Schizophrenia - the restructuring of the brain and outcomes

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

The volumes of the corpus callosum, thalamus, hippocampal formation, subiculum, parahippocampal gyrus, superior temporal gyrus, prefrontal and orbitofrontal cortices and amygdala-hippocampal complex are reduced in schizophrenics (1-4) (see Page 3, Fig 3 for normal brain structure) possibly leading to psychopathy which was given 20 characteristics by Hare (5).

 

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

Disruption of large scale networks (3) (6-8) (e.g. the default mode network) between prefrontal cortex and other parts of the limbic system (7) (see Page 3, Fig 3 for the limbic system) affects memory and short-term memory (3) leads to hallucinations (9) and cognitive dysmetria (10) ( difficulty in prioritizing, processing, coordinating, and responding to information) in schizophrenia. Intellect deteriorates as grey matter mass (cerebral cortex) declines (11-14) . One symptom is a lack of comprehension of metaphors resulting in a literal interpretation (15) . People with schizophrenia are also known to lack empathy (16) and other social cognitive areas such as social perception, emotion processing and perception and theory of mind (17) . Social cognition was found to be more strongly associated with community functioning than neurocognition (18) . Decreased social cognition was also found to be associated with increased symptoms of schizophrenia (19) .

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 (20-23).

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) (24, 25) , cerebellum (affecting basic movements etc.) (27) , auditory cortex (28),hippocampus (29) amongst other things including connectivity.

 

References

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

2. Mohammadi A, Rashidi E, Amooeian VG. Brain, blood, cerebrospinal fluid, and serum biomarkers in schizophrenia. Psychiatry Res 2018;265:25-38. doi: 10.1016/j.psychres.2018.04.036 [published Online First: 2018/04/24]

3. Karlsgodt KH, Sun D, Cannon TD. Structural and Functional Brain Abnormalities in Schizophrenia. Current directions in psychological science 2010;19(4):226-31. doi: 10.1177/0963721410377601

4. Gaser C, Volz H-P, Kiebel S, et al. Detecting Structural Changes in Whole Brain Based on Nonlinear Deformations—Application to Schizophrenia Research. NeuroImage 1999;10(2):107-13. doi: http://dx.doi.org/10.1006/nimg.1999.0458

5. Hare RD. Manual for the Revised Psychopathy Checklist (2nd ed.). Toronto, Canada: Multi-Health Systems 2003.

6. Haatveit B, Jensen J, Alnæs D, et al. Reduced load-dependent default mode network deactivation across executive tasks in schizophrenia spectrum disorders. NeuroImage: Clinical 2016;12(Supplement C):389-96. doi: https://doi.org/10.1016/j.nicl.2016.08.012

7. Zemankova MP, Losak DJ, Czekoova DK, et al. Theory of mind skills are related to resting-state fronto-limbic connectivity in schizophrenia. Brain connectivity;0(ja):null. doi: 10.1089/brain.2017.0563

8. Jiang Y, Luo C, Li X, et al. White-matter functional networks changes in patients with schizophrenia. Neuroimage 2018 doi: 10.1016/j.neuroimage.2018.04.018 [published Online First: 2018/04/17]

9. van Lutterveld R, Diederen KM, Otte WM, et al. Network analysis of auditory hallucinations in nonpsychotic individuals. Human brain mapping 2014;35(4):1436-45. doi: 10.1002/hbm.22264 [published Online First: 2013/02/22]

10. Wang L, Zou F, Shao Y, et al. Disruptive changes of cerebellar functional connectivity with the default mode network in schizophrenia. Schizophr Res 2014;160(1-3):67-72. doi: 10.1016/j.schres.2014.09.034 [published Online First: 2014/12/03]

11. Dedic N, Pohlmann ML, Richter JS, et al. Cross-disorder risk gene CACNA1C differentially modulates susceptibility to psychiatric disorders during development and adulthood. Mol Psychiatry 2017 doi: 10.1038/mp.2017.133

12. Hochberger WC, Combs T, Reilly JL, et al. Deviation from expected cognitive ability across psychotic disorders. Schizophrenia Research doi: 10.1016/j.schres.2017.05.019

13. Ammari N, Heinrichs RW, Pinnock F, et al. Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia. Neuropsychology 2014;28(3):353-8. doi: 10.1037/neu0000026 [published Online First: 2014/03/19]

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15. Rossetti I, Brambilla P, Papagno C. Metaphor Comprehension in Schizophrenic Patients. Frontiers in Psychology 2018;9:670. doi: 10.3389/fpsyg.2018.00670

16. Bonfils KA, Lysaker PH, Minor KS, et al. Affective empathy in schizophrenia: a meta-analysis. Schizophr Res 2016;175(1-3):109-17. doi: 10.1016/j.schres.2016.03.037 [published Online First: 2016/04/21]

17. Savla GN, Vella L, Armstrong CC, et al. Deficits in domains of social cognition in schizophrenia: a meta-analysis of the empirical evidence. Schizophr Bull 2013;39(5):979-92. doi: 10.1093/schbul/sbs080 [published Online First: 2012/09/06]

18. Fett AK, Viechtbauer W, Dominguez MD, et al. The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 2011;35(3):573-88. doi: 10.1016/j.neubiorev.2010.07.001 [published Online First: 2010/07/14]

19. Ventura J, Wood RC, Hellemann GS. Symptom domains and neurocognitive functioning can help differentiate social cognitive processes in schizophrenia: a meta-analysis. Schizophr Bull 2013;39(1):102-11. doi: 10.1093/schbul/sbr067 [published Online First: 2011/07/19]

20. Szepesi Z, Manouchehrian O, Bachiller S, et al. Bidirectional Microglia-Neuron Communication in Health and Disease. Front Cell Neurosci 2018;12:323. doi: 10.3389/fncel.2018.00323 [published Online First: 2018/10/16]

21. Belarbi K, Arellano C, Ferguson R, et al. Chronic neuroinflammation impacts the recruitment of adult-born neurons into behaviorally relevant hippocampal networks. Brain, Behavior, and Immunity 2012;26(1):18-23. doi: http://dx.doi.org/10.1016/j.bbi.2011.07.225

22. Cheray M, Joseph B. Epigenetics Control Microglia Plasticity. Front Cell Neurosci 2018;12:243. doi: 10.3389/fncel.2018.00243 [published Online First: 2018/08/21]

23. Sominsky L, De Luca S, Spencer SJ. Microglia: Key players in neurodevelopment and neuronal plasticity. Int J Biochem Cell Biol 2018;94:56-60. doi: 10.1016/j.biocel.2017.11.012 [published Online First: 2017/12/05]

24. Ordóñez AE, Luscher ZI, Gogtay N. Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings. Schizophr Res 2016;173(3):124-31. doi: 10.1016/j.schres.2015.03.003 [published Online First: 2015/03/31]

25. Rapoport JL, Gogtay N. Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder. Int J Dev Neurosci 2011;29(3):251-8. doi: 10.1016/j.ijdevneu.2010.10.003 [published Online First: 2010/10/20]

26. Thompson PM, Vidal C, Giedd JN, et al. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A 2001;98(20):11650-5. doi: 10.1073/pnas.201243998 [published Online First: 2001/09/27]

27. Schmitt A, Falkai P, Papiol S. Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors. J Neural Transm (Vienna) 2023;130(3):195-205. doi: 10.1007/s00702-022-02567-5 [published Online First: 2022/11/13]