Nathan Kolla

Centre for Addiction and Mental Health · Campbell Family Mental Health Research Institute​

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in 2013, includes an alternative model of personality disorders (AMPD) focusing on a maladaptive trait model utilized to diagnose several personality disorders. Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are two co...

Introduction Increased screen time coupled with public safety restrictions may pose a serious challenge to adequate social-emotional development in youth during the pandemic. Social-emotional competence (resilience, self-esteem, and self-compassion) are essential for youth to adapt to the “new normal” in the prolonged pandemic timeline. The current...

Background: Current literature indicates that safety measures, including lockdowns during the COVID-19 pandemic, severely disrupted our lifestyle, marked by increased screen time. The increased screen time is mostly associated with exacerbated physical and mental wellbeing. However, the studies that examine the relationship between specific types...

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this cond...

Excessive aggression in children and youth can lead to impairments in family, social or academic functioning. The aim of the present study was to review the evidence on the effectiveness of nutritional supplements in reducing excessive hetero-aggression in children and youth (up to 18 years). The Cochrane Library, EMBASE, MEDLINE, ProQuest Disserta...

Rationale: Coronavirus (COVID-19)-related stressors precipitated the mental health crisis and increased substance use in Canada and worldwide. As the pandemic continues to evolve, monitoring and updating substance use-related ED visit trends is essential to ensure the stability and quality of ED services under the prolonged pandemic timeline. Aim...

Individuals with borderline personality disorder (BPD) or antisocial personality disorder (ASPD) are overrepresented in forensic settings. Yet, despite the burden these disorders place on healthcare and criminal justice systems, there remains a lack of evidence‐based pharmacological treatments. Epidemiological data have shown that comorbid cannabis...

Health care organizations are obligated to provide safe and effective treatment to their patients and also protect the safety of their workers. This paper analyzes the tensions arising from legislative regimes that, respectively, protect privacy and workplace safety, using a large, tertiary high-secure forensic psychiatric hospital in Ontario, Cana...

Background: Notably higher rates of mental health issues have been reported among healthcare providers (HCPs) during the COVID-19 pandemic. Concerns over the impact of policy decisions on the well-being of HCPs is growing, yet it remains underexplored in the literature. Method: HCPs from a 301-bed mental health hospital and a 408-bed acute care...

Borderline personality disorder (BPD) and antisocial personality disorder (ASPD) are the two most frequently diagnosed and researched DSM-5 personality disorders, and both are characterized by high levels of trait neuroticism. Fatty acid amide hydrolase (FAAH), an enzyme of the endocannabinoid system (ECS), has been linked to regulation of mood thr...

Background Before the COVID-19 pandemic, healthcare providers (HCPs) were already experiencing a higher prevalence of mental health disorders compared with non-healthcare professionals. Here, we report on the psychosocial functioning and stress resilience of HCPs who worked during the COVID-19 pandemic in a large-sized psychiatric facility and a la...

Background: Stop, Now And Plan (SNAP) is a cognitive behavioral-based psychosocial intervention that has a strong evidence base for treating youth with high aggression and externalizing behaviors, many of whom have disruptive behavior disorders. In a pre-post design, we tested whether SNAP could improve externalizing behaviors, assessed by the pare...

The relationship between cannabis use and violence, and to what extent this association is causal in nature, remains unclear. The aim of this scoping review was to ascertain whether cannabis use increases the risk of violence and aggression in adults. Because cannabis use can result in irritability, disinhibition, and altered cognition, it is plaus...

Proactive aggression (PA) is a planned and unprovoked form of aggression that is most often enacted for personal gain or in anticipation of a reward. Frequently described as “cold-blooded” or goal oriented, PA is thought to be associated with low autonomic arousal. With this view in mind, we performed a scoping review of the biological correlates o...

Studies suggest that abnormalities of the dopaminergic system underlie decision-making deficits, a hallmark of antisocial personality disorder (ASPD) and psychopathy. The dopamine transporter gene (DAT1) is of particular interest due to a polymorphism that controls dopamine transporter (DAT) activity. However, the association between DAT1 genotypes...

