Identifying schizophrenia and other psychoses with psychological scales in the general population.

We study the predictive power and associations of several psychopathology and temperament scales with respect to schizophrenia and other psychotic disorders. Measures of psychopathology (Physical and Social Anhedonia Scales, Perceptual Aberration Scale, Hypomanic Personality Scale, Bipolar II Scale, and Schizoidia Scale) and the Temperament and Character Inventory were included in the 31-year follow-up of the prospective Northern Finland 1966 birth cohort (N = 4926). The Perceptual Aberration Scale was the best scale for concurrent validity in psychoses, and also the best psychopathology scale in terms of discriminant validity. Participants scoring high in hypomanic personality were at the highest risk for developing psychosis during the 11-year follow-up. Harm avoidance was a dominant temperament dimension in individuals with psychosis compared with participants without psychiatric diagnoses. These scales are useful as vulnerability markers in studying psychoses.

Comparison of urine results concerning co-consumption of illicit heroin and other drugs in heroin and methadone maintenance programs.

Urine samples of patients from a heroin maintenance program (HMP) and a methadone maintenance program (MMP) were chromatographically analyzed 1 month before and 6 and 12 months into treatment for the presence of classical markers of heroin use as well as for the presence of markers for illicit heroin abuse. Furthermore, the samples were immunochemically tested for cannabinoids, cocaine metabolites, amphetamine, methylendioxyamphetamines and benzodiazepines. A co-consumption of illicit heroin (HER) in the HMP was determined to be 50% but was significantly lower compared to the MMP with a co-use of 71%. The incidence was high because not only acetylcodeine (AC) as a very specific marker was considered but also other marker substances for illicit HER use. Amphetamines played only a minor part in both collectives, and the proportion of HER and methadone patients using cocaine was similar and decreased during treatment. Also, the benzodiazepine use decreased, and cannabis use was high in both collectives during treatment. Considering only the AC in the present study, a co-use of illicit HER in the HMP was similar to previous reports concerning HER-assisted treatment programs. If additional marker substances were examined, the suspicion of a co-use of illicit HER is markedly enhanced.

Data on schizotypy and affective scales are gender and education dependent--study in the Northern Finland 1966 Birth Cohort.

We present psychometric properties and normative data by gender and educational level in scales related to schizotypy and affective disorders in a large population-based adult sample. As part of the 31-year follow-up survey of the Northern Finland 1966 Birth Cohort; Bipolar II scale (BIP2), Hypomanic Personality Scale (HPS), Physical Anhedonia Scale (PAS), Social Anhedonia Scale (SAS), Perceptual Aberration Scale (PER) and Schizoidia Scale (SCHD) were filled in by 4928 subjects. In total sample mean scores were: BIP2 10.59 (3.80), HPS 11.26 (7.03), PAS 14.99 (S.D. 7.03), SAS 9.44 (5.52), PER 2.35 (3.26) and SCHD 2.56 (1.42). Men scored higher (had more psychopathological symptoms) in PAS and SAS (P<0.001), and in BIP2 (P=0.02). Women had higher scores in SCHD, HPS and PER (P<0.001). Participants with a lower level of education scored higher in all scales; differences were largest in BIP2, PAS and SAS (ES>0.5,P<0.001). The gender and education differences were moderate or large in all the included scales. These differences should be taken into account when considering normal values in these scales. The findings indicate that commonly used student samples are likely to be biased when compared to community based samples.

Cocaine and opiate concentrations in hair from subjects in a heroin maintenance program in comparison to a methadone substituted group.

