.

1. 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 Specialistin 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 Lightof Neuroscience Foundation House: 32/A, Road-03,
Prianka Housing,TuragCity, 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 nili nano drugdelivery 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 preventivableagents towards some kind of crime behavior
( i.ex raptus induced and related conditions ) ?

2. 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 wecall this
dysfunctions status as Disease? , drugs are needed or efficacy to controlit ?
A neuro- pharmacology research of amygdala can give the responsealso using
imaging Techniques.
Studies demonstred that Amygdala activation is involved in aggressivebehavior .
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 somecondition as anger Anxiety , fear , predatory behavior,
aggressivity ,defenceor subjugatebehavior and .in mathernal and sexual fisiology
Emotion : behavior and physiologicalresponce ( vegetative and hormonal )
involved in Behaviour and comunication adjustement
“The hippocampus, amygdala, bed nucleus of the stria terminalis, septal area,
cingulate gyrus, and prefrontalcortexproject to these structures directly or
indirectly and thus can modulate the intensity of attack and rage” (.Gregg et al ) ( 1)
Amygdala- SNC connections andother 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 responceand drugs as BDZ , morfin
reduce amygdala activation
Hypotalamus and aggressivity : defensiveand predation behaviour
periaqueductal grey substance defence and predation behaviour under amygdala
influece .
Orbitofrontalcortex: involved in emotion interpreting
Morality , caution behaviour in social situation .
Connected with temporal area, limbic. And amygdala cingolus

3. The temporal lobe is involved in theory of mind and its dysfunction is often
implicated in violent psychopathy.FUMAGALLI etal
Face emotional recognize. Innate, transculturalcontrolled by right hemisphere(
nuroimaging studies )
Face emotional expression : happpyness , sadness anger , fear and other
stereotyped behaviours
Aggressivebeahviour is involved in phsisiologial adjustement
Serotonin neuron activation reduce aggresivity and anti socialbehaviour .
Various aggressivebehaviour arerelated with reproductive functions and sexual
hormons .
Noradrenergic systems
Glucose level of use in prefrontal, frontal, temporal area
Androgen increase aggressivity and associateto etoh increaseaggressivity .
Preoptical medial area: male sexualaggressivity 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 environmentalfactors. “Fumagalli et al
“Hormones can modulate moral behaviour through their effects on the brain.
Finally, genetic polymorphisms can predisposeto aggressivity and violence, arguing
for a genetic-based predisposition to morality.” Fumagalli et al

4. “The violence-specific modulation of prefrontal-amygdala networks appears to
control aggressivebehavior and provides a neurobiologicalmodel for the anti-
aggressiveeffects of quetiapine” klasen et al (3)
“Biochemical data suggests thatheightened anxiety-like behavior and aggression is
associated with increased plasma levels of corticosterones and elevated oxidative
stress. Significantalterations in dopamine (DA), norepinephrine(NE) and
epinephrine (EPI) wereobserved within the hippocampus, amygdala, and the
prefrontalcortex, suggesting potential involvement of dopaminergic and
noradrenergic systems in regulation of aggressivebehaviors”. Patkiet al (4)
“We found novel evidence that childhood aggressivebehavior is related to
decreased amygdala volume, decreased sensorimotor corticalthickness, and
decreased global righthemisphere gyrification.”Thijssen et al (5)
J P Hayes, ET AL “In recent years, neuroimaging techniques such as functional
magnetic resonanceimaging (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 dorsalanterior 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 haveprovided 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, valenceand
stimulus type-havean effect on the magnitude and lateralization of amygdala
responses. …..weconducted a meta-analysis of functional neuroimaging studies of

5. visualemotional perception that reported amygdala activation. Critically, unlike
previous neuroimaging meta-analyses, wetook into account the magnitude (effect
size) and reliability (variance) associated with each of the activations. Our results
confirmthat the amygdala responds to both positive and negative stimuli, with a
preference for faces depicting emotional expressions. Wedid 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 PSYCHOPATHYEDITORIAL
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 responseto fearfuland sad facial expressions
( Blair et al, 1999). (8)
Itis 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 resonanceimaging (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 wereassociated with reduced amygdaloid volume,
Kiehl et al used functional MRI to examine neuralresponses in individuals with high
and low scores on the PCL-Rduring an emotional memory task where the
participant processed words of neutraland negative valence.
They found a reduced amygdala responsein the high-scoring group, relativeto the
low-scoring group, during theprocessing of words of negative valence.

