Paranoid Personality disorder (PPD) falls under cluster A of Personality Disorders, thus patients have odd and eccentric behavior.[1] Paranoid personality disorder patients have mistrust and suspicion towards their peers and the society even though they may not have a reason do so.[2] Due to this mistrust in peers, PPD patients have a difficult time getting along with others and maintaining close relationships.[2] They are under constant paranoia that others are trying to harm or demean them.[3] This disorder begins in early adulthood and is more prevalent in men compared to women.[2] PPD affects 0.5-2.5% of the general population; however the specific brain areas affected in this disorder are still unknown and research is still on-going.[3] This is why it is important to study and uncover the unknown about Paranoid Personality disorder. PPD may have a close genetic link to Schizophrenia as PPD is more common in people who are close relatives of patients.[2] There is also a strong link between PPD and maltreatment as a child, thus suggesting stressful situations during the development of the brain may factor in to causing PPD.[4] Even though medication is not used in PPD, in extreme cases anti-depressants, anti-anxiety or anti-psychotic drugs may be given.[3]

1.1 Symptoms of PPD and diagnostic criteria

Paranoid Personality disorder is part of Cluster A of Personality disorders, which also includes Schizoid and Schizotypal disorders.[1] Cluster A personality disorders are characterized by odd and eccentric behavior.[1]Paranoid Personality patients tend to have excessive mistrust and suspicion towards others as they feel that others are always trying to harm them.[1] On some occasions PPD presents itself together with other mental health disorders. For example, it has also been found that paranoid personality disorder can be found in patients with psychotic major depression.[5]


1.1a Diagnostic Criteria for Paranoid Personality disorder

1) Suspect their peers of trying to harm or damage them without any evidence
2) Question their friends’ loyalty
3) Do not open up to peers’ as they feel peers’ will use this information again them
4) Look for hidden meanings and motives behind their peers’ actions or remarks
5) Unforgiving of negative events such as injuries caused by others
6) Get furious or enraged over reasoning that are not apparent to others
7) Constantly suspect their partner or spouse of infidelity

1.2 Environmental causes of PPD

1.2a Nicotine addiction drugs and PPD

Varenicline is a common drug taken to prevent nicotine dependence in smokers.[7] However, recent case studies have shown that not only Varenicline can lead to psychiatric disorders in those with family history of psychiatric disorders but also can lead to paranoid personality in those with no family history of psychiatric problems.
[7] The mechanism for how this occurs is still not well grasped. It is known though that Varenicline is an agonist for alpha 2 and beta 4 subunits of nicotinic receptors, thus declining the need for smoking by releasing dopamine in the nucleus accumbens.[7]Spread of dopamine throughout the cortex together with the activation of alpha 7 subunits of nicotinic receptors can lead to psychiatric symptoms.[7]

1.2b Sleep deprivation may lead to symptoms of PPD

Sleep deprivation can lead to anxiety, depressed mood and anger, all of which are symptoms seen in personality disorders such as in Paranoid Personality disorder.[8]
Sleep deprivation slows down the glucose metabolism within the pre-frontal cortex of the brain altering its’ function, which is an area of the brain majorly affected through hypoactivity in PPD(See above [8]). Personality Assessment Inventory (PAI) scale is a clinical scale which assess mental disorders or psychopathology, and research shows that PAI scores are greatly increased after sleep deprivation for fifty six hours (See above[8]). PAI scores are significantly increased for paranoia compared to those who got normal hours of sleep; however these scores are still not at a clinically significant confinement (See above [8]). Even though research thus far show sleep deprivation only lead to non-pathological symptoms of PPD, many of the neurobiological aspects after sleep deprivation are similar to that of PPD (See above [8]). Therefore; sleep deprivation can be used as a model to assess the chemical and structural changes occurring within the brain in PPD (See above [8]).

Figure 1:PAI scores are significantly high for paranoia after sleep deprivation, thus sleep deprivation cause significant increase in Paranoia in healthy individuals ( p<0.05) (See above [8])

1.3 Genetics and heritability of PPD

In causation of paranoid personality genetic component is as equally as important as the environmental component if not more. Through a Norwegian twin study performed using 1386 adolescent twin pairs, it was discovered that personality disorders have 21-28% of genetic heritability.[9] Through the same study it was found that in PPD genetic liability shared with other Cluster A personality disorders (Schizoid and Schizotypal disorders) is 43%.[9]Recent research has been able to uncover that Schizotypal disorder shares endophenotypic genetic markers with Schizophrenia, thus PPD may also share genetic liability with Schziophrenia.[10]

1.3a Risk alleles

Recent studies have shown risk alleles of CACNA1C and ANK3 can lead to schizophrenic behavior and symptoms of paranoid personality disorder in healthy males.[11] Risk CACNA1C allele is strongly associated with introverted personality, paranoia, anxiety and depression. [11] This leads people with the mentioned allele to be overly cautious of their surroundings for harm as seen in paranoid personality disorder (See above [11]). However; these risk alleles do not affect the linguistic intelligence or executive functions which would be otherwise impaired in those with personality disorders.[11 ] Startle reactivity is high in those with the risk alleles of CACNA1C and ANK3, which is related to anxiety and psychosis. [11 ] This high startle reactivity may be due to hippocampal hypoactivity which is seen in carriers of CACNA1C risk alleles. [11 ] Also, as hippocampus is strongly linked to amygdala its' hypoactivity would affect the emotional memories thus leading to personality disorders such as PPD. [11 ] This shows that functional and structural changes occurring in the hippocampus during PPD symptoms are not only due to hormonal changes but it has strong genetic links.[11 ]
Although various functioning in the brain is linked to CACNA1C allele, not many functioning studies have been done concerning ANK3 allele. [11 ]

