The occurrence and nature of early signs of schizophrenia and psychotic mood disorders among former child and adolescent psychiatric patients followed into adulthood

<p>Abstract</p> <p>Background</p> <p>This investigation was designed to characterize psychotic disorders among patients originally treated as in- and outpatients by child and adolescent psychiatric services and subsequently followed-up into mid-adulthood. The age at the first onset on symptoms, possible changes in diagnoses, early signs noted prior to or upon admission to child and adolescent psychiatric care and possible differences between patients with early- and later-onset disorder were of particular interest.</p> <p>Methods</p> <p>The study population consisted of patients (285 in- and 1115 outpatients) born between 1957 and 1976 and admitted to and treated by child and adolescent psychiatric care units in Jämtland County, Sweden, between 1975 and 1990. The status of their mental health was monitored until 2003 using official registries and hospital records. Diagnoses based on the ICD-8 and -9 systems, which were used in Sweden from 1968–1997, converted to diagnoses according to ICD-10, which has been in use since 1997. The Comprehensive Assessment of at Risk Mental States was employed to assess the information concerning psychopathology provided by the hospital records.</p> <p>Results</p> <p>By the end of the follow-up period 62 former child and adolescent psychiatric patients (36 females and 26 males), 4.4% of the entire study group, had received an ICD-10 diagnosis of "F20–29: Schizophrenia, schizotypal and delusional disorders" (48) and/or "F30–39: Psychotic mood disorders" (14). One-third (21) of these individuals were given their initial diagnosis of psychosis in connection with child and adolescent psychiatric care. Two of these 21 were not treated later for this disorder in general (adult) psychiatric care whereas the remaining 19 individuals were diagnosed for the same type of disorder as adults. The other 41 patients were diagnosed as psychotic only in connection with general (adult) psychiatric care. The mean age at the time of first onset of symptoms was 21.4 years (SD 6.4) and corresponding median age was 18. Behavioural changes and positive symptoms were the most frequent signs associated with a diagnosis of "F20–F29: Schizophrenia, schizotypal and delusional disorders" made during child and adolescent psychiatric care. In cases where a specific psychopathology developed later on the initial admission to child and adolescent psychiatry involved unspecified psychopathology.</p> <p>Conclusion</p> <p>In summary, it appears that psychotic disorders are relatively uncommon among patients admitted to child and adolescent psychiatric care in Sweden. However, individuals experiencing early onset of disorders categorized as "F20–29: Schizophrenia, schizotypal and delusional disorders" may already exhibit typical symptoms upon admission to child and adolescent psychiatric care of the age of 13–17; whereas late-onset disorders it appear not be associated with any obvious signs or symptoms years before the disorder has developed fully. Finally, certain cases of psychotic disorder during adolescence seem to have been episodic.</p

Transgenic Introduction of a Glycolate Oxidative Cycle into A. thaliana Chloroplasts Leads to Growth Improvement

The photorespiratory pathway helps illuminated C3-plants under conditions of limited CO2 availability by effectively exporting reducing equivalents in form of glycolate out of the chloroplast and regenerating glycerate-3-P as substrate for RubisCO. On the other hand, this pathway is considered as probably futile because previously assimilated CO2 is released in mitochondria. Consequently, a lot of effort has been made to reduce this CO2 loss either by reducing fluxes via engineering RubisCO or circumventing mitochondrial CO2 release by the introduction of new enzyme activities. Here we present an approach following the latter route, introducing a complete glycolate catabolic cycle in chloroplasts of Arabidopsis thaliana comprising glycolate oxidase (GO), malate synthase (MS), and catalase (CAT). Results from plants bearing both GO and MS activities have already been reported (Fahnenstich et al., 2008). This previous work showed that the H2O2 produced by GO had strongly negative effects. These effects can be prevented by introducing a plastidial catalase activity, as reported here. Transgenic lines bearing all three transgenic enzyme activities were identified and some with higher CAT activity showed higher dry weight, higher photosynthetic rates, and changes in glycine/serine ratio compared to the wild type. This indicates that the fine-tuning of transgenic enzyme activities in the chloroplasts seems crucial and strongly suggests that the approach is valid and that it is possible to improve the growth of A. thaliana by introducing a synthetic glycolate oxidative cycle into chloroplasts

