Gender-Related Differences in the Relationship between Homovanillic Acid in the Cerebrospinal Fluid and Clinical Symptoms in Suicide Attempters.

INTRODUCTION: Decreased dopaminergic activity - as reflected by lower levels of the major metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) - may be involved in the pathophysiology of attempted suicide. An inverse association has also been found between dopaminergic activity and clinical symptoms of depression and anxiety in non-suicidal individuals. The aim of this study was to assess the relationship between CSF-HVA and clinical symptoms associated with an increased risk of suicide in individuals who attempted suicide. METHODS: Ninety-five people (52 women; 43 men) who had recently attempted suicide received lumbar punctures to analyse levels of HVA in the CSF. They were also evaluated with the Comprehensive Psychopathological Rating Scale, from which scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), the Brief Scale of Anxiety (BSA), and an item on suicidal thoughts were analysed. RESULTS: Among female participants, CSF-HVA was significantly and negatively correlated with BSA total scores, after adjusting for covariates (beta = -0.442, p = 0.002), but not with scores on the MADRS or suicidal thought item. No significant correlations were observed between CSF-HVA and symptoms among male participants. CONCLUSION: Our findings suggest that lower dopaminergic activity may be associated with clinical symptoms of anxiety among women who have recently attempted suicide.

Utilization of psychiatric services prior to suicide- a retrospective comparison of users with and without previous suicide attempts.

INTRODUCTION: The aim was to investigate psychiatric health care utilization two years before death by suicide among individuals with previous suicide attempts (PSA) compared with those without (NSA). METHOD: A retrospective population-based cohort study was conducted including 484 individuals who died by suicide in Sweden in 2015 and were in contact with psychiatric services within the two years preceding death, identified through the Cause of Death register. Data on psychiatric health care two years before death, including suicide attempts according to notes in the medical record was used. Associations between having at least one PSA vs. NSA and health care utilization were estimated as odds ratios (OR) with 95% confidence intervals (CI) by logistic regression analyses. RESULTS: Of the 484 individuals included, 51% had PSA. Those with PSA were more likely than NSA to have received a psychiatric diagnosis [OR 1.96 (CI 95% 1.17-3.30)], to have ongoing psychotropic medication [OR 1.96 (CI 95% 1.15-3.36)] and to have been absent from appointments during the last three months [1.97 (1.25-3.13)]. In addition, elevated suicide risk was more often noted in the psychiatric case records of those with a PSA than those without [OR 2.17 (CI 95% 1.24-3.79)]. CONCLUSION: The results underline the importance of improved suicide risk assessment as well as thorough diagnostic assessment and when indicated, psychiatric treatment as suicide preventive interventions regardless of PSA. Furthermore, the larger proportion of absence from appointments in individuals with PSA may indicate a need of improved alliance between psychiatric care providers and individuals with PSA.HIGHLIGHTSBeing assessed with elevated suicide risk was more common among those with previous attempt/s (PSA).One-fifth of all with no previous attempt (NSA) had no psychiatric diagnosis, compared to one in ten in those with PSA.Receiving psychotropic medication was more common among those with PSA.

Excess mortality by suicide in high-risk subgroups of suicide attempters: a prospective study of standardised mortality rates in suicide attempters examined at a medical emergency inpatient unit.

OBJECTIVES: The primary aim of the present study was to investigate the putative excess mortality by suicide in suicide attempters. As a secondary aim, we investigate excess mortality in specific, clinically relevant subgroups: individuals with repeated suicide attempts (RA); individuals who used violent method at the attempt (VA); and those who scored high on the Suicide Intent Scale (HS) at the time of the baseline attempt. Finally, we investigate excess mortality in men and women separately and within 5 years and over 5 years after hospital admission for attempted suicide. DESIGN: Prospective register-based follow-up for 21-32 years. Standardised mortality ratio (SMR) was calculated for suicide using national census data. Clinically relevant subgroups were investigated separately. SETTING: Medical emergency inpatient unit in the south of Sweden. PARTICIPANTS: 1039 individuals who were psychiatrically assessed at admission to medical inpatient care for attempted suicide between 1987 and 1998. OUTCOME MEASURE: Suicide. RESULTS: The overall SMR for suicide was 23.50 (95% CI 18.68 to 29.56); significantly higher (p<0.001) among women (30.49 (95% CI 22.27 to 41.72)) than men (18.61 (95% CI 13.30 to 26.05)). Mortality was highest within the first 5 years after the index suicide attempt (48.79 (95% CI 35.64 to 66.77)) compared with those who died after 5 years (p<0.001) (14.74 (10.53 to 20.63)). The highest independent SMR was found for VA (70.22 (95% CI 38.89 to 126.80)). In a regression model including RA, VA and HS all contributed significantly to excess suicide mortality. CONCLUSIONS: An elevated risk of premature death by suicide was found in suicide attempters compared with the general population. Assessment of previous suicide attempts is important, even though the attempt/s may have occurred decades ago. When assessing suicide risk, clinicians should consider repeated attempts and whether the attempts involved high suicidal intent and violent method. Healthcare interventions may benefit from targeting identified subgroups of attempters.