One month before (T-1) and 12 months after (T12) controlled i.v. administration of pharmaceutical heroin-HCl (10-100 mg/day) in the context of a heroin maintenance program (HMP), concentrations of opiates and cocaine as well as its metabolites were determined in head hair (n = 46) using a validated gas chromatographic-mass spectrometric method. In addition, a patient collective of a methadone maintenance program (MMP, daily doses 15-260 mg) was examined (n = 35). The incidence of additional cocaine consumption decreased in both groups during the study period (T-1 to T12): in HMP from 64.6% to 45.8% and in MMP from 71.4% to 60.0%. A significant reduction of cocaine consumption was defined as an at least 30% reduction of analyte concentrations in hair (Deltac > 30%). Accordingly, in HMP, a decrease in 45.8% of initially (T-1) cocaine-positive patients was determined; in MMP, the reduction was 48.6%. In 22.9% of HMP and 37.1% of MMP, an increase of cocaine concentrations was detected. Codeine and acetylcodeine were found in 50.0% and 43.5% (T-1) and 13.0% and 10.9% (T12) of the samples of the HMP, as well as in 45.7% and 25.7% (T-1) and 17.1% and 5.7% (T12) in MMP, respectively. The missing of acetylcodeine, in particular at T-1, questions its applicability as a characteristic marker of a preceding consumption of illicit heroin in hair analysis.

Novelty seeking among adult women is lower for the winter borns compared to the summer borns: replication in a large Finnish birth cohort.

OBJECTIVE: Earlier general population studies have shown that novelty seeking (NS) of the Temperament and Character Inventory (TCI) of personality is lower for persons born in winter compared to those born in summer, particularly for women. Here, we investigate if this result can be replicated in another population. METHOD: The Northern Finland 1966 Birth Cohort, comprising 4968 subjects (2725 women, 2243 men), was investigated with regard to the temperament dimensions of the TCI and the season of birth. RESULTS: Novelty seeking and reward dependence (RD) showed significant variations according to the month of birth. We found that women born during winter have significantly lower levels of NS compared to women born during summer, with a minimum for the birth month November and maximum for May. These results are similar to those found in a previous Swedish study. Furthermore, our study showed that men born during spring had significantly lower mean scores of RD compared to men born during autumn, with a minimum for birth month March. This was in contrast to the Swedish study, where the minimum of RD was obtained for the birth month December. CONCLUSION: Women born in winter have lower NS as adults compared to women born in summer. Because NS is modulated by dopamine, this study gives further support to the studies in the literature that show that dopamine turnover for those born in winter is higher than for those born in summer.

Pregnancy and birth under maintenance treatment with diamorphine (heroin): a case report.

BACKGROUND: Heroin-assisted treatment (HAT) is a new form of treatment for heroin-dependent patients not responding to conventional interventions such as methadone maintenance treatment. No pregnancies or births under HAT have been reported until now. CASE: The pregnancy course of a 31-year-old severely dependent multi-morbid woman receiving HAT and the birth of a healthy baby after premature delivery is described. HAT helped to reduce the use of illicit substances both before and during pregnancy. The neonatal abstinence syndrome was clinically well compensated. CONCLUSION: HAT seems to be feasible in pregnant women and normal birth is possible under HAT, which therefore may act as a harm reduction measure for polydrug-using pregnant women not responding to methadone maintenance treatment.

Temperament profiles in personality disorders among a young adult population.

The objective of this study was to describe the temperament dimension profiles assessed by the Temperament and Character Inventory (TCI) among young adults with the DSM-III-R personality disorder (PD). Our hypothesis was that PD clusters and separate PDs can be distinguished from one another by their specific temperament profiles. As a part of the 31-year follow-up survey of the prospective Northern Finland 1966 Birth Cohort, the cohort members living in the city of Oulu at the age of 31 years (n=1609) were invited to participate in a two-phase field study. The Structured Clinical Interview for DSM-III-R for PDs (SCID-II) was used as diagnostic instrument. The final study sample consisted of the 1311 subjects who had completed the Hopkins Symptom Check List-25 questionnaire for screening and had given a written informed consent. Of the 321 SCID interviewed subjects, 74 met the criteria for at least one PD and had completed the TCI. The mean TCI scores of subjects with PD and control subjects without PD (n=910) were compared. Low Novelty Seeking, high Harm Avoidance and low Reward Dependence characterized cluster A and C PDs. Subjects with a cluster B PD did not differ from controls, except for Novelty Seeking, which was high. The temperament dimensions could not distinguish different PDs very well, with the only exception of persons with obsessive-compulsive PD. PD clusters were associated with different profiles of temperament, lending some support for Cloninger's typology.

Temperament profiles and somatization--an epidemiological study of young adult people.

