Immunoglobulin G is a natural oxytocin carrier which modulates oxytocin receptor signaling: relevance to aggressive behavior in humans.

Oxytocin is a neuropeptide produced mainly in the hypothalamus and secreted in the CNS and blood. In the brain, it plays a major role in promoting social interactions. Here we show that in human plasma about 60% of oxytocin is naturally bound to IgG which modulates oxytocin receptor signaling. Further, we found that IgG of violent aggressive inmates were characterized by lower affinity for oxytocin, causing decreased oxytocin carrier capacity and reduced receptor activation as compared to men from the general population. Moreover, peripheral administration of oxytocin together with human oxytocin-reactive IgG to resident mice in a resident-intruder test, reduced c-fos activation in several brain regions involved in the regulation of aggressive/defensive behavior correlating with the attack number and duration. We conclude that IgG is a natural oxytocin carrier protein modulating oxytocin receptor signaling which can be relevant to the biological mechanisms of aggressive behavior.

Blood Levels of Neuropeptide 26RFa in Relation to Anxiety and Aggressive Behavior in Humans-An Exploratory Study.

26RFa, also referred to as QRFP, is a hypothalamic neuropeptide mainly known for its role in the regulation of appetite and glucose metabolism. Its possible relevance to emotional regulation is largely unexplored. To address this, in the present exploratory study, we analyzed the plasma concentrations of 26RFa in humans characterized by different levels of anxiety and aggressive behavior. For this purpose, the study included 13 prison inmates who have committed violent crimes and 19 age-matched healthy men from the general population as controls. Anxiety, depression and aggressive behavior were evaluated in both groups using standard questionnaires. The inmate group was characterized by increased aggression and anxiety compared to the controls. We found that the mean plasma levels of 26RFa did not significantly differ between the inmates and the controls. However, several high outliers were present only in the inmate group. The plasma levels of 26RFa correlated positively with the anxiety scores in all the studied subjects and controls. After removing the high outliers in the inmate group, positive correlations of 26RFa with anxiety and a subscale of hostility in the aggression scale were also recorded in this group. No significant correlations of 26RFa with depression scores or other parameters of aggressive behavior were found. Thus, the present results did not support an involvement of 26RFa in aggressive behavior in humans but pointed to a link between this neuropeptide and anxiety. Nevertheless, considering the exploratory nature of the present study, this conclusion should be verified in a larger cohort, including the clinical degree of anxiety.

Neurobiology of Aggressive Behavior-Role of Autoantibodies Reactive With Stress-Related Peptide Hormones.

Adrenocorticotropic hormone together with arginine vasopressin and oxytocin, the neuropeptides regulating the stress response and the hypothalamic-pituitary-adrenal axis activity, are known to modulate aggressive behavior. The functional role of the adrenocorticotropic hormone immunoglobulin G autoantibodies in peptidergic signaling and motivated behavior, including aggression, has been shown in experimental and in vitro models. This review summarizes some experimental data implicating autoantibodies reactive with stress-related peptides in aggressive behavior.

Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans.

Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11-24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1-13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident-intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors' sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.

Improving the systematic approach to pain and sedation management in the ICU by using assessment tools.

AIMS AND OBJECTIVES: To assess the effects of introducing a systematic approach to pain and sedation management in the ICU. BACKGROUND: Identification of ICU patients' analgesic and sedative needs decreases the risk of complications and the hospital length of stay. Several studies have reported a lack of systematic assessment. DESIGN AND METHODS: Three assessment tools were implemented in two Norwegian ICUs in a prospective two-site study (April-July 2009). Frequency of pain and sedation documentation, the number of days when a sedation level was prescribed, and the amount of analgesics and sedatives used were documented for 958 ICU days in 139 mechanically ventilated patients. Fifty-five ICU nurses completed a questionnaire on the effects of the assessment tools before and after implementation. RESULTS: Patients assessed by the tools had a documented pain score 2·5 times daily and a sedation score three times daily. A sedation level was prescribed for 70% of the total patient days. A documented match between prescribed and reported sedation level was achieved for 27% of the days. Combinations of continuous analgesia and sedation were prescribed with wide therapeutic ranges. Significant improvements were seen in the units' assessment and documentation routines scored by the nurses after the implementation of the tools. CONCLUSION: Although the tools were well accepted, they were not used as frequently as recommended. The proportion of missing written prescriptions and documentation of sedation levels most likely reflects the nurses' and physicians' poorly defined intentions for the prescribed treatment. The tools applied helped nurses to focus on significant signs and symptoms. RELEVANCE TO CLINICAL PRACTICE: Without well-organised pain treatment and sedation, the risk of oversedation is always present. Our results show that the implementation of tools contributes to a systematic approach of the assessment and treatment of pain and sedation in intensive care.

Depression, anxiety, and history of substance abuse among Norwegian inmates in preventive detention: reasons to worry?

