Borderline Personality Disorder – Deconstructing the Diagnosis from a Neurobiological and Psychodynamic Lens

The term “borderline” was first introduced in the psychiatric literature by Stern and Knight to describe a group of patients whose level of functioning appeared to lie between neurosis and schizophrenia. Initially, this group was not clearly defined, leading to ongoing debates about its classification and characteristics. [Leichsenring et al., 2024]

Patients with what is now recognised as Borderline Personality Disorder (BPD) were initially identified by the difficulties they posed in clinical settings.

Significant contributions from Kernberg, Kety, and Grinker established BPD’s importance in psychiatry over 50 years ago.

Diagnostic criteria were developed to distinguish BPD from schizophrenia and depression, leading to its inclusion in the DSM-III in 1980 and later in the ICD-10 as emotionally unstable personality disorder. [Gunderson et al., 2018]

Early research established that BPD could be accurately differentiated from schizophrenia, neurotic depression, and other personality disorders, confirming its status as a unique and clinically significant disorder.

Kernberg described a broader construct known as “borderline personality organisation,” which represents a level of psychic organisation rather than a specific nosological entity and can be understood as a middle level of personality organisation on a continuum from neurotic to psychotic personality organization. [Kernberg, 1967]

According to Kernberg, borderline states arise from the overwhelming intensity of destructive and aggressive impulses, coupled with the insufficient strength of the ego structures needed to manage them.

Kernberg described individuals with BPD as having “nonspecific ego weakness,” which includes:  [Kernberg, 1967]

1. Nonspecific manifestations of ego weakness:

• Lack of anxiety tolerance
• Lack of impulse control
• Failure to sublimate

2. Shift toward primary process thinking

• Disordered or regressive thought patterns

3. Specific defensive operations

• Splitting
• Primitive idealization
• Projection/projective identification
• Denial
• Omnipotence and devaluation

4. Pathologic internalised object relations, identity diffusion, loosened ego boundaries.

These patients showed intact reality testing but a propensity to shift towards dream-like thinking, differentiating individuals with BPD from psychosis.

Grinker’s Concept of the “Borderline Syndrome”:

Grinker et al. empirically identified four core features of the “borderline syndrome.” [Grinker et al, 1968].

• Anger
• Impaired close relationships
• Identity problems
• Depressive loneliness

Adler and Buie’s Concept of “Evocative Object Constancy”:

• Adler and Buie described a specific deficit in BPD patients called “evocative object constancy.” [Adler & Buie, 1979]
• This refers to the inability of individuals with BPD to self-soothe by recalling comforting memories, images, or experiences with others.
• This deficit originates from early childhood experiences with parents who are unempathetic, emotionally unavailable, or abusive. These parents do not effectively assist their children in learning how to regulate their emotions, which hinders the children’s ability to develop this skill independently over time.

DSM-5 Diagnosis: [American Psychiatric Association, 2013]

The DSM-5 characterises BPD as a pervasive pattern of instability of interpersonal relationships, self-image and affects, and marked impulsivity, emerging by early adulthood and present in a variety of contexts, as indicated by five or more of a set of nine criteria.

An important aspect omitted in the DSM-­ 5 criteria for BPD is regression proneness (i.e., showing emotions or behaviours not adequate to age) in unstructured situations, one of the reasons for many of the treatment problems occurring with the disorder. [Leichsenring et al., 2024]

With nine DSM—5 criteria and a threshold for diagnosis of five positive criteria, there are 256 theoretically possible ways to meet the criteria for BPD. Thus, despite conceptual coherence, BPD appears to be a heterogeneous diagnostic category that may include patient subtypes.

The DSM-5-TR Alternative Dimensional Model for Diagnosing BPD introduces a hybrid dimensional-categorical approach, defining personality disorders based on personality functioning and pathological traits.

DSM-5 Proposed Alternative Dimensional Model of Personality Disorders  [American Psychiatric Association, 2013]

The alternative dimensional model of personality disorders (AMPD) included in the DSM-5 assesses

1. The level of personality functioning and
2. Pathological personality traits.

With regard to personality functioning, the AMPD draws on psychodynamic concepts such as personality organisation and mentalisation.

Cluster Analysis : [Smits et al., 2017]

Three Clusters:

1. “Core” BPD symptoms (Large)
2. Extravert/externalising cluster characterised by high levels of histrionic, narcissistic and antisocial features.
3. Marked schizotypal and paranoid features. (Small)

ICD-11 diagnostic criteria for Borderline pattern of Personality disorder or Personality difficulty:

In the ICD-­ 11, the categorical system of personality disorders (PDs) has been replaced by a dimensional approach similar to the DSM-­ 5 alternative dimensional model. [WHO, 2022]

The ICD-11 focuses on global and shared features that apply to all PDs.

