Link between cognitive polygenic risk scores and clinical progression after a first-psychotic episode.

BACKGROUND: Clinical intervention in early stages of psychotic disorders is crucial for the prevention of severe symptomatology trajectories and poor outcomes. Genetic variability is studied as a promising modulator of prognosis, thus novel approaches considering the polygenic nature of these complex phenotypes are required to unravel the mechanisms underlying the early progression of the disorder. METHODS: The sample comprised of 233 first-episode psychosis (FEP) subjects with clinical and cognitive data assessed periodically for a 2-year period and 150 matched controls. Polygenic risk scores (PRSs) for schizophrenia, bipolar disorder, depression, education attainment and cognitive performance were used to assess the genetic risk of FEP and to characterize their association with premorbid, baseline and progression of clinical and cognitive status. RESULTS: Schizophrenia, bipolar disorder and cognitive performance PRSs were associated with an increased risk of FEP [false discovery rate (FDR) ⩽ 0.027]. In FEP patients, increased cognitive PRSs were found for FEP patients with more cognitive reserve (FDR ⩽ 0.037). PRSs reflecting a genetic liability for improved cognition were associated with a better course of symptoms, functionality and working memory (FDR ⩽ 0.039). Moreover, the PRS of depression was associated with a worse trajectory of the executive function and the general cognitive status (FDR ⩽ 0.001). CONCLUSIONS: Our study provides novel evidence of the polygenic bases of psychosis and its clinical manifestation in its first stage. The consistent effect of cognitive PRSs on the early clinical progression suggests that the mechanisms underlying the psychotic episode and its severity could be partially independent.

Obstetric complications and genetic risk for schizophrenia: Differential role of antenatal and perinatal events in first episode psychosis.

BACKGROUND: Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors. STUDY DESIGN: 405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these. RESULTS: Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case-control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe. CONCLUSIONS: We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.

[Olanzapine long-acting post-injection syndrome: a case report and brief review]. / Síndrome post-inyección por olanzapina de liberación retardada: Breve revisión a propósito de un caso.

The introduction of long-acting injectable atypical antipsychotics has ensured adherence to treatment in patients with low awareness of the disorder, with an acceptable rate of side effects. In the case of long acting olanzapine injection in particular, has particular relevance the existence of a special side-effect called post-injection syndrome. This rare side effect consisting in the presence of symptoms of olanzapine overdose after intramuscular administration of medication has led to restrictions on the use of the drug and the need for patient observation for three hours after each injection. We report a case of postinjection syndrome, to our knowledge, the first in Spain since the commercialization of Zypadhera. As in most cases described in the literature have symptoms of overdosage of olanzapine (dysarthria, sedation, fatigue, etc.) that are selflimiting without any therapeutic measure and are accompanied by supratherapeutic plasma levels of olanzapine.

Long-term outcomes of deep brain stimulation for treatment-resistant schizophrenia: Exploring potential targets.

BACKGROUND: Schizophrenia is a complex and disabling disorder. Around 30% of patients have treatment-resistant schizophrenia (TRS). OBJECTIVE: This study summarizes the outcomes after three years follow-up of the first series of patients with TRS treated with deep brain stimulation (DBS) and discuss surgical, clinical and imaging analysis. METHODS: Eight patients with TRS treated with DBS in the nucleus accumbens (NAcc) or the subgenual cingulate gyrus (SCG) were included. Symptoms were rated with the PANSS scale and normalized using the illness density index (IDI). A reduction in IDI-PANSS of ≥25% compared to baseline was the criterion of good response. The volume of activated tissue was calculated to perform a connectomic analysis for each patient. An estimation of the tracts and cortical areas modulated was generated. RESULTS: Five women and three men were analyzed. After 3 years' follow-up, positive symptoms improved in 50% of the SCG group and 75% of the NAcc group (p = 0.06), and general symptoms improved in 25% and 50% respectively (p = 0.06). The SCG group showed activation of the cingulate bundle and modulation of orbitofrontal and frontomesial regions; in contrast, the NAcc group showed activation of the ventral tegmental area projections pathway and modulation of regions associated with the "default mode network" (precuneus) and Brodmann areas 19 and 20. CONCLUSIONS: These results showed a trend toward improvement for positive and general symptoms in patients with TRS treated with DBS. The connectomic analysis will help us understand the interaction of this treatment with the disease to pursue future trial designs.