1.4 Structural and Chemical changes in a PPD patients brain

Prefrontal cortexis the major region of the brain affected in many of the personality disorders. [8]Specifically ventro-medial pre-frontal cortex maybe affected in PPD as lesions to this region of the brain have known to cause poor decision making and judgment as seen in personality disorder. [12] Lesions to this area of the brain have also shown to affect the socio-moral knowledge which may explain the anti-social behavior seen in PPD.[12 ]

Startle reactivity is highly correlated with anxiety symptom seen in Paranoid personality (See above [11]). There is a high startle reactivity in those with Cluster A personality disorders which may be due to hippocampal hypoactivity (See above [11]). Hippocampal hypoactivity can possibly lead to branching of the amygdala dendrites thus leading to excessive activity in the amygdala and increase in emotional stimulation (See above[11]). This excessive activity of amygdala may further have an effect upon nucleus reticularis pontis caudalis thus leading to the anxiety like symptoms seen in PPD (See above[11]). Hyperactivity of amygdala may also explain the aggressive and fearful behavior seen in PPD, as this area of the brain is specifically responsible for emotional memory and fear conditioning. [12]

Also, studies have been able to show increased right caudate volume is correlated with paranoia and anxiety, thus demonstrating right caudate in striatum is a major component in mood regulation. [13]

1.4a Event related potential

Event related potential is a measurement of brain activity directly due to a specific reflection or a perception, and it is measured through the use of electroencepholography (EEG).[14] When the feeling of “being seen through” is elicited in both normal individuals and individuals who are schizotypal prone, a positive deflection is seen 250 to 400 milliseconds after stimulus being presented (See above [14]). However; P3 amplitude in Schizotypal prone individuals are significantly smaller compared to that of normal individuals (See above[14]). P3 wave in the mentioned study represents the feeling of “being seen through” which a paranoid symptom (See above [14]). Through correlation analysis it can be seen that P3 wave difference is inversely related to Schizotypal personality disorder, meaning frontal temporal brain activity is inversely related to suspicious behavior (See above[14]).
During executive function testing tasks it can be seen that left frontal lobe activity is significantly reduced whereas right frontal lobe activity is increased in Schizotypal prone individuals (See above [14]). Also, these individuals would have decreased dorsal and ventromedial prefrontal cortex activity during self-other processing tasks (See above [14]). There can be reduced activity seen in various other regions of the brain as well, such as in left dorsolateral prefrontal cortex and left temporal lobe during various emotional tasks (See above [14]). Reduced amplitude in P3 is due to the hypoactivity of these various brain regions, which maybe the reasoning behind the suspicious thoughts (See above [14]). As Schizotypal disorder is related to Paranoid Personality disorder in both symptom wise and genetically, above mentioned findings are strongly true for PPD as well (See above [14]).

Figure 2: The current density distribution of non-Schizotypal prone individual versus Schizotypal prone individuals. It shows only superior parietal-occipital lobe in being activated in Schizotypal prone individuals during the time that suspicious thoughts are being induced. [14 ]

1.5 Treatment

There is no cure for paranoid personality disorder, all the treatments are therefore to make the lifestyle better for the patients by helping to reduce the symptoms.

1.5a Psychotherapy

Short term psychotherapy sessions are performed on personality disorder (PD) patients, such as Dialectical behavioral therapy and Cognitive behavioral therapy.[15] These last for about 20 weeks and are not as effective as the long term psychodynamic therapy which may last for years (See above [15]). Dialectical Behavioral therapy trains skills for a “normal” lifestyle by reducing impulsive behavior seen in most personality disorders such as in PPD (See above[15]). Cognitive Behavioral therapy helps transform beliefs and thoughts in specific PD disorders, which may help patients to have better social interactions (See above [15]). Long term psychodynamic therapy on the other hand focuses on altering the core traits which may have become of hindrance to the patient through close analysis of the patient.[15 ] However; it is important to realize in PPD patients psychotherapy maybe more difficult to be performed as they often mistrust and suspect their therapist thus therapists have a difficult time building a relationship with the patients (See above [15]).

1.5b Pharmocotherapy

Low doses of neuroleptics are prescribed for paranoid personality symptoms (PPD) such as constant suspicion and mistrust. [15] For patients who have difficulty controlling aggressive behavior as seen in PPD, selective serotonine-reuptake inhibitor (SSRI) or monoamine oxidase inhibitor (MAOI) may be prescribed (See above [15]). Fluoxetine may help deal with emotional stability, such as depressed mood, whereas benzodiazepines and buspirone may help with anxiety (See above [15]).
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    Roussos, P., Giakomaki, S. G., Georgakopoulos, A., Robakis, N. K., & Bitsios, P. (2011). "The CACNA1C and ANK3 risk allels impact on affective personality traits and startle reactivity but not cognition or gating in healthy males" Bipolar Disorders 13:250-259.
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    Mendez, M. F., Shapira, J. S., & Saul, R. E. (2011). "The Spectrum of Sociopathy in Dementia" J Neuropsychiatry Clin Neurosci 23:132-140.
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    Huang, J., Li, X.-b., Cheung, E. F., Gong, Q.-y., & Chan, R. C. (2011). "Event-related potential correlates of suspicious though in individuals with Schizotypal personality features" Social Neuroscience 6:559-568.
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    Zanni, G. R. (2007). "The Graying of Personality Disorders: Persistent, but Different" The Consultant Pharmacy 22: 995-1003.