BPD by the five-­ factor model of personality: [Streit et al., 2022][Koster et al., 2019]

• High levels of both neuroticism (anxiousness, angry hostility, depressiveness, impulsiveness, vulnerability) and openness (high openness to feelings and actions)
• Low levels of both agreeableness (low compliance) and conscientiousness (low deliberation).
• Meta-analytic work shows that BPD is positively associated with Neuroticism (N) and negatively associated with agreeableness (A) and conscientiousness (C) in adult samples. [Koster et al., 2019]

Symptom Phenotype Classification of BPD:

The core psychopathology of BPD can be divided into 4 symptom phenotypes [Gunderson et al., 2018]

1. Interpersonal Instability
2. Cognitive and/or self-disturbance
3. Affective and/or emotional dysregulation
4. Behavioural dysregulation

Interpersonal Instability Phenotype:

• Characterised by unstable and conflicted relationships.
• Alternating between becoming overly involved with others and withdrawing socially.
• The development of deep dependencies on certain individuals but may also become manipulative and demanding if their needs are not met.
• Dramatic shifts in how they view emotionally significant others are common—idealising them when needs are met and devaluing them when feeling disappointed or neglected.
• Difficulty in recognising the feelings and needs of others, coupled with hypersensitivity to social threats, especially perceived interpersonal rejection.
• Fear of abandonment is prevalent, leading to extreme efforts to avoid it, such as displaying clingy, threatening, or demanding behaviours.

Cognitive and/or Self-Disturbance Phenotype:

• Characterised by a markedly impoverished, unstable, or poorly developed self-image, which may include feelings of self-contempt.
• Chronic feelings of emptiness with low self-esteem, being prone to self-criticism and experiencing intense shame.
• Inconsistent personal goals, aspirations, values, and career plans, frequently changing, and pursued without strong conviction.
• Disturbed cognition, including transient paranoid ideation or dissociative symptoms under stress.

Affective and/or Emotional Dysregulation Phenotype:

• Emotional lability is a hallmark of this phenotype, with patients reacting intensely in interpersonal situations.
• These reactions often involve strongly felt dysphoric emotions such as depression, anxiety, or irritability.
• Patients may experience intense and inappropriate anger, which can result in physical altercations.

Behavioural Dysregulation Phenotype:

• This phenotype is characterised by problems with excessive behaviours that pose a risk of harm, coupled with poor impulse control.
• Patients may engage in impulsive activities such as reckless spending, indiscriminate sexual behaviour, substance abuse, reckless driving, and binge eating.
• Self-injurious behaviours (e.g., cutting, burning) and recurrent suicidal gestures, threats, or attempts are also common.
• Impulsivity is typically triggered by negative, distressing emotional states.

To summarise, there is agreement in research that the three dimensions which capture the essence of the disorder are:  [Trull & Hepp, 2023]

• Emotional dysregulation
• Impulsivity and behavioural dysregulation
• Interpersonal hypersensitivity

Gender Differences in Borderline Personality Disorder: [Bozzatello, 2024].

• Men with BPD are more likely to exhibit intense anger and impulsivity, while women more commonly experience chronic emptiness, affective instability, and suicidality/self-harm behaviours.
• Men with BPD show higher novelty-seeking and impulsive behaviours, while women display greater affective instability, identity disturbance, and unstable relationships.
• Women with BPD have higher rates of comorbid depressive, anxiety, eating, and somatoform disorders, whereas men are more prone to antisocial personality disorder and substance use disorder.
• Gender differences are observed in the prefrontal cortex, striatum, and amygdala activity during tasks that provoke anger or aggression. In males, trait anger negatively affects amygdala-prefrontal cortex connectivity, while in females, it enhances this coupling during anger and aggression tasks.
• Both genders use mental health services similarly, but men are more likely to use drug/alcohol rehabilitation services and receive less psychotherapy and pharmacotherapy compared to women.

Diagnosis in Childhood and Adolescence:

Borderline Personality Disorder (BPD) is believed to have its origins in childhood or early adolescence, typically gaining clinical attention in early adulthood. [Gunderson et al., 2018]

Historically, there has been reluctance among clinicians to diagnose personality disorders in youth due to concerns about the evolving nature of personality, the potential for misinterpreting developmentally appropriate behaviours, and the stigma associated with early diagnosis.

This is highlighted in the debate between Dr Paulina Kernberg and Dr Theodore Shapiro. [Kernberg, 1990]

According to Kernberg, borderline personalities in children are often linked to conditions such as conduct disorders, separation anxiety, identity disorders, eating disorders, selective mutism, ADHD, and developmental disorders.

She highlights the risk of under-diagnosis, which can lead to severe adult psychopathology, including schizophrenia-related psychoses, bipolar disorders, and antisocial personalities. [Kernberg, 1990]

Genetics:

• Borderline Personality Disorder tends to occur more frequently in individuals with a family history of the disorder.
• A large population-based study in Sweden, including over 1.8 million participants, estimated the heritability of BPD at approximately 46%, with the remaining 54% of variance attributed to nonshared environmental factors. The risk of BPD diagnosis was higher among identical twins. [Skoglund et al., 2021]
• Studies that controlled for interviewer variance and utilised both interview and self-report methods have estimated BPD heritability at around 70%, a figure supported by additional studies conducted over time. [Torgersen et al., 2012]
• The first genome-wide association study in patients with BPD indicated a genetic overlap with bipolar disorder, schizophrenia, and major depression. The implicated genes are involved in fundamental neural processes such as cell adhesion and myelination, suggesting that the genetic factors associated with BPD may also relate to a broader risk for psychiatric disorders. [Witt et al., 2017]

Epigenetics:

