Glutamate-mediated calcium signaling: a potential target for lithium action.

Bipolar disorder and schizophrenia are two debilitating mental health disorders associated with both severe impairment and increased suicide risk. Several lines of evidence indicate that these disorders are associated with disturbances in the glutamate system. For almost half a century, lithium has been the most effective drug for treatment of mood disorders. Lithium is still used mainly on empiric grounds and its molecular mechanisms of action are still largely unknown. This study was designed to explore the effects of continuous lithium exposure, in therapeutically relevant concentration, on the glutamate-mediated Ca2+ response in rat primary hippocampal neurons. We show that lithium treatment is associated with multiple perturbations in calcium signaling. Lithium attenuated calcium release after activation of both metabotropic glutamate receptors (mGluR)1/5 as well as muscarinic cholinergic receptors, two different Gq-coupled receptors. The attenuation of the calcium response was, for mGluR5 receptors, found to be associated with a downregulation of the plasma membrane expression of this receptor. Lithium also attenuated calcium influx after activation of the N-methyl-D-aspartate receptor, without affecting its cell surface expression. Furthermore lithium treatment was associated with a decrease in intracellular calcium concentration and a reduction of calcium content in intracellular stores. Thus we have shown that lithium attenuates the effects of glutamate-mediated calcium signaling and regulates intracellular calcium levels as well as calcium turnover in hippocampal neurons. These effects can be expected to influence the communication within and between neurons in a variety of ways since calcium may be considered as the most common and the most versatile signaling molecule in neurons.

"Maturational lag" hypothesis of attention deficit hyperactivity disorder: an update.

UNLABELLED: This article discusses the relationship of maturation to ADHD and hyperkinetic disorder (HKD), with an emphasis on current research in ADHD and HKD, persistence and remission of ADHD symptoms over time and brain maturational trajectories. CONCLUSION: ADHD is a broad, heterogeneous syndrome and only a subgroup of subjects has a diagnosis of HKD, which is a subset of individuals with severe ADHD combined subtype. Children showing symptoms above the threshold for a diagnosis of ADHD are at risk of developing comorbid conditions and increasing stress in both parents and teachers. In some subjects, ADHD symptoms can improve over time during maturation and development. These children with a diagnosis of ADHD could be viewed as showing variants of normal childhood behaviour with maturational trajectories that are lagging behind but will catch up. ADHD could therefore represent a continuum from normality at one extreme to a severe disorder, HKD according to ICD-10, at the other extreme.

Urinary peptide levels in women with eating disorders. A pilot study.

The aim of this study was to evaluate whether the urinary excretion of low molecular weight peptides is increased in women with a history of anorexia nervosa/self starvation. The study group consisted of 12 women aged 20-38 years who were treated in a specialised day care unit for eating disorders in Stockholm between January and December 1998; the controls were eight women with primary bulimia treated in the same unit (A) and ten healthy women without any eating disorder (B). The chromatographically measured urinary peptide levels in the study group were significantly higher than those in control group A (and B when one highly influential individual with very low peptide excretion in the study group was excluded from the analyses). These findings offer some support to the speculative hypothesis that eating disorder symptoms may be linked to increased levels of neuroactive peptides, although it is necessary to define the peptides further before any definite conclusion can be drawn. Furthermore, the study group was characterised by many interpersonal differences in eating behaviour that could explain the increased urinary peptide levels.

Prevalence and associated impairments of mild mental retardation in six- to ten-year old children in Pakistan: a prospective study.

UNLABELLED: The aim of this study was to find the prevalence of mild mental retardation (MMR) in 6-10-y-old children in a prospectively followed cohort in Pakistan from four areas with different socioeconomic conditions. Retarded children were identified by a two-step method, comprising a household screening with the Ten Questions Screening in 649 families followed by clinical investigation and psychometric testing (WISC-R and Griffiths) of the 132 children found by the screening. The overall prevalence of MMR among 6-10-y-old children was 6.2%. The distribution of MMR was uneven, with 1.2% among children from the upper-middle class, 4.8% in the village, 6.1% in the urban slum and 10.5% in the poor periurban slum area. Additional impairments were found in 75% of the children with MMR, of which speech impairment was the most common. CONCLUSION: The prevalence of MMR was found to be higher in a developing country than in developed countries. It also seemed to be related to poor socioeconomic conditions, as the prevalence in the upper-middle class was comparable to figures from developed countries, while the prevalence in children from poor population groups was much higher.