Child and adolescent psychiatric patients and later criminality

<p>Abstract</p> <p>Background</p> <p>Sweden has an extensive child and adolescent psychiatric (CAP) research tradition in which longitudinal methods are used to study juvenile delinquency. Up to the 1980s, results from descriptions and follow-ups of cohorts of CAP patients showed that children's behavioural disturbances or disorders and school problems, together with dysfunctional family situations, were the main reasons for families, children, and youth to seek help from CAP units. Such factors were also related to registered criminality and registered alcohol and drug abuse in former CAP patients as adults. This study investigated the risk for patients treated 1975–1990 to be registered as criminals until the end of 2003.</p> <p>Methods</p> <p>A regional sample of 1,400 former CAP patients, whose treatment occurred between 1975 and 1990, was followed to 2003, using database-record links to the Register of Persons Convicted of Offences at the National Council for Crime Prevention (NCCP).</p> <p>Results</p> <p>Every third CAP patient treated between 1975 and 1990 (every second man and every fifth woman) had entered the Register of Persons Convicted of Offences during the observation period, which is a significantly higher rate than the general population.</p> <p>Conclusion</p> <p>Results were compared to published results for CAP patients who were treated between 1953 and 1955 and followed over 20 years. Compared to the group of CAP patients from the 1950s, the results indicate that the risk for boys to enter the register for criminality has doubled and for girls, the risk seems to have increased sevenfold. The reasons for this change are discussed. Although hypothetical and perhaps speculative this higher risk of later criminality may be the result of lack of social control due to (1) rising consumption of alcohol, (2) changes in organisation of child social welfare work, (3) the school system, and (4) CAP methods that were implemented since 1970.</p

Suicides, psychotic disorders and criminality among former child and adolescent psychiatric patients followed into adulthood

The overall aim was to provide information about child and adolescent psychiatric (CAP) patients and their outcome as adults: Were their difficulties in childhood due to mental illness, disablement and/or behaviour disorders? What happened to them as adults? Who were the patients in need of psychiatric care (GenP) in adulthood that had not had previous contact with CAP? Did this group differ from the former CAP group? Methods: Paper I-III: 1,400 CAP patients admitted 1975-1990 to inpatient or outpatient CAP care in Jämtland County, Sweden were followed until 2003. Paper IV: A sample of 167 GenP patients not treated in CAP was compared to GenP patients with a history of CAP care. Hospital records at CAP were reassessed according to a study specific protocol. Outcome was measured in relation to register data on mortality, suicides, psychiatric/somatic care, and criminal convictions. CAP records were examined for those treated for psychosis either at CAP and or in GenP. Results: Every third CAP patient has later received GenP care. They constituted a small part of the GenP patients in the same age-groups. The CAP patients showed an elevated rate of early death. Two of the 19 who later committed suicide had been initially admitted because of attempted suicide. Every third CAP patient had a criminal record. Over the past 50 years, the percentage of Swedish boys admitted to CAP care and later registered as criminals seems to have doubled while the corresponding percentage for girls has increased almost seven times. Behavioural disorders as a reason for CAP care were the most substantial risk factor for later criminality. Sixty-two former CAP patients (4.4%) received a psychosis diagnosis during the observation time 48 of them within the Schizophrenia categories and 14 with Psychotic Mood Disorder. Mean age at first onset was 21.4 years. Changes in behaviour, including social isolation, refusal to go to school, loneliness and odd behaviour in general were the initial signs and symptoms most frequently observed prior or upon admission to CAP-care. The GenP patients with and without a previous history in CAP care had similar problems as adults. Both groups had a larger need of somatic hospital inpatient-care before the age of 18 years when compared to the general population. More than a third of the treatment occasions occurred in paediatric care. Conclusions: Psychosocial risk factors and social maladjustment in childhood seem to be the most important predictors of early death, including suicide. The increased risk of later criminality is hypothetically the result of rising alcohol consumption in Sweden, the comorbid use of illegal drugs, and changes in the organization of child social welfare work, the school system, and CAP methods that has occurred since 1970. Patients with onset of schizophrenia before 13-17 years of age showed typical symptoms upon admission to CAP care; while late-onset psychosis among former CAP could not be predicted from information gathered during CAP care. There is a group of patients treated in paediatrics and in CAP during childhood and adolescence before becoming later patients in GenP. These patients can most likely be identified during childhood if a closer collaboration is developed between paediatrics and CAP services. Hypothetically, the need of GenP care as adults in the larger group of GenP patients without a previous CAP history may develop from accumulated stressful life-events

Death and suicide among former child and adolescent psychiatric patients

BACKGROUND: Increased mortality rates among previous child and adolescent psychiatry (CAP) patients have been found in Scandinavian studies up to the 1980s. The suicide risk in this group has been estimated to be almost five times higher than expected. This article addresses two questions: Do Swedish CAP patients continue to risk premature death and what kind of information related to psychiatric symptoms and/or behavior problems can predict later suicide? METHODS: Hospital files, Sweden's census databases (including immigration and emigration) and administrative databases (including the Swedish Hospital Discharge register and the Persons Convicted of Offences register), and the Cause of Death register were examined to determine the mortality rate in a group of 1,400 former CAP inpatients and outpatients over a period of 12-33 years. Observed and expected numbers of deceased were calculated with the prospective method and the standardized mortality ratio (SMR) method. The relative risk or the risk ratio (RR) is presented with 95% confidence intervals (CIs). Significance level tests were made using two-by-two tables and chi-square tests. The Cox proportional-hazards regression model was used for survival analysis. RESULTS: Twenty-four males and 14 females died. Compared with the general population, the standardized mortality ratio in this group of CAP patients was significantly higher in both sexes. Behavioral problems, school problems, and co-morbid alcohol or drug abuse and criminality (including alcohol-related crimes) were found to be important predictors. Thirty-two deaths were attributed to suicide, intoxication, drug overdose, or accident; one patient died of an alcohol abuse-related disorder, and five patients died of natural causes. Suicide was the most common cause of death, but only 2 of these 19 cases were initially admitted for attempted suicide. CONCLUSION: We suggest that suicide and death prevention among CAP patients may not be a psychiatric issue per se but a future function of society's juvenile social-welfare investments and juvenile-delinquency prevention programs

Two d-2-Hydroxy-acid Dehydrogenases in Arabidopsis thaliana with Catalytic Capacities to Participate in the Last Reactions of the Methylglyoxal and β-Oxidation Pathways*

The Arabidopsis thaliana locus At5g06580 encodes an ortholog to Saccharomyces cerevisiae d-lactate dehydrogenase (AtD-LDH). The recombinant protein is a homodimer of 59-kDa subunits with one FAD per monomer. A substrate screen indicated that AtD-LDH catalyzes the oxidation of d- and l-lactate, d-2-hydroxybutyrate, glycerate, and glycolate using cytochrome c as an electron acceptor. AtD-LDH shows a clear preference for d-lactate, with a catalytic efficiency 200- and 2000-fold higher than that for l-lactate and glycolate, respectively, and a Km value for d-lactate of ∼160 μm. Knock-out mutants showed impaired growth in the presence of d-lactate or methylglyoxal. Collectively, the data indicated that the protein is a d-LDH that participates in planta in the methylglyoxal pathway. Web-based bioinformatic tools revealed the existence of a paralogous protein encoded by locus At4g36400. The recombinant protein is a homodimer of 61-kDa subunits with one FAD per monomer. A substrate screening revealed highly specific d-2-hydroxyglutarate (d-2HG) conversion in the presence of an organic cofactor with a Km value of ∼580 μm. Thus, the enzyme was characterized as a d-2HG dehydrogenase (AtD-2HGDH). Analysis of knock-out mutants demonstrated that AtD-2HGDH is responsible for the total d-2HGDH activity present in A. thaliana. Gene coexpression analysis indicated that AtD-2HGDH is in the same network as several genes involved in β-oxidation and degradation of branched-chain amino acids and chlorophyll. It is proposed that AtD-2HGDH participates in the catabolism of d-2HG most probably during the mobilization of alternative substrates from proteolysis and/or lipid degradation