OBJECTIVE: We assessed the temperament profiles of young adult somatizers in an epidemiological setting. We hypothesized that somatizers would have a characteristic temperament profile. METHODS: The sample consisted of 984 subjects at the age of 31 years. Data on somatization were gathered from a review of all public health outpatient records. Subjects with four or more somatization symptoms according to the DSM-III-R criteria were classified as somatizers. Temperament profiles were assessed using the Temperament and Character Inventory (TCI). RESULTS: Six males (1.3%) and 61 females (11.5%) met our criteria for somatization. Harm avoidance and reward dependence of the TCI profiles were associated with somatization symptoms in the whole sample. In logistic regression analysis, sex and psychological distress were associated with somatization but not with temperament profiles. CONCLUSION: We did not find a characteristic temperament profile for somatizers. This finding is in contrast to suggestions that somatization is associated with temperament profiles.

Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence.

High-dose methadone is well known to cause testosterone deficiency and sexual dysfunction in opioid-dependent men. Buprenorphine is a new drug for the pharmacotherapy of opioid dependence. Its influence on the gonadal axis has not been investigated to date. We therefore assayed testosterone, free testosterone, estradiol, SHBG, LH, FSH, and prolactin in 17 men treated with buprenorphine. Thirty-seven men treated with high-dose methadone and 51 healthy blood donors served as controls. Sexual function and depression were assessed using a self-rating sexual function questionnaire and the Beck Depression Inventory. Patients treated with buprenorphine had a significantly higher testosterone level [5.1 +/- 1.2 ng/ml (17.7 +/- 4.2 nmol/liter) vs. 2.8 +/- 1.2 ng/ml (9.7 +/- 4.2 nmol/liter); P < 0.0001] and a significantly lower frequency of sexual dysfunction (P < 0.0001) compared with patients treated with methadone. The testosterone level of buprenorphine-treated patients did not differ from that of healthy controls. In conclusion, we demonstrated for the first time that buprenorphine, in contrast with high-dose methadone, seems not to suppress plasma testosterone in heroin-addicted men. To this effect, buprenorphine was less frequently related to sexual side effects. Buprenorphine might therefore be favored in the treatment of opioid dependence to prevent patients from the clinical consequences of methadone-induced hypogonadism.

Association of DNA polymorphisms in the synaptic vesicular amine transporter gene (SLC18A2) with alcohol and nicotine dependence.

The brain synaptic vesicular amine transporter SLCA18A2 is a key component for the uptake of monoamines like dopamine or serotonin into vesicles. We have analyzed seven DNA polymorphisms located in the genomic region of SLC18A2 for association with alcohol- and nicotine dependence, using a family-based design. Our sample comprised 131 families with alcohol-dependent offspring and 96 families with at least one nicotine-dependent offspring. For the alcohol-dependent sample, we found statistical significant association for two single markers (rs363387, P=0.03; rs363333, P=0.0066) as well as for several haplotypes (minimal P=0.0038). When the sample with alcohol dependence was stratified according to gender, we observed increased association for the male subgroup (rs363387, P=0.0011). None of the markers showed association in the sample of families with nicotine dependence. However, analysis of a combined sample of alcohol and nicotine-dependent families resulted in single markers as well as several haplotypes showing statistical significant association with substance dependence (minimal P=0.0044). We conclude that DNA polymorphisms located in SLC18A2 might contribute to the development of substance dependence.

Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations.

