Miguel Angel Gonzalez-Torres

Affectively Salient Meaning in Random Noise: A Task Sensitive to Psychosis Liability

Stable differences in the tendency to attribute meaning and emotional value to experience may represent an indicator of liability to psychosis. A brief task was developed assessing variation in detecting affectively meaningful speech (speech illusion) in neutral random signals (white noise) and the degree to which this was associated with psychometric and familial vulnerability for psychosis. Thirty patients, 28 of their siblings, and 307 controls participated. The rate of speech illusion was compared between cases and controls. In controls, the association between speech illusion and interview-based positive schizotypy was assessed. The hypothesis of a dose-response increase in rate of speech illusion across increasing levels of familial vulnerability for psychosis (controls, siblings of patients, and patients) was examined. Patients were more likely to display speech illusions than controls (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.4-11.7), also after controlling for neurocognitive variables (OR = 3.8, 95% CI = 1.04-14.1). The case-control difference was more accentuated for speech illusion perceived as affectively salient (positively or negatively appraised) than for neutrally appraised speech illusions. Speech illusion in the controls was strongly associated with positive schizotypy but not with negative schizotypy. In addition, the rate of speech illusion increased with increasing level of familial risk for psychotic disorder. The data suggest that the white noise task may be sensitive to psychometric and familial vulnerability for psychosis associated with alterations in top-down processing and/or salience attribution.

Temperament and character dimensions in patients with schizophrenia, relatives, and controls.

Studies of patients with schizophrenia or schizophrenia spectrum disorders and general population control groups consistently show differences regarding personality dimensions. However, the profile of personality dimensions in first-degree relatives of those patients is not well understood. We used Temperament and Character Inventory to explore personality dimensions in 61 clinically stable patients with schizophrenia or schizophrenia spectrum disorders, 59 of their first-degree relatives, and 64 healthy controls. Patients scored significantly higher than controls in harm avoidance and self-transcendence and lower in self-directedness and cooperativeness. First-degree relatives showed a tendency to lower novelty seeking and self-transcendence than controls. Interpretations of these findings include the possibility that lower novelty seeking and lower self-transcendence provide a protective influence in the relatives. Further studies are needed to go into this issue in greater depth.

Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.

Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

GABA and Homovanillic Acid in the Plasma of Schizophrenic and Bipolar I Patients

We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research.

Lifetime Sexual Behavior of Psychiatric Inpatients

INTRODUCTION Sexual life of psychiatric patients, including risk behaviors related to sexually transmitted diseases, remains a poorly studied area, especially in those with severe mental illnesses. AIMS To assess some aspects of lifetime sexual behavior of psychiatric inpatients. METHODS Patients consecutively admitted to a psychiatric unit in a general hospital were interviewed about partner-related lifetime sexual behavior. MAIN OUTCOME MEASURES A semi-structured interview developed by the authors was used to collect information concerning their general sexual experience throughout life, homosexual and heterosexual relations, and relations with partners who were intravenous drug users (IVDU), HIV carriers or suffering from AIDS, and with sex workers. In each of these areas, time elapsed since last sexual contact; number of partners in previous year, frequency of these relations and condom use were investigated. RESULTS Five hundred forty-six patients (306 men and 240 women) were assessed, and 87.7% of them reported sexual relations at some point during their life. Of these, 90% reported heterosexual and 10% homosexual or bisexual sexual contacts. Further, 11.06% had had at least one partner who was an IVDU; 8.1% an HIV-positive partner, and 32.4% (50% of the men) had paid for sex. Overall 49.79% of the total sample reported never using condoms in their sexual relations, with similar percentages for those with HIV-positive (46%) and IVDU (47%) partners. Of those who paid for sex, 29% never used condoms. CONCLUSIONS Psychiatric patients admitted to a general hospital psychiatric unit have sexual experience close to the general population, with a higher percentage of homosexual contacts and lower rates of condom use, even in higher risk situations, such as men having sex with men, and partners who are HIV-positive or IVDUs. This information obliges clinicians to systematically explore the sexual behavior of psychiatric patients, evaluate risk behaviors, and adopt measures to promote safe sex practices in this population.

