Developmental trajectories of conduct problems and hyperactivity from ages 2 to 10

BACKGROUND: Conduct problems (CP) and hyperactivity/attention problems (HAP) are thought to covary with regularity, yet few studies have examined their co-occurrence or risk factors that discriminate their trajectories beginning in early childhood. METHOD: The present study sought to advance our understanding of this issue by examining separate trajectories of overt CP and HAP symptomatology among 284 boys from urban, low-income families followed from ages 1.5 to 10. We also investigated the co-occurrence of persistent CP and HAP and explored risk factors that discriminate CP and HAP trajectories. RESULTS: Four similar trajectory groups were identified for both CP and HAP symptoms. Chronic CP was differentiated from persistent low CP by risk factors in child, parenting, and family domains, while chronic trajectories of HAP were typified by elevated maternal depressive symptoms compared to children with persistent low HAP. CONCLUSIONS: The findings extend previous research with older children of HAP and/or CP, highlighting the effects of proximal family and child risk factors that are identifiable in the first two years of children's lives and associated with trajectories of disruptive behavior.     

Effects of response conflict on pain-evoked medial prefrontal cortex activity

Experimental studies of pain may introduce a response conflict, where the subject must inhibit an escape response and make a pain-rating response. Several lines of evidence have shown that the medial prefrontal cortex is activated by painful stimuli and by response conflict. It is not clear, however, to what extent pain-evoked medial prefrontal cortex activation reflects response conflict. We examined this question using the Simon task. The participants identified pain threshold and moderately painful target stimuli presented to the left or right sural nerves using their left or right hands. Response conflict occurred when the response was made with the hand contralateral to the target stimulus. The results suggest that pain-evoked medial prefrontal cortex activity occurring 70 to 190 ms poststimulus, as estimated from the sural nerve somatosensory evoked potential, is not involved in response conflict.     

Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases

Degeneration of nigrostriatal dopamine neurons and cholinergic cortical neurones are the main pathological features of Parkinson's disease (PD) and for the cognitive deficit in dementia of the Alzheimer' type (AD) and in dementia with Lewy bodies (DLB), respectively. Many PD and DLB subjects have dementia and depression resulting from possible degeneration of cholinergic and noradrenergic and serotonergic neurons. On the other hand, AD patients may also develop extrapyramidal features as well as depression. In both PD and AD there is, respectively, accumulation of iron within the melanin containing dopamine neurons of pars compacta and with in the plaques and tangle. It has been suggested that iron accumulation may contribute to the oxidative stress induced apoptosis reported in both diseases. This may result from increased glia hydrogen peroxide producing monoamine oxidase (MAO) activity that can generate of reactive hydroxyl radical formed from interaction of iron and hydrogen peroxide. We have therefore prepared a series of novel bifunctional drugs from the neuroprotective-antiapoptotic antiparkinson monoamine oxidase B inhibitor, rasagiline, by introducing a carbamate cholinesterase (ChE) inhibitory moiety into it. Ladostigil (TV-3326, N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate), has both ChE and MAO-AB inhibitory activity, as potential treatment of AD and DLB or PD subjects with dementia Being a brain selective MAO-AB inhibitor it has limited potentiation of the pressor response to oral tyramine and exhibits antidepressant activity similar to classical non-selective MAO inhibitor antidepressants by increasing brain serotonin and noradrenaline. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats and antagonizes scopolamine-induced inhibition of spatial learning. Ladostigil like MAO-B inhibitor it prevents MPTP Parkinsonism in mice model and retains the in vitro and in vivo neuroprotective activity of rasagiline. Ladostigil, rasagiline and other propargylamines have been demonstrated to have neuroprotective activity in several in vitro and in vivo models, which have been shown be associated with propargylamines moiety, since propargylamines itself possess these properties. The mechanism of neuroprotective activity has been attributed to the ability of propargylamines-inducing the antiapoptotic family proteins Bcl-2 and Bcl-xl, while decreasing Bad and Bax and preventing opening of mitochondrial permeability transition pore. Iron accumulates in brain regions associated with neurodegenerative diseases of PD, AD, amyotrophic lateral sclerosis and Huntington disease. It is thought to be involved in Fenton chemistry oxidative stress observed in these diseases. The neuroprotective activity of propargylamines led us to develop several novel bifunctional iron chelator from our prototype brain permeable iron chelators, VK-28, possessing propargylamine moiety (HLA-20, M30 and M30A) to iron out iron from the brain. These compounds have been shown to have iron chelating and monoamine oxidase A and B selective brain inhibitory and neuroprotective-antiapoptotic actions.     

Anterior cingulate cortex: an fMRI analysis of conflict specificity and functional differentiation

In this event-related functional magnetic resonance imaging (fMRI) study, we provide evidence that the role of the anterior cingulate cortex (ACC) in cognitive control may not be unitary, as the responses of different ACC subregions vary depending upon the nature of task-irrelevant information. More specifically, using the color-word Stroop task (congruent, incongruent, and neutral trial types), we examined the degree to which increases in neural activity within ACC are specific to conditions of conflict, as posited by the conflict monitoring theory (Botvinick et al. [1999]: Rev Neurosci 10:49-57; Carter et al. [1998]: Science 280:747-749). Although incongruent and congruent trials both involve two competing sources of color information (color word and ink color), only incongruent trials involve a direct conflict between task-relevant and task-irrelevant information. Although the anterior division of the ACC rostral zone exhibited conflict specific increases in neural activity (i.e., incongruent > congruent = neutral), the posterior division exhibited a more generalized pattern, increasing whenever the task-irrelevant information was color related, regardless of whether it was conflicting (i.e., incongruent and congruent > neutral). Our data thus suggest a possible functional differentiation within the ACC. As such, it is unlikely that the role of the ACC in cognitive control will be able to be accommodated by a single unifying theory.     

