Evidence on psychological side effects (PSEs) of antipsychotic medication after remission from first-episode psychosis (FEP), and their momentary impact on daily life, is limited. This study examined how Dopamine-2 (D2) affinity and antipsychotic dosage relate to momentary PSEs.

This ecological momentary assessment (EMA) study included baseline data from 56 participants in the ongoing Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment (HAMLETT) trial. Momentary mental states indicative of reduced affect intensity, stability, and variability, as well as avolition and mental fatigue, were assessed 10×/day for eight days (N = 3,005 data points). Since these PSEs may result from D2-receptor actions, antipsychotics were classified by receptor affinity and mechanism of action. Multilevel mixed-effects regression models examined serial cross-sectional associations between D2 affinity or dosage and concurrent PSEs, both overall and separately for mornings, daytimes, and evenings.

Higher antipsychotic dosages were associated with reduced affect variability (Beta [B] = −1.40 [95% confidence interval [CI]: −2.52; −0.29]) and decreased positive affect stability (B = 0.23 [95% CI: 0.04; 0.42]) and intensity (B = −1.11 [95% CI: −1.97; −0.24]). The latter was also associated with the use of high-affinity D2 antagonists versus partial D2 agonists (B = 12.98 [95% CI: 2.43; 23.53]) and versus low-affinity D2 antagonists (B = 10.04 [95% CI: 0.59; 19.49]). Other PSEs were not associated with D2 affinity/dosage. Results were relatively consistent across daytimes.

Higher antipsychotic dosage and high-affinity D2 antagonists were associated with decreased positive affect after remission from FEP, which may partly drive the frequently reported blunting of emotional experience.

Current evidence on psychological adverse effects (AEs) of antipsychotic medication after remission of First Episode Psychosis (FEP), and the impact of these AEs on daily life, is limited.

To investigate serial cross-sectional associations between antipsychotic medication regimen and psychological AEs after remission of FEP.

This Ecological Momentary Assessment (EMA) study investigates baseline data of 56 participants from the HAMLETT trial (Handling Antipsychotic Medication: Long-term Evaluation of Targeted Treatment). Momentary mental states indicative of blunted affect intensity and variability, reduced initiative of social contact, avolition and tiredness were assessed 10x/day for eight consecutive days. Based on neurobiological mechanisms likely mediating these psychological AEs, antipsychotic medications were grouped based on their Dopamine-2 (D2) and Histamine-1 (H1) receptor profile. Multilevel mixed-effects regression models were employed overall and separately for mornings, daytimes and evenings, to investigate serial cross-sectional associations between medication type or dosage and concurrent psychological AEs. All models were adjusted for fixed effects of age, gender, tobacco and cannabis use in the past month and symptom severity during FEP (based on the Comprehensive Assessment of Symptoms and History, CASH).

In total, 85 out of 453 HAMLETT-participants took part in the EMA add-on study. At baseline, 56 (66%) of those participants completed >26 EMA questionnaires and were currently taking antipsychotic medication, yielding a total of 3,005 questionnaires for our analyses. The distribution of antipsychotic medication regimens was relatively equally spread (25% high affinity D2 antagonists, 48% low affinity D2 antagonists, 27% partial D2 agonists). Higher dosage (Beta (B) = -1.11 [95% Confidence Interval (CI): -1.97; -0.24]) and use of high affinity D2 antagonists, as compared with partial D2 agonists (B = 12.98 [95%CI: 2.43; 23.53]) and low affinity D2 antagonists (B = 10.04 [95% CI: 0.59; 19.49]), were associated with decreased positive affect (PA) (see Figure 1). Higher dosage was also associated with small increases in PA variability (B = 0.23 [95% CI: 0.04; 0.42]. The remaining psychological AEs were not associated with dosage or D2 profile, neither was H1 profile associated with these AEs. Results were relatively consistent across daytimes, though effect sizes were greatest in the evenings.

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After remission of FEP, higher dosage of antipsychotic medication and use of high affinity D2 antagonists, as compared with partial D2 agonists and low affinity D2 antagonists, can be associated with decreased, though not invariable, positive affect as estimated using EMA.

None Declared

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.

The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).

The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.

Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.

There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.

This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.