A history of childhood schizophrenia and lessons for autism.

The diagnosis of childhood schizophrenia was widely employed in the U.S. from the 1930s to the late 1970s. In this paper I will provide a history of the diagnosis. Some of the earliest publications on childhood schizophrenia outlined the notion that childhood schizophrenia had different types. I will outline the development of these types, outlining differing symptoms and causes associated with various types. I outline how different types of childhood schizophrenia were demarcated from one another primarily on age of onset and the type of psychosis which was believed to be present. I will outline how various child psychiatrists viewed the types of childhood schizophrenia posited by other child psychiatrists. I will outline the process of abandoning childhood schizophrenia. I use my history to challenge what I believe are misconceptions about childhood schizophrenia. Also, I will use my history to draw lessons for thinking about modern notions of autism. It shows potential problems around formulating psychiatric diagnoses around causes and how compromises might be needed to prevent those problems. Additionally, childhood schizophrenia shows that psychiatrists could formulate subtypes that are not based upon functioning levels and that we can conceive of subtypes as dynamic whereby someone can change which subtype they exhibit over time.

Do Microplastics Have Neurological Implications in Relation to Schizophrenia Zebrafish Models? A Brain Immunohistochemistry, Neurotoxicity Assessment, and Oxidative Stress Analysis.

The effects of exposure to environmental pollutants on neurological processes are of increasing concern due to their potential to induce oxidative stress and neurotoxicity. Considering that many industries are currently using different types of plastics as raw materials, packaging, or distribution pipes, microplastics (MPs) have become one of the biggest threats to the environment and human health. These consequences have led to the need to raise the awareness regarding MPs negative neurological effects and implication in neuropsychiatric pathologies, such as schizophrenia. The study aims to use three zebrafish models of schizophrenia obtained by exposure to ketamine (Ket), methionine (Met), and their combination to investigate the effects of MP exposure on various nervous system structures and the possible interactions with oxidative stress. The results showed that MPs can interact with ketamine and methionine, increasing the severity and frequency of optic tectum lesions, while co-exposure (MP+Met+Ket) resulted in attenuated effects. Regarding oxidative status, we found that all exposure formulations led to oxidative stress, changes in antioxidant defense mechanisms, or compensatory responses to oxidative damage. Met exposure induced structural changes such as necrosis and edema, while paradoxically activating periventricular cell proliferation. Taken together, these findings highlight the complex interplay between environmental pollutants and neurotoxicants in modulating neurotoxicity.

Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection.

Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.

Heavy metal concentrations and clinical symptoms in patients diagnosed with schizophrenia related to cigarette smoking.

In our study, blood concentrations of lead (Pb), arsenic (As), and cadmium (Cd) and urine concentrations of thallium (Tl) were measured together with related symptoms of heavy metal poisoning in cigarette smoking volunteers diagnosed with schizophrenia, in cigarette smokers not diagnosed with schizophrenia, and in the control group of non-smokers and not diagnosed with schizophrenia volunteers. Our study was performed on 171 volunteers divided into the following subgroups: patients diagnosed with schizophrenia with at least 1 year of continuous cigarette smoking experience (56 participants), cigarette smokers not diagnosed with schizophrenia with at least one year of continuous smoking experience (58), and control group (not diagnosed with schizophrenia and non-smoking volunteers) (57). Smoking durations of cigarette smokers diagnosed with schizophrenia and cigarette smokers not diagnosed with schizophrenia are not similar (p = 0.431). Blood Pb, As, and Cd concentrations and urine Tl concentrations were the highest in the subgroup of cigarette smokers not diagnosed with schizophrenia, followed by the subgroup of cigarette smokers diagnosed with schizophrenia, and the control group. Only blood Pb concentrations were significantly higher (probability value p < 0.05) in the group of cigarette smokers not diagnosed with schizophrenia (5.16 µg/dL), comparing to the group of cigarette smokers diagnosed with schizophrenia (3.83 µg/dL) and to the control group (3.43 µg/dL). Blood Cd and As concentrations and urine Tl concentrations were significantly higher (p < 0.05) in cigarette smokers not diagnosed with schizophrenia than in the control group. The results revealed a statistically significant positive correlation (p < 0.001) in the cigarette smokers in the schizophrenia diagnosed group between blood Pb, blood As, and urine Tl concentrations and the duration of cigarette smoking.