Depersonalization in Patients with Schizophrenia Spectrum Disorders, First-Degree Relatives and Normal Controls

Background: Depersonalization occurs in healthy individuals and across a broad range of psychiatric patients. Data on depersonalization in persons linked to patients through genetics, environment or education are scarce. Due to their higher risk of developing psychosis, first-degree healthy relatives might show differences with the general population. This study examines depersonalization in patients with schizophrenia or schizophrenia spectrum disorders, their first-degree healthy relatives and normal controls. Methods: The Cambridge Depersonalization Scale was used to measure depersonalization in a sample of 147 clinically stable patients with schizophrenia or schizophrenia spectrum disorders, 73 first-degree relatives with no psychiatric history and 172 healthy controls. Mixed effect models were used to account for both the familial structure of the data and the effect of sociodemographic characteristics. Results: Patients obtained higher scores than relatives and controls for frequency and duration of depersonalization experiences, number of items responded positively and total depersonalization, while first-degree relatives obtained lower scores than patients and controls for all these characteristics. Conclusions: First-degree relatives of patients reported fewer episodes of depersonalization, which were less intense and of shorter duration, than healthy controls. This finding might be related to a protection mechanism that keeps first-degree relatives away from near-psychotic experiences. The nature of such a mechanism remains to be discovered.

Data Gathering Bias: Trait Vulnerability to Psychotic Symptoms?

Background Jumping to conclusions (JTC) is associated with psychotic disorder and psychotic symptoms. If JTC represents a trait, the rate should be (i) increased in people with elevated levels of psychosis proneness such as individuals diagnosed with borderline personality disorder (BPD), and (ii) show a degree of stability over time. Methods The JTC rate was examined in 3 groups: patients with first episode psychosis (FEP), BPD patients and controls, using the Beads Task. PANSS, SIS-R and CAPE scales were used to assess positive psychotic symptoms. Four WAIS III subtests were used to assess IQ. Results A total of 61 FEP, 26 BPD and 150 controls were evaluated. 29 FEP were revaluated after one year. 44% of FEP (OR = 8.4, 95% CI: 3.9–17.9) displayed a JTC reasoning bias versus 19% of BPD (OR = 2.5, 95% CI: 0.8–7.8) and 9% of controls. JTC was not associated with level of psychotic symptoms or specifically delusionality across the different groups. Differences between FEP and controls were independent of sex, educational level, cannabis use and IQ. After one year, 47.8% of FEP with JTC at baseline again displayed JTC. Conclusions JTC in part reflects trait vulnerability to develop disorders with expression of psychotic symptoms.

The Influence of the Val158Met Catechol-O-Methyltransferase Polymorphism on the Personality Traits of Bipolar Patients

Introduction Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger’s Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1) and self-transcendence (45.3±12.8 vs. 32.7±8.2) and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1), cooperativeness (77.1±9.1 vs. 83.9±6.5) and persistence (60.4±15.1 vs. 67.1±8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val. Conclusions Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain’s reward circuits.

Biological Correlates of the Congruence and Incongruence of Psychotic Symptoms in Patients with Type 1 Bipolar Disorder

We examined the catechol-O-methyl transferase (COMT) Val108/158Met genotype in 160 type 1 bipolar patients. We also analyzed the plasma concentrations of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG) and 3,4-dihydroxyphenylacetic acid in 60 of those patients who had been without mood stabilizers or neuroleptic treatment for at least 8 days. Results: Patients with congruent psychotic symptoms presented a higher plasma concentration of HVA than mood incongruent psychotic patients. The Val/Val genotype was associated with higher plasma concentrations of HVA and MHPG. We detected a larger proportion of patients with psychotic symptoms in the Val/Val genotype group, although this did not reach statistical significance. It was found that the distribution of the COMT genotype was not influenced by the congruent/incongruent nature of the psychotic symptoms. Limitations: The proportion of patients without psychotic symptoms in our sample was low. This fact limits the value of some comparisons. Conclusions: Congruent and incongruent psychotic patients can be distinguished in terms of the concentration of plasma HVA. Based on the presence or absence of mood incongruent symptoms, the Val108/158Met polymorphism of the COMT gene alone does not appear to be a crucial determinant in the division of psychotic bipolar patients. Nevertheless, COMT polymorphisms may influence some of the characteristics of the patients by their effect on monoamine metabolism.

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD.