Mutation screen of the GAD2 gene and association study of alcoholism in three populations.

Synaptic actions of gamma-amino butyric acid (GABA) have been implicated in many facets of ethanol's effects and risk for alcoholism. We examined whether variation in glutamate decarboxylase-2 (GAD2), a gene encoding for a major enzyme in the synthesis of GABA, contributes to risk of alcohol dependence (AD). We screened GAD2 for sequence variants using dHPLC in a population of 96 individuals. Several single nucleotide polymorphisms (SNPs), including four rare non-synonymous polymorphisms, were identified. Thirteen SNPs located in the GAD2 gene were genotyped in a sample of 113 Russian males with AD and 100 Russian male controls. These analyses revealed a modest association between the functional GAD2 -243 A > G SNP (rs2236418) and AD (allele P = 0.038, genotype P = 0.008). An additional sample of 138 Russian males with AD were genotyped for the GAD2 -243 A > G. These analyses supported an association of this polymorphism with AD (combined sample allele P = 0.038, genotype P = 0.0009). We extended these findings to additional populations: a sample of 538 college students assessed using the AUDIT and a sample of European-American (EA) AD subjects (n = 235) and controls (n = 310). Analyses in these populations did not support a role for GAD2 in alcoholism. In summary, the results of an extensive search for an association of GAD2 with AD suggest that variation in GAD2 is not a major risk factor for AD in EAs. The functional promoter GAD2 -243 A > G variant may influence risk for AD in some populations, or its role may be limited to susceptibility to severe AD.

Familial risks, conduct disorder and violence: A Finnish study of 278 adolescent boys and girls.

OBJECTIVE: The aim was to investigate the impact of familial risk factors on the development of violent behaviour and conduct disorder (CD) by gender in a sample of adolescent psychiatric patients. METHODS: The study sample consisted of 278 adolescents (age 12-17) consecutively admitted to psychiatric inpatient care between April 2001 and January 2004. DSMIV psychiatric diagnoses were obtained from the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL). RESULTS: Logistic regression analyses revealed that girls who had been physically abused at home had a 4.2-fold risk of having conduct disorder with violent behaviour (95% CI 1.4-12.2) compared to those not exposed to domestic violence. A broken primary family also increased the risk for having both violent CD (OR 7.8 95 % CI 1.7-36.4) and non-violent CD (OR 7.0 95% CI 1.5-33.5) among girls. Among boys, no statistically significant association was found between any familial risk factors and later CD. CONCLUSIONS: The results suggest that being physically abused by parents may influence the development of conduct disorder including violent behaviour among girls. This emphasizes the importance of early recognition of domestic violence. In girls, the absence of primary family seems to associate strongly with the development of CD, and should be taken into consideration by physicians and other professionals working with young people.

Nicotine use and dependence and their association to psychiatric disorders in a large sample of adolescent psychiatric inpatients.

The purpose of this research was to evaluate the level of nicotine dependence (ND) and to examine its association to psychiatric disorders in a representative clinical sample of adolescent psychiatric inpatients. The modified Fagerstrom Tolerance Questionnaire (mFTQ) was used to assess the level of ND. Psychiatric DSM-IV diagnoses were obtained by using the Schedule for affective disorder and schizophrenia for school-age children (K-SADS-PL). Of the total of 342 inpatients in the study sample, 259 (75.7%) reported to be current smokers. A sum score 6 or higher in the mFTQ, indicating a high level of ND, was found in 37.9% of all smokers. An increased likelihood for high level of ND was associated with substance related disorders (OR 5.1, 95% CI 2.8-9.3), conduct disorder and oppositional defiant disorders (OR 2.4, 95% CI 1.4-4.4). The usefulness of mFTQ in measuring ND among adolescent inpatients is apparent. Therefore, it can be recommended to be used as a routine screening instrument for ND among adolescents hospitalized due to psychiatric disorders.

Temporal relationship between the age of onset of phobic disorders and development of substance dependence in adolescent psychiatric patients.

AIMS: To investigate the age of onset of phobic disorders in relation to later development of substance dependence in a sample of adolescent psychiatric patients. DESIGN, SETTING AND PARTICIPANTS: Clinical sample of 238 adolescents (age 12-17) admitted to psychiatric inpatient hospitalization between April 2001 and July 2003. MEASUREMENTS: Psychiatric diagnoses and onset ages obtained from the schedule for affective disorders and schizophrenia for school aged children-present and lifetime (K-SADS-PL). FINDINGS: Logistic regression analyses revealed that adolescents with phobic disorders had a 4.9-fold risk for comorbid substance dependence compared to those without phobia. The mean onset age was 11.4 and 14.4 years for phobias and comorbid substance dependence, respectively. Boys (13.7 years) had a statistically significantly lower onset age for substance dependence than girls (15.4 years). Over one-half of the adolescents with phobic disorders had developed substance dependence within three years after the onset of phobia. CONCLUSIONS: We found that phobias might influence the development of secondary substance dependence within a few years from the onset of phobia already in adolescence.