Relapse of first-episode schizophrenia patients and neurocognitive impairment: The role of dopaminergic and anticholinergic burden.

BACKGROUND: The prevention of relapse may be a key factor to diminish the cognitive impairment of first-episode schizophrenia (FES) patients. We aimed to ascertain the effects of relapse, and dopaminergic and anticholinergic treatment burdens on cognitive functioning in the follow-up. METHODS: Ninety-nine FES patients participated in this study. Cognitive assessments were performed at baseline and after 3 years of follow-up or, in those patients who relapsed, after >2 months of stabilization of the new acute psychotic episode. The primary outcomes were final cognitive dimensions. RESULTS: Repeated measures MANOVA analyses showed improvements in the whole sample on the end-point assessments in processing speed and social cognition. However, only impairment in social cognition showed a significant interaction with relapse by time in this sample. Relapse in FES patients was significantly associated with poor performance on end-point assessments of working memory, social cognition and global cognitive score. Anticholinergic burden, but not dopaminergic burden, was associated with verbal memory impairment. These significant associations resulted after controlling for baseline cognitive functioning, relapse and dopaminergic burden. CONCLUSIONS: The relationship between relapse and cognitive impairment in recovered FES patients seems to be particularly complex at the short-term follow-up of these patients. While relapse was associated with working memory, social cognition impairments and global cognitive score, anticholinergic burden might play an additional worsening effect on verbal memory. Thus, tailoring or changing antipsychotics and other drugs to reduce their anticholinergic burden may be a potential modifiable factor to diminish cognitive impairment at this stage of the illness.

Síndrome post-inyección por olanzapina de liberación retardada: Breve revisión a propósito de un caso / Olanzapine long-acting post-injection syndrome: A case report and brief review

La introducción de los antipsicóticos atípicos de liberación retardada ha permitido asegurar la adherencia al tratamiento en aquellos pacientes con baja conciencia de trastorno, con una tasa aceptable de efectos secundarios. En el caso de la olanzapina de liberación retardada en concreto, tiene especial relevancia la existencia del llamado Síndrome post-inyección. Este efecto secundario poco común consistente en la presencia de síntomas de sobredosis de olanzapina tras la administración intramuscular de la medicación ha supuesto restricción del uso del medicamento y la necesidad de observación del paciente durante tres horas después de cada inyección. Se presenta un caso de Síndrome post-inyección, a nuestro conocimiento, el primero en España desde la comercialización de Zypadhera. Al igual que en la mayoría de casos descritos en la bibliografía el paciente presenta síntomas de sobredosificación de olanzapina (disartria, sedación, astenia, etc.) que se auto limitan sin medida terapéutica alguna y se acompañan de niveles plasmáticos supraterapéuticos de olanzapina(AU)

The introduction of long-acting injectable atypical antipsychotics has ensured adherence to treatment in patients with low awareness of the disorder, with an acceptable rate of side effects. In the case of long acting olanzapine injection in particular, has particular relevance the existence of a special side-effect called post-injection syndrome. This rare side effect consisting in the presence of symptoms of olanzapine overdose after intramuscular administration of medication has led to restrictions on the use of the drug and the need for patient observation for three hours after each injection. We report a case of postinjection syndrome, to our knowledge, the first in Spain since the commercialization of Zypadhera. As in most cases described in the literature have symptoms of over dosage of olanzapine (dysarthria, sedation, fatigue, etc.) that are selflimiting without any therapeutic measure and are accompanied by supra therapeutic plasma levels of olanzapine(AU)