Mario Catena

Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Women who have experienced childhood sexual abuse (CSA) have an increased risk of alcoholism and antisocial personality disorder (ASPD). Among male subjects, a functional polymorphism (MAOA-LPR, monoamine oxidase A linked polymorphic region) in the promoter region of the monoamine oxidase A gene (MAOA) appears to moderate the effect of childhood maltreatment on antisocial behavior. Our aim was to test whether MAOA-LPR influences the impact of CSA on alcoholism and ASPD in a sample of 291 women, 50% of whom have experienced CSA; we also tested whether haplotypes covering the region where both MAOA and monoamine oxidase B (MAOB) genes are located predict risk of alcoholism and ASPD better than the MAOA-LPR locus alone. Participants included 168 alcoholics (39 with ASPD (antisocial alcoholics) and 123 controls (no alcoholics, no ASPD). Antisocial behavior was also modeled as a continuous trait: ASPD symptoms count. The MAOA-LPR low activity allele was associated with alcoholism (P=0.005), particularly antisocial alcoholism (P=0.00009), only among sexually abused subjects. Sexually abused women who were homozygous for the low activity allele had higher rates of alcoholism and ASPD, and more ASPD symptoms, than abused women homozygous for the high activity allele. Heterozygous women displayed an intermediate risk pattern. In contrast, there was no relationship between alcoholism/antisocial behavior and MAOA-LPR genotype among non-abused women. The MAOA-LPR low activity allele was found on three different haplotypes. The most abundant MAOA haplotype containing the MAOA-LPR low activity allele was found in excess among alcoholics (P=0.008) and antisocial alcoholics (P=0.001). Finally, a MAOB haplotype, which we termed haplotype C, was significantly associated with alcoholism (P=0.006), and to a lesser extent with antisocial alcoholism (P=0.03). In conclusions, MAOA seems to moderate the impact of childhood trauma on adult psychopathology in female subjects in the same way as previously shown among male subjects. The MAOA-LPR low activity allele appears to confer increased vulnerability to the adverse psychosocial consequences of CSA. Haplotype-based analysis of the MAOA gene appeared to strengthen the association, as compared to the MAOA-LPR locus alone. A MAOB haplotype was associated with alcoholism independently from ASPD.

Impairment in visual and spatial perception in schizophrenia and delusional disorder.

The Judgment of Line Orientation Test, a visuospatial processing task, was administered to normal subjects, to schizophrenic patients and to patients with delusional disorder. Significantly better performance was seen in the normal subjects than in the schizophrenic and delusional patients. Delusional patients, in turn, showed better performance than the schizophrenic patients.

Insight in body dysmorphic disorder with and without comorbid obsessive-compulsive disorder.

INTRODUCTION The aim of this study was to compare the level of insight in patients with body dysmorphic disorder (BDD) with and without comorbid obsessive-compulsive disorder (OCD), and to measure its possible relationships with clinical features. METHODS Thirty outpatients affected by BDD, according to Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria, of whom 18 were also suffering from OCD, were included in the study. Clinical assessment was carried out by means of the Yale-Brown Obsessive-Compulsive Scale modified for BDD and a specially designed OCD Questionnaire. The level of insight was measured by means of the score at item 11 of the Yale-Brown Obsessive-Compulsive Scale modified for BDD. RESULTS The insight resulted to be excellent in four cases, good in four, fair in five, poor in 15 and absent in two. Significant and positive correlations were observed between the level of insight and the following items: resistance to thoughts and to activities as well as to time spent on activities and control on activities related to the defect. The insight was significantly lower in patients affected by both BDD and OCD. CONCLUSION The findings indicate that the majority of BDD patients in this study, and especially those with comorbid OCD, have a low degree of insight that is significantly correlated to symptoms specific of the disorder.

Predictors of response in a sample of treatment-resistant psychotic patients on clozapine.

This study aims at identifying potential predictors of clinical response and functional outcome in 101 neuroleptic-refractory patients with a DSM-III-R diagnosis of schizophrenia (N = 34), schizoaffective disorder (N = 30) or bipolar disorder with psychotic features (N = 37), naturalistically treated with clozapine over a 48-month period. The “clinical response” and “functional outcome” criteria were respectively defined a priori as: a reduction of at least 50 % in the Brief Psychiatric Rating Scale total score in one evaluation with respect to baseline; and a Global Assessment of Functioning Scale score of at least 50. Several clinical and socio- demographic variables were assessed at baseline and only the diagnosis of bipolar disorder was significantly related with the clinical response. Variables significantly related with the functional outcome were female gender, university education and early age at onset.

