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BACKGROUND AND PURPOSEThe antidepressant efficacy of selective 5-HT reuptake inhibitors (SSRI) and other 5-HT-enhancing drugs is compromised by a negative feedback mechanism involving 5-HT1A autoreceptor activation by the excess 5-HT produced by these drugs in the somatodendritic region of 5-HT neurones. 5-HT1A receptor antagonists augment antidepressant-like effects in rodents by preventing this negative feedback, and the mixed b-adrenoceptor/5-HT1A receptor antagonist pindolol improves clinical antidepressant effects by preferentially interacting with 5-HT1A autoreceptors. However, it is unclear whether 5-HT1A receptor antagonists not discriminating between pre-and post-synaptic 5-HT1A receptors would be clinically effective. EXPERIMENTAL APPROACHWe characterized the pharmacological properties of the 5-HT1A receptor antagonist DU-125530 using receptor autoradiography, intracerebral microdialysis and electrophysiological recordings. Its capacity to accelerate/enhance the clinical effects of fluoxetine was assessed in a double-blind, randomized, 6 week placebo-controlled trial in 50 patients with major depression (clinicaltrials.gov identifier NCT01119430). KEY RESULTSDU-125530 showed equal (low nM) potency to displace agonist and antagonist binding to pre-and post-synaptic 5-HT1A receptors in rat and human brain. It antagonized suppression of 5-hydroxytryptaminergic activity evoked by 8-OH-DPAT and SSRIs in vivo. DU-125530 augmented SSRI-induced increases in extracellular 5-HT as effectively as in mice lacking 5-HT1A receptors, indicating a silent, maximal occupancy of pre-synaptic 5-HT1A receptors at the dose used. However, DU-125530 addition to fluoxetine did not accelerate nor augment its antidepressant effects. CONCLUSIONS AND IMPLICATIONSDU-125530 is an excellent pre-and post-synaptic 5-HT1A receptor antagonist. However, blockade of post-synaptic 5-HT1A receptors by DU-125530 cancels benefits obtained by enhancing pre-synaptic 5-hydroxytryptaminergic function.

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IntroductionDespite multiple clinical and preclinical studies investigating schizophrenia, the neurobiological basis of this disease is still unknown. The dysregulation of the serotonergic system, in particular the 5-HT2A receptor and the endocannabinoid system have been postulated as possible causes of schizophrenia.ObjectivesThe aim of this study is to evaluate the expression of CB1-5-HT2A receptor heteromers in primary cultures of pro-neurons from the olfactory epithelium in schizophrenia patients and control subjects.MethodsWe recruited a group of 10 healthy volunteers and 10 patients diagnosed with schizophrenia, who were treated with atypical antipsychotics, were clinically stable and had an illness duration range from 1 up to 15 years. The patients were diagnosed with schizophrenia from the medical record and confirmed by the structured clinical interview for DSM disorders. The expression of CB1-5-HT2A receptor heteromers in primary cultures of pro-neurons from the olfactory epithelium was quantified using proximity ligation assays and confocal microscopy.ResultsOlfactory epithelium pro-neurons were viable and expressed the neuronal marker, III-β tubulin. We also established the presence and the functionality of CB1-5-HT2A receptor heteromers in these cells using the proximity ligation and cAMP activity assays, respectively. Heteromer expression was significantly increased in schizophrenia patients with respect to controls.ConclusionsThis highly innovative methodology will allow the noninvasive, low-cost study of new biomarkers for schizophrenia in a model closely related to the central nervous system.Disclosure of interestThe authors have not supplied their declaration of competing interest.AcknowledgmentsThis work was supported by grants from DIUE-Generalitat-de Catalunya (2014SGR 680), Instituto de Salud Carlos III (PI14/00210) and (PI10/01708) FIS-FEDER-Funds. LG is supported by the Instituto-de Salud Carlos III through a “Río Hortega” (CM14/00111).

BackgroundCognitive remediation (CR) and physical exercise have separately shown promising results in schizophrenia cognitive improvement, despite this, the impact on daily functionality is still limited. Physical exercise increases Brain Derived Neurotrophic Factor (BDNF) levels, promoting neuronal and cognitive plasticity, which can maximize the impact of CR. We are conducting a randomised controlled trial to determine the efficacy of an intensive program that combines CR and physical exercise on cognition and related outcomes for patients with schizophrenia. In addition, we investigate functional and structural brain effects of this intervention and its association to BDNF.MethodsThis study protocol describes a randomized controlled trial in which 74 patients are randomly assigned to either CR and physical exercise or CR and health promotion. The interventions are 12-week long and consist of three weekly sessions (90min of CR and 40min of either aerobic exercise or health promotion). To be included in the study, patients must be diagnosed with schizophrenia or schizoaffective disorder, aged 28–60 years, and do low physical activity, as measured by International Physical Activity Questionnaire, IPAQ. Exclusion Criteria for participation in the study are the presence of neurological or substance use disorders, IQ < 70 and somatic illnesses that contraindicate physical exercise. Healthy control participants (n=18) are screened for the presence of lifetime Axis I psychotic disorders and for the presence of a first-degree relative with schizophrenia. Primary outcome measures are cognitive performance, functional outcome, negative symptoms, BDNF levels and neuroimaging measures. Secondary outcome measures are quality of life and metabolic parameters. All measures are blindly assessed at baseline, at 3 months follow up and at 15 months follow up.This trial was approved by the Comité Ètic d’Investigació Clínica de l’Hospital del Mar (CEIC) 2015/6209/IResultsThis poster is a study protocol. We will correct data from now on.DiscussionThe results of this trial will provide valuable information about whether cognitive remediation efficacy for patients with schizophrenia can be enhanced by aerobic exercise-induced BDNF upregulation.TRIAL REGISTRATIONThe trial is registered at www.clinicaltrials.gov (NCT02864576)

IntroductionHyperthyroidism due to Graves-Basedow disease is a common cause of neuropsychiatric manifestations, such as anxiety, psychomotor restlessness, mood disturbances, insomnia and psychosis. Hashimoto’s encephalopathy rarely occurs in so-called autoimmune thyroiditis, which can present with hyperthyroidism and neuropsychiatric symptoms similar to Graves’ disease. We add that the mystical-religious beliefs, present in all human cultures, and decisive in the case at hand, make us propose an evolutionary origin of them.ObjectivesClinical case descriptionMethodsA clinical case based on medical reports is describedResultsWe present the case of a 72-year-old woman, a member of the Seventh-day Adventist Church, well adapted to the Community. Known history of elevated antithyroid antibodies since 2019, brought to the emergency room involuntarily due to a mystical-religious delusional condition associated with behavioral disturbance. On examination, cachectic appearance, distal tremor, emotional exaltation and megalomanic speech were highlighted. Laboratory tests revealed primary hyperthyroidism with elevated antibodies. During admission, the differential diagnosis between Graves-Basedow disease and Hashimoto’s encephalopathy was considered. Thyroid scintigraphy oriented the diagnosis to Graves-Basedow disease, not requiring lumbar puncture or corticosteroid treatment. Treatment was based on high-dose antithyroid and antipsychotic drugs, with clinical and analytical remission at 3 weeks. The patient was referred to a Social Health Center for functional recovery. The family refers to a similar episode in 2014, of less intensity and self-limited, which is proposed to be a hashitoxicosis.ConclusionsDifferential diagnosis between Graves-Basedow and Hashimoto disease is essential as they differ in treatment and prognosis. The continuity that the delusion presents with the previous beliefs of the patient, differing mainly in the affective-behavioral implication, makes us consider a predisposition to psychosis in our patient. Religiosity can be adaptive in certain environments, since mystical beliefs have existed throughout the history of the human species and seem to be part of our nature.Disclosure of InterestNone Declared

IntroductionLate-onset psychosis appears in people over the age of 40. Some preliminary studies show that LOP has fewer severe positive symptoms, more systematic persecutory delusions, more bizarre-type delusions, less affective flattening, and more social withdrawal than early onset psychosis.There are some studies that consider late-onset and very late-onset psychosis as prodromes of neurodegenerative disease. There are some differences in neuropsychological profiles and specific cognitive function alterations discovered. More evidence, however, is required to make an accurate diagnosis.ObjectivesThe objective of this study was to reflect the difficulties in differentiating between late-onset psychosis and dementia by reporting the case of a 77-year-old woman who presented with mystical-religious delusions and hallucinations during her hospitalization.MethodsWe present the case of a 77-year-old woman who was hospitalized because of a stroke. During her stay, she began receiving follow-up from the mental health team because she verbalized some mystical-religious delusional ideas. During the psychiatric interview, the patient verbalized mystical-religious ideas and oscillated between coherent, organized, and disaggregated speech. No problems were detected with orientation, or florid affective symptoms that could point to a delirium or affective disorder. The premorbid personality was extravagant, with interpersonal difficulties and magical thinking. Nonetheless, she had no prior contact with the mental health system or hospitalization. We could approximate the beginning of the symptomatology at around 60 years old, thanks to her relatives. Prior to this age, she maintained good function by working as a chef on a regular basis. She gradually isolated herself due to her lack of mobility. Similarly, she decreases her self-care activities, begins hoarding items around the house, and gradually develops more psychotic symptoms.A brain scan was performed, and no acute pathology was found. A neuropsychological test was not executed due to a lack of collaboration from the patient.Results-ConclusionsThis case reflects the complexity of differentiating between dementia and late-onset psychosis. Supplementary testing and follow-up are essential for establishing a diagnosis. Related to that, more research is needed to identify the differential characteristics between the two disorders and the temporal correlation between them.Disclosure of InterestNone Declared

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