The Genesis of Schizophrenia: An Origin Story.

Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem brain studies, and analyses from cellular models that recapitulate neurodevelopment. Emerging insights into schizophrenia genetic risk continue to converge on brain development, particularly stages of early brain development, that may be perturbed to deviate from a typical, normative course, resulting in schizophrenia clinical symptomatology. As the authors explicate, schizophrenia genetic risk is likely dynamic and context dependent, with effects of genetic risk varying spatiotemporally, across the neurodevelopmental continuum. Optimizing therapeutic strategies for the heterogeneous collective of individuals with schizophrenia may likely be guided by leveraging markers of genetic risk and derivative functional insights, well before the emergence of psychosis. Ultimately, rather than a focus on therapeutic intervention during adolescence or adulthood, principles of prediction and prophylaxis in the pre- and perinatal and neonatal stages may best comport with the biology of schizophrenia to address the early-stage perturbations that alter the normative neurodevelopmental trajectory.

Nrg1 intracellular signaling regulates the development of interhemispheric callosal axons in mice.

Schizophrenia is associated with altered cortical circuitry. Although the schizophrenia risk gene NRG1 is known to affect the wiring of inhibitory interneurons, its role in excitatory neurons and axonal development is unclear. Here, we investigated the role of Nrg1 in the development of the corpus callosum, the major interhemispheric connection formed by cortical excitatory neurons. We found that deletion of Nrg1 impaired callosal axon development in vivo. Experiments in vitro and in vivo demonstrated that Nrg1 is cell-autonomously required for axonal outgrowth and that intracellular signaling of Nrg1 is sufficient to promote axonal development in cortical neurons and specifically in callosal axons. Furthermore, our data suggest that Nrg1 signaling regulates the expression of Growth Associated Protein 43, a key regulator of axonal growth. In conclusion, our study demonstrates that NRG1 is involved in the formation of interhemispheric callosal connections and provides a novel perspective on the relevance of NRG1 in excitatory neurons and in the etiology of schizophrenia.

Multimorbidity and the Etiology of Schizophrenia.

PURPOSE OF REVIEW: A global study of multimorbidity in schizophrenia, especially of the association with physical conditions, might offer much needed etiological insights. RECENT FINDINGS: Our review suggests that life-style factors and medication related to schizophrenia are only part of the explanation of the increase in risk for cardiovascular, metabolic, pulmonary disorders, and some cancers. Positive associations with autoimmune disorders (with the exception of rheumatoid arthritis) and epilepsy are promising avenues of research but to date have not been fully exploited. The same holds for the negative comorbidity seen for rheumatoid arthritis and some cancers (e.g., prostate). As a whole, our review suggests that most of the explored conditions have a different prevalence in schizophrenia than in the general population. Several hypotheses emerged from this review such as the role of immune and genetic factors, of sex hormones, and of more general variability factors.

The Role of Innate and Adaptive Immune System in the Pathogenesis of Schizophrenia.

Schizophrenia is one of the most severely debilitating mental disorders that affects 1.1% of the world's population. The exact cause of the disease is not known, but genetics, environmental factors (such as infectious agents, season and region of birth, exposure to viruses, low birth weight, advanced paternal age, and tobacco), and immune system dysfunction can all contribute to the development of schizophrenia. Recently, the role of the immune system in schizophrenia has received much attention. Both acquired and innate immune systems are involved in the pathogenesis of schizophrenia and facilitate the disease's progression. Almost all cells of the immune system including microglia, B cells, and T cells play an important role in the blood-brain barrier damage, inflammation, and in the progression of this disease. In schizophrenia, the integrity of the blood-brain barrier is reduced and then the immune cells are recruited into the endothelium following an increase in the expression of cell adhesion molecules. The entry of immune cells and cytokines leads to inflammation and antibody production in the brain. Accordingly, the results of this study strengthen the hypothesis that the innate and acquired immune systems are involved in the pathogenesis of schizophrenia.

Urbanization and psychosis: an update of recent evidence.