• Increased methylation of certain genes, including MIR124-3, which is involved in neural plasticity and amygdala function, has been reported in individuals with BPD, particularly those with a history of childhood maltreatment. This suggests a potential pathway from early-life adversity to the development of BPD in adulthood.
• Altered methylation patterns in other genes, such as BDNF (brain-derived neurotrophic factor), have also been linked to early-life maltreatment and an increased susceptibility to BPD.
• Polymorphisms in genes associated with the hypothalamic-pituitary-adrenal (HPA) axis, such as FKBP5 and CRHR1, may also play a role in BPD’s aetiology. These genetic variants are associated with heightened cortisol secretion, leading to structural and functional changes in brain regions like the hippocampus.
• Chronic stress can induce epigenetic modifications, such as DNA methylation, through exhaustive stimulation of the HPA axis, leaving a lasting impact on gene activity. This process involves genes such as NR3C1 and FKBP5, which are critical in neuronal development, brain plasticity, and the body’s stress response. [Gescher et al., 2024]

Adverse Childhood Experiences: [Leichsenring et al., 2024]

• In BPD, both genetic factors and adverse childhood experiences interact to influence brain development through the modulation of hormones and neuropeptides.
• Adverse childhood experiences are believed to affect gene expression, leading to stable personality traits that may increase the predisposition to developing BPD.
• Significant associations have been found between BPD and experiences of physical, sexual, and emotional abuse, as well as neglect.
• 30% to 90% of patients who meet the criteria for borderline personality disorder (BPD) have a history of child abuse or trauma. [Yen et al., 2002]
• Inconsistent parenting, maternal over-involvement, aversive parental behaviours, and low parental affection are all associated with the development of Borderline Personality Disorder (BPD), though these factors are not unique to the disorder. [Stepp et al., 2012].
• Additionally, separating children from their mothers before the age of five has been found to predispose individuals to BPD in adulthood. [Gunderson et al., 2018]
• BPD has also been linked to high levels of disorganised and unresolved attachment patterns, particularly among individuals with a history of significant negative experiences during childhood.
• Emerging evidence indicates that BPD is connected to both early and later life adversity, contributing to persistent and harmful interpersonal cycles.
• For example, high levels of re-victimisation in romantic relationships and bullying among peers contribute to increased distrust and social isolation in individuals with BPD.
• Additionally, social deprivation and societal inequality are emerging factors that may elevate the risk of BPD by increasing distrust and sensitivity to social rejection and injustice.

Frontolimbic Dysfunction:

The prevalent hypothesis suggests that BPD is characterised by fronto-limbic dysfunction, where emotion dysregulation arises from hyperactivity in limbic structures such as the amygdala, hippocampus, and anterior cingulate cortex, with abnormal functioning of prefrontal regions. [Leichsenring et al., 2024]

This dysfunction may reflect a transdiagnostic phenomenon linked to negative affectivity and social stress.

Moreover, neuroimaging findings in BPD may lack specificity, potentially reflecting broader psychopathology or the impact of childhood maltreatment rather than features unique to BPD.

Amygdala Hyper-reactivity:

• BPD patients show consistent left amygdala hyperactivity in response to negative stimuli.
• Meta-analyses confirm that amygdala and hippocampal hyperactivity during emotional processing are the most robust neuroimaging findings in BPD. [Leichsenring et al., 2024]
• This hyperactivity persists due to a habituation deficit, making it difficult for BPD patients to reduce their response to repeated negative stimuli.
• Maladaptive top-down processes likely sustain this heightened amygdala response, contributing to emotional dysregulation in BPD.

Dorsal ACC Activation:

• The dorsal anterior cingulate cortex (dACC) acts as a neural alarm signal for both physical and social pain.
• In BPD patients, dACC shows heightened activation across all conditions, indicating a higher sensitivity to potential threats or rejection, even when no such threat is present. [Wrege et al., 2019].
• Alterations in affective pain processing circuits may mediate hypoalgesia in non-suicidal self-injurious behaviour. [Nance et al, 2024]

Triple-Network Model of BPD:

• BPD symptoms are linked to impairments in the salience network (SN), default mode network (DMN), and executive control network (ECN), as proposed by the “triple network model.” [Quattrini et al., 2022]
• Research shows impaired connectivity in these networks in BPD, particularly with anterior and right-lateralised microstructural changes, which correlate with behavioural dysregulation and may represent targets for future non-invasive treatments. [Quattrini et al., 2022]

Neurocognition and Social Cognition: [Leichsenring et al., 2024]

• Meta-analyses reveal a complex pattern of cognitive and social impairments in BPD.
• Key findings include deficits in emotion recognition accuracy, an attentional bias towards negative stimuli, heightened rejection sensitivity in social exclusion and inclusion scenarios, imbalances in mentalizing capacities, dysfunctional emotion regulation, and neurocognitive deficits.

From a neurobiological perspective, it may be helpful to consider the identified neuroimaging changes in the context of the symptom phenotypes.