Binding of 3H-WIN-35,428 and 125I-RTI-121 to Human Platelet Membranes

The dopamine transporter (DAT) is a protein regulating dopamine concentration in the synaptic cleft through the re-uptake mechanism. The DAT is the main target of psychostimulants and seems to play a pivotal role in neuronal degeneration and different neuropsychiatric disorders involving the dopamine system. Exhaustive research, however, regarding the presence of this protein in human platelets is still inconclusive, although it is thought that it might provide a peripheral tool to serve as a mean of exploring the same structure present in the brain. Therefore, we assessed some binding assays in platelets derived from healthy human subjects by means of 3H-WIN 35,428, a compound which is considered a selective ligand for the labelling of this protein, and by means of 125I-RTI-121, another compound with high specificity for DAT. The results showed that the binding of 3H-WIN-35,428 was too low to enable the detection of any structure; the binding of 125I-RTI-121, on the other hand, revealed the presence of two binding sites with pharmacological profiles similar to that of the serotonin transporter (SERT). In conclusions, therefore, platelets would not seem to be a useful model for exploring the DAT, given the prevalence therein of the SERT and the difficulty of labelling the DAT with the currently available ligands.

Lymphocyte subsets, cardiovascular measures and anxiety state before and after a professional examination

Controversies exist regarding the impact of psychological stress on the functioning of the immune system in humans. The aim of the present study, therefore, was to evaluate whether the condition of a pre-exam stress may or not modify resting lymphocyte subsets, as well as blood pressure and heart rate. About 22 medical residents of both sexes not suffering from any medical or psychiatric disorder were included in the study. Anxiety levels were measured by means of the Hamilton rating scale for anxiety (HRSA) and anxiety traits by means of the panic-agoraphobic spectrum self-report (PAS-SR) version and the obsessive-compulsive spectrum self-report (OBS-SR) version. The results showed that systolic blood pressure and heart rate increased significantly just before sitting an examination (t1) in all subjects, as compared with a calm situation (t2), in parallel with the increase in the HRSA total score, while no significant difference was observed in lymphocyte subsets at the two assessment times. However, men had a higher number of CD4+ cells than women at t1 and t2, while women showed a higher heart rate at t1. In addition, significant correlations between CD4+ lymphocyte count and heart rate at t1 or HRSA at t2 were detected. These findings indicate that the acute stress determined by sitting for examination provokes changes in autonomic nervous system parameters, such as blood pressure and heart rate, as well as in the subjective feeling of anxiety, as shown by the increased HRSA total scores, which were not paralleled by modifications of lymphocyte subsets. However, individual differences, related to both sex and personality traits yet to be identified, seem to have an impact in shaping the stress response.

Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study

OBJECTIVE The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [3H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding. RESULTS Our experiments revealed the presence of specific and saturable binding of [3H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 +/- 25 fmol/mg protein, and the dissociation constant was 0.8 +/- 0.4 nM. DISCUSSION AND CONCLUSIONS Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.

The Rabbit Syndrome: State of the Art

INTRODUCTION The rabbit syndrome (RS) is a rare movement disorder generally associated with prolonged use of antipsychotics and characterized by inwilling, rhythmic, fast and fine movements of oral and masticatory muscles along the vertical axis of the mouth. PREVALENCE The prevalence of RS ranges between 1.5% and 4.4%; middle and elderly ages, the female gender, as well as past brain injuries are considered risk factors for its development. PATHOPHYSIOLOGY Although a dysbalance of the cholinergic and dopaminergic neurotransmission in the basal ganglia seems to be involved in the pathophysiology of RS, its precise mechanisms need to be clarified as yet. RELATIONSHIPS WITH ANTIPSYCHOTICS: Fifty cases of RS have been published up-to-now: 34 and 10 occurred during treatments with typical and atypical antipsychotics, respectively, while 6 seemed unrelated to these drugs. DIFFERENTIAL DIAGNOSIS The differential diagnosis between RS and tardive dyskinesias involving the mouth may be based mainly on the evidence that in these last conditions the movements of the mouth are less regular and slower and involve the tongue. Treatment strategy: The available data suggest that RS responds favourably to anticholinergic drugs and to the change of the antipsychotic.

Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study = Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

OBJECTIVE The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [3H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding. RESULTS Our experiments revealed the presence of specific and saturable binding of [3H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 +/- 25 fmol/mg protein, and the dissociation constant was 0.8 +/- 0.4 nM. DISCUSSION AND CONCLUSIONS Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.

Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

OBJECTIVE The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [3H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding. RESULTS Our experiments revealed the presence of specific and saturable binding of [3H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 +/- 25 fmol/mg protein, and the dissociation constant was 0.8 +/- 0.4 nM. DISCUSSION AND CONCLUSIONS Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.