6. …….. on the basis of neuropsychologicaland neuroimaging findings for violent
offenders, it has been argued that the frontal cortex could be dysfunctional(
Morgan & Lilienfield, 2000; Soderstrometal, 2000).
…….there are crucial differences between the general population of violent
offenders and these individuals.
Nneuropsychologicalwork with individuals with psychopathy, unlikework 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 systemcan 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)
Fromwbsite http://www.neuroscienze.net/?p=518
“Raine et al., 1997 (10), Soderstrometal., 2000), a study on female patients
borderline 2003 Pittsburgh, U.S.A.( psycotic and violent criminals) aggressive
bahavior is often related to abnormalbrain blood fluss and glucosemethabolism
(Raine et al., 1997, Soderstrometal., 2000), in prefrontalarea , frontal and temporal
level;
was finded an iverserelationship between blood fluss and glucose with the gravity
of pathology
neuropsycologicaltestin patient with BDP or antisocial showed deficit in executive
function in frontal cortex ( problemsolving , 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).

7. 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 prefrontalcortec 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-ItemCriminogenic Cognitions Scale (CCS)JunePrice Tangney, Jeffrey
Stuewig, Emi Furukawa, Sarah Kopelovich, Patrick Meyer, and Brandon Cosby:
“Theory, research, and clinical reports suggestthat 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-TermOrientation; Insensitivity to Impactof Crime; and
Negative Attitudes Toward Authority. Results from552 jail inmates supportthe
reliability, validity, and predictive utility of the measure.
The CCS was linked to criminal justicesysteminvolvement, self-reportmeasures of
aggression, impulsivity, and lack of empathy. Additionally,
the CCS was associated with violent criminal history, antisocialpersonality, and
clinicians’ ratings of risk for futureviolence 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 aggressivebehaviour in collaboration
with other systems
RESULTS
The article on pubmed demonstrates a strictly influence of amygdala and related
systems in behavior and aggressivity.

8. J.Downer at University College London firstidentified amygdala in the reason of
agreesive behaviour and hetested 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, pathophysiologicalfindings,
neurochemistry, molecular genetics, regional volumes, functionalstudies,
neuropharmacology, interregionalconnectivity says that amygdala-frontalcircuitry
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 PsychologiocalAssociation (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 morethan three times aggreesive. This traitremains in a man beforemany
years than the people crimes. (BiologicalPsychiatry, 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

9. amygdala is associated with crime and agression and therapies can be given on
amygdala.
Functional imaging studies suggestabnormalities in limbic brain activity during
emotional information processing in impulsively aggressivesubjects with
Intermittent Explosive Disorder (IED). COCCARO ETAL (12)
These data reveal that IED IntermittentExplosive 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 ?
Neuropharmacologicalinterventions IS the key to prevent theses kind
of amygdala related agreesivebehavior ?
In futurecan be interesting to investigate in this filed.
DISCUSSION
Because abnormalmoral behaviour can arisefrom both functionaland 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 atthe level of
brain areas and neuralcircuits such as the orbitoprefrontalcortex, anterior cortex,
amygdala, hippocampus, periaqueductalgray, and septal nuclei, wherethe
receptors of these neurotransmitters areexpressed. The neurobiological mechanism