Neurobiology of the Interpersonal Instability Phenotype:

• Abnormalities in circuits related to theory of mind (ToM) and empathy, affecting the ability to infer others’ emotional and cognitive states. [Gunderson et al., 2018]
• Dysfunctions in circuits involved in self-disturbance, crucial for disruptions in self-referential thinking and sense of self in BPD.
• Stronger coupling between the amygdala and medial PFC, leading to challenges in shifting attention from self-relevant information, contributing to interpersonal difficulties, high levels of alexithymia in BPD and possible dissociative phenomena. [Krause-Utz et al, 2021].
• In BPD, there is a tendency to hypermentalize, leading to overattributing intentions and emotions to oneself and others, which can result in misunderstandings and interpersonal conflicts.
• Hypermentalisation may be linked to midline brain structures, including the medial PFC, ACC, precuneus, and temporoparietal junction, which overlap with the default mode network. Their dysregulation may lead to exaggerated interpretations of social cues, perpetuating interpersonal conflict. [Gunderson et al., 2018]

The Neuroscience of Dissociation – Clinical Application in Trauma Disorders

Neurobiology of the Affective and Emotional Dysregulation Phenotype:

Involvement of the bottom-up and top-down processes contributes to affective and behavioural dysregulation.

Affective instability is a key feature of BPD, characterised by rapidly fluctuating negative emotions in response to stress, with a delayed return to baseline.

Two key phenomena mediating this instability include:

1. Emotional and Rejection Hypersensitivity

• BPD patients exhibit hypervigilance towards negative stimuli, leading to distress and interpersonal challenges.
• High sensitivity to perceived rejection, worsened by ineffective affect regulation, results in severe emotional dysregulation.

2. Affect-Dominated Perception

• BPD perception is more emotionally driven than cognitive, increasing vulnerability to emotional contagion and blurring the distinction between self and others.
• This results in confusion between the emotions of others and self, lacking the mature empathy where self-other emotional distinction is maintained.

Neurobiology of the Behavioural Dysregulation Phenotype:

• Fronto-striatal circuits involved in predicting negative outcomes and inhibitory control are implicated in the behavioural dysregulation phenotype.
• Impulsivity in BPD is a multifaceted construct involving impaired delay discounting, heightened emotional interference in cognitive tasks, and reduced response inhibition, especially under stress.
• Individuals with BPD often demonstrate impulsivity by choosing immediate, smaller rewards over larger, delayed ones, which is linked to abnormalities in the inferior frontal cortex, potentially underlying motor impulsivity in BPD.
• Importantly, while response inhibition failures are often associated with BPD, they are more characteristic of ADHD, a common comorbid condition with BPD. However, the impulsivity observed in BPD is more context-dependent, particularly under conditions of emotional stress.

Neurobiology of Attention Deficit Hyperactivity Disorder (ADHD) – A Primer

Preliminary data suggest that successful psychotherapy can normalise low prefronto-limbic connectivity in BPD, indicating that core neurobiological features may be reversible and lead to improvements in cortical representation of bodily signals. [Iskric & Barkley-Levenson, 2021] [Schmitt et al., 2016]

Reward Prediction Errors (RPEs) and the Salience Network in Borderline Personality Disorder (BPD)

Accurate prediction of rewarding or aversive outcomes is essential for adaptive responses to environmental stimuli.

In a typically developing brain, prediction errors (PEs)—mismatches between expectations and outcomes—are signalled by rapid, phasic firing of dopamine and serotonin neurons that project to the brain’s reward and salience networks.

Prediction error signals within these networks are crucial for directing attention, assigning meaning, and integrating internal and external information, which helps in developing and updating the brain’s “internal model” of the environment. This process is known as predictive processing. [Millman et al., 2022]

Salience Network Activation: 

In Borderline Personality Disorder (BPD), the salience network is implicated in the exaggerated reactivity to negative stimuli.

This heightened response may be due to impaired habituation and exaggerated sensitisation within these neural circuits, leading patients to perceive negative social situations as overly salient. [Denny et al., 2018]

Childhood maltreatment, prevalent among individuals with BPD, significantly disrupts the development of the brain’s predictive processing systems, thereby contributing to emotional instability and heightened sensitivity to social cues.

Trauma may sensitise the amygdala, leading to increased vigilance and attention to unexpected outcomes, which can result in fear, rumination, and referential thinking. [Millman et al., 2022]

This often culminates in a rigid, impoverished model of self and others, characterised by alexithymia, where individuals face challenges in identifying and describing their emotions, ultimately hindering belief updating even when confronted with contradictory evidence. [Herzog et al., 2022]

For instance, a child subjected to repeated invalidation by caregivers may internalise the belief that their emotions are “wrong,” fostering hypersensitivity to social cues and subsequent emotional instability.

In BPD, this distorted belief updating manifests either as rapid shifts in beliefs in response to minor stimuli or as an inability to revise beliefs despite clear disconfirmatory evidence. [Musser et al., 2018]

Altered Reward Processing:

Altered reward processing represents another critical element in the pathology of BPD.

Individuals with BPD frequently exhibit exaggerated responses to reward prediction errors (RPEs), which contribute to abrupt mood swings and pervasive emotional instability.

This heightened sensitivity to discrepancies between expectations and outcomes, particularly within social and reward contexts, intensifies emotional reactivity. [Csukly et al., 2023], [Goldberg, 2023]

Additionally, impaired negative feedback processing in BPD, evidenced by reduced Feedback-Related Negativity (FRN), leads to a lack of behavioural adjustments following feedback, thus compromising the ability to form positive expectations and make adaptive decisions, further exacerbating core BPD symptoms such as impulsivity and unstable interpersonal relationships. [Vega et al., 2013]

Inconsistent parenting and invalidating environments exacerbate distorted predictive processing in BPD. [Boucher et al, 2017]. 

