behavioural-epigenetics

Delisi et al. (2006) (1) is a review of structural changes to the schizophrenic brain (see image below).

Image above from: DeLisi LE, Szulc KU, Bertisch HC, et al. Understanding structural brain changes in schizophrenia. Dialogues in Clinical Neuroscience 2006;8(1):71-78

Twin studies

Twin studies have demonstated that monozygotic twins can deveklop differences in their brains when they have undergone different environmental treatments.

The image below shows transverse sections of the brains of discordant monozygotic twins. The scan of the healthy twin is on the left and the one on the right has schizophrenia. It shows the brain tissue has atrophied leaving enlarged ventricles due to brain damage. Please click on the image to see the research:

Neuroimaging in schizophrenia: what does it tell the clinician? J. Woolley and P. McGuireAdvances in Psychiatric Treatment 2005 Vol. 11 Issue 3 Pages 195-202

Disruption of large scale networks (3) (7-9) (e.g. the default mode network) between prefrontal cortex and other parts of the limbic system (8) (see Page 3, Fig 3 for the limbic system) affects memory and short-term memory (3) leads to hallucinations (10) and cognitive dysmetria (11) ( difficulty in prioritizing, processing, coordinating, and responding to information) in schizophrenia. Intellect deteriorates as grey matter mass (cerebral cortex) declines (12-15) . One symptom is a lack of comprehension of metaphors resulting in a literal interpretation (16) . People with schizophrenia are also known to lack empathy (17) and other social cognitive areas such as social perception, emotion processing and perception and theory of mind (18) . Social cognition was found to be more strongly associated with community functioning than neurocognition (19) . Decreased social cognition was also found to be associated with increased symptoms of schizophrenia (20) .

Damage to neurons which result in disruption to networks and structural change is brought about epigenetically through the contribution of microglia (small amoeboid cells) involved in neuronal and synaptic pruning and damage (21-24).

Childhood onset schizophrenia

The structure of the brain is more seriously affected in childhood onset schizophrenia. The parts of the brain most seriously affected are the cortex (leading to intellectual difficulties) (25, 26) , cerebellum (affecting basic movements etc.) (28), auditory cortex (29),hippocampus (30) amongst other things including connectivity.

Recent research looked in epigenetic modification of specific genes in specimens taken from the autopsies, social intereventions and scans of the brains of maltreated children. It found that certain genes were epigenetically changed specifically FOXP1 which modified brain structure following different types of maltreatement (31). Other research papers show structural brain changes caused by Child Sexual Abuse are linked to psychological conditions e.g. schizophrenia (32-34)

Microglia

The diagrams below are from: Szydlowska, K. 2026 Defining functional states and roles of microglia in neuropsychiatric disorders

Figure above: Microglia as critical mediators of neuroplasticity in affective disorders (6).

Schizoaffective disorder is a crossover of symptoms of schizophrenia and mood disorder. The diagram above shows the possible mechanisms invoved in schizophrenia.

Figure below: Mechanisms of aberrant microglial function in schizophrenia (6)

This diagram only takes account of genetic risks. Epigenetic risks as shown in the diagram above are shown to lead to schizophrenia. For example epigenetic alterations have been found in the genes of microglia and astrocytes (34) and in DNA methylation patterns (35) Epigenetic alteration of the BDNF (Brain-Derived Neurotrophic Factor) promotor (36).