RESEARCH ARTICLE

DOI: 10.13140/RG.2.1.1391.6566

Amygdala pharmacology and crime behavior , dysfunctions to be considered as a disease ? WORKING PAPER

authors

1. M. Luisetto, Applied pharmacologist, European Specialist in Laboratory Medicine, Italy, maurolu65@gmail.com

2 prof Dr. Farhan Ahmad Khan Professor and Head, Department of Pharmacology Teerthanker Mahaveer

Medical College and Research Centre, TMU, Moradabad, India Email: dr.farhan.k@gmail.com

3. Luca Cabianca, Biomedical Laboratory, lcabianca@cittadellasalute.to.it, italy

4. Mobin Ibne Mokbul, Founder & President, International Light of Neuroscience Foundation House: 32/A, Road-03,

Prianka Housing, Turag City, Mirpur-1, Dhaka-1216, Bangladesh mobin.glab@gmail.con

5 Ahmed Yesvi Rafa Co-Founder & General Secretary, ILNF Independent Neuroscience Researcher,Independent

Applied Physics Researcher, Dhaka, Bangladesh ahmed.yesvi@gmail.com

6 behzad nil i nano drug delivery usa

KEYWORDS: amygdala, activation level, pharmacology Neuro Imaging . Antisocial

personality disorder; Event-related functional magnetic resonance imaging; Violent

criminal offending, intermittent explosive disorder (IED); emotional processing

ABSTRACTS

Why we don’ t have today drugs specifically registered for amygdala dysfunctions

as preventivable agents towards some kind of crime behavior

( i.ex raptus induced and related conditions ) ?

This Neuro psychiatric condition or organ state are to be considered and treated

in preventive way as common disease ?

There is a amygdala physio-patological Level of activation? Can we call this

dysfunctions status as Disease? , drugs are needed or efficacy to control it ?

A neuro- pharmacology research of amygdala can give the response also using

imaging Techniques.

Studies demonstred that Amygdala activation is involved in aggressive behavior .

The aim of this work is to investigate in this relationship and to find if there is a level

of activation .

Amygdala is activated in some condition as anger Anxiety , fear , predatory behavior,

aggressivity ,defence or subjugate behavior and .in mathernal and sexual fisiology

Emotion : behavior and physiological responce ( vegetative and hormonal )

involved in Behaviour and comunication adjustement

“The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area,

cingulate gyrus, and prefrontal cortex project to these structures directly or

indirectly and thus can modulate the intensity of attack and rage” (.Gregg et al ) ( 1)

Amygdala- SNC connections and other systems involved

Receive conncetions from frontal temporal linbic ( olfactory way ) and send

connections to frontal, ippocampus , hyptalamus encefalic trunk (behavior and

vegetative response )

Amygdala stimolation increase emotional responce and drugs as BDZ , morfin

reduce amygdala activation

Hypotalamus and aggressivity : defensive and predation behaviour

periaqueductal grey substance defence and predation behaviour under amygdala

influece .

Orbitofrontal cortex: involved in emotion interpreting

Morality , caution behaviour in social situation .

Connected with temporal area, limbic. And amygdala cingolus

The temporal lobe is involved in theory of mind and its dysfunction is often

implicated in violent psychopathy.FUMAGALLI et al

Face emotional recognize. Innate , transcultural controlled by right hemisphere (

nuroimaging studies )

Face emotional expression : happpyness , sadness anger , fear and other

stereotyped behaviours

Aggressive beahviour is involved in phsisiologial adjustement

Serotonin neuron activation reduce aggresivity and anti social behaviour .

Various aggressive behaviour are related with reproductive functions and sexual

hormons .

Noradrenergic systems

Glucose level of use in prefrontal, frontal, temporal area

Androgen increase aggressivity and associate to etoh increase aggressivity .