Differences in antipsychotic treatment between depressive patients with and without a suicide attempt.

BACKGROUND: Depressed suicide attempters are, according to some earlier studies, treated more often with antipsychotics than depressive non-suicide attempters. Cluster B personality disorders, especially borderline personality disorder, are associated with a high suicide risk, and antipsychotics are commonly used for the reduction of symptoms. However, no previous study has taken comorbid personality disorders into account when assessing the use of antipsychotics in patients with unipolar depression. Therefore, the aim of this study was to investigate the clinical selection of pharmacotherapy in unipolar depression with and without a previous suicide attempt, taking into account potential confounders such as cluster B personality disorders. METHODS: The study sample consisted of 247 patients with unipolar depression. The study was approved by the Regional Ethical Review Board in Lund, Sweden. Study participants were recruited from 4 different secondary psychiatric care clinics in Sweden and were diagnosed according to the DSM-IV-TR with the MINI and SCID II. Previous and ongoing psychiatric treatments were investigated in detail and medical records were assessed. RESULTS: Thirty percent of the patients had made previous suicide attempts. Depressed suicide attempters underwent both lifetime treatment with antipsychotics and an ongoing antipsychotic treatment significantly more often than non-attempters. Significances remained after a regression analysis, adjusting for cluster B personality disorders, symptom severity, age at the onset of depression, and lifetime psychotic symptoms. CONCLUSIONS: This is the first study to consider the effect of comorbidity with cluster B personality disorders when comparing treatment of depressive suicide and non-suicide attempters. Our findings suggest that suicide attempters are more frequently treated with antipsychotics compared to non-suicide attempters, regardless of cluster B personality disorder comorbidity. These findings are important for clinicians to consider and would also be relevant to future studies evaluating reduction of suicide risk with antipsychotics in patients with psychiatric comorbidity and a history of attempted suicide.

Recognition of personality disorder and anxiety disorder comorbidity in patients treated for depression in secondary psychiatric care.

OBJECTIVES: Depression is a common illness with substantial economic consequences for society and a great burden for affected individuals. About 30% of patients with depression do not respond to repeated treatments. Psychiatric comorbidity is known to affect duration, recurrence and treatment outcome of depression. However, there is a lack of knowledge on the extent to which psychiatric comorbidity is identified in the clinical setting for depressed patients in secondary psychiatric care. Therefore, the aim of this study was to compare the agreement between traditional diagnostic assessment (TDA) and a structured and comprehensive diagnostic procedure (SCDP) for identification of personality and anxiety disorder comorbidity in depressed patients in secondary psychiatric care. METHODS: 274 patients aged 18-77 were referred from four secondary psychiatric care clinics in Sweden during 2012-2017. ICD-10 diagnoses according to TDA (mostly unstructured by psychiatric specialist and residents in psychiatry), were retrieved from medical records and compared to diagnoses resulting from the SCDP in the study. This included the Mini International Neuropsychiatric Interview, the Structured Interview for DSM Axis II Personality Disorders and semi-structured questions on psychosocial circumstances, life-events, psychiatric symptoms, psychiatric treatments, substance use, and suicidal and self-harm behaviour. The assessment was carried out by psychiatric specialists or by residents in psychiatry with at least three years of psychiatric training. RESULTS: SCDP identified personality disorder comorbidity in 43% of the patients compared to 11% in TDA (p<0,0001). Anxiety disorder comorbidity was identified in 58% with SCDP compared to 12% with TDA (p<0,0001). CONCLUSIONS: Important psychiatric comorbidity seems to be unrecognized in depressive patients when using TDA, which is routine in secondary psychiatric care. Comorbidities are better identified using the proposed model involving structured and semi-structured interviews together with clinical evaluations by clinical experts.