Influence of history of head trauma and epilepsy on delinquents in a juvenile classification home

Juvenile delinquents often show poor impulse control and cognitive abnormalities, which may be related to disturbances in brain development due to head trauma and/or epilepsy. The aim of the present study was to examine the influence of head trauma and/or epilepsy on delinquent behavior. We examined 1,336 juvenile delinquents (1,151 males and 185 females) who had been admitted to the Nagoya Juvenile Classification Home, Aichi, Japan. Among them, 52 subjects with a history of epilepsy, convulsion or loss of consciousness, head injury requiring neurological assessment and/or treatment, or neurosurgical operation (head trauma/epilepsy group), were examined by electroencephalography and compared to subjects without these histories (control group) with respect to types of crime, history of amphetamine use, psychiatric treatment, child abuse, and family history. Among the 52 subjects, 43 (82.7%) showed abnormal findings. The head trauma/epilepsy group had significantly higher rates of psychiatric treatment (P<0.0001, OR=16.852, 95% CI=8.068-35.199) and family history of drug abuse (P<0.05, OR=2.303, 95% CI=1.003-5.290). Furthermore, the percentage of members who were sent to juvenile training school by the family court was significantly higher in the head trauma/epilepsy group (72.5%) than in the control group (38.9%, P<0.0001). The juvenile delinquents who had a history of head trauma and/or epilepsy showed a high prevalence of electroencephalograph abnormality, and higher rates of psychiatric treatment and family history of drug abuse, and were more likely to be sent to juvenile training school by the family court.     

Child Behavioral Health Service Use and Caregiver Strain: Comparison of Managed Care and Fee-For-Service Medicaid Systems

This study compares behavioral health service utilization patterns and their determinants among Medicaid-enrolled children, ages 5–17 (N = 676) who were being served under managed care in Tennessee or a traditional fee-for-service system in Mississippi. Children in the fee-for-service program were significantly more likely than their counterparts in the managed care Medicaid program to receive behavioral health services (i.e., any service, support services, traditional outpatient services, day treatment, inpatient/residential care) and to receive more services overall. This finding held after controlling for the influence of other factors. Although child, family, and community variables were related to service use patterns, the relationships differed across systems. Caregiver strain was associated with several service use variables, but its influence was more pronounced in Tennessee. These findings support continued focus on the multi-level factors that shape behavioral health service use among children.     

Part I. General practitioner-specialist relationship

This article is the first of a two-part series that seeks to explore the relationship and interaction between general practitioners (GPs) and medical specialists. A historical account of the medical profession is given, beginning from the tripartite division (i.e. the physicians, surgeons or barbers and the apothecaries), the Apothecaries Act of 1815, and the Medical Act of 1858. An account is also given of factors that exacerbated the division and friction between GPs and specialists, and how general practice developed in Australia. The role of the GP is stated as the provision of primary care, preventive care, patient-centred care, continuing care, comprehensive care, and community-based care to individuals and their families. The role of the specialists on the other hand is that of a consultant to advise GPs who carry on the management after the patient leaves the specialist. The dynamics of the GP-specialist relationship are discussed in relation to power, interdependence, morale, public image, education and training, and support from the Colleges, and we conclude by discussing the importance of collaboration between professions.     

Expression pattern of apoptosis-related markers in Huntington’s disease

Inappropriate apoptosis has been implicated in the mechanism of neuronal death in Huntingtons disease (HD). In this study, we report the expression of apoptotic markers in HD caudate nucleus (grades 1–4) and compare this with controls without neurological disease. Terminal transferase-mediated biotinylated-UTP nick end-labeling (TUNEL)-positive cells were detected in both control and HD brains. However, typical apoptotic cells were present only in HD, especially in grade 3 and 4 specimens. Expression of the pro-apoptotic protein Bax was increased in HD brains compared to controls, demonstrating a cytoplasmic expression pattern in predominantly shrunken and dark neurons, which were most frequently seen in grades 2 and 3. Control brains displayed weak perinuclear expression of the anti-apoptotic protein Bcl-2, whereas in HD brains Bcl-2 immunoreactivity was markedly enhanced, especially in severely affected grade 4 brains, and was observed in both healthy neurons and dark neurons. Caspase-3, an executioner protease, was only found in four HD brains of different grades and was not expressed in controls. A strong neuronal and glial expression of poly(ADP-ribose) polymerase (PARP)-immunoreactivity was observed in HD brains. These data strongly suggest the involvement of apoptosis in HD. The exact apoptotic pathway occurring in HD neurodegeneration remains yet unclear. However, the presence of late apoptotic events, such as enhanced PARP expression and many TUNEL-positive cells accompanied with weak caspase-3 immunoreactivity in severely affected HD brains, suggests that caspase-mediated neuronal death only plays a minor role in HD.     

Clinical features of depressed patients with or without a family history of alcoholism

OBJECTIVE: To compare clinical features of depressed subjects without alcoholism but with a family history of alcoholism to a depressed group without alcoholism and without a family history of alcoholism. METHOD: Clinical and demographic data of 209 depressed subjects without a history of alcoholism in first-degree relatives and 73 depressed individuals with a history of alcoholism in first-degree relatives were compared. Subjects with a personal history of alcoholism were excluded. RESULTS: Depressed subjects with a family history of alcoholism have a significantly higher prevalence of reported childhood physical and sexual abuse and post-traumatic stress disorder (PTSD), make more suicide attempts, and have greater intent to die at the time of their most lethal suicide attempt, compared to depressed subjects without a family history of alcoholism. CONCLUSION: Depressed patients with a family history of alcoholism are at greater risk for suicidal behavior and PTSD and may require more careful management.