PURPOSE OF REVIEW: Urbanization, a complex global phenomenon, has a significant bearing on schizophrenia/psychosis burden through various socioeconomic and environmental factors. This review focuses on recent evidence (2019-2023) linking urbanization, schizophrenia, and the role of green space. RECENT FINDINGS: This review analyzed 43 articles that examined the correlation between urban birth or upbringing, urban living (urbanicity), and various schizophrenia/psychosis-related outcomes such as incidence, psychotic experiences, etc. The studies showed differing results across geographical locations. Socioeconomic factors like area deprivation, migrant status (ethnic density) and social fragmentation were independently associated with the risk of schizophrenia/psychosis irrespective of urbanicity. More recently, environmental factors such as green space reduction and air pollution have been explored in urban living conditions and were positively associated with an increased risk of schizophrenia/psychosis. SUMMARY: There is a need for further investigation in low and middle-income countries. The impact of urbanization-related factors and green space on the risk of schizophrenia/psychosis calls for appropriate governmental commitments toward structured and healthy urban planning.

Cell adhesion molecules in the pathogenesis of the schizophrenia.

The causes of schizophrenia remain obscure and complex to identify. Alterations in dopaminergic and serotonergic neurotransmission are, to date, the primary pharmacological targets in treatment. Underlying abnormalities in neural networks have been identified as cell adhesion molecules (CAMs) involved in synaptic remodeling and interplay between neurons-neurons and neurons-glial cells. Among the CAMs, several families have been identified, such as integrins, selectins, cadherins, immunoglobulins, nectins, and the neuroligin-neurexin complex. In this paper, cell adhesion molecules involved in the pathogenesis of schizophrenia will be described.

Managing drug-induced psychosis.

Substance-induced psychosis is a secondary psychotic disorder resulting from drug abuse, characterized by one or more psychotic episodes. Drug-induced psychosis is expected to resolve after a 30-day period of sobriety, however, individuals with this condition are more likely to develop severe drug addiction. Compared to primary psychosis, participants with drug-induced psychosis exhibit poorer family history of psychotic diseases, higher insight, fewer positive and negative symptoms, more depressive symptoms, and greater anxiety. Substance-induced psychosis is strongly associated with the emergence of bipolar illness or schizophrenia spectrum disorder, with an increased chance of developing schizophrenia at a younger age. Episodes of self-harm after substance-induced psychosis are strongly linked to an elevated likelihood of developing schizophrenia or bipolar disorder. Effective treatment involves ruling out emergencies, investigating underlying causes, and addressing acute intoxication and withdrawal. Management includes dynamic assessment, intervention, and vigilant monitoring in cases of suicidal behaviour. Antipsychotics may be used for short term, with gradual discontinuation when a person is in a stable condition. Relapse prevention strategies, both medication and non-medication-based, are crucial in long-term management. Conversion rates to schizophrenia or bipolar disorder can be as high as one in three individuals, with cannabis users and those with early-onset substance abuse at the highest risk.

Neurobiological associations between smoking and internalizing disorders.

People with severe mental disorders have a higher mortality rate due to preventable conditions like cardiovascular diseases and respiratory diseases. Nicotine addiction is a preventable risk factor, with tobacco use being twice as high in people with mental disorders. An integrative model that divides mental disorders into externalising, internalising, and thought disorders could be useful for identifying common causalities and risk factors. This review aims to examine the interface between smoking and internalising disorders, specifically schizophrenia, depressive disorders, and anxiety disorders. The review finds that there is a clear association between smoking behaviour and these disorders. Schizophrenia is associated with polymorphisms that result in an imbalance between glutamate and GABA release and abnormalities of dopaminergic pathways. Nicotine improves dopaminergic signalling and balances glutamatergic and GABAergic pathways, improving symptoms and increasing the risk of nicotine dependence. In depressive disorders, smoking is associated with functional changes in brain regions affected by smoking and self-medication. In anxiety disorders, there is a bidirectional relationship with smoking, involving the amygdala and changes in dopaminergic pathways and cortisol production. Smoking poses a threat to people living with psychiatric disorders and calls for further research to assess the interactions between nicotine dependence and internalising and thought disorders.

