Regulation of feeding and anxiety by alpha-MSH reactive autoantibodies

alpha-Melanocyte-stimulating hormone (alpha-MSH) is a stress-related neuropeptide involved in the regulation of motivated behavior, appetite and emotion including stimulation of satiety and anxiety. Although autoantibodies (autoAbs) reactive with alpha-MSH have been identified in human subjects and in rats, it remained unknown if these autoAbs are involved in the regulation of feeding and anxiety and if their production is related to stress. Here we show that repeated exposure of rats to anxiolytic mild stress by handling increases the levels and affinity of alpha-MSH reactive IgG autoAbs and that these changes are associated with adaptive feeding and anxiety responses during exposure of rats to a strong stress by food restriction. Importantly, an increase in affinity of alpha-MSH reactive autoAbs was associated with changes of their functional roles from stimulation to inhibition of alpha-MSH-mediated behavioural responses, suggesting that these autoAbs can be a carrier or a neutralizing molecule of alpha-MSH peptide, respectively. Using a model of passive transfer into the brain, we show that alpha-MSH autoAbs affinity purified from blood of rats exposed to repeated mild stress, but not from control rats, are able to increase acutely food intake, suppress anxiety and modify gene expression of hypothalamic neuropeptides in na?ve rats. These data provide the first evidence that autoAbs reactive with alpha-MSH are involved in the physiological regulation of feeding and mood, supporting a further role of the immune system in the control of motivated behavior and adaptation to stress.     

Autoantibodies reacting with vasopressin and oxytocin in relation to cortisol secretion in mild and moderate depression

Background

Abnormal vasopressin (VP) and oxytocin (OT) signaling may contribute to the altered activity of the hypothalamo-pituitary-adrenal (HPA) axis in major depression; however, the underlying mechanisms remain uncertain. This study characterized plasma levels and affinities of OT- and VP-reactive autoantibodies (autoAbs) in relation to disease severity and plasma cortisol response to physical exercise in patients with mild and moderate depression and healthy controls.

Methods

Physical exercise was used to elicit plasma cortisol response in 23 male patients with depression and 20 healthy controls and plasma samples were obtained before and after the exercise. Just before the exercise, patients and controls were evaluated by the Montgomery and Åsberg Depression Rating Scale (MADRS) and divided according to depression severity (14 mild and 9 moderate). Plasma levels of total and free VP- and OT-reactive IgG, IgA and IgM autoAbs were measured by ELISA and affinity of IgG and IgM autoAbs were measured by plasmon resonance technique at baseline before the exercise and analyzed with relation to the MADRS and cortisol response. Immunohistochemistry was used to evaluate autoAbs binding to the rat hypothalamus.

Results

Plasma levels of OT- and VP-reactive total IgG autoAbs were lower in patients with moderate depression vs. controls and patients with mild depression. Plasma levels of both OT- and VP-free IgG autoAbs were negatively correlated with MADRS scores. Affinity values of IgG and IgM autoAbs for both OT and VP displayed 100 fold variability among patients or controls but no significant group differences were found. Patients with moderate depression displayed blunted response of cortisol secretion to physical exercise. Baseline levels of VP total IgG and IgM autoAbs correlated negatively and VP-free IgG autoAbs correlated positively with plasma cortisol after physical exercise. Immunostaining of magnocellular hypothalamic neurons of the supraoptic and paraventricular nuclei by plasma IgG was present in 35% of the depression and in 14% of the controls groups, but this staining was not abolished by plasma preabsorption with OT or VP peptides.

Conclusion

These data show that changes of levels but not affinity of OT- and VP-reactive autoAbs can be associated with the altered mood in subjects with moderate depression and that levels of VP-reactive autoAbs are associated with cortisol secretion.     

Anti-neuropeptide Y plasma immunoglobulins in relation to mood and appetite in depressive disorder

Depression and eating disorders are frequently associated, but the molecular pathways responsible for co-occurrence of altered mood, appetite and body weight are not yet fully understood. Neuropeptide Y (NPY) has potent antidepressant and orexigenic properties and low central NPY levels have been reported in major depression. In the present study, we hypothesized that in patients with major depression alteration of mood, appetite and body weight may be related to NPY-reactive autoantibodies (autoAbs). To test this hypothesis, we compared plasma levels and affinities of NPY-reactive autoAbs between patients with major depression and healthy controls. Then, to evaluate if changes of NPY autoAb properties can be causally related to altered mood and appetite, we developed central and peripheral passive transfer models of human autoAbs in mice and studied depressive-like behavior in forced-swim test and food intake. We found that plasma levels of NPY IgG autoAbs were lower in patients with moderate but not with mild depression correlating negatively with the Montgomery-?sberg Depression Rating Scale scores and with immobility time of the forced-swim test in mice after peripheral injection of autoAbs. No significant differences in NPY IgG autoAb affinities between patients with depression and controls were found, but higher affinity of IgG autoAbs for NPY was associated with lower body mass index and prevented NPY-induced orexigenic response in mice after their central injection. These data suggest that changes of plasma levels of anti-NPY autoAbs are relevant to altered mood, while changes of their affinity may participate in altered appetite and body weight in patients with depressive disorder.     

Galanin and α-MSH autoantibodies in cerebrospinal fluid of patients with Alzheimer's disease

BackgroundNeuropeptides galanin and α-melanocyte-stimulating hormone (α-MSH) are involved in the regulation of memory and appetite. Increased galanin and decreased α-MSH levels were reported in postmortem brains of patients with Alzheimer's disease (AD) but the underlying mechanisms are uncertain. Here we studied if autoantibodies (autoAbs) reacting with galanin and α-MSH are altered in AD.MethodsLevels of free and total IgG autoAbs reacting with galanin and α-MSH were measured in sera and cerebrospinal fluid (CSF) of 18 subjects with AD and in 15 age-matched non-demented controls. Values were correlated with Mini-Mental State Examination (MMSE) score, body mass index (BMI) and CSF levels of AD biomarkers.ResultsCSF levels of total but not free IgG autoAbs against galanin were increased in AD, resulting in increased percentage of galanin autoAbs present as immune complexes. CSF levels of galanin total autoAbs and α-MSH free autoAbs correlated negatively with the severity of cognitive impairment as measured by MMSE. Both total and free autoAbs against galanin and α-MSH in CSF correlated negatively with age in AD patients but not in controls. CSF levels of galanin autoAbs and free α-MSH AutoAbs negatively correlated with CSF levels of t-Tau, p-Tau and ratios of t-Tau/Aβ42 or p-Tau/Aβ42 in AD patients but not in controls.ConclusionsAutoAbs reacting with galanin and α-MSH are present in CSF and are associated with clinical characteristics of AD patients. The functional significance and therapeutic potential of these autoAbs should be further clarified.     

Idiopathic polyneuropathy associated with cytotoxic anti-neuroblastoma serum. IgG and IgM immunoglobulin studies.

Serums from six patients with progressive idiopathic acute or chronic polyneuropathy possessed a cytolytic activity against transformed mouse cholinergic or noncholinergic neuroblasts but not against transformed rat astrocytes. This activity was not qualitatively nor quantitatively present in serums from normal controls or from patients with a variety of other motor system disorders and other neurologic disorders. Fluorescein conjugated goat antihuman IgG and IgM monospecific immunoglubulins were used to characterize further the cytotoxic activity from patient serums and these studies suggested the presence of immunoglobulin G (IgG) and immunoglobulin M (IgM) directed against a cell surface neuroblastoma antigen. Cold reactive immunoglobulins of the IgG and IgM type were present in the serums of all six patients. A bioassay is described that may be helpful in evaluating other patients with progressive idiopathic polyneuropathies.     

Serum immunogloblin levels in myasthenia gravis, polymyositis, and dermatomyositis.

Analyses of serum immunoglobulin (Ig) levels were performed in patients with myasthenia gravis, polymyositis and dermatomyositis, and in normal subjects. The mean IgG levels were elevated in the disease groups and there was minimal depression of serum IgM levels in nonthymectomized myasthenic patients. There was no consistent pattern with regard to selective immunoglobulin class abnormalities, effect of thymectomy in serial studies, and no evidence of gross humoral immunological deficiency as manifested by consistent depression of serum IgA, IgG, or IgM in the disease groups.     

Antibodies against light neurofilaments in multiple sclerosis patients

OBJECTIVES: Axonal damage in multiple sclerosis (MS) may be reflected by antibodies against axon-specific proteins - the light subunit of neurofilaments (NFL). MATERIALS AND METHODS: The serum and cerebrospinal fluid obtained from 58 MS patients, 24 normal controls (CN), 49 control patients with miscellaneous diseases (CD) and 31 patients with neurodegenerative disorders (CDEG) were tested for both immunoglobulin G and M antibodies against NFL, using an ELISA. RESULTS: Intrathecal IgG antibodies to NFL were elevated in MS patients compared with that in CD patients (P = 0.001) and were not related to clinical variables. No differences in IgM anti-NFL levels were found between the MS and CN/CD groups. IgM to NFL was higher in the CDEG group than in either the CD group or even the MS group (P < 0.0005). CONCLUSIONS - Intrathecal IgM or IgG antibodies to NFL are not useful surrogate markers for axonal damage or disease subtypes in MS.     

Response to emotional stimuli in boys with conduct disorder

OBJECTIVE: Boys with conduct disorder are at risk of persistently showing antisocial behavior in adult life, particularly if they have an additional diagnosis of attention deficit hyperactivity disorder (ADHD). In the search for biological risk factors that predispose children to the development of antisocial personality disorder, research has provided substantial data suggesting that autonomic hyporesponsiveness indicates a greater likelihood of future antisocial behavior. The purpose of this study was to examine autonomic arousal in boys with conduct disorder, comorbid conduct disorder and ADHD, and ADHD only. METHOD: In addition to self-ratings, electrodermal responses to pleasant, neutral, and unpleasant slides were obtained for 21 boys with conduct disorder and 54 boys with ADHD plus conduct disorder. Forty-three boys with a diagnosis of ADHD only were recruited as a clinical comparison group, and 43 boys with no conduct disorder or ADHD were included as a healthy comparison group. All subjects were ages 8-13 years. RESULTS: Compared to the healthy subjects and the subjects with ADHD only, the boys with conduct disorder and with ADHD plus conduct disorder reported lower levels of emotional response to aversive stimuli and lower autonomic responses to all slides independent of valence. CONCLUSIONS: Although the self-report data supported a deficit in reactivity to explicit fear cues, the psychophysiological data indicated that boys with conduct disorder both with and without a comorbid condition of ADHD are characterized by a generalized deficit in autonomic responsivity in an experimental situation in which children were exposed to complex visual stimuli of unpredictable affective quality. Psychophysiological findings may point to a deficit in associative information processing systems that normally produce adaptive cognitive-emotional reactions.     

Serum IgA, IgG, and IgM concentrations in patients with epilepsy and matched controls: a cohort-based cross-sectional study

Conflicting reports have been published on serum immunoglobulin (Ig) concentrations in patients with epilepsy. Serum IgA, IgG, and IgM concentrations were determined in a cohort of 958 patients and in a reference population of 581 subjects. Overall, 8.2% of patients with epilepsy and 1.9% of control subjects had low serum IgA concentrations. Low serum IgA levels were measured in 19.1% of patients currently on phenytoin therapy and in 11.9% of patients who had previously been treated with phenytoin, whereas only 3.8% of patients who had never been on phenytoin therapy had low serum IgA. In multivariate analysis low serum IgA concentrations were associated with phenytoin medication and female gender. No differences in serum IgG and IgM concentrations were observed between patients and control subjects. However, in patients with epilepsy, low serum IgG concentrations were associated with concomitant autoimmune diseases, and low IgM levels with older age at the onset of epilepsy, long duration of epilepsy, and autoimmune diseases. In conclusion, the prevalence of low serum IgA concentrations was increased in patients with epilepsy, but serum IgG and IgM concentrations were similar in patients with epilepsy and reference subjects. The low serum IgA concentrations were associated with phenytoin medication. In addition to current phenytoin medication, previous phenytoin therapy also was associated with low serum IgA concentrations. This implies that phenytoin medication may have permanent immunological effects in some patients.     

IgM-containing fraction suppressed voltage-gated potassium channels in acquired neuromyotonia

OBJECTIVES: Acquired neuromyotonia (ANM) is an autoimmune disorder caused by antibodies to voltage-gated potassium channels (VGKC). Previously, we reported a patient with immunoglobulin M (IgM), instead of immunoglobulin G (IgG), anti-VGKC antibody. The purpose of this study was to determine the function of IgM-containing fraction in ANM patients. MATERIALS AND METHODS: We determined whether anti-VGKC antibodies in the IgG or IgM-containing fractions suppressed outward potassium current (OKC) using the patch clamp method in three patients with ANM. Whole sera from all patients suppressed OKCs. RESULT: Only the purified IgG, not the IgM-containing fractions from two patients suppressed VGKCs, whereas in a patient with IgM anti-VGKC antibody, only the IgM-containing fractions, not the IgG-containing fractions suppressed VGKCs. CONCLUSION: Anti-VGKC antibodies belonging to the IgM subclass should be determined in seronegative ANM patients.     

Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis

Neurofilaments are cytoskeletal proteins localized within axons, which may interact with the immune system during and following tissue destruction in multiple sclerosis (MS). Antibodies against the medium neurofilament subunit synthesized intrathecally may reflect axonal damage in MS patients. Both immunoglobulin G (IgG) and M (IgM) responses against the purified native medium subunit of neurofilaments (NFM) using enzyme-linked immunosorbent assay (ELISA) were determined in paired serum and cerebrospinal fluid samples obtained from 49 MS patients, 16 normal controls (CN), 21 control patients with miscellaneous diseases (CD) and 14 patients with neurodegenerative disorders (CDEG). Intrathecal production of IgM and IgG antibodies to NFM were elevated in MS patients compared with the CN or CD groups (p < 0.04 for IgM, p < 0.01 for IgG). The increase was present in all the MS courses (relapsing-remitting, primary and secondary progressive). Similar local anti-NFM IgG and IgM synthesis occurred in the MS and CDEG groups. MS patients with short and long disease duration did not differ in terms of their anti-NFM IgM and IgG responses. Repeated examinations showed stable intrathecal anti-NFM production. Intrathecal IgG and IgM antibodies against NFM were increased in MS patients and may serve as a potential marker for axonal pathology. The extent of anti-NFM levels did not correspond to any individualized clinical profiles of MS patients.     

Anti-GM1 ganglioside antibodies in Parkinson's disease

OBJECTIVES: To determine whether anti-GM1 antibodies are increased in Parkinson's disease (PD). METHODS: Serum immunoglobulin M (IgM) and IgG anti-GM1 antibodies were detected by enzyme-linked immunosorbent assay (ELISA) in 147 patients with PD and in 186 age-matched normal control subjects. Sera were assayed at initial dilution of 1:800 for IgM and 1:200 for IgG and were considered positive at absorbance values exceeding the value of 0.05 for IgM and 0.1 for IgG. RESULTS: Forty patients with PD (27.2%) had sera positive for IgM anti-GM1 antibodies, whereas only five normal controls (2.7%) resulted positive (P < 0.0001). Most of patients (75%) with positive sera had a tremor-dominant form of PD. Only two patients with PD (1.4%) and none of normal controls had sera positive for IgG anti-GM1 antibodies. CONCLUSION: A consistent portion of parkinsonians, mainly with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1 antibodies.     

Immunoglobulins in cerebrospinal fluid: Enzyme-immunoassay

Using an enzyme-immunoassay (EIA) technique we established control values for IgA and IgM in cerebrospinal fluid (CSF). These values, together with IgG values determined by single radial immunodiffusion (SRID) technique, showed significant positive correlations with CSF total protein values. The CSF IgA and IgM levels were related to corresponding levels determined in serum. In addition, the values for all 3 immunoglobulin classes in CSF as well as CSF total protein values showed positive correlation with age of subjects, and IgG% and IgA% increased with age. This new EIA procedure can be completed within 24 h and is sensitive enough for determining all 3 immunoglobulin classes using a small amount (100 μl or less) of native CSF.     

Plasmalemmal and vesicular γ‐aminobutyric acid transporter expression in the developing mouse retina

Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L‐amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff‐man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain γ‐aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC‐containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D‐group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple‐labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as,, e.g.,, shown in stiff‐man syndrome. J. Comp. Neurol. 513:1–20, 2009. © 2008 Wiley‐Liss, Inc.     

Plasmalemmal and vesicular γ‐aminobutyric acid transporter expression in the developing mouse retina

Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L‐amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff‐man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain γ‐aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC‐containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D‐group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple‐labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in stiff‐man syndrome. J. Comp. Neurol. 513:1–20, 2009. © 2009 Wiley‐Liss, Inc.     

Passages 2009 changing an institution: Refocusing JCN on systems neuroscience

Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L‐amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff‐man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain γ‐aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC‐containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D‐group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple‐labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in previous studies in stiff‐man syndrome. J. Comp. Neurol. 513:1–20, 2009. © 2008 Wiley‐Liss, Inc.     

