Schizophrenia, a severe psychiatric, neurodevelopmental disorder affecting about 0.29-1 % of the global population, is characterized by hallucinations, delusions, cognitive impairments, disorganized thoughts and speech, leading to significant social withdrawal and emotional blunting. During the 1980s, considerations about diseases that result from complex interactions of genetic background and environmental factors started to appear. One of the critical times of vulnerability is the perinatal period. Concerning schizophrenia, obstetric complications that are associated with hypoxia of the fetus or neonate were identified as a risk. Also, maternal infections during pregnancy were linked to schizophrenia by epidemiological, serologic and genetic studies. Research efforts then led to the development of experimental models testing the impact of perinatal hypoxia or maternal immune activation on neurodevelopmental disorders. These perinatal factors are usually studied separately, but given that the models are now validated, it is feasible to investigate both factors together. Inclusion of additional factors, such as metabolic disturbances or chronic stress, may need to be considered also. Understanding the interplay of perinatal factors in schizophrenia's etiology is crucial for developing targeted prevention and therapeutic strategies.

• MeSH
• COVID-19 * imunologie   epidemiologie   MeSH
• hypoxie plodu imunologie   komplikace   MeSH
• hypoxie komplikace   imunologie   MeSH
• imunitní systém imunologie   MeSH
• infekční komplikace v těhotenství imunologie   MeSH
• lidé MeSH
• novorozenec MeSH
• schizofrenie * imunologie   epidemiologie   etiologie   MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Atypical antipsychotics have greatly enhanced the treatment of schizophrenia. The mechanisms underlying the effectiveness and adverse effects of these drugs are, to date, not sufficiently explained. This article summarises the hypothetical mechanisms of action of atypical antipsychotics with respect to the neurobiology of schizophrenia.When considering treatment models for schizophrenia, the role of dopamine receptor blockade and modulation remains dominant. The optimal occupancy of dopamine D(2) receptors seems to be crucial to balancing efficacy and adverse effects - transient D(2) receptor antagonism (such as that attained with, for example, quetiapine and clozapine) is sufficient to obtain an antipsychotic effect, while permanent D(2) receptor antagonism (as is caused by conventional antipsychotics) increases the risk of adverse effects such as extrapyramidal symptoms. Partial D(2) receptor agonism (induced by aripiprazole) offers the possibility of maintaining optimal blockade and function of D(2) receptors. Balancing presynaptic and postsynaptic D(2) receptor antagonism (e.g. induced by amisulpride) is another mechanism that can, through increased release of endogenous dopamine in the striatum, protect against excessive blockade of D(2) receptors. Serotonergic modulation is associated with a beneficial increase in striatal dopamine release. Effects on the negative and cognitive symptoms of schizophrenia relate to dopamine release in the prefrontal cortex; this can be modulated by combined D(2) and serotonin 5-HT(2A) receptor antagonism (e.g. by olanzapine and risperidone), partial D(2) receptor antagonism or the preferential blockade of inhibitory dopamine autoreceptors. In the context of the neurodevelopmental disconnection hypothesis of schizophrenia, atypical antipsychotics (in contrast to conventional antipsychotics) induce neuronal plasticity and synaptic remodelling, not only in the striatum but also in other brain areas such as the prefrontal cortex and hippocampus. This mechanism may normalise glutamatergic dysfunction and structural abnormalities and affect the core pathophysiological substrates for schizophrenia.

• MeSH
• antipsychotika klasifikace   terapeutické užití   MeSH
• dopamin fyziologie   MeSH
• lidé MeSH
• neurobiologie * MeSH
• neuroplasticita účinky léků   MeSH
• schizofrenie farmakoterapie   metabolismus   patofyziologie   MeSH
• serotonin fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antipsychotika MeSH
• dopamin MeSH
• serotonin MeSH