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are two neuroimaging techniques that have led to important insights into the pathophysiology of borderline personality disorder (BPD) and its symptom clusters. This paper provides the most up-to-date review of PET and SPECT studies targeting BPD. A systematic...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and patterns of restrictive and repetitive behavior. Although the neurological underpinnings of ASD remain elusive, the endocannabinoid system (ECS) may play a role in modulating social behavior in ASD. Preclinical studies have suggested t...

Background While psychosis is a risk factor for violence, the majority of individuals who perpetrate aggression do not present psychotic symptoms. Pathological aggressive behavior is associated with brain gray matter differences, which, in turn, has shown a relationship with increased psychopathic traits. However, no study, to our knowledge, has ev...

A growing body of evidence links the late chronotype to mental illness, aggression, and aversive personality traits. However, much of what we know about these associations is based on healthy cohorts, and it is unclear how individuals with high levels of aggression, including forensic psychiatric populations, but not offenders, are affected. The pr...

According to the stress-diathesis model of suicidal behavior, completed suicide depends on the interaction between psychosocial stressors and a trait-like susceptibility. While there are likely multiple biological processes at play in suicidal behavior, recent findings point to over-activation of microglia, the resident macrophages of the central n...

Background Existing studies of attention deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and substance use or substance use disorders have produced mixed results, with some identifying a direct link between ADHD and general or disordered substance use and others suggesting that comorbid CD may explain this relationship. Insufficient r...

Detained youth display substantive mental health and substance use problems. However, Canadian information is limited. The purpose of this study was 1) to assess mental health and substance use problems of youth in residential detention/custody facilities in Ontario, Canada, at intake, using the interRAI Youth Justice in Custodial Facilities (YJCF)...

Over the past two decades, research has revealed that genetic factors shape the propensity for aggressive, antisocial, and violent behavior. The best-documented gene implicated in aggression is MAOA (Monoamine oxidase A), which encodes the key enzyme for the degradation of serotonin and catecholamines. Congenital MAOA deficiency, as well as low-act...

This review focuses on the contribution of circadian rhythms to aggression with a multifaceted approach incorporating genetics, neural networks, and behavior. We explore the hypothesis that chronic circadian misalignment is contributing to increased aggression. Genes involved in both circadian rhythms and aggression are discussed as a possible mech...

Background: Approximately 40-70% of justice-involved youth have untreated mental health problems. There is no current research that directly compares the mental health profiles of youth involved in the justice system to that of inpatients and outpatients. The research reported is significant because it directly compares the needs of these populati...

Background: Mental health legislation in Ontario, Canada, permits inpatients to refuse treatment while appealing their incapacity finding to the Consent and Capacity Board (CCB). Lack of treatment during this period poses safety concerns, as inpatients who remain untreated are at higher risk of engaging in violent behavior. The present study explor...

As the main excitatory neurotransmitter in the central nervous system, glutamate, as measured in combination with glutamine (Glx), is implicated in several psychopathologies when levels are aberrant. One illness that shows heightened Glx levels is bipolar disorder (BD), an illness characterized by high impulsivity. In addition, although animal stud...

Purpose of Review This paper aims to provide a comprehensive discussion of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies of antisocial personality disorder (ASPD) and aggression. Recent Findings Among ASPD males with high impulsivity, the density of brainstem serotonin (5-HT) transporters shows a...

Introduction: Despite limited research, existing evidence suggests that there is an association between conduct disorder (CD) and various risky driver behaviours, such as driver aggression and driving after drinking. The current study sought to estimate the association between probable CD during childhood and past-year collision risk. Methods: Dat...

Objective The role of serotonin (5‐HT) in human aggression has been the subject a large number of studies, mostly with adults. Meta‐analyses indicate a small but significant inverse relationship between central nervous 5‐HT availability and aggression, but genetically‐informed studies suggest two pathways: one to reactive aggression, the other to p...

Background: The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucle...

Endogenous and exogenous cannabinoids bind to central cannabinoid receptors to control a multitude of behavioral functions, including aggression. The first main objective of this review is to dissect components of the endocannabinoid system, including cannabinoid 1 and cannabinoid 2 receptors; the endogenous cannabinoids anandamide and 2-arachidono...

The article Monoamine Oxidase A in Antisocial Personality Disorder and Borderline Personality Disorder, written by Nathan J. Kolla and Sarah A. Vinette, was originally published Online First without open access.

Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic va...