Perda significativa de peso em pacientes com esquizofrenia na dieta hipocalórica de longo prazo: estudo piloto / Significant weight loss in patients with schizophrenia in long-term hypocaloric diet: a pilot study

Objetivo: A esquizofrenia está associada ao aumento da obesidade e morbidade por doença cardiovascular. O objetivo do presente estudo foi avaliar alterações no peso e índice de massa corporal (IMC) de pacientes com esquizofrenia após tratamento nutricional de longo prazo. Método: Estudo piloto retrospectivo envolvendo 42 indivíduos com esquizofrenia em tratamento nutricional entre 2004 e 2010. Os prontuários médicos foram revisados após aprovação institucional e coleta de dados para peso, índice de massa corporal (IMC), idade, gênero e dieta. O peso e o IMC foram avaliados no início do tratamento nutricional, após seis meses, após 12 meses e no momento da coleta de dados. Resultados: Houve perda significativa de peso e diminuição significativa do IMC quando comparados a cada grupo com o valor basal (p<0,001). Conclusões: Demonstramos que as intervenções nutricionais podem promover uma significativa perda de peso na esquizofrenia. Estes resultados suportam a importância da intervenção nutricional na esquizofrenia e trazem evidências de que a perda de peso permanece ao longo do tempo.(AU)

Objective: Schizophrenia is associated with increased obesity and morbidity from cardiovascular disease. The aim of the present study was to evaluate changes in weight and body mass index (BMI) of patients with schizophrenia following a long-term nutritional treatment. Methods: Retrospective pilot study involving 42 individuals with schizophrenia on nutritional treatment from 2004 to 2010. Medical charts were reviewed after institutional approval and data collection was conducted for weight, body mass index (BMI), age, gender and diet prescription. Weight and BMI were evaluated at baseline of nutrition treatment, after six months, after 12 months and at the time of data collection. Results: There was a significant weight loss and significant decreased in BMI when compared each group to baseline (p<0.001). Conclusions: We demonstrate that nutritional interventions can promote a significant weight loss in schizophrenia. These results support the importance of nutritional intervention in schizophrenia and bring evidences that weight loss remains along the time.(AU)

Schizophrenia and reelin: a model based on prenatal stress to study epigenetics, brain development and behavior

Schizophrenia is a severe psychiatric disorder that results in a significant disability for the patient. The disorder is characterized by impairment of the adaptive orchestration of actions, a cognitive function that is mainly dependent on the prefrontal cortex. This behavioral deficit, together with cellular and neurophysiological alterations in the prefrontal cortex, as well as reduced density of GABAergic cells and aberrant oscillatory activity, all indicate structural and functional deficits of the prefrontal cortex in schizophrenia. Among the several risk factors for the development of schizophrenia, stress during the prenatal period has been identified as crucial. Thus, it is proposed that prenatal stress induces neurodevelopmental alterations in the prefrontal cortex that are expressed as cognitive impairment observed in schizophrenia. However, the precise mechanisms that link prenatal stress with the impairment of prefrontal cortex function is largely unknown. Reelin is an extracellular matrix protein involved in the development of cortical neural connectivity at embryonic stages, and in synaptic plasticity at postnatal stages. Interestingly, down-regulation of reelin expression has been associated with epigenetic changes in the reelin gene of the prefrontal cortex of schizophrenic patients. We recently showed that, similar to schizophrenic patients, prenatal stress induces down-expression of reelin associated with the methylation of its promoter in the rodent prefrontal cortex. These alterations were paralleled with altered prefrontal cortex functional connectivity and impairment in prefrontal cortex-dependent behavioral tasks. Therefore, considering molecular, cellular, physiological and behavioral evidence, we propose a unifying framework that links prenatal stress and prefrontal malfunction through epigenetic alterations of the reelin gene.

Comparative analysis of non-adherence to medication treatment for systemic arterial hypertension in urban and rural populations / Análise comparativa da não adesão ao tratamento medicamentoso da hipertensão arterial sistêmica em população urbana e rural / Análisis comparativa de la no adhesión al tratamiento medicamentoso de la hipertensión arterial sistémica en población urbana y rural

