A NEW APPROACH FOR BORDERLINE PERSONALITY DISORDER

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1 A NEW APPROACH FOR BORDERLINE PERSONALITY DISORDER WPA Melbourne Feb 2018 Professor Jayashri Kulkarni Monash Alfred Psychiatry Research Centre. Melbourne

2 Funding disclosure NHMRC grant : A Randomised Controlled Trial of NMDA Antagonist, Memantine, for the Treatment of Borderline Personality Disorder: Funding commenced in 2017 (3 years funding) No conflicts of interest to declare

3 WOMEN S MENTAL HEALTH

4 EMMA

5 EMMA Emma, now 26 was raised by her single mother. Her father left when Emma was 5. She was sexually abused by her mother s boyfriend when she was aged 8 to age 14. She told her mother who did not believe her. Emma left home at age 16 and has a history of amphetamine abuse, alcohol abuse.

6 EMMA She cuts her arms and wrists and says this makes her feel alive. Emma could not complete school and said she was unable to concentrate and has a bad memory. She feels empty inside and often looks dazed. Emma has angry outbursts over minor things.

7 EMMA Emma is very overweight. She has made 11 suicide attempts. Emma has had 4 admissions to psychiatry wards.

8 Emma s diagnosis is BORDERLINE PERSONALITY DISORDER (DSM 5 Diagnosis)

9 BORDERLINE PERSONALITY DISORDER What a useless, stigmatising term!! A better term is COMPLEX OR CHRONIC TRAUMA DISORDER ( CTD)

10 Relationship of Trauma to Borderline PD A higher prevalence of trauma, in particular early, severe and chronic trauma among adult borderline patients Overall severe early traumatization and attachment disturbances are frequent in the history of BPD patients Horesh et al 2008; Tyrka et al, 2009; Ball & Links, 2009). (Zanarini, 2000; Zanarini, Yong, Frankenburg et al, 2002

11 BPD Borderline personality disorder (BPD) is a serious and highly prevalent (5.9%) *psychiatric disorder. BPD sufferers experience severe emotional instability, social and occupational dysfunction, engage in chronic self-mutilation and suicidal behaviours. BPD is associated with high levels of mortality, morbidity, and health service use. BPD patients are a complex group that are challenging to treat. Grant BF et al 2008

12 BPD/CTD BPD is a complex disorder that is often misunderstood. People may self-harm due to low self esteem, to momentarily express and release emotional pain or even to punish themselves. The anger and rejection that people with BPD display mean they are sometimes labelled as bad, manipulative or attention-seeking. Push pull dynamic in relationships People with BPD can get better. While there is no cure yet, BPD is a treatable disorder.

13 BPD/CTD Cognitive disturbances have traditionally been viewed as secondary to the hallmark features of emotional instability and impulsivity in BPD. Cognitive difficulties underpin the symptoms of this disabling disorder (e.g. faulty cognition resulting in misinterpreting others emotional/behavioural cues as rejection leading to self-harm). Disrupted cognitive processes are crucial to the pathophysiology, and therefore treatment, of BPD. Fertuck EA 2006

14 Current Treatments Psychotherapy (e.g. dialectical behaviour therapy, mentalisation) can be effective BUT these programs can be expensive, low number of expert health practitioners trained to deliver these therapies. For many in this large patient group, access to these psychological treatments is severely limited. Pharmacotherapy for BPD is a mess!!! Antipsychotics, mood stabilisers and antidepressants, with very modest and inconsistent effects* All this adds up to HUGE STIGMA (* Commonwealth of Australia. Clinical practice guideline for the management of borderline personality disorder )

15 Aetiology of BPD Complex interaction of genetic, neurobiological and environmental factors * A history of childhood trauma **: actual cruelty, neglect and brutality by the parents ***. It is now well-established that childhood maltreatment + genetic vulnerability evokes a stress response that can promote pathophysiological processes ****. *Grosjean B 2007 **Battle C 2004 ***Stern A 1938 ****Lupien S 2009

16 A BIOPSYCHOSOCIAL MODEL FOR BPD To date, BPD sufferers have not received rational bio treatments, nor a clear explanation of the social (often about violence) aspect of aetiology Treatment has mainly been psychological with patchy, difficult to access, long treatments

17 BPD Bio Aetiology Childhood maltreatment can trigger major neurobiological destabilization Disruptions in neuroendocrine, neurochemical and neuroimmunological systems with feedback system loops between all of the critical central nervous system anatomical and neurochemical pathways * Growing evidence that glutamate dysregulation is critical in the development of the hallmark symptoms of BPD*. *Grossjean B 2007

18 Glutamate & BPD The NMDA receptor is a glutamate receptor. Activated when glutamate and glycine (or D-serine) bind to it. The glutamatergic system, in particular, the NMDA subtype receptor, has major role in cognition and memory, and its critical role in experiencedependent neuroplasticity. * *Javitt D 2004

19 Kulkarni 2015 Theoretical Bio Aetiology of BPD STRESS (early life & chronic) Immune system dysregulation Altered neuroinflammatory markers, increased infections, autoimmune diseases, sensitivities to drugs Neuroendocrine Disruption HPG Axis dysfunction PCOS, PMDD, perimenopausal relapse of symptoms Glutamate overactivity HPA axis dysfunctionanxiety, low threshold for retrauma Cognitive symptoms, deliberate self harm, poor self esteem, rage

20 In summary Early traumatic experiences and genetic vulnerability lead to stress-related neuroendocrine, immune and cognitive changes thereby contributing to the development of BPD and ongoing symptoms. Altered glutamate signaling appears to be a key event in the pathophysiology of BPD, Molecular mechanisms capable of regulating glutamate release represent novel and potentially promising treatment targets.

21 Memantine an NMDA antagonist Memantine a cognitive enhancer used in Alzheimer s NMDA antagonist Doesn't cause dissociation like ketamine Study under way NHMRC Project grant 2016

22 WE NEED TO DO BETTER FOR EMMA