This study describes the association between history of traumatic brain injury (TBI) and childhood symptoms of conduct disorder (CD). Data were based on telephone interviews with 6048 respondents derived from the 2011-2013 cycles of a representative cross-sectional survey of adults aged 18+ years in Ontario, Canada. TBI was defined as loss of consc...

Background: Several studies have found a connection between attentional deficit hyperactivity disorder (ADHD) and criminal behaviour in clinical and prison samples of adults, but there is a lack of representative general population data on this. Aim: To test relationships between histories of ADHD and arrest. Our main research question was wheth...

Purpose of Review Variation in the monoamine oxidase A (MAO-A) gene and MAO-A enzyme levels have been linked to antisocial behavior and aggression in clinical and non-clinical populations. Here, we provide an overview of the genetic, epigenetic, and neuroimaging research that has examined MAO-A structure and function in antisocial personality disor...

Objectives: While some existing studies suggest that conduct disorder (CD) significantly increases risk of driving after drinking, outcomes have typically been assessed only up to age 21 years. Therefore, the current study sought to assess the relationship between symptoms of CD during childhood (before age 15 years) and the risk of engaging in dri...

Antisocial personality disorder (ASPD) and borderline personality disorder (BPD) are common conditions in forensic settings that present high rates of violence. Personality traits related to the five-factor model personality domains of neuroticism and agreeableness have shown a relationship with physical aggression in nonclinical and general psychi...

Objective: Although a minority of persons with schizophrenia (SCZ) commits violent acts, SCZ remains a risk factor for violence. Here, we present a broad overview of evidence-based treatments for violence in SCZ, including biological and psychosocial interventions. Method: We conducted MEDLINE and PsychINFO literature searches to retrieve articl...

Background: Adult attention deficit hyperactivity disorder (ADHD) shows a robust association with alcohol and cannabis misuse, and these relationships are expressed differently in males and females. Manifestation of specific ADHD symptom profiles, even in the absence of the full disorder, may also be related to problems with alcohol and cannabis,...

Impulsivity is a core feature of antisocial personality disorder (ASPD) associated with abnormal brain function and neurochemical alterations. The ventral striatum (VS) is a key region of the neural circuitry mediating impulsive behavior, and low monoamine oxidase-A (MAO-A) level in the VS has shown a specific relationship to the impulsivity of ASP...

Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical st...

Monoamine oxidase inhibitors (MAOIs) are being developed for major depressive disorder, Alzheimer's, and Parkinson's Disease. Newer MAOIs have minimal sensitivity to tyramine, but a key limitation for optimizing their development is that standards for in vivo monoamine oxidase-A (MAO-A) occupancy in humans are not well established. The objectives w...

Antisocial personality disorder (ASPD) often presents with highly impulsive, violent behavior, and pathological changes in the orbitofrontal cortex (OFC) and ventral striatum (VS) are implicated. Several compelling reasons support a relationship between low monoamine oxidase-A (MAO-A), an enzyme that regulates neurotransmitters, and ASPD. These inc...

Background. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that can persist in adolescence and adulthood. Aim. To examine prevalence of ADHD symptoms and correlates in a representative sample of adults 18 years and older living in Ontario, Canada. Method. We used the Centre for Addiction and Mental Health Monitor,...

The objective of the study was to examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) symptoms in a representative population survey of adults and the association of these factors with health outcomes. Hierarchical and correlated factor analysis models were compared, and regression analyses with these models were used to...

Purpose: The purpose of this study is to examine the relationships among self-reported screening measures of attention deficit hyperactivity disorder (ADHD), other psychiatric problems, and driving-related outcomes in a provincially representative sample of adults 18 years and older living in the province of Ontario, Canada. Methods: The study e...

Monoamine oxidase-A (MAO-A) is a treatment target in neurodegenerative illness and mood disorders that increases oxidative stress and predisposition toward apoptosis. Increased MAO-A levels in prefrontal cortex (PFC) and anterior cingulate cortex (ACC) occur in rodent models of depressive behavior and human studies of depressed moods. Extreme dysph...

We conducted exploratory analyses in violent offenders and non-offenders to estimate associations between MAOA genotype, childhood physical abuse, reactive and proactive aggression, and factor 1 and 2 PCL-R scores. MAOA-H was associated with proactive aggression. Childhood physical abuse was associated with both proactive aggression and lifelong an...

