Scott T. Wilson

Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures.This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients.

Enhanced ‘Reading the Mind in the Eyes’ in borderline personality disorder compared to healthy controls

BACKGROUND Borderline personality disorder (BPD) is partly characterized by chronic instability in interpersonal relationships, which exacerbates other symptom dimensions of the disorder and can interfere with treatment engagement. Facial emotion recognition paradigms have been used to investigate the bases of interpersonal impairments in BPD, yielding mixed results. We sought to clarify and extend past findings by using the Reading the Mind in the Eyes Test (RMET), a measure of the capacity to discriminate the mental state of others from expressions in the eye region of the face. METHOD Thirty individuals diagnosed with BPD were compared to 25 healthy controls (HCs) on RMET performance. Participants were also assessed for depression severity, emotional state at the time of assessment, history of childhood abuse, and other Axis I and personality disorders (PDs). RESULTS The BPD group performed significantly better than the HC group on the RMET, particularly for the Total Score and Neutral emotional valences. Effect sizes were in the large range for the Total Score and for Neutral RMET performance. The results could not be accounted for by demographics, co-occurring Axis I or II conditions, medication status, abuse history, or emotional state. However, depression severity partially mediated the relationship between RMET and BPD status. CONCLUSIONS Mental state discrimination based on the eye region of the face is enhanced in BPD. An enhanced sensitivity to the mental states of others may be a basis for the social impairments in BPD.

Non-suicidal self-injurious behavior, endogenous opioids and monoamine neurotransmitters

BACKGROUND Self-inflicted injury, including cutting or burning, is the most frequent reason for psychiatric visits to medical emergency departments. This behavior, particularly when there is no apparent suicidal intent, is poorly understood from both biological and clinical perspectives. OBJECTIVE To examine the role of endogenous opioids and monoamine neurotransmitters in non-suicidal self-injury (NSSI). METHODS We compared cerebrospinal fluid (CSF) levels of endogenous opioids, 5 hydroxyindolacetic acid (5-HIAA) and homovanillic acid (HVA) in individuals with a history of repetitive non-suicidal self-injury with a diagnostically-matched group of individuals who had never engaged in non-suicidal self-injury. History of suicidal behavior, demographic background and psychopathology was assessed. All patients were diagnosed with a Cluster B personality disorder (i.e. borderline, antisocial, narcissistic or histrionic) (N=29) and had a history of at least one suicide attempt. Fourteen participants had a history of repeated non-suicidal self-injurious behavior (NSSI) in adulthood and 15 did not (no NSSI). RESULTS The NSSI group had significantly lower levels of CSF beta-endorphin and met-enkephalin when compared with the non-NSSI group. CSF dynorphin, HVA and 5-HIAA levels did not differ. Severity of depression, hopelessness and overall psychopathology was greater in the NSSI group. CONCLUSION beta-endorphin and met-enkephalin, opioids acting upon receptors involved in mediating stress-induced and physical pain analgesia respectively, are implicated in NSSI. Serotonergic and dopaminergic dysfunctions do not appear to be related to NSSI. Based on our findings, we propose a model of non-suicidal self-injury. Our results suggest that drugs acting on the opioid system warrant exploration as pharmacological treatments for NSSI.

Impulsivity, suicidality and alcohol use disorders in adolescents and young adults with borderline personality disorder.

Borderline Personality Disorder (BPD) is a severe and disabling psychiatric condition that typically emerges in late adolescence or early adulthood. Nearly 50% of individuals with BPD have a co-occurring Alcohol Use Disorder (AUD) at some point in the course of their illness. This study explores clinical characteristics of adolescents and young adults (age 30 years and younger) with BPD and AUD (N=21) compared to BPD without any history of substance use disorders (N=17). Based on theoretical considerations and previous findings, we hypothesized that adolescents and young adults with BPD and AUDs would be more impulsive and exhibit higher rates of suicidal behavior than individuals with BPD and no substance use disorders. Consistent with our first hypothesis, the BPD/AUD group was more impulsive than the BPD only group. However, the two groups did not differ on measures of suicidal behavior. Overall, impulsivity was correlated with total number of suicide attempts in the adolescent/young adult group. When older BPD participants were included in the comparison (up to age 55), the BPD/AUD group exhibited more lifetime suicide attempts that were higher in medical lethality than the BPD only group, suggesting an overall increased lifetime suicide risk in the BPD/AUD group. The relationship between impulsivity, AUD, and suicidal behavior and lifetime suicide risk in adolescent and young adults with BPD is discussed.

The tryptophan hydroxylase-1 A218C polymorphism is associated with diagnosis, but not suicidal behavior, in borderline personality disorder.