BACKGROUND: Inmates on preventive detention are a small and select group sentenced to an indefinite term of imprisonment. Mood disorders and substance abuse are risk factors for inmate violence and recidivism, so the prevalence of depression, anxiety, and substance abuse was examined in this cohort using psychometric tests. METHODS: Completion of self-report questionnaires was followed by face-to-face clinical interviews with 26 of the 56 male inmates on preventive detention in Norway's Ila Prison. Substance abuse histories and information about the type of psychiatric treatment received were compiled. To assess anxiety and depression, the Hospital Anxiety and Depression Scale (HADS), the Clinical Anxiety Scale (CAS), and the Montgomery Asberg Depression Rating Scale (MADRS) were used. RESULTS: Scores on the MADRS revealed that 46.1% of inmates had symptoms of mild depression. The HADS depression subscale showed that 19.2% scored above the cut-off for depression (κ = 0.57). The CAS anxiety score was above the cut-off for 30.7% of the subjects, while 34.6% also scored above the cut-off on the HADS anxiety subscale (κ = 0.61). Almost 70% of all these inmates, and more than 80% of those convicted of sex crimes, had a history of alcohol and/or drug abuse. CONCLUSIONS: Mild anxiety and depression was found frequently among inmates on preventive detention. Likewise, the majority of the inmates had a history of alcohol and drug abuse. Mood disorders and substance abuse may enhance recidivism, so rehabilitation programs should be tailored to address these problems.

A study of amnesia in homicide cases and forensic psychiatric experts' examination of such claims.

About one third of defendants in homicide cases claim amnesia during the time of their alleged act. Examining the authenticity of claimed amnesia is a special challenge for forensic experts. Because the experts' conclusions have legal implications, it is useful to study the characteristics of defendants who claim amnesia regarding a homicidal act and how forensic experts assess these defendants' claims. The forensic psychiatric reports from 2001 to 2007 on 102 Norwegian defendants charged with homicide were assessed quantitatively with a structured rating form. Due to multiple comparisons p of .003 was chosen. Twenty-six defendants claimed partial and 17 claimed total amnesia. No significant differences in the characteristics of the defendants were found between the partial, total, and no amnesia claiming groups. Claims of partial or total amnesia did not change the procedures and content of the forensic experts' examination. A memory test was applied in only one case. Despite the seriousness of the crime and the difficulty of assessing amnesia, the experts did not apply psychological testing of memory function or appropriate tests of possible malingering. Guidelines or standardized procedures for evaluation of defendants who claim amnesia should be developed. This could eventually contribute to more reliable and valid evaluations by forensic experts and increase the probability of just court outcomes.

Symptoms of depression and anxiety in functionally disabled rheumatic pain patients.

The aim of the present work was to study correlations between self-assessment of symptoms of depression, anxiety, rheumatic pain and functional disability. One hundred patients admitted to a university rheumatology clinic were tested in a consecutive manner, applying the Hospital Anxiety and Depression Scale (HADS). In addition, the patients were asked to express a quantitative measure of their subjective pain and functional disability on visual analogue scales (VAS). Regression analysis (analysis of variance) showed significant correlation between rheumatic pain and depression (P=0.04), between rheumatic pain and anxiety (P=0.03) and between rheumatic pain and functional disability (P<0.000). Significant correlations were also seen between depressive symptoms and functional disability (P=0.01) and between anxiety and functional disability (P=0.002). The correlation between symptoms of anxiety and depression was at a P=0.000 level. Applying the experience from this study and introducing, as part of a clinical examination, a minimum of psychiatric investigation based on self-assessment of anxiety and depression will provide relevant and reliable information sufficient for following up with specific psychiatric investigations and therapy. This in turn will be positive for those of the rheumatic patients having a comorbid mental health problem.

No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7.

The CSF levels of Met-enkephalin-Arg6-Phe7 and dynorphin A were measured in patients with fibromyalgia. The mean CSF Met-enkephalin-Arg6-Phe7 level was 35.1 +/- 2.4 fmol/ml (mean +/- S.E.M.). The mean CSF level of dynorphin A was 14.3 +/- 0.9 fmol/ml. Regression analysis showed a statistically significant correlation between Met-enkephalin-Arg6-Phe7 and dynorphin A (r = 0.5369, P = 0.001). When correlated to the previously measured CSF levels of beta-endorphin, a statistically significant correlation was found with Met-enkephalin-Arg6-Phe7 (r = 0.5055, P = 0.03) but not with dynorphin A (P greater than 0.05). The Met-enkephalin-Arg6-Phe7 and dynorphin A levels are elevated compared to the levels available for comparison groups. Therefore, a lack of endorphin secretion does not seem to be the basis for the hyperalgesia observed in these patients.

Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis.

In 30 patients with diagnosed fibromyalgia, the CSF level of immunoreactive substance P (SP) was investigated. Compared to normal values (9.6 +/- 3.2 fmol/ml), all the patients had elevated CSF levels of SP (36.1 +/- 2.7 fmol/ml, range 16.5-79.1 fmol/ml). Anamnestic information from the patients revealed that 53.3% had Raynaud/Raynaud-like phenomenon localized in the fingers, the toes or both. Although SP levels did not differ significantly in patients with or without the Raynaud phenomenon, elevated activity may be present in the peripheral branches of SP neurons which could be responsible for the last (rubor) phase of the triphasic Raynaud's phenomenon. SP levels were significantly higher in patients who were smokers (40.1 +/- 2.7 fmol/ml, range 25.3-64.1 fmol/ml), compared to patients who were non-smokers (29.2 +/- 5.0 fmol/ml, range 16.5-79.1 fmol/ml). We propose elevated CSF levels of SP and the Raynaud phenomenon as characteristic features for fibromyalgia with potential as diagnostic markers of the disease and further that smoking might be an aggravating factor for its pathogenesis or development.