[Antisocial behavior of adolescents and home environment--need for a multidisciplinary model]. / Ungdomsasocialitet och hemmiljö--behov av tvärvetenskaplig modell.

In Swedish child and adolescent psychiatry there is a more than 60-year long tradition of using longitudinal methods in research on juvenile delinquency. Since the 1940's, results have been presented using either prospective or retrospective longitudinal designs for this purpose. Starting from genetics as scientific paradigm, new approaches including neuropsychiatry and social psychiatry showed the need for a multidisciplinary view at the border between medicine and behavioral sciences. Both Swedish and international research in the area has clearly demonstrated that factors relating to gender, maturation, resilience vs. vulnerability, the mental health of the parents, the social network and the organization of the school are of importance when trying to understand, prevent and treat juvenile delinquents. The challenge presented to today's and future researchers is to understand how the complexity of the modern western society will impact already established knowledge.

[What happens with child and adolescent psychiatric patients? Cooperation between pediatrics and psychiatry is required]. / Hur går det för barn- och ungdomspsykiatrins patienter? Samverkan krävs mellan pediatrik, barn- och vuxenpsykiatri.

1,420 child and adolescent psychiatric patients from a County Council in Northern Sweden were prospectively monitored during observation periods ranging from 5-20 years. These follow-ups focused on the patients phi risk of future suicide, need of psychiatric care in adulthood, and risk of future criminality. In as much as every fourth child and adolescent psychiatric patient (male:female ratio = 1:2) required subsequent psychiatric care, while every third (male:female ratio = 2:1) demonstrated criminal behavior, these results indicate that improvements are needed in co-operative efforts linking child and adolescent psychiatry on the one hand with general psychiatry and social welfare authorities on the other. However, the majority of patients in general psychiatric care in corresponding age-groups were not the same former child and adolescent psychiatric patients. In a previous investigation of pediatric patients in ambulatory care it was found that every seventh patient was not physically ill although presenting with somatic symptoms, but suffered from undiscovered psychiatric problems. Considering the fact that patients in this group might well become patients in general psychiatry, yet never treated in child and adolescent psychiatry, then questions arise concerning ways to improve preventive measures and care. The following results also merit attention: 25 former child psychiatric patients died during follow-up. Mean age at death was 22 years (range 12-33 years). 14 suicided and another two died of "uncertain causes". None of those who suicided had previously been admitted to a child psychiatric unit after attempted suicide. The majority had suffered from serious psychosocial problems related to parental factors such as parental psychiatric illness, alcoholism/drug-abuse and neglect.

Parents' perception of mental development and behavioural problems in 8 to 9-year-old children.

UNLABELLED: A slow maturational rate may be an underlying antecedent of a psychiatric disorder. If this is correct, differences in behavioural problems could be related to the maturity level in children of the same chronological age. The aim of the study was to compare the parents' perceptions and assessments of their children's maturational status and behavioural problems. A population based on a nationwide sample from the Swedish twin-register of 8 to 9-y-old children (n = 1079) was used. The parents completed a questionnaire including their views on their child's maturity level, the Swedish version of the Child Behaviour Checklist (CBCL) and an Attention Deficit Hyperactivity Disorder (ADHD) checklist based on the DSM-III-R criteria. Multivariate analyses showed a statistically significant relationship between immaturity reported by the parents and several behavioural problems reported on the CBCL: somatic complaints, anxious and depressed, social problems, thought problems, attention problems, behaviour problems and aggressive behaviour. There was also a statistically significant relationship between the maturity factor and the CBCL grouping of syndromes (internalizing, externalizing, total behaviour problems score) as well as between the maturity factor and ADHD. CONCLUSION: We conclude that at least from the parents' point of view the behaviour problems in their children may be related to maturity.

Measurements of attention deficits and impulsivity: a Swedish study of the Gordon Diagnostic System.