Unpredictable caregiver interactions undermine the development of stable social expectations, fostering a reliance on external feedback and impairing emotion regulation.

Early life exposure to inconsistent and unpredictable caregiving environments fosters an asymmetry in precision weighting. [Herzog et al., 2022]

Negative or threatening stimuli are afforded increased precision, resulting in an amplified influence of negative feedback-whether real or perceived—on future predictions about social interactions.

This heightened precision increases the focus on negative social cues, reinforcing maladaptive beliefs about the self and others.

Consequently, individuals with BPD exhibit greater sensitivity to perceived negative feedback, which contributes to emotional dysregulation and a persistently negative self-concept.

In contrast, positive or neutral feedback is assigned lower precision, diminishing its impact on the individual’s internal predictive models. This imbalance hinders updating beliefs in response to favourable or neutral experiences, perpetuating maladaptive cognitive and behavioural patterns.

This asymmetry in prediction error processing underlies core symptoms of BPD, including emotional lability, impulsivity, and instability of self-image, as individuals continuously engage in maladaptive attempts to mitigate the uncertainty and emotional discomfort driven by this biased precision-weighting mechanism.

This frequently results in the adoption of dysfunctional emotion regulation strategies such as suppression, rumination, and avoidance, which are common in BPD. [Herzog et al., 2022]

Moreover, this developmental disruption promotes dichotomous thinking, wherein individuals with BPD struggle to interpret others’ intentions with nuance, leading to oversimplified explanations for unpredicted outcomes, such as self-blame or external blame. [Herzog et al., 2022]

Thus, therapeutic approaches should focus on enhancing the precision of patients’ predictive models and improving their ability to update beliefs based on new information.

Interventions that increase attention to RPEs, such as mindfulness and cognitive-behavioural techniques, can assist patients in critically examining the validity of their beliefs and adjusting their expectations more accurately.

By refining predictive models, these therapeutic strategies may reduce emotional reactivity, promote adaptive decision-making, and alleviate core BPD symptoms.

Endogenous Opioid System (EOS) Imbalance:

The endogenous opioid system (EOS) is a complex neuromodulatory network involving receptor families like mu (MOR) and kappa (KOR) opioid receptors and ligands such as beta-endorphins, enkephalins, and dynorphins.

In addition to its roles in pain modulation and stress response, including endocrine and immune functions, the EOS is crucial for mood regulation, reward processing, and social bonding, particularly in separation-induced distress.[Gescher et al., 2024]

MORs are primarily associated with the regulation of pleasure and reward, whereas KORs are linked to stress and dysphoria.

The impact of chronic stress and trauma, particularly when these experiences occur during early childhood, can significantly alter the expression of these receptors.

For example, hypomethylation of the OPRK1 gene promoter can lead to the overexpression of KORs, which suppresses dopamine activity in the brain’s reward pathways, contributing to the anhedonia and dysphoria frequently observed in Borderline Personality Disorder (BPD).

Simultaneously, persistent neglect or a lack of social support might result in the chronic under-stimulation of MORs, crucial for fostering social bonds and emotional reward.

This underactivation may lead individuals with BPD to engage in behaviours that artificially stimulate the EOS, such as substance abuse, self-injury, or other risky behaviours, in a misguided attempt to address hedonic deficits.

As a compensatory mechanism, the body may attempt to upregulate MORs, increasing their activity.

However, this upregulation can trigger a corresponding rise in KOR activity, perpetuating a cycle of dysphoria and emotional instability.

This pattern is particularly evident in the addictive behaviours exhibited by many BPD patients, including substance abuse, binge eating, and non-suicidal self-injury (NSSI).

These behaviours can be understood as efforts to activate the EOS and achieve temporary relief from emotional pain, though they ultimately lead to a cycle of dependency akin to substance addiction. [Blasco-Fontecilla et al., 2016]

This process mirrors the allostatic model of addiction. 

The mesocortical dopamine reward system, in conjunction with the EOS, is likely implicated in these addictive behaviours.

Chronic stress elevates dynorphin levels, which activate KORs and inhibit dopamine release, inducing a state of dysphoria and emotional pain. This dysphoric state may drive individuals to engage in self-harm or substance use as a means of seeking relief.

The hypothalamic-pituitary-adrenal (HPA) axis, which plays a critical role in the body’s stress response, also interacts with the opioid system.

During periods of acute or chronic stress, increased corticotropin-releasing factor (CRF) levels activate the HPA axis, which may lead to heightened opioid production.

Although this opioid increase may initially provide stress relief, it can contribute to tolerance and addiction over time.

Modulating the EOS, particularly through opioid receptor antagonists like naltrexone, shows promise in alleviating BPD symptoms such as self-injury, binge eating, and suicidality, highlighting its potential in managing impulsivity and emotional dysregulation in BPD. [Timäus et al., 2021]

Women with borderline personality disorder (BPD) often exhibit higher than expected serum androgen levels and a higher incidence of polycystic ovaries, which are key features of polycystic ovary syndrome (PCOS). [Tan et al., 2018]

Postulated mechanisms include:

1. Increased HPA Axis Activity Due to Childhood Trauma

Individuals with BPD were 3.15 times more likely to report childhood adversity. [Porter et al., 2020]. 

