The Neurobiology of Personality Disorders: Implications for Psychoanalysis - summary of part of an article by Siever, Larry J, and Lissa N Weinstein (2009)

 “The Neurobiology of Personality Disorders: Implications for Psychoanalysis”
Siever, Larry J, and Lissa N Weinstein (2009)
Journal of the American Psychoanalytic Association 57, no. 2 361–98. doi:10.1177/0003065109333502

Abstract

A low threshold for impulsive aggression, as observed in borderline and anti-social personality disorders, may be related to excessive amygdala reactivity, reduced prefrontal inhibition, and diminished serotonergic facilitation of prefrontal controls.

Affective instability may be mediated by excessive limbic reactivity in gabaminergic/glutamatergic/cholinergic circuits. This results in an increased sensitivity or reactivity to environmental emotional stimuli.

Disturbances in cognitive organization and information processing may contribute to detachment, desynchrony with the environment and cognitive/perceptual distortions.

A low threshold for anxiety may contribute to the avoidant, dependent and compulsive personality disorders.

Alterations in critical regulatory domains will influence how representations of self and others are internalized. Aspects of neurobiological functioning become cognized through the medium of figurative language into an ongoing narrative of the self.

Introduction

Temperamental abnormalities lie at the basis of the personality disorders emerging in the context of a specific experiential developmental trajectory.

Most personality characteristics are influenced by the underlying variability in biological endowments.

Individual differences in temperament along dimensions of affect regulation, impulse control, cognitive organisation, modulation of anxiety, and social information processing may contribute to the unique characterological constellation of each individual.

Temperament influences how an individual internalizes experiences.

Dimensional vs categorical approaches

This paper is based on a continuum model in which personality is seen as organized around basic psychological dimensions.

Four broad psychological dimensions based on disturbances are: Mood/affect, impulse/action, attention/cognition and anxiety.

These dimensions can be formulated as affective dysregulation or instability, impulsivity, cognitive disorganization and anxiety. Vulnerability to the development of personality disorders is patterned by genes expressing themselves in these dimensions, which are shaped by the environment. Difficulties in some of these domains cluster together and are associated with specific personality disorders.

Within the normal range, individual variations on the four domains will form the template for character traits.

Domains of temperament

Impulse aggression

Impulsivity/aggression is a lowered threshold for the activation of motoric responses to external stimuli without reflection or appropriate constraint.

Aggression expressed clinically must be understood form the perspective both of the more primitive limbic systems involved in its generation and of the cortical control mechanisms involved in its modulation.

Pathophysiology

Impulsive aggressive behaviours emerge following emotional provocation.

Excessive aggressive behaviour represents a failure of cortical ‘top-down’ control of limbic emotional systems hyperresponsive to events or situations that can trigger frustration, anger, or fear.

The basal metabolism of the frontal lobe is reduced in aggressive individuals. Activity in the amygdala is enhanced.

Serotonin is a modulatory/inhibitory system implicated in the regulation of mood, appetite, and aggression. Lesions of serotonergic neurons result in unconstrained aggression. Reduced serotonergic activity may be associated with self-directed aggression.

Reductions in serotonergic activity and imbalances in serotonin postsynaptic receptors lead to impulsivity.

Net serotonergic activity is reduced in impulsive aggression.

The anterior angulate cortex is critical in the emotional evaluation of current experience. Its activation is predicted by pervious conflict and suppresses amygdala activation to resolve the conflict.

Top-down control form the prefrontal cortex is critical in modulating aggression stemming from emotional provocation or conflict.

Areas in the prefrontal cortex responsible for social judgment and emotion evaluation are not efficiently used in suppressing limbic activity that generates aggression.

Genetics

Aggression is heritable. Candidate genes contributing to aggression include polymorphisms in genes that regulate the activity of neuromodulators such as serotonin and catecholamines., as well as neuropeptides.

Impulsive aggression is associated with allelic variation in dopaminergic and serotonergic genes.

Genetic susceptibilities to impulsive aggression are more likely to be expressed behaviourally in the face of an adverse environment, specifically a history of abuse or trauma in childhood.

Polymorphisms in genes related to synthesis, metabolism, and receptor responsiveness in the serotonin system are implicated in impulsive aggression.

Affective regulation

The brain regions that modulate anger have been associated with the control of fear and other emotions.

Pathophysiology

Patients with borderline personality disorder demonstrate amygdala hyper-responsivity, especially in response to anger-provoking stimuli.

The modulation of limbic structures, including the amygdala, the enterorhinal cortex, and the insula, is likely to depend on glutamatergic/gabaminergic balance in interaction with the cholinergic system.1)  Procaine produces dissociation in BPD patients and modifies limbic activity in bipolar patients 2) Choliergic agents induce dysphoria in BPD patients 3) Valproate has stabilized affect-driven impulsivity in BPD patients

Excessive excitation of glamatergic and cholinergic systems and reduced inhibition by gabaminergic systems may contribute to a hyperactive limbic system.

Neuropeptides and neurosteriods that modulate affective response include: oxytocin (Approach and affiliative behaviours. Modulates aggression, anxiety and social behaviour. Modulates amygdala activity in response to faces towards inhibition of negative responses and enhancement of trusting and affiliative responses), vasopressin, CFR, ACTH and cortisol

Opiates are implicated in separation distress and ‘social pain’ as well as physical pain.

Genetics

Polymorphisms of the mu-opoid receptor may be associated with affective instability and borderline personality disorder. Polymorphism of oxytocin is associated with anger dyscontrol.

Cognition/attention

Pathophysiology

Patients with SPD have a profile of cognitive impairment and structural brain abnormalities, particularly in the temporal cortex, that is similar to that seen in patients with schizophrenia. They appear to have greater reserves in the prefrontal cortex so that they have less impaired executive function. Their dopaminergic activity is better buffered subcortically.

Dopaminergic activity may be relatively increased or decreased depending on de predominance of psychosis-like and deficit-like symptoms. Increases in dopamine activity are associated with hypervigilance and stereotypic cognitions/behaviours that are precursors of psychosis. Decreases in dopamine activity are associated with deficits in working memory, cognitive processing and hedonic tone.

Reduced dopaminergic and noradrenergic activity in the prefrontal cortex may contribute to the cognitive impairment in SPD.

Patients with SPD show increased ventricular volume, in addition to temporal volume reductions in the superior temporal gyrus, as well as in the other temporal regions. Reduced prefrontal volumes may be associated with the cognitive impairment and deficit symptoms in SPD.

SPD patients show cognitive and physiological impairments in part reflecting reduced dopamine activity in the prefrontal cortex that can be partly reversed with dopamine agonists and compensated in part by activation in other brain areas not normally utilized in healthy controls.

Genetics

A polymorphism of COMT, which metabolizes dopamine, and regulates its activity in the frontal cortex, has been associated with working memory and other cognitive deficits in schizotypal subjects.

Anxiety

Pathophysiology

Low dopamine metabolism has been found in generalized anxiety disorders.

There are serotonergic deficits in OCPD, and this is consistent with a continuum between impulsive and compulsive personality disorders.

Genetics

There is evidence for heritability, but no candidate genes involved.

Temperament and psychological development

Infancy

Some individuals, for genetic reasons, are more susceptible to both positive and negative child-rearing experiences.

There is an interaction between temperament and how mothers relate with their children.

Children whose neurocognitive endowment includes altered sensory, motor, or perceptual equipment will find it more difficult to discern the repetitive and predictable contingencies that are the essence of the development of secure attachment.

Temperament will alter the infant’s crucial ability to discover the patterns of maternal behaviour central to the formation of a secure bond.