CONTEXT: Dopamine receptor-mediated pathways play critical roles in the mechanism of addiction. However, associations of the D(2) dopamine receptor gene (DRD2) with substance abuse are controversial. OBJECTIVE: To determine whether susceptibility sites resided at DRD2. DESIGN: Haplotype-based case-control analysis of 2 distinct populations using 10 single nucleotide polymorphisms (SNPs) with heroin dependence. SETTING: Universities of Mainz and Bonn, Germany, and 3 local hospitals in southwestern China. Patients Cases and control subjects recruited from China (486 cases, 313 controls) and Germany (471 cases, 192 controls). INTERVENTIONS: Genotyping for 10 SNPs by 5'-exonuclease fluorescence assays. The D' value of linkage disequilibrium and haplotypes were generated by the expectation-maximization algorithm. MAIN OUTCOME MEASURES: Genotype, allele, and haplotype frequencies were compared between cases and controls by chi(2) tests constructed for each population. An additional 32 SNPs randomly distributed in the genome were genotyped for detecting population admixture in the 2 populations. RESULTS: A haplotype block of 25.8 kilobases (kb) was defined by 8 SNPs extending from SNP3 (TaqIB) at the 5' end to SNP10 site (TaqIA) located 10 kb distal to the 3' end of the gene. Within this block, specific haplotype cluster A (carrying TaqIB1 allele) was associated with a high risk of heroin dependence in Chinese patients (P = 1.425 x 10(-22); odds ratio, 52.80; 95% confidence interval, 7.290-382.5 for 8-SNP analysis). A putative recombination "hot spot" was found near SNP6 (intron 6 ins/del G), creating 2 new daughter haplotypes that were associated with a lower risk of heroin dependence in Germans (P = 1.94 x 10(-11) for 8-SNP analysis). There was no evidence of population stratification in either population. CONCLUSIONS: These results strongly support a role of DRD2 as a susceptibility gene with heroin dependence in Chinese patients and was associated with low risk of heroin dependence in Germans.

Opiate concentrations in hair from subjects in a controlled heroin-maintenance program and from opiate-associated fatalities.

One month before (T-1) and 12 months after (T12) controlled intravenous administration of pharmaceutical heroin-HCl (10-1000 mg/d) in the context of a heroin-maintenance program, concentrations of opiates in head hair were determined (n = 46), using a validated gas chromatography-mass spectrometry method with limits of detection (LOD) between 0.02 and 0.04 ng/mg. In addition, a collective of opiate-associated fatalities was examined (n = 24). The obtained concentrations in the proximal segment (1 cm) of the patients were between 0.04 and 1.16 ng/mg (mean 0.13 ng/mg) for heroin (HER), between 0.02 and 32.41 ng/mg (mean 1.48 ng/mg) for 6-monoacetylmorphine (MAM) and between 0.03 and 11.79 ng/mg (mean 1.19 ng/mg) for morphine (MOR). With the exception of the analyte HER, there was no other statistically significant difference in the concentrations in comparison to the opiate fatalities [HER 1.55-5.20 ng/mg mean 3.38 ng/mg), MAM 0.04-30.01 ng/mg (mean 2.14 ng/mg), and MOR 0.03-11.87 ng/mg (mean 1.15 ng/mg) in the proximal segments]. After controlled HER administration, a correlation between the dose and the total opiate concentration in the hair was found (r = 0.66). These results disagree with the observations of authors who found only limited dose-concentration relationships after heroin abuse in hair. When considering a single analyte, the coefficient of correlation increased in correspondence to the respective plasma half-life (r = 0.42, r = 0.58, and r = 0.69 for HER, MAM, and MOR). The latter findings are in agreement with the report that states that this correlation is influenced by the plasma half-lifes of analytes. Codeine and acetylcodeine (AC) were detected in 50% and 43.5% (T-1) and 13% and 10.9% (T12) of the samples of the HER-maintenance program, as well as in 33.3% and 16.7% in opiate-associated fatalities, respectively. The lack of differences between obtained opiate concentrations in the hair of participants in a controlled heroin maintenance program and of opiate-associated fatalities does not support the hypothesis that an absence of tolerance can be regarded as a potential cause of death. In addition, the lack of AC, which was also observed in the majority of the deaths, questions its applicability as a characteristic marker of the consumption of illicit heroin.

Seasonal affective disorder and the G-protein beta-3-subunit C825T polymorphism.

BACKGROUND: Guanine nucleotide-binding proteins (G-proteins) have been implicated in affective disorders, with reports of altered signal transduction and G-protein levels. Association with seasonal affective disorder (SAD) has been found for the higher activity T-allele of the G-protein beta-3-subunit C825T polymorphism. METHODS: European SAD patients (n = 159) and matched controls (n = 159) were genotyped for the C825T. Seasonality and diurnal preference were investigated in subsets of the material (n = 177 and 92, respectively). RESULTS: We found no association between C825T and SAD (chi(2) =.09, p =.96) or seasonality (F = 1.76, p =.18). There was some evidence for an effect on diurnal preference but only in the control group (n = 46, t = -2.8, Bonferroni corrected p =.045). CONCLUSIONS: These results suggest that the G-protein beta-3-subunit 825 T-allele does not play a major role in susceptibility to seasonal affective disorder in the population studied.

Circadian clock-related polymorphisms in seasonal affective disorder and their relevance to diurnal preference.

Disturbed circadian rhythms have been observed in seasonal affective disorder (SAD). The aim of this study was to further investigate this connection, and to test for potential association between polymorphisms in circadian clock-related genes and SAD, seasonality (seasonal variations in mood and behavior), or diurnal preference (morningness-eveningness tendencies). A total of 159 European SAD patients and 159 matched controls were included in the genetic analysis, and subsets were screened for seasonality (n=177) and diurnal preference (n=92). We found that diurnal preference was associated with both SAD and seasonality, supporting the hypothesis of a link between circadian rhythms and seasonal depression. The complete case-control material was genotyped for polymorphisms in the CLOCK, Period2, Period3, and NPAS2 genes. A significant difference between patients and controls was found for NPAS2 471 Leu/Ser (chi(2)=9.90, Bonferroni corrected P=0.035), indicating a recessive effect of the leucine allele on disease susceptibility (chi(2)=6.61, Bonferroni corrected P=0.050). Period3 647 Val/Gly was associated with self-reported morningness-eveningness scores (n=92, one-way ANOVA: F=4.99, Bonferroni corrected P=0.044), with higher scores found in individuals with at least one glycine allele (t=3.1, Bonferroni corrected P=0.013). A second, population-based sample of individuals selected for high (n=127) or low (n=98) degrees of seasonality, was also genotyped for NPAS2 471 Leu/Ser. There was no significant difference between these seasonality extreme groups, and none of the polymorphisms studied were associated with seasonality in the SAD case-control material (n=177). In conclusion, our results suggest involvement of circadian clock-related polymorphisms both in susceptibility to SAD and diurnal preference.

Association between the type 4 dopamine receptor gene polymorphism and novelty seeking.

OBJECTIVE: Mixed results have been reported on the association between the type 4 dopamine receptor gene (DRD4) and the temperament dimension of novelty seeking. We tested this association by specifying the analysis to components of novelty seeking. METHODS: Participants were 150 high and low novelty-seeking scorers (the highest and lowest 10%) from a randomized, population-based sample of Finnish citizens in six age cohorts. We genotyped a 48-bp repeat polymorphism in the DRD4 gene. Novelty seeking was assessed by the Temperament and Character Inventory. RESULTS: No difference in overall novelty seeking between individuals with no seven-repeat allele (short) and any seven-repeat allele (long), between the 4,4 and 4,7 genotype groups, and between long (l/l and s/l) and short (s/s) polymorphism groups were found. The odds ratio for high overall novelty seeking in the presence of any two- or five-repeated alleles vs. none was 2.41 (95% CI, 1.11-5.20). Corresponding odds ratios were significant for exploratory excitability (2.94; 95% CI, 1.32-6.59) and impulsiveness (2.74; 95% CI, 1.23-6.11) but not for other components of novelty seeking. No interactions with age or gender were detected. CONCLUSIONS: The present study confirmed previous findings on the association between the type 4 dopamine receptor gene and novelty seeking, in particular exploratory excitability and impulsiveness. The tendency to avoid or approach a novel situation is a core concept of several temperamental theories. The present findings support the hypothesis that this tendency is associated with DRD4 and might concern temperament psychology in general, not only the concept of novelty seeking.

The dichotomy of schizophrenia and affective disorders in extended pedigrees.