A female’s endocrine system responds differently to perceived threats and is highly influenced by CRF neurons in key stress-related brain regions independent of circulating sex steroids. [Navigating Female-Specific Complexities in Psychiatry: Implications for Clinical Practice & Psychopharmacology]

Females have a higher expression of CRF receptors in the Central amygdala (CE) and Basolateral Amygdala (BLA) regions of the amygdala, which may increase fear consolidation and impair extinction. Sex differences in the corticotropin-releasing factor 1 receptor (CRF1) make noradrenergic neurons in the LC more sensitive in females.

Chronic stress exposure often results in hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, a condition linked to the increased production of androgens such as DHEA, DHEAS, and androstenedione.

These androgens are precursors that can be converted into more potent forms, such as testosterone and dihydrotestosterone (DHT), which contribute to clinical hyperandrogenism—a hallmark of Polycystic Ovary Syndrome (PCOS).

Additionally, an adrenal component has been observed in 30–50% of women with PCOS, further suggesting a connection between HPA axis hyperactivation and the elevated androgen levels observed in both BPD and PCOS.

2. Impact on the HPG Axis and Ovarian Cysts Development

Cortisol, as a result of hyperactivation of the HPA axis, exerts inhibitory effects on the HPG axis, contributing to menstrual dysfunction commonly observed in Polycystic Ovary Syndrome (PCOS).

Additionally, stress-induced activation of a sympathetic neural pathway in the hypothalamus releases noradrenaline into the ovaries, potentially playing a role in the formation of ovarian cysts.

Oxytocin: [Herpertz & Bertsch, 2015]

Peripheral oxytocin levels are reduced in adults with Borderline Personality Disorder (BPD), especially in those with early-life maltreatment and disorganised attachment.

This decrease, likely due to genetic factors and early trauma, influences oxytocin’s role in modulating amygdala activity, which typically buffers against social stress and reduces threat sensitivity.

Low oxytocin levels may exacerbate key BPD symptoms, such as impaired affect regulation, heightened threat sensitivity, and social difficulties. These deficits suggest oxytocin’s involvement in the transmission of trauma and maladaptive behaviours in BPD.

While oxytocin administration shows potential in reducing amygdala-driven hypersensitivity and avoidant behaviours, its therapeutic efficacy in BPD remains uncertain, and its effects are not specific to this disorder.

Intranasal oxytocin is under investigation for treating self-harming behaviours linked to social stressors, but further research is needed to confirm its effectiveness. [di Giacomo et al, 2024]. 

Testosterone, Oestrogen and Progesterone:

Testosterone levels are elevated in both female and male patients with BPD, as indicated by short-term measures (saliva) and long-term measures (hair). [Rausch et al., 2015]

Testosterone plays a role in prefronto-amygdala inhibition during social tasks, potentially promoting social approach and dominant behaviour.

Additionally, fluctuations in female sex hormones, such as oestradiol and progesterone, higher progesterone in the luteal phase, 17β-oestradiol fluctuations at ovulation and in the luteal phase during the menstrual cycle, may influence the expression of BPD symptoms.[Eisenlohr-Moul et al., 2015]

Borderline Personality Disorder (BPD) can be reconceptualised as an interpersonal pain syndrome due to the significant interplay between pain, both physical and psychological, and the dynamics of relationships in individuals with BPD.

Studies consistently demonstrate a high prevalence of chronic pain in BPD patients, with up to 65% reporting a lifetime diagnosis of chronic pain. [Heath et al., 2018] [Zanarini et al., 1998]

This chronic pain not only exacerbates the psychological symptoms of BPD, such as anxiety and emotional dysregulation, but also predicts a lower likelihood of BPD remission. [Johnson et al., 2020]

Moreover, patients with chronic pain frequently exhibit BPD symptoms, with up to 30% meeting the diagnostic criteria for BPD. [Johnson et al., 2020]

The relationship between BPD and pain is bidirectional and complex, with BPD symptoms often leading to increased pain severity and interference in daily life, alongside a unique manifestation of pain characterised by heightened affective pain and central sensitisation. [Johnson et al., 2020]

Pain Processing Circuits:

Patients with BPD often exhibit increased pain thresholds, which may be due to two primary mechanisms: [Gunderson et al., 2018]

1. Amygdala Deactivation:

Amygdala deactivation and enhanced top-down inhibition from limbic to medial prefrontal areas may reflect a neurobiological adaptation that increases pain thresholds in BPD by reducing the emotional impact of pain.

The enhanced top-down inhibition is also a feature in the emotional overmodulation phenotype of PTSD associated with dissociation in PTSD. [The Neuroscience of Dissociation – Clinical Application in Trauma Disorders]

2. Abnormal Insula-PFC Coupling:

Enhanced coupling between the posterior insula and dorsolateral prefrontal cortex, which is involved in affect-related pain processing, may contribute to hypoalgesia in BPD.

Non-suicidal self-injurious behaviour (NSSI) in individuals with BPD serves as a coping mechanism for stress relief and is linked to reduced affect-related pain processing.