Preoptical medial area: male sexual aggressivity involved

Neuroimaging results say that Amygdala has a level of activation for GABAergic

Geneand it excretes serotonin

“Among the anatomical structures implicated in morality are the frontal, temporal

and cingulate cortices”. Fumagalli et al (2)

“Brain areas participating in moral processing can be influenced also by genetic,

endocrine and environmental factors. “Fumagalli et al

“Hormones can modulate moral behaviour through their effects on the brain.

Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing

for a genetic-based predisposition to morality.” Fumagalli et al

“The violence-specific modulation of prefrontal-amygdala networks appears to

control aggressive behavior and provides a neurobiological model for the anti-

aggressive effects of quetiapine” klasen et al (3)

“Biochemical data suggests that heightened anxiety-like behavior and aggression is

associated with increased plasma levels of corticosterones and elevated oxidative

stress. Significant alterations in dopamine (DA), norepinephrine (NE) and

epinephrine (EPI) were observed within the hippocampus, amygdala, and the

prefrontal cortex, suggesting potential involvement of dopaminergic and

noradrenergic systems in regulation of aggressive behaviors”. Patki et al (4)

“We found novel evidence that childhood aggressive behavior is related to

decreased amygdala volume, decreased sensorimotor cortical thickness, and

decreased global right hemisphere gyrification.” Thijssen et al (5)

J P Hayes, ET AL “In recent years, neuroimaging techniques such as functional

magnetic resonance imaging (fMRI) and positron emission tomography (PET) have

played a significant role in elucidating the neural underpinnings of posttraumatic

stress disorder (PTSD.)(6)

Results demonstrated that the regions most consistently hyperactivated in PTSD

patients included mid- and dorsal anterior cingulate cortex, and when ROI studies

were included, bilateral amygdala. These results provide evidence for a

neurocircuitry model of PTSD that emphasizes alteration in neural networks

important for salience detection and emotion regulation.” Hayes

Sergerie K, et al. (7) “Functional neuroimaging studies have provided strong support

for a critical role of the amygdala in emotional processing. However, several

controversies remain in terms of whether different factors-such as sex, valence and

stimulus type-have an effect on the magnitude and lateralization of amygdala

responses. …..we conducted a meta-analysis of functional neuroimaging studies of

visual emotional perception that reported amygdala activation. Critically, unlike

previous neuroimaging meta-analyses, we took into account the magnitude (effect

size) and reliability (variance) associated with each of the activations. Our results

confirm that the amygdala responds to both positive and negative stimuli, with a

preference for faces depicting emotional expressions. We did not find evidence for

amygdala lateralization as a function of sex or valence.. Taken together, results from

this meta-analysis shed new light on several of the models proposed in the literature

regarding the neural basis of emotional processing”

From “THE NEURAL BASIS OF PSYCHOPATHY EDITORIAL

Neurobiological basis of psychopathy,R. JAMES R. Blair

The British Journal of Psychiatry Jan 2003, 182 (1) 5-7

“The amygdala is involved …..in the response to fearful and sad facial expressions

( Blair et al, 1999). (8)

It is suggested that amygdala dysfunction is one of the core neural systems

implicated in the pathology of psychopathy ( Patrick, 1994; Blair et al, 1999).

Neuroimaging studies confirmed that amygdala dysfunction is associated with

psychopathy ( Tiihonen et al, 2000; Kiehl et al, 2001).

Tiihonen et al used volumetric magnetic resonance imaging (MRI) to explore the

relationship between amygdaloid volume and degree of psychopathy in violent

offenders as measured by the PCL-R.

High levels of psychopathy were associated with reduced amygdaloid volume,

Kiehl et al used functional MRI to examine neural responses in individuals with high

and low scores on the PCL-R during an emotional memory task where the

participant processed words of neutral and negative valence.

They found a reduced amygdala response in the high-scoring group, relative to the

low-scoring group, during the processing of words of negative valence.

…….. on the basis of neuropsychological and neuroimaging findings for violent

offenders, it has been argued that the frontal cortex could be dysfunctional (

Morgan & Lilienfield, 2000; Soderstrom et al, 2000).