Abstract Hypersexuality remains an increasingly common but poorly understood patient complaint. Despite diversity in clinical presentations of patients referred for hypersexuality, the literature has maintained treatment approaches that are assumed to apply to the entire phenomenon. This approach has proven ineffective, despite its application over...

Importance Perimenopause is a period of high risk for mood disorders, and it has been proposed that perimenopause is also a window of risk for processes linked to later dementia. However, in human perimenopause, the neurobiological changes implicated in the genesis of mood disorders or dementia have not been identified. Monoamine oxidase A (MAO-A)...

Background: Conduct disorder (CD) is diagnosed based on a prolonged pattern of antisocial behaviour including serious violation of laws and social norms [1]. There has been speculation that those with a history or current diagnosis of CD are more likely to demonstrate reckless and aggressive driving. Yet there has been little research examining the...

Violent offenders with psychopathy present a lifelong pattern of callousness and aggression and fail to benefit from rehabilitation programs. This study presents the first, albeit preliminary, evidence suggesting that some of the structural brain anomalies distinguishing violent offenders with psychopathy may result from physical abuse in childhood...

Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDE), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs primarily in the prefrontal and anterior cingulate cortex (PFC...

Objective To document experiences of childhood maltreatment among violent offenders with antisocial personality disorder (ASPD) distinguishing between those with and without the syndrome of psychopathy (+P and -P), and to determine whether maltreatment is associated with proactive and reactive aggression. Method The sample included 10 violent offe...

Objective: To document experiences of childhood maltreatment among violent offenders with antisocial personality disorder (ASPD) distinguishing between those with and without the syndrome of psychopathy (+P and -P), and to determine whether maltreatment is associated with proactive and reactive aggression. Method: The sample included 10 violent...

This chapter provides a review of the empirical literature that considers the effectiveness of services and treatments that aim to prevent antisocial and aggressive behaviour among persons with schizophrenia living in the community. It begins by summarizing the pathways through which individuals with schizophrenia and a history of criminal offendin...

Objective: People with borderline personality disorder (BPD) are at high risk for attempting suicide. There are some data to suggest that risk factors for suicide attempts change over time. We conducted a prospective cohort study to examine risk factors for suicide attempts in a treated sample of patients with BPD. Method: One hundred eighty par...

Two of the most common and important questions addressed by forensic psychiatrists working in the criminal court system are competence to stand trial (present mental capacity) and legal insanity (mental state at the time of the crime). Neuroimaging studies of criminal defendants have been used to assist in answering these questions with increasing...

Not all males undergoing phallometric testing for assessment of deviant sexual interests respond adequately to test stimuli. As poor response may be linked to hormonal, neurologic, vascular, or psychogenic causes, we studied the ability of sildenafil, an effective proerectile agent, to increase penile blood flow during phallometric testing. Twenty-...

Despite the utility of penile plethysmography in helping diagnose sexual offenders, some men respond minimally to the test stimuli. This pilot investigation examined the effect of sildenafil on phallometric responding in a non-forensic sample (n = 12) of middle-aged males. Participants underwent phallometric testing on two separate occasions and we...

In adults, the desire for a healthy limb amputation has been reported in both the lay press and the scientific literature. While the etiology of this condition is currently unknown, prevailing theories have tended to conceptualize the phenomenon as paraphilic in origin. In this report, we present the case of a 25-year-old, nonhomosexual male-to-fem...

To describe the development and implementation of General Psychiatric Management (GPM), a dynamically informed psychotherapeutic and case management approach along with symptom-targeted pharmacological interventions for the treatment of borderline personality disorder (BPD), derived from the American Psychiatric Association's (APA) guidelines for t...

Borderline personality disorder (BPD) is a chronic psychiatric condition characterized by a pervasive pattern of instability in affect regulation and impulse control. These maladaptive coping strategies predispose individuals with BPD to suicidal behavior, and this diagnosis increases the risk for completed suicide. Empirical data indicate that adv...

This study investigated whether the previously observed association of pedophilia with lower IQs is an artifact of heterogeneity in referral source. The subjects were 832 adult male patients referred to a specialty clinic for evaluation of their sexual behavior. The patients' erotic preferences for prepubescent, pubescent, or adult partners were as...