This suggests that these behaviours may provide temporary emotional relief through altered pain perception.

Dialectical Behaviour Therapy (DBT) and other interventions that focus on improving affect regulation strategies might help to decrease this maladaptive top-down modulation, thereby reducing the reliance on self-injury for emotional regulation.

The Role of Identity Formation and Interpersonal Dysregulation in the Pathogenesis of Pain in Borderline Personality Disorder:

In the clinical understanding of borderline personality disorder (BPD), the processes of identity formation and the quality of interpersonal relationships are central to the psychogenesis of psychological pain.

The development of identity in individuals with BPD is often marked by intense fears of abandonment and chronic relational instability.

This dynamic can be understood as a form of interpersonal pain that is deeply rooted in the developmental trajectory of these patients.

Engel conceptualised pain- whether physical or psychological- not merely as a sensory experience but as a complex psychological phenomenon arising from the interaction of higher nervous centres with peripheral sensory inputs. [Engel, 1959]

He posited that the psychic organisation necessary for the experience of pain evolves through early developmental stages, where pain and its relief become integral to the formation of interpersonal (object) relations.

As children develop, they internalise pain as a means of assuaging guilt, influencing the concepts of good and bad, reward and punishment, thereby shaping object relationships. [Engel, 1959]

The understanding of Borderline Personality Disorder (BPD) originated in psychodynamic theory, which connected the disorder to early developmental disruptions and problematic caregiver-child relationships.

While these insights remain relevant, advances in empirical research have highlighted the complex interplay between genetic predispositions and environmental influences.

Early psychodynamic factors, such as disrupted attachments, are now recognised as contributing to neurobiological changes that influence later psychological outcomes.

Since Kernberg’s foundational work in 1975, numerous theories have further clarified the multifaceted aetiology of BPD.

Kernberg’s Theory (1975):[Kernberg, 1975]

• Kernberg proposed that borderline phenomena stem from a failure to integrate representations of good and bad aspects of the self and others.
• Due to excessive negative feelings, often rooted in temperament or severe environmental frustrations, individuals store memories of good and bad experiences separately.
• Those who develop borderline character structures strive to protect “good” representations of others while fending off negative associations, leading to a continuous internal conflict between rage and idealisation.

Kohut’s Perspective (1977): [Kohut, 2009]

• Kohut argued that children develop a coherent sense of self and emotional regulation through “transmuting internalisations” of early caregivers’ soothing and mirroring functions.
• Optimal development occurs when children experience their parents as both admirable and admiring, leading to the formation of stable self-esteem and ideal self-standards.
• Failures in empathic caregiving can disrupt this process, contributing to difficulties in self-regulation and the development of borderline personality traits.

Adler and Buie’s Application of Kohut’s Constructs:

• Adler and Buie expanded on Kohut’s ideas, suggesting that individuals with BPD have a deficit in the ability to evoke comforting memories of “good objects” to soothe themselves during distress. [Adler & Buie, 1979]
• This deficit, combined with difficulties integrating representations of self and others, impairs the capacity for self-soothing and emotional regulation.
• The inability to reconcile the idealised and flawed aspects of caregivers may further complicate the development of stable self-identity.

Masterson’s View (1976):

• Masterson proposed that borderline dynamics arise in relationships with caregivers who struggle with their own emotional regulation and fears of abandonment. [Masterson, 2013].
• These caregivers may depend on their children for emotional stability, leading to role-reversed relationships where the child is used to meet the caregiver’s needs.
• The child’s normal efforts toward autonomy or expression of anger are often met with misattunement or rejection, leading to the development of a “false self” that prioritises the caregiver’s needs over the child’s own.
• This environment contributes to deficits in emotional understanding, sense of self, and the ability to navigate social relationships.

Object Relations Theory:

Psychoanalytic theorists have emphasised several key aspects of object relations in BPD [Bradley & Westen, 2005]

• Splitting: Patients with BPD often split representations of others into all-good or all-bad, with poor integration of these aspects across different mood states.
• Fear of Abandonment: They tend to fear rejection and abandonment in intimate relationships, often attributing malevolent intentions to others, which can lead to self-fulfilling prophecies.
• Difficulty in Relationships: As a result of these dynamics, individuals with BPD struggle to form and maintain stable, lasting relationships, frequently experiencing relational instability.

Identity Diffusion and Self-Concept:

• A central psychodynamic feature in BPD is identity diffusion, where individuals experience significant contradictions in their behaviour and self-perception, temporal discontinuity, and a lack of authenticity.
• They may exhibit a chameleon-like tendency to change personalities based on their social context, struggle with feelings of emptiness, and have confusion about gender identity and moral values. [Bradley & Westen, 2005]
• These features contribute to an unstable and fragmented sense of self.

Akhtar identified six key features of identity diffusion as outlined by Kernberg : [Akhtar, 1984], [Akhtar, 1992]

1. Contradictory Character Traits: Individuals exhibit significant contradictions in behaviour, self-perception, or vocational interests.
2. Temporal Discontinuity of the Self: There is a failure to experience the self as continuous over time.
3. Lack of Authenticity: A tendency to adopt the characteristics of others, leading to a chameleon-like change in personality across different situations.
4. Feelings of Emptiness: Reflecting the absence of a consistent, internal sense of self.
5. Gender Dysphoria: Confusion regarding gender identity and sexual orientation.
6. Inordinate Ethnic and Moral Relativism: A lack of a stable set of values, with beliefs and morals shifting to align with those of a surrounding social group.