…….there are crucial differences between the general population of violent

offenders and these individuals.

Nneuropsychological work with individuals with psychopathy, unlike work with

individuals who are violent, has repeatedly found frontal functioning to be intact (

Kandel & Freed, 1989).”

The basic causes of the pathology remain unclear; however, there are interesting

possibilities. One is that pathology in the noradrenergic system can lead to the

observed amygdala dysfunction. Certainly, administration of the β-adrenergic

blocker propranolol, as well as amygdala damage, blocks the improvement in

episodic memory for emotionally arousing events, as well as disrupting the

processing of sad facial expressions ( Harmer et al, 2001). “ (9)

From wbsite http://www.neuroscienze.net/?p=518

“Raine et al., 1997 (10), Soderstrom et al., 2000), a study on female patients

borderline 2003 Pittsburgh, U.S.A.( psycotic and violent criminals) aggressive

bahavior is often related to abnormal brain blood fluss and glucose methabolism

(Raine et al., 1997, Soderstrom et al., 2000), in prefrontal area , frontal and temporal

level;

was finded an iverse relationship between blood fluss and glucose with the gravity

of pathology

neuropsycological test in patient with BDP or antisocial showed deficit in executive

function in frontal cortex ( problem solving , planning , inibithory behavior)

Level of gluose methabolism was verified using PET

Orbitofrontalcomplex is involved in social regulation , behavior control , emotion

even if by faces recognize (Hornak et al (11)., 1996, Blair e Cipollotti, 2000).

Neuro Imaging functional Studies ( that used the paradigm of induced anger ) ,

showed that the acivation of orbitofrontal cortex is inibitory towards emotions

regulation .

Injury in prefrontal cortec are associated with reduction in inhibitory capacity to

control emotions and violent behavior even if other cognitive function remain the

same .

Crim Justice Behav. 2012 Oct; 39(10): 1340–1360.Reliability, Validity, and Predictive

Utility of the 25-Item Criminogenic Cognitions Scale (CCS)June Price Tangney, Jeffrey

Stuewig, Emi Furukawa, Sarah Kopelovich, Patrick Meyer, and Brandon Cosby:

“Theory, research, and clinical reports suggest that moral cognitions play a role in

initiating and sustaining criminal behavior. The 25 item Criminogenic Cognitions

Scale (CCS) was designed to tap 5 dimensions: Notions of entitlement; Failure to

Accept Responsibility; Short-Term Orientation; Insensitivity to Impact of Crime; and

Negative Attitudes Toward Authority. Results from 552 jail inmates support the

reliability, validity, and predictive utility of the measure.

The CCS was linked to criminal justice system involvement, self-report measures of

aggression, impulsivity, and lack of empathy. Additionally,

the CCS was associated with violent criminal history, antisocial personality, and

clinicians’ ratings of risk for future violence and psychopathy (PCL:SV). “

MATERIALS AND METHODS

With Pubmed research using keyword amygdala associated to the word :

crime,pharmacology ,neuroimaging we have finded various scientific articles that

demonstred a link between amygdala and aggressive behaviour in collaboration

with other systems

RESULTS

The article on pubmed demonstrates a strictly influence of amygdala and related

systems in behavior and aggressivity.

J.Downer at University College London first identified amygdala in the reason of

agreesive behaviour and he tested it onrhesus monkey.( 1950)

Nuro- Psychological and neuroimaging studies results say that amygdala plays a

crucial role in aggression and violance.

Neurobilogy and anatomy, heterogenity, phenotypes, pathophysiological findings,

neurochemistry, molecular genetics, regional volumes, functional studies,

neuropharmacology, interregional connectivity says that amygdala-frontal circuitry

is very related to crime.

Pharmacological researches say that this region excretes serotonin 5,7-

dihydroxytryptamine (5,7-DHT)

(www.ncbi.nlm.nih.gov/m/pubmed/26476009/?i=2&from=amygdala%205,7-

dihydroxytryptamine%20(5,7-DHT)

- www.apa.org/monitor/2014/02/criminal-mind.aspx

The basolateral and lateral amygdala nuclei complex (BLC) is associated with crime

behavior .( Pardini )

American Psychologiocal Association (APA) published a paper on a criminal mind.

