele of STin2. Data suggest that polymorphisms in SLC6A4 may influence the expression of the brain serotonin transporter in suicide attempters.

Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy.

To study different aspects of regional pre-synaptic brain (123)I-beta-CIT uptake on serotonin and dopamine re-uptake sites in drug-free suicide attempters in comparison with age- and sex matched control subjects, single photon emission computed tomography (SPECT) measurements were analysed for regional serotonin re-uptake (5HTT) and dopamine re-uptake (DAT) capacity (binding potential, BP()) after i.v. (123)I-beta-CIT administration. All suicide attempters were examined concerning seriousness of the attempt, and DSM-IV diagnosis. Both suicide attempters and control subjects were tested for psychotropic drugs, and completed the Marke-Nyman Temperament (MNT) test, including solidity (level of impulsiveness/initiative) and validity (level of mental energy). We found no significant difference between suicide attempters and control subjects concerning the regional levels of 5HTT BP() or DAT BP(). However, in suicide attempters, but not controls, we found significant regional correlations between MNT variables and SPECT results. We interpret the discrepant findings in suicide attempters and control subjects to be due to a disability of the suicide attempters to regulate their serotonin and dopamine levels, e.g. in response to external stress.

Impulsivity related to brain serotonin transporter binding capacity in suicide attempters.

Altered monoaminergic activity has earlier been associated with violent suicidal behaviour. In this study whole brain binding potential of the serotonin transporter (5HTT) and dopamine transporter (DAT) was measured by single photon emission computerised tomography (SPECT) in 12 patients after a serious suicide attempt and in 12 age, sex and season matched healthy controls. Clinical and temperamental assessments were analysed for possible associations with 5HTT and DAT. We found no significant 5HTT or DAT differences between patients and controls. In patients, but not in controls, there was a significant correlation between whole brain 5HTT and DAT. Impulsiveness according to the Marke Nyman Temperament (MNT) was significantly correlated to 5HTT in suicide attempters, but not in controls. Neither of the transporters could be regarded as a marker for serious suicidal behaviour. A previously discussed connection between serotonin and dopamine was replicated in this study. In suicide attempters, low 5HTT was associated with impulsivity and to some extent with depressive disorder-key factors for suicidal behaviour.

A new model for separation between brain dopamine and serotonin transporters in 123I-beta-CIT SPECT measurements: normal values and sex and age dependence.

123I-beta-CIT is a radioactive ligand for single-photon emission computed tomography (SPECT) imaging of the pre-synaptic (transporter) re-uptake sites for dopamine (DAT) and serotonin (5HTT), and it is widely used to visualize monoamine turnover. Since 123I-beta-CIT uptake occurs at 5HTT and DAT sites in conjunction with the presence of freely soluble 123I-beta-CIT in brain tissue, adequate separation of these three components is necessary. However, only partial separation is possible with current methods. Two main strategies have previously been used for 123I-beta-CIT component separation, based on the following considerations: (1) the faster uptake rate for 5HTT compared with DAT enables temporal separation by performing 5HTT imaging at 1-2 h and DAT imaging at 20-24 h; (2) blocking the 5HTT re-uptake with citalopram renders 123I-beta-CIT imaging DAT (non-5HTT) specific. In a new analytical model, we combined these two approaches with methods to isolate the passively dissolved 123I-beta-CIT in brain tissue from the monoamine transporter uptake, and to correct the 5HTT and DAT values for concomitant uptake. The new analytical model was used to study brain 5HTT and DAT in 23 normal subjects, with the aim of clarifying the effect of age and sex. A significant correlation between 5HTT and DAT values was found only in the thalamus, indicating successful component separation. Negative correlations between age and DAT were found for basal ganglia, thalami, brain stem and temporal lobes, but not for the frontal, parietal or occipital regions. No correlation with age was found for 5HTT. We found no sex difference for 5HTT or DAT.

Suicide-attempters having immunoglobulin G with affinity for dopamine in cerebrospinal fluid.

Altered immunological functions and changes in the monoaminergic neurotransmitter systems are two important observations made previously in the study of possible etiological and pathophysiological factors for psychiatric disorders. In search of tentative autoimmune mechanisms involved in these disorders we studied the presence of immunoglobulin G (DA-IgG) with affinity for the monoamine dopamine (DA) in cerebrospinal fluid (CSF) using ELISA. In CSF from 49 suicide attempters the titer of DA-IgG was significantly higher (P<0.001) than in CSF obtained from control subjects undergoing neurological investigation. The results in the present study indicate that an autoimmune mechanism may be involved in the dopaminergic neurotransmitter system and may be of pathophysiological importance in psychiatric disorders connected to an attempt of suicide.