[Caspase activity in peripheral blood mononuclear cells (PBMC) of patients with depression and anxiety of different severity]. / Izmenenie aktivnosti kaspaz v limfotsitakh patsientov s depressiei i trevogoi raznoi stepeni tiazhesti.

Though borderline psychiatric disorders (BPD) are quite common diseases, their pathogenesis remains obscure. Data from several groups and our previous results suggest that the pathological changes are typical not only for brain cells, but also for cells of the immune system. One of the evident illustrations of immune and nervous systems relationship in pathogenesis of mental diseases is the death of PBMC occurring in patients with depression. We have shown previously that activities of the caspases increase in some types of BPD. In this study, we have investigated caspase activities in PBMC of patients with BPD of different severity. It has been found that in severe depressive disorder activities of caspases were reduced either as compared to healthy controls or to patients with depression lesser severity. In contrast, in patients with severe anxiety activities of caspases were higher than in both control and patients with less severe forms of anxiety disorders. Thus, the study of caspase activity in PBMC makes it possible to differentiate between severe and mild forms of BPD.

[Activation of caspases in lymphocytes of patients with depression and anxiety].

The processes in the nervous and immune systems are closely interrelated. In particular, increased apoptosis was reported in lymphocytes of patients with depression. The aim of this study was to assess activities of proteases associated with cell death in lymphocytes of patient with personality disorders accompanied by depression and anxiety. In patients with personality disorders associated with organic brain dysfunction caspase activities were reduced in patients with depression and increased in patients with anxiety. The results may be useful for elucidation of pathogenetic mechanisms of personality disorders and in search of new biomarkers of these diseases.

Platelet protein kinase C and brain-derived neurotrophic factor levels in borderline personality disorder patients.

Borderline personality disorder (BPD) is a prevalent and difficult to treat psychiatric condition characterized by abrupt mood swings, intense anger and depression, unstable interpersonal relationships, impulsive self-destructive behavior and a suicide rate of approximately 10%. Possible underlying molecular dysregulations in BPD have not been well explored. Protein kinase C (PKC) and brain-derived neurotrophic factor (BDNF) have both been implicated in affective disorders, but their role in BPD has not been examined. Platelets were isolated from blood obtained from 24 medication-free BPD patients and 18 healthy control subjects. PKC-α, phosphorylated-PKC-α (p-PKCα), PKC-ßII, and BDNF were measured in platelet homogenates by immunoblotting. In the males, platelet BDNF and PKC-α levels were lower in patients than controls. p-PKC-α and PKC-ßII were lower at trend levels. In the entire sample, platelet p-PKCα and PKC-α activity were lower, at a trend level, in patients compared to controls. This is the first report to our knowledge of PKC and BDNF activity in BPD and calls for replication. These findings are consistent with altered PKC and BDNF activity in a range of neuropsychiatric conditions including bipolar disorder, depression and suicide.

COMT val158met polymorphism and neural pain processing.

A functional polymorphism (val158met) of the gene coding for Catechol-O-methyltransferase (COM) has been demonstrated to be related to processing of emotional stimuli. Also, this polymorphism has been found to be associated with pain regulation in healthy subjects. Therefore, we investigated a possible influence of this polymorphism on pain processing in healthy persons as well as in subjects with markedly reduced pain sensitivity in the context of Borderline Personality Disorder (BPD). Fifty females (25 patients with BPD and 25 healthy control participants) were included in this study. Genotype had a significant--though moderate--effect on pain sensitivity, but only in healthies. The number of val alleles was correlated with the BOLD response in several pain-processing brain regions, including dorsolateral prefrontal cortex, posterior parietal cortex, lateral globus pallidus, anterior and posterior insula. Within the subgroup of healthy participants, the number of val alleles was positively correlated with the BOLD response in posterior parietal, posterior cingulate, and dorsolateral prefrontal cortex. BPD patients revealed a positive correlation between the number of val alleles and BOLD signal in anterior and posterior insula. Thus, our data show that the val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people, this polymorphism was more related to cognitive aspects of pain processing, whereas BPD patients with reduced pain sensitivity showed an association with activity in brain regions related to affective pain processing.

Interaction between tryptophan hydroxylase I polymorphisms and childhood abuse is associated with increased risk for borderline personality disorder in adulthood.

INTRODUCTION: Borderline personality disorder (BPD) is a severe disorder with high morbidity and mortality, but unknown etiology. Childhood abuse has been proposed as an etiological factor, but the mechanism by which an abuse history could influence the risk for BPD has not been determined. The aim of this study was to determine whether the tryptophan hydroxylase 1 (TPH1) gene is related to BPD in a clinical sample, and whether TPH1 genotypes or haplotypes moderate the relationship between abuse history and BPD. METHODS: Three hundred and ninety-eight patients diagnosed with mood disorders were genotyped for TPH1 G-6526A promoter polymorphism (rs4537731) and the A218C intron 7 polymorphism (rs1800532) and a set of ancestry informative markers, assessed for Diagnostic and Statistical Manual of Mental Disorders, 4th edition diagnoses, and assessed for a history of physical and sexual abuse. RESULTS: Patients with a diagnosis of BPD were more likely to be risk allele carriers (A alleles at both loci) than the non-BPD group. Logistic regression analysis predicting BPD diagnosis with both single-nucleotide polymorphisms and haplotypes showed significant interaction effects between genotype and abuse history. Poisson regression predicting the number of BPD diagnostic criteria met with the same predictor set also included a significant interaction term. Risk allele carriers with a history of abuse had an increased likelihood of a BPD diagnosis. CONCLUSION: Variation in TPH1 may increase risk for developing BPD as a result of childhood abuse. Elements of BPD pathology may be due in part to a genetically influenced serotonergic dysfunction, which in turn may lead to a differential response to environmental stressors.