OBJECTIVE: to evaluate the indexes and the main factors associated with non-adherence to medication treatment for systemic arterial hypertension between urban and rural areas. METHOD: analytical study based on an epidemiological survey with a sample of 247 hypertensive residents of rural and urban areas, with application of a socio-demographic and economic questionnaire, and treatment adherence assessment. The Pearson's Chi-square test was used and the odds ratio (OD) was calculated to analyze the factors related to non-adherence. RESULTS: the prevalence of non-adherence was 61.9% and it was higher in urban areas (63.4%). Factors significantly associated with non-adherence were: male gender (OR=1.95; 95% CI 1.08-3.50), age 20-59 years old (OR=2.51; 95% CI 1.44-4.39), low economic status (OR=1.95; 95% CI 1.09-3.47), alcohol consumption (OR=5.92, 95% CI 1.73-20.21), short time of hypertension diagnosis (OR=3.07; 95% CI 1.35-6.96) and not attending the health service for routine consultations (OR=2.45; 1.35-4.42). CONCLUSION: the socio-demographic/economic characteristics, lifestyle habits and how to relate to health services were the factors that presented association with non-adherence regardless of the place of residence. .

OBJETIVO: avaliar os índices e os principais fatores associados a não adesão ao tratamento medicamentoso da hipertensão arterial sistêmica, entre área urbana e rural. MÉTODO: estudo analítico baseado em inquérito epidemiológico, realizado com amostra de 247 hipertensos moradores das áreas rural e urbana, com aplicação de questionário sociodemográfico, econômico e avaliação da adesão. Foi utilizado o teste quiquadrado de Pearson e calculado o Odds Ratio (OD) para análise dos fatores relacionados a não adesão. RESULTADOS: a prevalência da não adesão foi de 61,9%, sendo maior na área urbana (63,4%). Os fatores que apresentaram associação estatisticamente significativa com a não adesão foram: gênero masculino (OR=1,95; IC95% 1,08-3,50), faixa etária entre 20 e 59 anos (OR=2,51; IC95% 1,44-4,39), baixa classe econômica (OR=1,95; IC95% 1,09-3,47), etilismo (OR=5,92; IC 95% 1,73-20,21), tempo curto de diagnóstico de hipertensão (OR=3,07; IC95% 1,35-6,96) e não procura pelo serviço de saúde para consultas de rotina (OR=2,45; 1,35-4,42). CONCLUSÃO: as características sociodemográficas, econômicas, hábitos de vida e o modo de relacionar-se com os serviços de saúde foram os fatores que apresentaram associação com a não adesão, independentemente do local de residência. .

OBJETIVO: evaluar los índices y los principales factores asociados a la no adhesión al tratamiento medicamentoso de la hipertensión arterial sistémica entre área urbana y rural. MÉTODO: estudio analítico basado en investigación epidemiológica desarrollada con una muestra de 247 hipertensos moradores del área rural y urbana, con aplicación de un cuestionario sociodemográfico, económico y evaluación de la adhesión. Fue utilizado la prueba chi-cuadrado de Pearson y calculado el odds ratio (OD) para análisis de los factores relacionados a la no adhesión. RESULTADOS: la prevalencia de la no adhesión correspondió a 61,9%, siendo mayor en el área urbana (63,4%). Los factores que mostraron asociación estadísticamente significativa con la no adhesión fueron: género masculino (OR=1,95; IC95% 1,08-3,50), rango de edad entre 20 a 59 años (OR=2,51; IC95% 1,44-4,39), clase económica baja (OR=1,95; IC95% 1,09-3,47), etilismo (OR=5,92; IC 95% 1,73-20,21), tiempo corto de diagnóstico de hipertensión (OR=3,07; IC95% 1,35-6,96) y no procurar el servicio de salud para consultas de rutina (OR=2,45; 1,35-4,42). CONCLUSIÓN: las características sociodemográficas/económicas, hábitos de vida y el modo de relacionar con los servicios de salud fueron los factores que mostraron asociación con la no adhesión independientemente del local de residencia. .

