Circuits Regulating Pleasure and Happiness in Schizophrenia: The Neurobiological Mechanism of Delusions

Abstract

A recently developed model describes how evolutionary old neuronal systems allow freemoving animals, including humans, to escape from threats and discomfort and to acquire sufficient necessities to maintain life and to continue as a species. The amygdala has an essential role in regulating these fundamental reward-seeking and misery-fleeing behaviours. This is probably related to the ancient character of the corticoid and ganglionic parts of the amygdaloid complex. During evolution almost the entire ventral and lateral pallium (cortex) of the first vertebrates went up into the superficial and deep amygdalar nuclei, and their entire striatum and pallidum went up into the extended amygdala. An important role of the amygdala is selecting the sensory cues which are relevant for reward-seeking and misery-fleeing behaviour and should be paid attention to in order to increase the animal's chances. This corresponds to attentive salience. Disturbances of this process in humans may lead to delusions. It has been suggested that in patients with schizophrenia this aberrant salience results from dopaminergic hyperactivity. The authors of this chapter believe that aberrant salience can result from dysfunctions everywhere within the chain: neocortex, corticoid amygdala, hippocampal complex, medial septum, medial habenula, midbrain nuclei and ventral tegmental area.

Circuits Regulating Pleasure and Happiness: The Evolution of the Amygdalar-Hippocampal-Habenular Connectivity in Vertebrates

“…Alterations in the display of these two types of behaviors are eye-catching components of most, if not all, mental disorders. We have summarized evidence indicating involvement of the mechanisms regulating these two type of behaviors in depression (Loonen and Ivanova, 2016b), bipolar disorder (Loonen et al, submitted), addiction (Loonen et al, 2016), delusions (Loonen and Ivanova, in press), and specific anxiety disorders (in preparation). This is not very surprising considering the primary character of these regulatory processes, and does not conflict with the role of cerebral cortex in inducing the diseased mental state in patients suffering from them.…”

Autoimmunity and immune system dysregulation in schizophrenia: IgGs from sera of patients hydrolyze myelin basic protein

“…SCZ is usually a progressive mental illness with very different polymorphic symptoms characterized by a persistent violation of social adaptation and ability to work. Different violation of synaptic transmission resulting in neuronal damage and severe dysfunction in SCZ patients was revealed . SCZ can begin to develop even in utero or in early childhood .…”

<p>Association of Cholinergic Muscarinic M4 Receptor Gene Polymorphism with Schizophrenia</p>

“…Further study of the role of CHRM4 for the activity of fibres originating within amygdala and hippocampus and projecting to ventral striatum 31 and/or via the habenula to monoaminergic midbrain centers 32 is of potential interest to explain delusional symptoms of schizophrenia. 30 Scarr et al did not report finding any de novo mutations in the CHRM4 gene neither in patients nor in controls. 16 Out of eight common variants reported for the gene, they only found two (rs2067482 and rs72910092), and only the first one was shown to be associated with schizophrenia (albeit at the border of significance).…”

“…28,29 We have argued that the primary mechanism could also be the other way around meaning that dysfunction of amygdala and hippocampus results in activation of monoaminergic centers of the midbrain which activate circuits regulating pleasure and happiness. 30 This would place the suggestion by Scarr et al 7 about altered CHRM4 expression in hippocampus of patients with schizophrenia in another perspective. Further study of the role of CHRM4 for the activity of fibres originating within amygdala and hippocampus and projecting to ventral striatum 31 and/or via the habenula to monoaminergic midbrain centers 32 is of potential interest to explain delusional symptoms of schizophrenia.…”