Göran Regnéll

Reduced cerebrospinal HVA concentrations and HVA/5-HIAA ratios in suicide attempters. Monoamine metabolites in 120 suicide attempters and 47 controls

Dysfunctions of central monoaminergic systems are important elements of the leading biological hypotheses of suicide and depression. The purpose of the present paper was to study the levels and the relationships between the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the dopamine metabolite homovanillic acid (HVA) and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in the cerebrospinal fluid (CSF) in 120 hospitalised suicide attempters and 47 controls (healthy volunteers or patients admitted for minor surgery). The suicide attempters showed significantly lower HVA levels (174+/-82 vs. 216+/-96 nmol/L, P=0.004), HVA/5HIAA ratios (1.6+/-0.5 vs. 2.1+/-0.6, P=0.0001) and HVA/MHPG ratios (4.2+/-2.1 vs. 4.8+/-1.7, P=0.02) than the controls. The correlations between the monoamine metabolites were markedly lower in patients than in controls. CSF 5-HIAA showed no significant differences between patients and controls (107+/-40 vs. 108+/-51 nmol/L) or between violent and non-violent attempters (112+/-58 vs. 105+/-33 nmol/L). The monoamine metabolites showed no significant differences between survivors and patients who subsequently completed suicide, or between suicide attempters subgrouped by psychiatric diagnoses. The results suggest that low HVA levels and altered relationships between the monoamine metabolites are associated with suicidal behaviour.

Prediction of suicidal behavior from biologic tests

Biochemical studies related with suicidal behavior have mainly dealt with monoaminergic and cortico-steroidal measures. We used some of these measures in a study of 61 suicide attempters who, except for occasional doses of benzodiazepines, had been medication free for a mean of 16 days. The monoamine metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenylglycol were measured in lumbar cerebrospinal fluid (CSF). We found that violent suicide attempters (N = 18) had 5-hydroxyindoleacetic acid concentrations below the median of all patients, whereas the concentrations of 3-methoxy-4-hydroxyphenylglycol were mainly above the median. We found no significant differences between violent and nonviolent (N = 43) attempters concerning CSF homovanillic acid, 24-hour urinary norepinephrine-epinephrine and cortisol, activity of monoamine oxidase in platelets, or post-dexamethasone plasma cortisol. Four patients completed suicide, and 3 of them had CSF 5-hydroxyindoleacetic acid concentrations at or below the median. All completed suicides had CSF 3-methoxy-4-hydroxyphenylglycol concentrations above the median. Urinary measures and platelet monoamine oxidase activity of completed suicides were in the higher concentration ranges. Patients who repeated suicidal behavior after the index investigation had low 24-hour urinary cortisol levels more often than those who did not repeat. Because our subgroups of patients are small, we cannot draw any firm conclusions about the value of our CSF and urinary biochemical findings predicting suicidal behavior. However, our CSF findings in violent suicide attempters are similar to those observed in other studies.

HPA-related CSF neuropeptides in suicide attempters.

Corticotropin-releasing hormone (CRH), somatostatin (SOM), delta-sleep-inducing peptide (DSIP), neuropeptide Y (NPY), beta-endorphin (beta-END), and vasopressin (AVP), which are regarded as being involved in the HPA-regulation were investigated in lumbar CSF of 44 suicide attempters. The patients were diagnosed according to the DSM-III-R, and rated with the MADRS. The neuropeptides were compared with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF and with post-dexamethasone plasma cortisol. We found strong correlations between CRH and the peptides SOM and beta-END. The latter also correlated positively with SOM. There were no differences between men and women. Patients with major depressive disorders had significantly lower SOM, CRH, and DSIP than other patients. Both SOM and beta-END correlated negatively with post dexamethasone plasma cortisol in all patients. We found no significant relationships between neuropeptides and CSF 5-HIAA. Patients who had made previous suicide attempts had significantly lower CRH than those who had not. No other significant associations between neuropeptides and suicidal subgroups of patients appeared, and there was no indication of specific neuropeptide patterns in patients who later completed suicide. Intercorrelations of some neuropeptides and low SOM and DSIP in major depressed patients are findings in line with those by others.

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.