Smoking and suicidality among adolescent psychiatric patients.

PURPOSE: To investigate the relationship between smoking and suicidality among adolescent psychiatric patients in Finland. METHODS: Data from 157 patients (aged 12-17 years) admitted to inpatient psychiatric hospitalization between April 2001 and July 2002 were collected. Logistic regression analyses were used to examine the association between regular daily smoking and suicidality. The data were adjusted for several sociodemographic and clinical characteristics. RESULTS: The results showed over four-fold risk for definite and/or life-threatening suicide attempts among smoking adolescents in inpatient psychiatric facility compared with nonsmoking ones (OR 4.33, 95% CI 1.23-15.20). Also, the smoking adolescents had three times greater risk for occasional (OR 3.32, 95% CI 1.09-10.10) or frequent (OR 3.00, 95% CI 1.08-10.10) self-mutilation. Suicidality was more common among girls than boys and among those adolescents who suffered from depression. CONCLUSIONS: Among teens hospitalized for psychiatric illnesses, daily smoking was significantly related to suicide attempts and self-mutilation, even after controlling for several confounding factors, including psychiatric diagnosis.

Reasons for the diagnostic discordance between clinicians and researchers in schizophrenia in the Northern Finland 1966 Birth Cohort.

BACKGROUND: The diagnosis of schizophrenia by clinicians is not always accurate in terms of operational diagnostic criteria despite the fact that these diagnoses form the basis of case registers and routine statistics. This poses a challenge to psychiatric research. We studied the reasons for diagnostic discordance between clinicians and researchers. METHODS: The Northern Finland 1966 Birth Cohort (n = 11,017) was followed from mid-gestation to the end of the 31st year. Psychiatric outcome was ascertained through linkage to the national hospital discharge register containing clinical diagnoses made by the attending physician. The hospital notes of all subjects admitted to hospital during the period 1982-1997 due to psychiatric disorder were reviewed and 475 research, operational DSM-III-R diagnoses were formulated. RESULTS: Ninety-six cases met operational criteria for schizophrenia. Fifty-five (57 %) had concordant diagnoses: both the clinical and research diagnoses were schizophrenia. Forty-one (43 %) had discordant diagnoses: the clinical diagnosis was other than schizophrenia (mainly schizophreniform or other psychosis). Discordant cases were more likely to be older at onset, experience a shorter treatment duration, fewer treatment episodes, and to have a comorbid diagnosis mental retardation. CONCLUSIONS: Clinicians do not make the diagnosis of schizophrenia as often as the application of operational criteria would suggest they should. The discordance between clinical diagnosis and the research, operational diagnosis is especially likely in cases having late onset and few contacts to psychiatric hospital.

Somatic morbidity and criminality: the Northern Finland 1966 Birth Cohort Study.

OBJECTIVE: The aim of this study was to investigate the association between adverse physical disorders and violent/non-violent criminal behaviour. DESIGN: The study material consisted of the large, prospectively followed, unselected and genetically homogeneous Northern Finland 1966 Birth Cohort, the Finnish Hospital Discharge Registers and the National Crime Register (n=10934). MAIN RESULTS: The results of the logistic regression analyses showed that male offenders had statistically significantly more injuries (adj. OR=1.81, 95% CI=1.51-2.17), when compared with males without a criminal history. Violent male offenders exhibited greater morbidity to the diseases of the respiratory system (adj. OR=1.64, 95% CI=1.03-2.60) when compared with non-violent criminals. Female offenders suffered more commonly from poisonings (adj. OR=3.84, 95% CI=1.69-8.72), injuries (adj. OR=2.79, 95% CI=1.67-4.66), infections (adj. OR=1.87, 95% CI=1.16-2.99) and indefinite symptoms (adj. OR=2.02, 95% CI=1.20-3.40) than non-offending females. CONCLUSIONS: At epidemiological level, criminal behaviour seems to be associated especially with an increased risk of injuries for both sexes. The observed increase of the diseases of the respiratory system among violent but not among non-violent males calls for further investigations.