Deliberate self‐poisoning : repeaters and nonrepeaters admitted to an intensive care unit

Seventy‐nine patients admitted to the Lund Intensive Care Unit after deliberate self‐poisoning were investigated by a psychiatrist and a social worker by means of a semi structured interview. Suicide risk evaluation included statistical risk factors according to the SAD PERSONS Scale, severity of suicidal intent according to the Suicidal Intent Scale, and interviewer reaction according to Motto. Two‐thirds of the patients were in treatment or had had counselling with a social worker. More than half of the sample were repeaters. Compared with nonrepeaters, repeaters were less often employed, lacked social support and more often had relational problems. The majority of the repeaters had ongoing treatment, mostly psychiatric treatment. Repeaters more often acted impulsively, and their suicidal intent tended to be less severe than those of nonrepeaters. Interviewers more often reacted with negative or neutral feelings towards repeaters. Our results indicate that those who repeat suicidal behaviour differ from nonrepeaters. Self‐poisoners, and especially repeaters, often had ongoing or previous psychiatric treatment. For the repeater group it is important to consider their impulse dyscontrol and their hostile attitude when alternative treatment strategies are devised and evaluated

The social network of people who attempt suicide

Social characteristics and self‐rating of social support by means of the Interview Schedule for Social Interaction were investigated in 75 inpatients after a suicide attempt. We found that very few suicide attempters (13%) had a well functioning relationship, and two‐thirds had problems in their occupational situation. Divorced patients had unsatisfactory social interaction compared with those who were married or cohabiting and with those who were single or widowed. Employees and students more often had deep emotional relations than those who were unemployed or in vocational rehabilitation. The latter were also less satisfied with their social interaction than those who were retired or had a disability pension. Poor social interaction was more commonly reported by patients with dysthymia than by those in other diagnostic subgroups. We conclude that an evaluation of the social network should be an integral part of the clinical handling of suicide attempters, since it forms a basis for planning psychiatric treatment

A 5-year follow-up study of suicide attempts

Seventy-five patients were admitted to the ward of the Lund Suicide Research Center following a suicide attempt. After 5 years, the patients were followed up by a personal semistructured interview covering sociodemographic, psychosocial and psychiatric areas. Ten patients (13%) had committed suicide during the follow-up period, the majority within 2 years. They tended to be older at the index attempt admission, and most of them had a mood disorder in comparison with the others. Two patients had died from somatic diseases. Forty-two patients were interviewed, of whom 17 (40%) had reattempted during the follow-up period, most of them within 3 years. Predictors for reattempt were young age, personality disorder, parents having received treatment for psychiatric disorder, and a poor social network. At the index attempt, none of the reattempters had diagnoses of adjustment disorders or anxiety disorders. At follow-up, reattempters had more psychiatric symptoms (SCL-90), and their overall functioning (CAF) was poor compared to those who did not reattempt. All of the reattempters had had long-lasting treatment (> 3 years) as compared to 56% of the others. It is of great clinical importance to focus on treatment strategies for the vulnerable subgroup of self-destructive reattempters

Clinical characteristics and biological parameters in temperamental clusters of suicide attempters

A sample of 215 suicide attempters was categorized in a cluster analysis into four groups according to temperamental trails. Monoamine metabolites in the cerebrospinal fluid were analysed (n = 106). Dexamethasone suppression tests (DST) were performed (n = 154) and the activity of the enzyme monoamine oxidase in platelets (pl-MAO) was assessed (n = 103). Patients belonging to the two clusters with the most deviant temperament profiles (nos 2 and 3) were young and scored high on the Beck Hopelessness Scale and the Suicide Assessment Scale. "Cluster 3" ("neurotic, impulsive, aggressive") patients often had dysthymia and axis II, cluster B diagnoses (e.g. borderline or histrionic personality). "Cluster 2" ("neurotic and introverted") patients often had major depression. The "Cluster 1", with on the whole a normal temperament profile, had significantly higher levels of post-DST cortisol than the other clusters. The "Cluster 4" had a normal temperament profile. Adjustment disorders were most common in "Cluster 1" and "Cluster 4". The monoamine metabolite levels did not differ between the clusters, and the differences in pl-MAO activity disappeared after adjusting for age and gender. The results suggest that temperament profiles in suicide attempters are related to psychiatric diagnoses, suicidality, hopelessness, and post-DST cortisol, but are not predictive of completed suicide

