Abstract

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia’s development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

Schizophrenia

Schizophrenia is a complex, heterogeneous psychiatric disorder influenced by both genetic and environmental factors, with a lifetime prevalence of approximately 1 % in the general population [1] . This condition manifests through a spectrum of symptoms: (i) positive symptoms such as delusions, hallucinations, paranoia, thought disorders, and psychomotor agitation; (ii) negative symptoms including emotional blunting, social withdrawal, and deficits in motivation and reward processing; (iii) cognitive impairment affecting learning, attention, executive function, and memory, particularly working memory [2] , [3] . Mood disturbances such as depression and anxiety are also common among patients.

The pathogenesis of schizophrenia is currently explained by several theories, the most notable being the dopaminergic hypothesis. This hypothesis proposes that positive symptoms arise from dysregulated dopaminergic neurotransmission in the limbic system of the midbrain, while disruptions in cortical pathways contribute to negative symptoms [4] . The glutamatergic hypothesis posits that changes in NMDA receptor-mediated glutamatergic transmission affect prefrontal neuronal connectivity [5] , and the serotonergic hypothesis attributes disturbances in neuronal activity to serotonin overload from the dorsal raphe nucleus serotonergic hypothesis suggests that stress causes overload of serotonin from the dorsal raphe nucleus [6] . The GABAergic hypothesis suggests that an imbalance between cortical excitation and inhibition, driven by disruptions in GABAergic neurotransmission, underlies the disorder [7] . Additionally, nicotinic receptors play a role in cholinergic transmission; studies have shown that nicotine can improve attention and memory performance in schizophrenic patients [8] . Cognitive dysfunction, a core feature observed in over 80 % of individuals with schizophrenics, involves multiple brain regions, including the dorsolateral and medial prefrontal cortices and the parietal regions [9] , [10] , [11] . Structural abnormalities in the medial temporal lobe, particularly the hippocampus, have been linked to memory deficits and play a significant role in the neural networks responsible for memory and spatial navigation [12] , [13] , [14] , [15] , [16] .