To increase physical activity in sedentary patients with affective - or schizophrenia spectrum disorders - a clinical study of adjuvant physical therapy in mental health.

Purpose: To understand if physical therapy in addition to individualized psychiatric specialist treatment could aid sedentary patients with schizophrenia spectrum disorders or affective spectrum disorders to become more physically active and also to identify assessments suitable for measuring physical activity, physical function and movement motivation.Materials and methods: In a longitudinal, clinical study 18 sedentary patients that filled inclusion criteria were consecutively included. The patients were diagnosed with affective disorders (n = 10) or schizophrenia spectrum disorders (n = 8).Results: Fifteen patients fulfilled the 6-month treatment. The affective group significantly improved physical activity, walking capacity, physical function, exercise habits and attitudes. The schizophrenia spectrum group significantly improved the attitudes to the body and movements but did not increase their physical activity. Instruments to study physical activity, physical function and movement motivation were identified.Conclusion: The study revealed that physical therapy in addition to individualized psychiatric specialist treatment might be an aid for the patients to become more physically active. Patients with affective disorders reached recommended levels of moderate physical activity according to World Health Organization guidelines. Sedentary patients with schizophrenia spectrum disorders revealed positive attitude-changes, but no behavioral change.

Coping and suicide risk in high risk psychiatric patients.

Background: A dysfunctional use of coping strategies has repeatedly been linked to suicidal behaviour in non-psychiatric populations. However, data regarding association between coping strategies and suicidal behaviour in psychiatric populations are limited.Aims: The aim of the study was to investigate the possible relationship between self-reported suicide risk, suicidal ideation and coping strategies in three psychiatric cohorts.Method: Three cohorts of psychiatric patients were involved in the study; recent suicide attempters (n = 55), suicide attempters at follow-up 12 years after a suicide attempt (n = 38) and patients with ongoing depression without attempted suicide (n = 72). Patients filled in the self-rating version of The Suicide Assessment Scale (SUAS-S) from which items no. 17-20 addressing current suicidal ideation were extracted. To investigate coping strategies, the Coping Orientation of Problem Experience Inventory (COPE) was used.Results: In all cohorts, regression analyses showed that only avoidant coping was significantly correlated with the scores of SUAS-S adjusted for covariates. The items no. 17-20 correlated significantly to avoidant coping but not with other coping strategies in all cohorts.Conclusion: The results of this study indicate that among coping strategies only avoidant coping may be associated with suicide risk in psychiatric patients independently of history of attempted suicide.

Leptin, Anxiety Symptoms, and Hypothalamic-Pituitary-Adrenal Axis Activity among Drug-Free, Female Suicide Attempters.

BACKGROUND: Dysregulation of leptin secretion and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the pathophysiology of suicide. Preclinical and clinical studies have shown interactions between the HPA axis and leptin. There is also evidence for a negative relationship between leptin and anxiety in humans. However, these possible associations have not been studied in individuals with attempted suicide. OBJECTIVES: To examine the relationship between leptin, HPA axis activity, and anxiety in individuals with a recent suicide attempt. METHOD: Sixty-nine individuals with a recent suicide attempt (n = 37 females; n = 32 males) were recruited and subjected to the Dexamethasone Suppression Test (DST), lumbar puncture, and evaluation with the Comprehensive Psychopathological Rating Scale from which the Brief Scale for Anxiety (BSA) was derived. Leptin was analyzed in cerebrospinal fluid (CSF) and cortisol in serum. Leptin was corrected for body mass index (BMI) by dividing CSF-leptin by BMI (CSF-leptin/BMI). Due to gender-related differences in leptin secretion and HPA axis activity, calculations were made for males and females separately. RESULTS: Significant differences were only found among females; CSF-leptin/BMI levels correlated significantly and negatively with BSA (p < 0.05), pre-DST cortisol, and post-DST serum cortisol at 8 a.m. and 3 p.m. (all p < 0.05). Furthermore, CSF-leptin/BMI was significantly lower in nonsuppressors of dexamethasone as compared to suppressors (p < 0.05). CONCLUSIONS: These findings suggest that in females with a recent suicide attempt, low CSF leptin may be related to symptoms of anxiety and a hyperactive HPA axis.

Inverse association between serum albumin and depressive symptoms among drug-free individuals with a recent suicide attempt.

Background and aim: Albumin is a protein with multifaceted functions in the human body. According to many studies, lower serum albumin may be associated with depression in various groups of psychiatric and non-psychiatric patients, as well as with attempted suicide. As more severe depressive symptoms have been identified as a reliable risk factor for suicide in patients with high suicide risk, it would be of interest to study whether, the inverse association between depressive symptoms and albumin may exist among patients with attempted suicide. Therefore, the aim of the study was to investigate the possible association between albumin and depressive symptoms among individuals who recently attempted suicide. Methods: One-hundred twenty-seven individuals with a recent suicide attempt were involved in the study between 1987 and 2001. Albumin was analyzed in serum. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which the Montgomery-Åsberg Depression Rating Scale (MADRS) and the item assessing Apparent sadness were derived. Results: Only among patients aged ≥45, serum albumin levels were significantly and negatively correlated with total scores of MADRS and the item Apparent sadness (all p values <.00625). Conclusions: Our findings indicate an inverse association between serum albumin and the severity of depressive symptoms in individuals who attempted suicide, older than 45 years.

Low total cholesterol and low-density lipoprotein associated with aggression and hostility in recent suicide attempters.

Low cholesterol levels have been correlated with both suicidal and aggressive behavior in psychiatric patients. Few studies have investigated associations between serum lipid profiles and both aggressive state and trait. Fifty-two psychiatric medication-free inpatients were included in this study after a suicide attempt. Composite scores of "State Aggression" and "Trait Aggression" were calculated using relevant items from the Comprehensive Psychopathological Rating Scale and the Karolinska Scales of Personality. State Aggression was significantly and negatively correlated with total cholesterol (TC) and low-density lipoprotein (LDL). Trait Aggression was also significantly and negatively correlated with LDL, but not TC. There were small but significant mediation effects of severity of anxiety symptoms on the relationship between State Aggression and TC as well as LDL. In exploratory analyses we found that low cholesterol was also associated with personality traits of hostility. Moreover, low cholesterol was more robustly associated with personality trait items related to interpersonal aggression, as opposed to items related to irritability or more indirect, non-overt aggression. Our findings suggest that low cholesterol is associated with both state and trait aggression in suicide attempters. Future mechanistic studies are warranted to better understand the relationship between low cholesterol and high aggression in suicide attempters.

Plasma Brain-Derived Neurotrophic Factor and Psychopathology in Attempted Suicide.

BACKGROUND/AIMS: Increasing evidence suggests a link between brain-derived neurotrophic factor (BDNF) and suicidal behaviour (SB). Furthermore, decreased peripheral BDNF levels have been associated with clinical symptoms in various psychiatric disorders as well as with personality dimensions in healthy individuals. However, the relationship between BDNF and psychopathology is poorly investigated regarding SB. METHODS: Plasma BDNF concentrations were analysed in 61 recent suicide attempters. Clinical symptoms were evaluated using the Comprehensive Psychopathological Rating Scale. Personality dimensions were assessed using the Marke-Nyman Temperament Scale. RESULTS: Plasma BDNF correlated positively and significantly with the personality dimension Solidity but not with the other personality dimensions or with clinical symptoms. CONCLUSION: BDNF plays an important role in the regulation of neuroplasticity and neurogenesis in humans. Our results indicate that lower BDNF concentrations are associated with higher levels of impulsiveness and changeability (low scores on the Solidity scale). Furthermore, low plasma BDNF levels may be proposed as a trait marker rather than a state marker for attempted suicide.

Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters.

INTRODUCTION: Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. METHOD: Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items 'Concentration difficulties' and 'Failing memory' were extracted. RESULTS: Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = -0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = -0.372, p = 0.020). CONCLUSION: The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.

Associations between avoidant focused coping strategies and polymorphisms in genes coding for brain-derived neurotrophic factor and vascular endothelial growth factor in suicide attempters: a preliminary study.

In this study we investigated whether single nucleotide polymorphisms (SNP) in the genes coding for BDNF (Val66Met) and VEGF (C2578A) may be associated with maladaptive strategies among suicide attempt patients. We found that BDNF Val66Met gene polymorphism probably affect avoidant coping strategies.