The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression

The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P</=0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes

Circulating cell-free mitochondrial dna. a novel marker of mitochondrial stress associated with suicidality and major depressive disorder

Background: Mitochondrial DNA copy number (mtDNA-cn), which represents the number of mitochondrial genomes per cell, can be quantified in peripheral blood mononuclear cells (PBMC) and is thought to reflect variations in mitochondrial biogenesis. Additionally, mtDNA may be released at low levels into the circulation from mitochondria under cellular stress, resulting in circulating cell-free mtDNA (ccf-mtDNA) detectable in plasma. The source or physiological significance of ccf-mtDNA in psychiatric illness is unknown but may reflect cell damage, cell death, or bioenergetic compromise. Methods: We enrolled suicide attempters (across diagnoses), non-suicidal subjects with Major Depressive Disorder (MDD), and healthy controls (all medication-free) in two independent cohorts (n=110 & n=74). MtDNA was quantified in cell-free plasma and in PBMCs. Results: Ccf-mtDNA was elevated in suicide attempters and in non-suicidal MDD subjects, compared to healthy controls. These group effects were very large (Cohen’s d ranging from 0.9 to 4.0, all p<0.00001). Ccf-mtDNA and cellular PBMC mtDNA-cn were not significantly correlated with each other (r=0.02, p=0.87), suggesting they reflect different processes. Ccf-mtDNA correlated with post-dexamethasone cortisol (r=0.5, p<0.001), suggesting that HPA-axis hyperactivity may be associated with cellular damage and release of ccf-mtDNA into the blood. Ccf-mtDNA also directly correlated with the antioxidant enzyme glutathione peroxidase (r=0.32, p=0.001), possibly reflecting a compensatory attempt to upregulate antioxidant defence mechanisms due to cellular stress. Conclusions: Ccf-mtDNA may represent a novel marker of cellular stress, which is increased in certain psychiatric conditions. These results call for replication in larger cohorts and in longitudinal studies

A key role for orexin in panic anxiety

Panic disorder is a severe anxiety disorder with recurrent, debilitating panic attacks. In individuals with panic disorder there is evidence of decreased central gamma-aminobutyric acid (GABA) activity as well as marked increases in autonomic and respiratory responses after intravenous infusions of hypertonic sodium lactate(1-3). In a rat model of panic disorder, chronic inhibition of GABA synthesis in the dorsomedial-perifornical hypothalamus of rats produces anxiety-like states and a similar vulnerability to sodium lactate-induced cardioexcitatory responses(4-9). The dorsomedial-perifornical hypothalamus is enriched in neurons containing orexin (ORX, also known as hypocretin)(10), which have a crucial role in arousal(10,11), vigilance(10) and central autonomic mobilization(12), all of which are key components of panic. Here we show that activation of ORX-synthesizing neurons is necessary for developing a panic-prone state in the rat panic model, and either silencing of the hypothalamic gene encoding ORX (Hcrt) with RNAi or systemic ORX-1 receptor antagonists blocks the panic responses. Moreover, we show that human subjects with panic anxiety have elevated levels of ORX in the cerebrospinal fluid compared to subjects without panic anxiety. Taken together, our results suggest that the ORX system may be involved in the pathophysiology of panic anxiety and that ORX antagonists constitute a potential new treatment strategy for panic disorder. (C) 2010 Nature America, Inc. All rights reserved