Medicine self-poisoning and the sources of the drugs in Lund, Sweden

The purpose of this study was to investigate the prevalence of toxic agents in attempted and completed suicides. The purpose was also to explore the sources of the drugs taken by suicide attempters. Verbal information on drug intake was collected from 280 suicide attempters during 1987–1990 in the Lund‐Orup catchment area. Information on the sources of the drugs was collected from 143 of these attempters. The study also includes toxicological screening from 73 fatal poisonings in southern Sweden during 1989. According to verbal information, the most common drugs used by suicide attempters were benzodiazepines (51%), analgesics (29%) and antidepressants (20%). In suicide attempters, diazepam and levomepromazine were reported more than expected from prescription data. Toxicological screenings of fatal poisonings showed that benzodiazepines were most common (55%), followed by analgesics (38%), mainly propoxyphene (29%) and antidepressants (30%), mainly amitriptyline (22%). Amitriptyline and diazepam were more commonly detected in completed suicides than expected from prescription data. The most common sources of drugs to attempted suicides were physicians, and especially psychiatrists. We therefore conclude that continuous information to physicians on drug overdose is important, and it is also important to introduce alternative strategies to prevent suicidal behaviour.

The role of monoamines in suicidal behavior

Cerebrospinal fluid (CSF), urine, platelet and neuroendochrine challenge tests of monoaminergic function give evidence of monoamines, especially serotonin, playing an important role in suicidal behavior. However, additional clinical, social and biochemical factors are necessary to better define suicide‐prone psychiatric patients.

The role of psychiatric factors in symptoms of hiatus hernia or gastric reflux

Abstract— The study comprised 26 patients with somatic symptoms indicating a hernia‐reflux syndrome referred to a university hospital ear, nose and throat department. The aim was to throw light on the hypothesis that this syndrome is largely a psychosomatic problem. The patients were divided into two groups: subjects with and without laboratory findings of physical pathology of hernia and/or reflux. Intergroup comparisons were made of symptoms, a psychological test and psychiatric ratings. Those who had no laboratory findings of physical pathology often reported “phobia” and “feeling of lump in the throat”, which were interpreted as signs of hysterical or somatizing mechanisms. Most of these patients showed a high level of anxiety in the psychological test. “Agitation”, “depression” and “frustration” were characteristics of patients with laboratory findings of reflux. “Depression” was interpreted as a reaction to the somatic illness. The group with reflux contained more old male patients and that without more younger female patients.

Cerebrospinal neuropeptide Y and substance P in suicide attempters during long-term antidepressant treatment

This study describes cerebrospinal fluid (CSF), neuropeptide Y (NPY) and substance P (SP) in patients with a recent suicide attempt and during antidepressant treatment. Seven out of 13 patients received antidepressants. The patients were examined on three separate occasions, i.e. at pre-treatment, followed by every 3 or 4 months. Antidepressant treatment seemed to affect the levels of CSF NPY, which decreased significantly between the second and last lumbar puncture despite no significant changes of clinical scores. When the whole group was taken into consideration, both CSF NPY and SP decreased significantly. At pre-treatment, Brief Scale of Anxiety scores were significantly and negatively correlated to CSF SP and tended to be negatively correlated to CSF NPY. There were also significant positive correlations between CSF NPY and SP during the entire study in the whole group, possibly reflecting an inter-relationship between these neuropeptides.

A follow up study of suicide attempters: Increase of CSF-somatostatin but no change in CSF-CRH

Concentrations of somatostatin and corticotrophin releasing hormone (CRH), measured in cerebrospinal fluid (CSF) have been reported to be low in suicidal patients with major depressive disorder (MDD). Often have MDD patients in general, high CSF-CRH and low CSF-somatostatin concentrations, which both seem to normalise with clinical recovery. The present study was designed to look for CSF-CRH and CSF-somatostatin alterations along with clinical changes in patients studied repeatedly after a suicide attempt. Sixteen patients with different diagnoses, initially inpatients after a suicide attempt (baseline), participated. Lumbar punctures and ratings according to the Suicidal Assessment Scale (SUAS) and the Montgomery-Asberg Depression Rating Scale (MADRS) were performed while patients were drug-free (baseline) and after a median of 7 (5 to 9) months. At follow up MADRS- and SUAS-scores were significantly decreased (P<0.05), whereas CSF-somatostatin was significantly increased (P=0.013) and CSF-CRH had not changed significantly. Thus, the patients showed long-lasting low CSF-CRH concentrations, in spite of changed CSF-somatostatin concentrations and clinical amelioration.

Peripheral serotonergic markers in patients with suicidal behavior

Peripheral serotonergic parameters were studied in 17 patients with a history of suicidal behavior and in 17 age- and sex-matched healthy controls. Serotonin2 receptor function in platelets, measured as serotonin-induced [32P]phosphatidylinositol 4,5-bisphosphate hydrolysis, was significantly higher in patients than in age- and sex-matched controls. Increased serotonin2 receptor transduction was not correlated to psychiatric diagnosis, drug treatment or a history of violent suicide attempt. Monoamine oxidase activity was lower in platelets from patients with a history of suicidal behavior than in controls. In addition, whole blood serotonin was analyzed but no significant alterations were found in blood from patients.