The paper reports the first controlled family study investigating not only 1st but also 2nd and 3rd degree relatives of patients with schizophrenia by direct diagnostic interviews. Regardless of their degree of relationship, all biological relatives of the patients were found to be at an elevated risk of schizophrenia (5.0% in 1st, 3.1% in 2nd, 1.5% in 3rd degree relatives compared to 0.8% among controls). Schizoaffective and affective disorders have also been found to be more common in the three groups of relatives but without a monotone decline of prevalence rates across the groups. Other psychiatric disorders were not found to be at an elevated risk in relatives of patients compared to controls. Thus, our findings support the hypothesis that psychotic, as well as affective disorders, aggregate in families of individuals with schizophrenia.However, in our study, the risk of schizophrenia and the risk of affective disorders correlated. Particularly, the magnitude of the risk of schizophrenia among relatives of probands with schizophrenia varied with the occurrence of affective disorders in relatives. In relatives, the risk of schizophrenia was maximal in absence of a family history of affective disorder. This constellation holds true even if only families of index cases without any affective syndrome during lifetime are considered.

Lack of evidence for association between serotonin transporter gene (5-HTTLPR) and obsessive-compulsive disorder by case control and family association study in humans.

Association studies of the serotonin transporter (SLC6A4) gene in obsessive-compulsive disorder (OCD) have generated discrepant results. Here, we genotyped the 5-HTTLPR polymorphism in 106 French OCD patients and 171 healthy controls (case control study). We also performed a family association study on 116 trios including an OCD patient (73 French and 43 German). No association was detected between the 5-HTTLPR polymorphism and OCD in either the case control study or the family study.

DISC1 conditioned GWAS for psychosis proneness in a large Finnish birth cohort.

BACKGROUND: Genetic evidence implicates the DISC1 gene in the etiology of a number of mental illnesses. Previously, we have reported association between DISC1 and measures of psychosis proneness, the Revised Social Anhedonia Scale (RSAS) and Revised Physical Anhedonia Scale (RPAS), in the Northern Finland Birth Cohort 1966 (NFBC66). As part of the studies of this Finnish birth cohort genome-wide association analysis has recently been performed. METHODOLOGY: In the present study, we re-analyzed the genome-wide association data with regard to these two measures of psychosis proneness, conditioning on our previous DISC1 observation. From the original NFBC66 sample (N = 12 058), 4 561 individuals provided phenotype and genotype data. No markers were significant at the genome-wide level. However, several genes with biological relevance to mental illnesses were highlighted through loci displaying suggestive evidence for association (≥3 SNP with P<10E-4). These included the protein coding genes, CXCL3, KIAA1128, LCT, MED13L, TMCO7, TTN, and the micro RNA MIR620. CONCLUSIONS: By conditioning a previous genome-wide association study on DISC1, we have been able to identify eight genes as associating to psychosis proneness. Further, these molecules predominantly link to the DISC1 pathway, strengthening the evidence for the role of this gene network in the etiology of mental illness. The use of quantitative measures of psychosis proneness in a large population cohort will make these findings, once verified; more generalized to a broad selection of disorders related to psychoses and psychosis proneness.

Predicting depression with psychopathology and temperament traits: the northern Finland 1966 birth cohort.

We studied the concurrent, predictive, and discriminate validity of psychopathology scales (e.g., schizotypal and depressive) and temperament traits for hospitalisations due to major depression. Temperament, perceptual aberration, physical and social anhedonia, Depression Subscale of Symptom Checklist (SCL-D), Hypomanic Personality Scale, Schizoidia Scale, and Bipolar II Scale were completed as part of the 31-year follow-up survey of the prospective Northern Finland 1966 Birth Cohort (n = 4941; 2214 males). Several of the scales were related to depression. Concurrent depression was especially related to higher perceptual aberration (effect size when compared to controls, d = 1.29), subsequent depression to high scores in SCL-D (d = 0.48). Physical anhedonia was lower in subjects with subsequent depression than those with other psychiatric disorders (d = -0.33, nonsignificant). Participants with concurrent (d = 0.70) and subsequent (d = 0.54) depression had high harm avoidance compared to controls, while differences compared to other psychiatric patients were small. Subjects with depression differed from healthy controls in most of the scales. Many of the scales were useful predictors for future hospital treatments, but were not diagnosis-specific. High harm avoidance is a potential indicator for subsequent depression.