Serum immunoglobulins in brain tumours and lumbar disc diseases

Changes of serum immunoglobulin (Ig) concentrations may occur in both brain tumours and lumbar disc diseases (LDD). The purpose of this study was to investigate the changes of pre- and post-operative serum Ig levels in brain tumours and LDDs. Serum IgG, IgA and IgM levels were measured in 127 patients with brain tumour, 100 patients with LDD and 20 healthy subjects without neurological disease. Increases in one or more of the pre-operative serum Ig levels were observed in the patients with both brain tumours and LDDs compared with controls. However pre-operative serum IgG level was highly increased in all brain tumour types and LDDs (p<0.001). Serum IgA levels and IgM levels in the post-operative stage were significantly decreased in patients with acoustic neurinoma (p<0.01, p<0.001, respectively). Post-operative serum IgG, IgA and IgM levels were significantly decreased (p<0.001) in patients with meningioma. Post-operative serum IgG and IgM levels were significantly decreased (p<0.001) in patients with glioma. Patients with LDD showed a significantly decline in post-operative serum IgA and IgM levels (p<0.001). We think that decline in post-operative serum Ig levels may be of prognostic value in the patients with brain tumours and LDDs.     

Cryptococcal meningoencephalitis: intrathecal immunological response

Summary The intrathecal immune response is reported in a patient with cryptococcal meningoencephalitis. CSF IgM and IgG levels were significantly related to the favourable clinical evolution. IgM response was specifically directed against the pathological agent, while IgG were mostly non-specific. The data are discussed and compared with the other chronic infections of the central nervous system.     

Maternal infections and subsequent psychosis among offspring.

BACKGROUND: We tested the hypothesis that maternal infections during pregnancy are associated with the subsequent development of schizophrenia and other psychoses in adulthood. METHODS: We conducted a nested case-control study of 27 adults with schizophrenia and other psychotic illnesses and 54 matched unaffected control subjects (matched for sex, ethnicity, and date of birth) from the Providence, RI, cohort of the Collaborative Perinatal Project. We retrieved stored blood samples that had been obtained from these mothers at the end of pregnancy. These samples were analyzed for total class-specific immunoglobulins and for specific antibodies directed at recognized perinatal pathogens capable of affecting brain development. RESULTS: Maternal levels of IgG and IgM class immunoglobulins before the mothers were delivered of their neonates were significantly elevated among the case series (t = 3.06, P =.003; t = 2.93, P =.004, respectively, for IgG and IgM immunoglobulin-albumin ratios). Secondary analyses indicated a significant association between maternal antibodies to herpes simplex virus type 2 glycoprotein gG2 and subsequent psychotic illness (matched t test = 2.43, P =.02). We did not find significant differences between case and control mothers in the serum levels of IgA class immunoglobulins, or in specific IgG antibodies to herpes simplex virus type 1, cytomegalovirus, Toxoplasma gondii, rubella virus, human parvovirus B19, Chlamydia trachomatis, or human papillomavirus type 16. CONCLUSIONS: The offspring of mothers with elevated levels of total IgG and IgM immunoglobulins and antibodies to herpes simplex virus type 2 are at increased risk for the development of schizophrenia and other psychotic illnesses in adulthood.     

Apolipoprotein A-I/apolipoprotein B ratio and aggression in violent and nonviolent young adult males

Epidemiological, clinical, and experimental studies have linked low or lowered cholesterol levels to aggressive behavior. However, no study has measured the relationship between aggression and apolipoprotein A-I/apolipoprotein B ratio, a robust indicator of cardiac risk. Plasma levels of total cholesterol, HDL-C, LDL-C, triglycerides, apolipoprotein A-I, and apolipoprotein B were measured and correlated with Aggression Questionnaire ratings in 20 young adult males with personality disorders and/or a high propensity toward aggressive behavior and in 40 control subjects. Compared with the control subjects, the subjects in the aggressive group had lower levels of apo A-I and a lower apo A-I/apo B ratio. Whereas in the control subjects, higher levels of aggression were correlated with lower levels of atherogenic lipoproteins (LDL-C and apo B), in the aggressive subjects higher levels of aggression were correlated with lower levels of anti-atherogenic lipoproteins (HDL-C and apo A-I) and higher levels of LDL-C. The results of this study confirm the existence of a relationship between blood lipids and aggressive behavior in young adult males and suggest that the apo A-I/apo B ratio might be an additional marker in the search for biological correlates of increased risk of violence.