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure

Impaired temporal control is symptomatic of several neurological disorders; recently, it has been implicated in schizophrenia. An animal model of schizophrenia using 6-hydroxydopamine (6-OHDA) infused to the medial pre-frontal cortex (mPFC) was employed to examine its effects on temporal control. Twelve rats were trained on a peak-interval procedure (PIP) until stable patterns of behavior were obtained. Rats infused with 6-OHDA responded less during peak trials and their peak functions were flatter than sham rats. These results are consistent with similar studies with transgenic mice with increased striatal dopamine D2 receptor activity. Lesions in the mPFC decreased motivation to respond in a PIP. These effects may be considered analogous to negative symptoms of schizophrenia.(AU)

6-Hydroxydopamine lesions in the medial prefrontal cortex of rats exposed to a peak-interval procedure

Impaired temporal control is symptomatic of several neurological disorders; recently, it has been implicated in schizophrenia. An animal model of schizophrenia using 6-hydroxydopamine (6-OHDA) infused to the medial pre-frontal cortex (mPFC) was employed to examine its effects on temporal control. Twelve rats were trained on a peak-interval procedure (PIP) until stable patterns of behavior were obtained. Rats infused with 6-OHDA responded less during peak trials and their peak functions were flatter than sham rats. These results are consistent with similar studies with transgenic mice with increased striatal dopamine D2 receptor activity. Lesions in the mPFC decreased motivation to respond in a PIP. These effects may be considered analogous to negative symptoms of schizophrenia...

Sinaptogénesis y esquizofrenia: rol de la proteína DISC 1 / Synaptogenesis and Schizophrenia: The role of DISC 1 protein

El presente trabajo aporta información respecto del posible rol en la esquizofrenia del gen DISC 1 y la proteína que este gen codifica. Se realiza un recorrido desde el hallazgo de la translocación cromosómica que llevó a su descubrimiento, hasta la perspectiva actual, que lo conceptualiza como un modulador funcional complejo. La mencionada translocación fue originariamente identificada en una familia escocesa, y se observó que cosegregaba con esquizofrenia y otros trastornos mentales. Actualmente, se considera a DISC 1 como una proteína central dentro de una red de interacciones con otras proteínas - lo que en varios trabajos se denomina interactoma -, tales como NDEL 1, LIS 1 y PDE 4B, entre otras.

This paper provides information regarding the possible role in schizophrenia of the DISC 1 gene and the protein it encodes. It is a tour from the discovery of the chromosomal translocation that led to its discovery, up to the current perspective, which is conceptualized as a complex functional modulator. The above translocation was originally identified in a Scottish family, and it was noted that it cosegregated with schizophrenia and other mental discorders. Currently, DISC 1 is considered as a central protein within its network of protein interactions (named as interactome in several papers), such as NDEL 1, LIS 1 and PDE 4B, among others.

Esquizofrenia en niños y adolescentes / Schizophrenia in children and adolescents

La población infantil y adolescente es considerada, junto con los ancianos y embarazadas, vulnerable por representar un sistema fisiológico que dista del adulto promedio para el cual están basadas la mayoría de prácticas terapéuticas. La esquizofrenia tiene una especial importancia en este grupo ya que es considerada una enfermedad del neurodesarrollo. Para poder instaurar un tratamiento adecuado resulta capital conocer los procesos y circuitos neurobilógicos que constituyen la base de la patología. Las hipótesis mejor estudiadas son la dopaminérgica, de la cual deriva el arsenal farmacológico actual, y la hipoglutamatérgica. Esta última invita al desarrollo de nuevas moléculas con potencial antipsicótico pero que no posean blancos terapéuticos dopaminérgicos. Hasta hoy, no existe un fármaco comercializado que actúe sobre las vías glutamatérgicas para tratar la esquizofrenia pero sí existen varios ejemplos en ensayos clínicos de fases I y II. También es necesario establecer las pautas de dosificación para los grupos vulnerables las cuales derivan, en su mayoría, de las establecidas para adultos.

The population of children and adolescents is considered, along with the elderly and pregnant women, vulnerable, for representing a physiological system that is far from the average adult, for whom most therapeutic practices are based on. Schizophrenia has special relevance within this group, since it is considered a neurodevelopmental disorder. In order to establish an adquate treatment, it is key to know the processes and neurobiological circuits which form the basis of this disease. The best studied hypotheses are the dopaminergic hypothesis, from which the current pharmacological studies derive, and the hypoglutamatergic hypothesis. The latter proposes the development of new molecules with antipsychotic potential, which do not have dopaminergic therapeutic targets. Up to now, there is no marketed drug which acts on glutamatergic pathways to treat schizophrenia, although several examples can be found in phase I and II clinical trials. It is also necessary to establish dosing guidelines for vulnerable groups, most of which result from the ones established for adults.