Proposed ways in which abnormal behaviour can change brain pathways and structure leading to schizophrenia/psychopathy

The previous pages describe different aspects of schizophrenia and psychosis ranging from the mechanisms involved in how epigenetic modification happens to the structural and functional changes that take place in the brain. These changes together with changes in neurotransmitter symmetry are the outcomes of schizophrenia and psychosis.

This page deals with how the changes involved in schizophrenia and psychosis can happen through abnormal behaviour. Specifically, how this behaviour disrupts the connections and networks between different areas of the brain and results in structural changes.

 

Please click on the image above for a more detailed diagram and reference list

 

Here it is proposed that people override prefrontal cortex protective decision-making to enable abnormal behaviour such as child-abuse (1, 2) which is promoted by certain cult groups in Organised Ritual Abuse (ORA) (3) and can result in psychopathy/schizophrenia (3) . This is also known as child abuse linked to faith or belief (CALFB) and includes different practices including witchcraft (4) . The prefrontal cortex along with other areas atrophy (5) (possibly through lack of use) and the size of the ventricles increase (5, 6) as schizophrenia and psychosis develop. Decreased grey matter and amygdala volumes have been found in paedophiles who also demonstrate psychopathology (7) . Connectivity is reduced between cortical areas and other areas of the brain involved in different networks for instance the Default Mode network (DMN) (8) (9-13) including certain limbic areas (14, 15, 16, 17, 18) (see also on previous page). The lack of connectivity and cortical atrophy lead to “amygdala hijack” thus increased emotions.

The reward circuit is described in Lee et al. 2018 in their study into obesity (18) which is graphically illustrated in figure 1 of their paper (18) . Several circuits are implicated and involve the reward and saliency circuit (the VTA, Nucleus accumbens and the caudate); the orbitofrontal and subgenual cingulate cortex (motivation and drive functions) and learning and memory circuits (amygdala, hippocampus and putamen) (18) . Inhibitory control involves the prefrontal cortex and anterior cingulate cortex (18) . Normally, these circuits act together homeostatically (19) . The homeostatic function of the circuitry can be overridden by addiction of some kind for example over-eating or drug taking (19) which involves increased dopamine secretion (19) . It is then possible for negative feedback mechanisms to be overridden by positive feedback. This also happens in schizophrenia. Lisman et al. (20) describe a trigger for sudden-onset schizophrenia as being because of positive feedback in the VTA, thalamus, hippocampus circuit in response to types of stress. The researchers noted that stress may be caused by, for instance, drugs of abuse. The VTA then secretes more dopamine because of lack of inhibition. Dopamine increases the response to reward i.e. increased “wanting” (21) but also responds to stress (21) . Johnson et el. (21) describe a multi-circuit response in addiction. This theory combines documented theories of addiction which are a dopamine-based positive reinforcement model and a stressed based negative reinforcement model.

Here (illustrated in the figure) it is proposed that the overriding of the prefrontal cortex decision making and other mechanisms by abnormal behaviour result in the limbic system becoming dominant particularly the amygdala. The increase in emotions that are elicited instigate increased dopamine release and a cycle of addiction to the abnormal behaviour. This leads to the degenerative nature of schizophrenia i.e. disruption to networks, cortical atrophy, other brain area atrophy and increased ventricle size (5) . This relationship between cortical thickness and amygdalar reactivity was found in a population of adolescents where reduced cortical thickness was found to be related to increased amygdalar reactivity to different facial image expressions (22).

References

1. Kargel C, Massau C, Weiss S, et al. Diminished functional connectivity on the road to child sexual abuse in pedophilia. The journal of sexual medicine 2015;12(3):783-95. doi: 10.1111/jsm.12819 [published Online First: 2015/01/24]

2. Kneer J, Borchardt V, Kargel C, et al. Diminished fronto-limbic functional connectivity in child sexual offenders. J Psychiatr Res 2018 doi: 10.1016/j.jpsychires.2018.01.012 [published Online First: 2018/03/14]

3. Schroder J, Nick S, Richter-Appelt H, et al. Psychiatric Impact of Organized and Ritual Child Sexual Abuse: Cross-Sectional Findings from Individuals Who Report Being Victimized. International journal of environmental research and public health 2018;15(11) doi: 10.3390/ijerph15112417 [published Online First: 2018/11/06]

