Hyperactivity schizophrenia
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Hyperactivity in Schizophrenia: Neural and Behavioral Insights
Default Mode Network Hyperactivity in Schizophrenia
Research has shown that individuals with schizophrenia exhibit hyperactivity and hyperconnectivity within the default mode network (DMN), particularly in the medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. This hyperactivity is evident during both rest and task performance, where patients and their first-degree relatives show reduced task-related suppression in these regions compared to controls. This reduced suppression correlates with poorer working memory performance and greater psychopathology1. Additionally, patients demonstrate abnormal functional connectivity within the DMN, which is associated with the severity of their symptoms1.
Hypofrontality and Posterior Hyperactivity
In early schizophrenia, there is a notable pattern of hypofrontality (reduced activity in the frontal cortex) and posterior hyperactivity (increased activity in the visual cortex). This has been observed in preclinical models, where rats with induced schizophrenia-like symptoms showed lower connectivity and neuronal activity in the orbitofrontal cortex, but higher activity in the visual cortex. These changes are linked to cognitive deficits and abnormal decision-making processes, which may parallel the perceptual and cognitive disturbances seen in schizophrenia2.
Impulsivity in Schizophrenia and ADHD
Both schizophrenia and attention-deficit/hyperactivity disorder (ADHD) share clinical features such as cognitive impairments and impulsivity. Adolescents with early-onset schizophrenia spectrum disorders (EOS) and ADHD exhibit increased motor, attentional, and non-planning impulsivity. However, while ADHD patients show significant reflection impulsivity, this is not as pronounced in EOS patients. These shared impulsivity traits suggest overlapping neurodevelopmental impairments between the two disorders3.
HPA Axis Hyperactivity
Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis is another feature observed in schizophrenia. Studies using animal models have shown that prenatal exposure to stressors like lipopolysaccharide (LPS) leads to elevated corticosterone levels and alterations in glucocorticoid receptor concentrations in the hippocampus and frontal cortex. These changes are associated with schizophrenia-like behaviors, such as deficits in prepulse inhibition and increased locomotor activity. Antipsychotic drugs like clozapine can reverse many of these alterations, highlighting the role of HPA axis dysregulation in the pathogenesis of schizophrenia4.
Neuropsychological Deficits
Adolescents with schizophrenia exhibit more pronounced deficits in abstraction, visual memory, and motor function compared to those with ADHD. Conversely, ADHD patients show greater impairments in attention, verbal memory, and learning. This suggests that while schizophrenia involves a more generalized brain dysfunction, ADHD is characterized by specific frontal lobe-related deficits5.
Hippocampal Hyperactivity
The hippocampus, particularly the anterior region, is hyperactive in schizophrenia. This hyperactivity is linked to reduced task-related recruitment during cognitive tasks, such as scene processing. Increased baseline activity in the anterior hippocampus correlates with decreased task-related activation, suggesting that hyperactivity in this region impairs its functional engagement during cognitive tasks. This finding underscores the anterior hippocampus as a potential therapeutic target for cognitive deficits in schizophrenia8.
Hyperactive Associative Processes
Hyperactive associative processes are thought to underlie many symptoms of psychosis, including those seen in schizophrenia. This hyperactivity can lead to disordered thought processes and heightened anxiety due to the ambiguity of mental images. The interplay between high anxiety and hyperactive associations may contribute to the variability in response to treatment and the persistence of positive symptoms in schizophrenia9.
Genetic Overlap with ADHD and Autism
Schizophrenia shares genetic risk factors with ADHD and autism spectrum disorder (ASD). Certain copy number variations (CNVs) associated with neurodevelopmental disorders are also found in individuals with ADHD, suggesting a pleiotropic effect. This genetic overlap supports the notion that these disorders are related rather than distinct entities, with shared underlying neurodevelopmental mechanisms10.
Conclusion
Hyperactivity in various brain regions and systems is a hallmark of schizophrenia, contributing to its complex symptomatology. From the default mode network to the hippocampus and HPA axis, these hyperactive processes are linked to cognitive deficits, impulsivity, and other clinical features. Understanding these mechanisms provides valuable insights into potential therapeutic targets and the shared neurodevelopmental pathways with related disorders like ADHD and ASD.
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Most relevant research papers on this topic
Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia
Hyperactivation and hyperconnectivity of the default network contribute to disturbed thought in schizophrenia and risk for the illness in first-degree relatives.
Observational Study
Highly CitedHypofrontality and Posterior Hyperactivity in Early Schizophrenia: Imaging and Behavior in a Preclinical Model
Two novel biomarkers, hypofrontality and posterior hyperactivity, were identified in a preclinical rat model of schizophrenia, which could contribute to early diagnosis and the development of novel therapies.
Non-RCT
Animal Study
Very Rigorous JournalOverlapping and disease specific trait, response, and reflection impulsivity in adolescents with first-episode schizophrenia spectrum disorders or attention-deficit/hyperactivity disorder
ADHD and first-episode schizophrenia spectrum disorders share increased personality subtraits of attentional, non-planning, and motor impulsivity, with ADHD showing more pronounced motor impulsivity.
Observational StudyVery Rigorous JournalHyperactivity of the hypothalamus-pituitary-adrenal axis in lipopolysaccharide-induced neurodevelopmental model of schizophrenia in rats: effects of antipsychotic drugs.
Schizophrenia is linked to hypothalamic-pituitary-adrenal hyperactivity, with a decrease in hippocampal glucocorticoid receptor levels and a decrease in FKBP51 in the frontal cortex.
Non-RCTAnimal Study
Rigorous JournalNeuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder.
Adolescent-onset schizophrenia shows more general brain dysfunction, while ADHD impairments are more specific to frontal lobe function.
Observational StudyHighly CitedGABAergic mechanisms of hippocampal hyperactivity in schizophrenia
GABAergic abnormalities in the hippocampus contribute to hippocampal hyperactivity in schizophrenia, which may explain cognitive deficits and psychotic symptoms.
Highly CitedLeft striato-pallidal hyperactivity in schizophrenia. Part II: Phenomenology and thought disorder.
Left striato-pallidal hyperactivity in schizophrenia may contribute to cognitive and phenomenological aspects of the disorder by affecting higher functions like language and thought control.
Highly CitedHyperactivity and Reduced Activation of Anterior Hippocampus in Early Psychosis.
Anterior hippocampal hyperactivity in early psychosis patients limits effective recruitment of this region during task performance, suggesting it as a potential therapeutic target for cognitive deficits.
Non-RCTHighly CitedHyperactivity of Associations in Psychosis
Hyperactive associations of thought underlie many of the symptoms of psychosis, including Schneiderian symptoms, high anxiety levels, and the variability in response to neuroleptic treatment.
Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder
ADHD shares high risk CNV alleles with schizophrenia and autism spectrum disorder, highlighting their relationship as related neurodevelopmental disorders rather than distinct entities.
Observational StudyVery Rigorous JournalHighly Cited