In 1992, Akhtar added a seventh feature:

Disturbances in Body Image. [Akhtar, 1992]

Individuals with Borderline Personality Disorder (BPD) can be understood through several psychodynamic concepts that highlight the complex interplay between self-perception, object relations, and emotional regulation.

Self and Identity:

Patients with BPD experience a conflict between their intense need for connection and their fear, mistrust, and anger, often pushing others away.

This dynamic leads to a reliance on the physical presence of others to manage emotions as they struggle with self-soothing. [Shedler & Westen, 2004]

Self-representations in BPD are fragmented, with individuals often unable to integrate differing aspects of their self, such as holding representations of themselves as both angry and loving.

This results in sharp discontinuities in self-perception, fluctuating between extremes, especially negative ones. Patients often view themselves as permanently damaged or evil.

Identity diffusion in BPD is characterised by role absorption, painful incoherence, inconsistency in behaviour and attitudes, and a lack of commitment to values and goals.

These factors contribute to a pervasive sense of a “false self” and difficulty maintaining a coherent sense of identity.

Cyclical Psychodynamics:

BPD patients often experience what Wachtel describes as “cyclical psychodynamics,” where their fears and conflicts inadvertently lead to the outcomes they most fear, such as abandonment. [Wachtel, 2017]

This cycle often results in intense but unstable relationships, where patients may resort to self-harm or suicidal threats that further alienate others.

Attachment and Mentalization:

BPD is strongly linked to disorganised attachment patterns, where individuals struggle with incoherent and contradictory behaviours in relationships. [Bateman & Fonagy, 2020]

This stems from early experiences with unpredictable or abusive caregivers, leading to an inability to form stable internal models of relationships.

The failure to develop mentalization, or reflective function, is a key aspect of BPD.

This ability, which usually emerges in the context of healthy attachment relationships, allows individuals to understand their own and others’ mental states.

Without it, BPD patients often equate their perceptions of others’ intentions with reality, leading to difficulties in considering alternative perspectives.

Emotional Regulation and Object Relations:

BPD patients often have deficits in emotional regulation, relying heavily on external relationships to manage their emotions.

This can manifest as a desperate need for intimacy, followed by rejection or distrust when it is offered, perpetuating feelings of alienation and victimisation [Shedler & Westen, 2004]

In terms of object relations, BPD patients typically struggle to maintain complex representations of others, often splitting them into all-good or all-bad categories.

This splitting, coupled with intense fears of rejection and abandonment, makes it difficult for them to sustain lasting intimate relationships.

The Victim-Victimizer Dynamic:

The victim-victimizer dynamic in BPD involves the patient perceiving themselves as a victim, projecting unmet needs and unresolved aggression onto others, who are then seen as persecutors when the patient’s idealised expectations are not fulfilled.

This dynamic reflects underlying conflicts in object relations and the use of splitting as a defence mechanism, where others are viewed in polarised terms of all good or all bad, depending on whether they meet or frustrate the patient’s emotional needs.

In this article, which represents the first part of a comprehensive review of Borderline Personality Disorder (BPD), we have explored the historical evolution, diagnostic construct, and aetiological underpinnings of BPD through both neurobiological and psychodynamic lenses.

This review highlights the advances in empirical research that have expanded our understanding of BPD, demonstrating that it is a multifaceted condition where genetic predispositions interact with environmental factors, particularly early life stress and trauma.

We examine the complex neurobiological circuits and neurotransmitter systems implicated in BPD, including the dysregulation of affective and pain processing pathways.

These insights are integrated with psychodynamic perspectives, which continue to offer valuable explanations for the internal conflicts, attachment disturbances, and maladaptive coping mechanisms observed in individuals with BPD.

By bridging the neurobiological and psychodynamic theories, we provide a more integrated view of BPD’s pathogenesis, recognising it as a condition that encompasses both biological and psychological dimensions.

This integrated understanding sets the stage for the forthcoming second part of our review, where we will cover the diagnostic approach and management strategies for BPD.

We aim to equip clinicians with a deeper comprehension of the disorder’s core pathophysiology, ultimately improving diagnostic accuracy and treatment outcomes in this often misunderstood and challenging condition.

Related learning on The Academy

• To build on the assessment and management of emotional dysregulation in borderline personality disorder, clinicians may find Dialectical Behaviour Therapy – A Practical Guide for Clinicians on The Academy by Psych Scene particularly valuable. The course covers core DBT principles, including mindfulness, distress tolerance, emotion regulation, and interpersonal effectiveness, and offers practical frameworks for supporting individuals with complex presentations.
• Clinicians interested in the overlap between trauma-related presentations and borderline personality disorder may also find Complex Post-traumatic Stress Disorder (C-PTSD) – A Practical Guide valuable. The course explores adverse childhood experiences, the clinical features of C-PTSD, diagnostic challenges, the overlap and differentiation between PTSD, C-PTSD and BPD, and phase-oriented approaches to managing complex trauma.