The Gordon Diagnostic System (GDS) is a portable easily operated computerized tool developed to measure impulse control, attention and vigilance. In 1988, it was standardized for use among American children. The aim of this study was to evaluate the GDS for use among Swedish children. A clinical sample of 71 Swedish children, mean age 10.5 y, fulfilling the ADHD criteria according to the DSM-IV was compared with a control sample of 88 children, mean age 10.2-y, with no known psychiatric diagnosis. The clinical sample showed lower GDS scores in all age groups, with some exceptions. The GDS scores were not associated with gender, but strongly associated with age, especially in the control sample. The accuracy of the GDS referring a specific child to either of the samples was, as expected, not impressive. With respect to the practical usefulness, the GDS was well accepted by the children and parents in both samples. The findings in age variation and when comparing children with ADHD and controls are in agreement with results from other studies.

[Children of letters--ghosts from the past with a new name. A small group if stringent criteria are used]. / Bokstavsbarn--gengångare från förr med ny beteckning. Liten grupp om sakliga kriterier används.

Hyperkinetic disorders, MBD (minimal brain dysfunction), DAMP [deficits in attention, motor function (or muscular control) and perception], ADD (attention deficit disorder), and ADHD (attention deficit hyperactivity disorder), are currently the focus of interest among parents, clinicians and researchers in Sweden; and guidelines for the assessment and treatment of such disorders were published in the USA in 1997, and in Europe in 1998. However, despite the accumulated knowledge, and new hypotheses which have been proposed, e.g., that ADHD is "a disorder of adaptation," there is no consensus as to the understanding, treatment and prevention of these disorders. In a consensus statement published by an NIH (National Institutes of Health) panel in the USA it was concluded that, after years of clinical research and experience, our knowledge of the aetiology of ADHD remains speculative, and no documented strategies for its prevention are available. A review of Swedish views and concepts of these disorders since 1950 showed discussion to have been characterised by more similarities than differences, and that nothing really new had emerged. However, differences have existed in the sphere of general education. Since WWI, changes in the organisation of the statutory school system have been designed to improve both education and health among schoolchildren. Such changes seem to have had both beneficial and adverse effects on the overall health of the children. The prevalence of ADHD-like problems declined during the period, 1949-70, when all Swedish six-year-olds were screened for school-readiness with a standardised national test, and the class in which a child started school was dependent on intellectual capacity, overall mental age, and the presence or absence of reading, spelling and learning difficulties, and of behavioural problems. Since this was discontinued after reorganisation of the school system in 1970, the prevalence of problematic behaviour has once again increased. Thus, in the search for new approaches to the support of children with hyperactivity and attention deficit problems, analysis of the organisation of the school system should not be forgotten.

Symptoms of depression are important to psychological adaptation and metabolic control in children with diabetes mellitus.

AIMS: Sixty-two children (37 girls, 25 boys) between 9 and 18 years of age were enrolled to investigate: (1) the relationship between adaptation to diabetes mellitus (DM) and psychological functioning; (2) if adaptation or psychological functioning was related to metabolic control; and (3) if the patients' ability to cope with diabetes as assessed by physicians, was correlated to adaptation or psychological functioning. METHODS: Psychological functioning was measured by three general psychological instruments for depressive symptoms, self-esteem and fear. Diabetes adaptation was evaluated by questionnaires and coping with diabetes by an assessment of the physicians. Metabolic control was expressed by the individual HbA1c measured during the last year. RESULTS: Adaptation to diabetes correlated to psychological functioning (depression, P<0.001; self-esteem, P<0.01; and fear, P<0.01). Multiple regression analyses showed that metabolic control was predicted by adaptation (P=0.0013) with monitoring of diabetes as the only significant aspect of the adaptation (P < or = 0.0001). In turn, adaptation was predicted by symptoms of depression and metabolic control (P<0.0001). In support of this observation, a depressed (n = 9) and a non depressed (n= 53) group showed significant differences in metabolic control (P < or = 0.01), adaptation (P < or = 0.001) and self-esteem (P < or = 0.001). The only significant variable for the physicians assessment was metabolic control, which explained 35 % of the variance (P < 0.001). CONCLUSIONS: The major conclusion is that symptoms of depression affect both adaptation and metabolic control. It should be of concern to identify patients with depressive symptoms, offer treatment for their emotional difficulties and increase the support for taking care of their diabetes.