10. of aggression is important to understand the rationale for using atypical
antipsychotics, anticonvulsants, and lithium in treating aggressivebehavior ( comai
et al )(14)
“A better understanding of the neurobiologicalbases of psychopathy could improve
therapeutic interventions, reducing the related social costs.” ( del casale et al )(15)
Emotional processing and learning, and severalsocial and affective decision-making
functions are impaired in psychopathy, which correlates with specific changes in
neural functions. (DEL CASALEET 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 etal )
Various physiologicalsystemareinvolved in aggressivebehavior. But As every
organs and apparatus we can think a physiological level of function that classify as
physiologicalfrompathological 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 systemto 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

11. REFERENCES :
1 Gregg TR1, Siegel A. et al Prog NeuropsychopharmacolBiolPsychiatry. 2001
Jan;25(1):91-140.Brain structures and neurotransmitters regulating aggression in
cats: implications for human aggression.
2) Fumagalli M, Priori A. (2)Brain. 2012 Jul;135(Pt7):2006-21. doi:
10.1093/brain/awr334.Epub 2012 Feb 13.
Functional and clinical neuroanatomy of morality.
(3) Klasen M1, Zvyagintsev M, Schwenzer M, Mathiak KA, Sarkheil P, Weber R,
Mathiak K.Neuroimage. 2013 Jul15;75:20-6. doi:
10.1016/j.neuroimage.2013.02.053. Epub 2013 Mar 7.Quetiapinemodulates
functional connectivity in brain aggression networks.
(4)Patki G1, Atrooz F1, Alkadhi I1, SolankiN1, Salim S2NeurosciLett. 2015 Jan
1;584:308-13. doi: 10.1016/j.neulet.2014.10.051. Epub 2014 Nov 1.
High aggression in rats is associated with elevated stress, anxiety-likebehavior, and
altered catecholamine content in the brain.
(5) Thijssen S1, Ringoot AP, Wildeboer A, Bakermans-Kranenburg MJ, El Marroun H,
Hofman A, Jaddoe VW, VerhulstFC, Tiemeier H, van IJzendoorn MH, White T.Cogn
Affect Behav Neurosci. 2015 Sep;15(3):564-77

12. Brain morphology of childhood aggressivebehavior: A multi-informant study in
school-agechildren.
(6) Hayes,2,3,4and Amanda M Mikedis1 Quantitative meta-analysis of neural
activity in posttraumatic stress disorder
(7) Sergerie K, et al. NeurosciBiobehav Rev. 2008. The role of the amygdala in
emotional processing: a quantitative meta-analysis of functional neuroimaging
studies.
(8) Blair at al Brain. 1999 May;122 ( Pt5):883-93.
Dissociableneural responses to facial expressions of sadness and anger.
Blair RJ1, Morris JS, Frith CD, Perrett DI, Dolan RJ.
(9) Neurobiological basis of psychopathy R. JAMESR. Blair
The British Journalof Psychiatry Jan 2003, 182(1) 5-7; DOI:
10.1192/bjp.182.1.5
(10) Raine et al., 1997, BiolPsychiatry. 1997 Sep 15;42(6):495-508.Brain
abnormalities in murderers indicated by positron emission tomography.
(11)., Hornak J, Rolls ET, Wade D. Face and voice expression identification in
patients with emotional and behavioralchanges following ventralfrontal lobe
damage. Neuropsychologia. 1996;34:247–61

13. (12) Coccaro EF1, Lee R2, McCloskey M3, Csernansky JG4, Wang L5. J Morphometric
analysis of amygdla and hippocampus shapein impulsively aggressiveand healthy
control subjects.Psychiatr Res. 2015 Oct;69:80-6.
13)Goodman et. al. Dialectical behavior therapy alters emotion regulation and
amygdala activity in patients with borderlinepersonality disorderPsychiatr Res. 2014
October ; 57: 108–116.
14) Comai S1, Tau M, Gobbi G.J Clin Psychopharmacol. 2012 Feb;32(1):83-94
The psychopharmacology of aggressivebehavior: a translational approach:part1:
neurobiology.
15)delcasale et al Neuropsychobiology 2015;72:97–117
Functional Neuroimaging inPsychopathy