They told that that amygdala is the main reason behind crime and agressive

behaviour.

D. Pardini found in the University of Pittsburgh found that lower amygdala volumes

were more than three times aggreesive. This trait remains in a man before many

years than the people crimes. (Biological Psychiatry, 2013).

A Raine in Department of Criminology ( the University of Pennsylvania )studied on

amygdala function on 1,795 children of 3 years old. After 20 years, they discoverd

that the children which had deficit of fear conditioning in amygdala predisposes to

crime at 23 years.

The anterior cingulate cortex which plays a major role in behavior regulation and

impulsivity, has also been linked to crime , this volume is reduced in the criminals or

prisoners

Goodman et. al. demonstrated that dialectical behavior therapy( DBT) can be used

as a therapy for amygdala functions. So the neurobiology of crime says that

amygdala is associated with crime and agression and therapies can be given on

amygdala.

Functional imaging studies suggest abnormalities in limbic brain activity during

emotional information processing in impulsively aggressive subjects with

Intermittent Explosive Disorder (IED). COCCARO ET AL (12)

These data reveal that IED Intermittent Explosive Disorder (IED). is associated with a

significant loss of neurons in both the amygdala and hippocampus COCCARO ET AL

Goodman et. al. (13) demonstrated that dialectical behavior therapy(DBT)

can be used as a therapy for amygdala dysfunctions.

Neurobiology of crime indicates that amygdala is associated with crime and

aggression

therapies can be given on a pathological amygdala which could be consieder a

solution of criminal behaviour in future ?

Neuropharmacological interventions IS the key to prevent theses kind

of amygdala related agreesive behavior ?

In future can be interesting to investigate in this filed.

DISCUSSION

Because abnormal moral behaviour can arise from both functional and structural

brain abnormalities that should be diagnosed and treated, the neurology of moral

behaviour has potential implications for clinical practice and raises ethical concerns.

Fumagalli et al

“The complex interaction among these neurotransmitters occurs at the level of

brain areas and neural circuits such as the orbitoprefrontal cortex, anterior cortex,

amygdala, hippocampus, periaqueductal gray, and septal nuclei, where the

receptors of these neurotransmitters are expressed. The neurobiological mechanism

of aggression is important to understand the rationale for using atypical

antipsychotics, anticonvulsants, and lithium in treating aggressive behavior ( comai

et al )(14)

“A better understanding of the neurobiological bases of psychopathy could improve

therapeutic interventions, reducing the related social costs.” ( del casale et al )(15)

Emotional processing and learning, and several social and affective decision-making

functions are impaired in psychopathy, which correlates with specific changes in

neural functions. (DEL CASALE ET AL )

“a better understanding of the neural mechanisms and substrates regulating

aggression and rage and thus establish a rational basis for treatment of disorders

associated with these forms of aggression”.(Gregg et al )

Various physiological system are involved in aggressive behavior. But As every

organs and apparatus we can think a physiological level of function that classify as

physiological from pathological State we can find also for amygdala systems a Basal

level to think a pathological status or malfunctions .

For various organ and apparatus we have diagnostic tests in order to monitoring

Physiology or pathological status ( ex imaging or other lab. Test ) but in order

To verify amygdala functionality we do not have a diagnostic systems to

Delimited pathological status of iper activation.in objective way.

CONCLUSION

we conclude that is needed to find a objective diagnostic system to verify the basic

level of activation status of amygdala in stress conditions and also to find if a drugs

therapy systems can be considered if we have an organic pathology conditions.

As others physiological apparatus : a pathological activation and status can be

controlled by specific pharmacological therapy ?

Other implication ( moral, etical , legal) are not considered in this paper .

This article has not diagnostics or therapy intent

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Functional Neuroimaging inPsychopathy