While there is some preliminary evidence that the tryptophan hydroxylase I (TPH1) polymorphisms are related to Borderline Personality Disorder (BPD), it is not clear if this association is due to the high rates of suicidal behavior in this patient group. Because of the reported association between TPH1 polymorphisms and suicidal behavior, determining whether TPH1 is related to BPD independent of suicidal behavior is of particular importance. One hundred patients diagnosed with BPD and 101 healthy controls were genotyped for TPH1 intron 7 A218C polymorphism and assessed for impulsiveness and hostility. The BPD patient group had a higher frequency of A allele carriers (AA/AC genotypes) than the control group (χ2 = 6.12, df = 1, P = 0.01), and differed by genotype frequencies (P = 0.03). Suicide attempter status in the patient group was not related to genotype. Logistic regression analysis controlling for age and gender predicted BPD diagnosis from TPH1 allele group (AA/AC vs. CC, P = 0.03), and TPH1 heterozygotes (AC) appeared to have the highest risk for BPD (P = 0.03). In the full sample, participants with the AC genotype had higher impulsiveness and hostility scores. However, TPH1 did not predict these traits in either of the groups independently, suggesting the association may be an artifact of the association between TPH1 and BPD. Results suggest that the A allele of the tryptophan hydroxylase‐1 A218 polymorphism may be associated with BPD, and that it does not appear to be related to suicidal behavior in this population. An aspect of BPD pathology may be due to serotonergic dysfunction.

Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.

Introduction Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship between abuse history and BPD. Methods Three hundred and ninety-eight patients diagnosed with mood disorders were genotyped for TPH1 G-6526A promoter polymorphism (rs4537731) and the A218C intron 7 polymorphism (rs1800532) and a set of ancestry informative markers, assessed for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnoses, and assessed for a history of physical and sexual abuse. Results Patients with a diagnosis of BPD were more likely to be risk allele carriers (A alleles at both loci) than the non-BPD group. Logistic regression analysis predicting BPD diagnosis with both single-nucleotide polymorphisms and haplotypes showed significant interaction effects between genotype and abuse history. Poisson regression predicting the number of BPD diagnostic criteria met with the same predictor set also included a significant interaction term. Risk allele carriers with a history of abuse had an increased likelihood of a BPD diagnosis. Conclusion Variation in TPH1may increase risk for developing BPD as a result of childhood abuse. Elements of BPD pathology may be due in part to a genetically influenced serotonergic dysfunction, which in turn may lead to a differential response to environmental stressors.

Higher Executive Control and Visual Memory Performance Predict Treatment Completion in Borderline Personality Disorder

Background: Non-completion of a prescribed course of treatment occurs in 20–60% of individuals diagnosed with borderline personality disorder (BPD). While symptom severity, personality traits and environmental factors have been implicated as predictors of treatment non-completion (TNC), there have been no studies of neuropsychological predictors in this population. Methods: From a randomized controlled trial, a subsample of 31, unmedicated outpatients diagnosed with BPD with recent self-injurious behavior was assessed on 5 neuropsychological domains. Patients were also assessed for general IQ, demographic and other salient clinical variables. Patients were randomized to one of four treatment conditions, which lasted up to 1 year. Number of weeks in treatment (WIT) up to 1 year was utilized as the index of TNC. Results: Thirty-three percent of the subsample (n = 12) did not complete 1 year of treatment. However, more WIT were predicted by better baseline executive control (Trails B; p < 0.01) and visual memory performance (Benton visual retention; p < 0.001); other neuropsychological domains did not predict WIT. Conclusion: In the treatment of outpatients with BPD, better executive control and visual memory performance predict more WIT. Assessing and addressing these neurocognitive factors in treatment may reduce TNC in this high-risk population.

Heart rate variability and suicidal behavior

Identification of biological indicators of suicide risk is important given advantages of biomarker-based models. Decreased high frequency heart rate variability (HF HRV) may be a biomarker of suicide risk. The aim of this research was to determine whether HF HRV differs between suicide attempters and non-attempters. Using the Trier Social Stress Test (TSST), we compared HF HRV between females with and without a history of suicide attempt, all with a lifetime diagnosis of a mood disorder. To investigate a potential mechanism explaining association between HF HRV and suicide, we examined the association between self-reported anger and HF HRV. Results of an Area under the Curve (AUC) analysis showed attempters had a lower cumulative HF HRV during the TSST than non-attempters. In addition, while there was no difference in self-reported anger at baseline, the increase in anger was greater in attempters, and negatively associated with HF HRV. Results suggest that suicide attempters have a reduced capacity to regulate their response to stress, and that reduced capacity to regulate anger may be a mechanism through which decreased HF HRV can lead to an increase in suicide risk. Our results have implications for the prevention of suicidal behavior in at-risk populations.