Borderline personality symptomatology and sexual impulsivity.

OBJECTIVE: According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, borderline personality disorder (BPD) is an Axis II phenomenon that is characterized by impulsivity, including sexual impulsivity. However, little empirical research has been undertaken to confirm and/or define the nature of sexual impulsivity in patients with BPD, which is the focus of the present study. METHOD: Using a cross-sectional approach and sample of convenience, we surveyed 76 women who were being seen as outpatients in an internal medicine clinic regarding: a) borderline personality symptoms using two measures (i.e., the borderline personality scale of the Personality Diagnostic Questionnaire-4, McLean Screening Inventory for Borderline Personality Disorder); and b) their sexual histories. RESULTS: We found two statistically significant differences--those with borderline personality symptomatology were more likely to have an earlier onset of sexual intercourse as well as to report date rape. CONCLUSIONS: Individuals with borderline personality symptomatology report earlier sexual exposure as well as date rape, but not other aspects of sexual impulsivity such a greater number of sexual partners, more frequent treatment for sexually transmitted diseases, etc.

Monoamine oxidase a gene is associated with borderline personality disorder.

OBJECTIVE: Monoamine oxidase A is a mitochondrial enzyme involved in the degradation of certain neurotransmitter amines: serotonin and norepinephrine. As for its role in aggression, impulsivity, suicide and mood liability, monoamine oxidase A can be considered a functional candidate in borderline personality disorder. METHODS: To test for this hypothesis we genotyped two polymorphic markers in monoamine oxidase A gene, a promoter VNTR and an rs6323 (T941G) in exon 8, in 111 Caucasian borderline personality disorder patients and 289 Caucasian healthy controls. Association analyses using individual marker and haplotype data were performed by a program of COCAPHASE in UNPHASED (MRC Human Genome Mapping Project Resource Centre, Cambridge, UK). RESULTS: We found that the borderline personality disorder patients had a high frequency of the high activity VNTR alleles (chi=4.696, P=0.03) and a low frequency of the low activity haplotype (chi=5.089, P=0.02). CONCLUSION: These results show that the monoamine oxidase A gene may play an important role in the etiological development of the borderline personality disorder.

Prevalence of acute intermittent porphyria in a Mexican psychiatric population.

BACKGROUND: Acute intermittent porphyria is a hereditary error of porphyrin metabolism in which the main metabolic defect is caused by a decrease in porphobilinogen deaminase activity. Previous work has demonstrated a higher prevalence of acute intermittent porphyria in the psychiatric patient population than in the general population. The goal of this study was evaluate 300 psychiatric patients and 150 control subjects to detect acute intermittent porphyria by measurement of porphobilinogen (PBG) deaminase activity in blood. METHODS: Screening for porphobilinogen deaminase activity was carried out by fluorometric measurement of porphyrins synthesized during 1 h in blood and the measurement of delta-aminolevulinic acid and porphobilinogen in urine. RESULTS: We found two psychiatric patients, one male and one female, with decreased porphobilinogen deaminase activity. When the families of these patients were studied, one brother was found to have an abnormality. Among controls, a woman was found to have the abnormality and her father was found to have typical features of the disease. CONCLUSIONS: These results indicate a prevalence of porphyria in Mexican psychiatric patients similar to controls, and that measurement of PBG deaminase activity is a good tool for defining acute intermittent porphyria carriers.

Platelet MAO activity in personality disorders and normal controls.

Platelet monoamine oxidase (MAO) activity has been related to several psychiatric disorders and personality dimensions. The purpose of this study was to measure platelet MAO activity in personality disorders and determine its relationship to symptoms analogous to sensation seeking. Twenty-eight males admitted to a psychiatric unit with a DSM-III-R diagnosis of personality disorder were compared to normal controls. Patients with Axis I diagnoses other than adjustment disorder were excluded. There was no difference in MAO activity between patients and normals, although it was lower in borderline patients. MAO activity was inversely correlated with sensation seeking, especially in the patient group, as predicted. The results are consistent with the view that platelet MAO activity is a marker of general psychopathology.

Low platelet monoamine oxidase activity in borderline personality disorder.

Platelet monoamine oxidase (MAO) activity was significantly lower in nonpsychotic, nonorganic, unmedicated male inpatients with DSM-III-R borderline personality disorder (BPD) than in nonpsychiatric controls. Patients with BPD who also met DSM-III-R criteria for antisocial personality disorder had significantly lower MAO activity than those with BPD alone. Low MAO activity in this sample did not appear to be related to the comorbid presence of major depressive disorder or a history of substance abuse.