4. Oakley L, Kinmond K, Humphreys J, et al. Practitioner and communities' awareness of CALFB: Child abuse linked to faith or belief. Child Abuse Negl 2017;72:276-82. doi: 10.1016/j.chiabu.2017.08.024 [published Online First: 2017/09/03]

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

6. Kubota M, van Haren NM, Haijma SV, et al. Association of iq changes and progressive brain changes in patients with schizophrenia. JAMA Psychiatry 2015;72(8):803-12. doi: 10.1001/jamapsychiatry.2015.0712

7. Poeppl TB, Nitschke J, Santtila P, et al. Association between brain structure and phenotypic characteristics in pedophilia. J Psychiatr Res 2013;47(5):678-85. doi: 10.1016/j.jpsychires.2013.01.003 [published Online First: 2013/02/13]

8. 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]

9. Mingoia G, Wagner G, Langbein K, et al. Default mode network activity in schizophrenia studied at resting state using probabilistic ICA. Schizophr Res 2012;138(2-3):143-9. doi: 10.1016/j.schres.2012.01.036 [published Online First: 2012/05/15]

10. Zhang F, Qiu L, Yuan L, et al. Evidence for progressive brain abnormalities in early schizophrenia: a cross-sectional structural and functional connectivity study. Schizophr Res 2014;159(1):31-5. doi: 10.1016/j.schres.2014.07.050 [published Online First: 2014/09/02]

11. Woodward ND, Rogers B, Heckers S. Functional resting-state networks are differentially affected in schizophrenia. Schizophr Res 2011;130(1-3):86-93. doi: 10.1016/j.schres.2011.03.010 [published Online First: 2011/04/05]

12. Orliac F, Naveau M, Joliot M, et al. Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia. Schizophr Res 2013;148(1-3):74-80. doi: 10.1016/j.schres.2013.05.007 [published Online First: 2013/06/04]

13. Krishnadas R. Resting state functional hyperconnectivity within a triple network model in paranoid schizophrenia (poster), 2014.

14. Hadley JA, Nenert R, Kraguljac NV, et al. Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia. Neuropsychopharmacology 2014;39(4):1020-30. doi: 10.1038/npp.2013.305 [published Online First: 2013/10/30]

15. Benes FM, Berretta S. GABAergic Interneurons: Implications for Understanding Schizophrenia and Bipolar Disorder. Neuropsychopharmacology 2001;25:1. doi: 10.1016/S0893-133X(01)00225-1

16. Karbasforoushan H, Woodward ND. Resting-state networks in schizophrenia. Current topics in medicinal chemistry 2012;12(21):2404-14. [published Online First: 2013/01/03]

17. Petra Z, Jan L, Kristína C, et al. Theory of Mind Skills Are Related to Resting-State Frontolimbic Connectivity in Schizophrenia. Brain connectivity 2018;8(6):350-61. doi: 10.1089/brain.2017.0563

18. Lee DJ, Elias GJB, Lozano AM. Neuromodulation for the treatment of eating disorders and obesity. Therapeutic advances in psychopharmacology 2018;8(2):73-92. doi: 10.1177/2045125317743435 [published Online First: 2018/02/06]

19. Volkow ND, Wise RA, Baler R. The dopamine motive system: implications for drug and food addiction. Nat Rev Neurosci 2017;18(12):741-52. doi: 10.1038/nrn.2017.130 [published Online First: 2017/11/17]

20. Lisman JE, Pi HJ, Zhang Y, et al. A thalamo-hippocampal-ventral tegmental area loop may produce the positive feedback that underlies the psychotic break in schizophrenia. Biol Psychiatry 2010;68(1):17-24. doi: 10.1016/j.biopsych.2010.04.007 [published Online First: 2010/06/18]

21. Johnston JH, Linden DE, van den Bree MB. Combining Stress and Dopamine Based Models of Addiction: Towards a Psycho-Neuro-Endocrinological Theory of Addiction. Current drug abuse reviews 2016;9(1):61-74. [published Online First: 2015/12/10]

22 Albaugh MD, Hudziak JJ, Orr C, et al. Amygdalar reactivity is associated with prefrontal cortical thickness in a large population-based sample of adolescents. PLoS One 2019;14(5):e0216152. doi: 10.1371/journal.pone.0216152 [published Online First: 2019/05/03]