Everyday emotional experience of adults with attention deficit hyperactivity disorder: evidence for reactive and endogenous emotional lability.

BACKGROUND: Emotional lability (EL), characterized by negative emotional traits and emotional instability, is frequently reported in children and adults with attention deficit hyperactivity disorder (ADHD). However, EL is primarily assessed using retrospective self-report, which is subject to reporting bias and does not consider the potential influence of positive and negative everyday experiences. METHOD: Ambulatory assessment was carried out in 41 men with ADHD without co-morbidity, current medication or substance abuse, and 47 healthy control participants. Reports of negative and positive emotions (irritability, frustration, anger, happiness, excitement) and the occurrence of bad and good events were completed eight times daily during a working week. Group differences in emotional intensity and instability were investigated using multilevel models, and explored in relation to bad and good events and the Affective Lability Scale - Short Form (ALS-SF), an EL questionnaire. RESULTS: The ADHD group reported significantly more frequent bad events, heightened intensity and instability of irritability and frustration, and greater intensity of anger. The results for positive emotions were equivocal or negative. Bad events significantly contributed to the intensity and instability of negative emotions, and showed a stronger influence in the ADHD group. However, covariation for their effect did not eliminate group differences. Small-to-moderate correlations were seen between intensity and instability of negative emotions and the ALS-SF. CONCLUSIONS: Adults with ADHD report heightened intensity and instability of negative emotions in daily life. The results suggest two components of EL in ADHD: a reactive component responsive to bad events and an endogenous component, independent of negative everyday events.

Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study.

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal 'control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate-glutamine levels are not explained by use of stimulant medication.

Long-term intellectual outcome after temporal lobe surgery in childhood.

OBJECTIVE: Temporal lobe resection is an established treatment for medication-resistant temporal lobe epilepsy, which in recent years has increasingly been performed in children. However, little is known about the long-term outcome in these children. The aim of this study was to characterize intellectual and psychosocial functioning of children after temporal lobe resection as they progress into late adolescence and adulthood. METHODS: We report the long-term follow-up of 42 children who underwent temporal lobe surgery after an average postoperative period of 9 years. Longitudinal change in IQ was documented, psychosocial outcome including quality of life was assessed, and preoperative and postoperative T1-weighted MRI brain scans were evaluated quantitatively. A well-matched nonsurgical comparison group of 11 children with similar clinical characteristics was also assessed. RESULTS: At follow-up, 86% of the surgical group were seizure-free, and 57% were no longer taking antiepileptic medication. A significant increase in IQ was found in the surgical group after an extended follow-up period of >5 years. This IQ change was not found in the nonsurgical comparison group. IQ increases were associated with cessation of antiepileptic medication and changes in MRI-derived gray matter volume. The surgical group also reported better psychosocial outcome including quality of life, which was more strongly associated with seizure freedom rather than surgery per se. CONCLUSIONS: Surgery for temporal lobe epilepsy performed in childhood results in excellent long-term seizure control and favorable cognitive outcome along with positive effects on brain development. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that temporal lobectomy in children with temporal lobe epilepsy is associated with improved long-term intellectual outcomes compared with those undergoing standard medical treatment.

Intra-mitochondrial degradation of Tim23 curtails the survival of cells rescued from apoptosis by caspase inhibitors.

Caspase inhibition can extend the survival of cells undergoing apoptosis beyond the point of mitochondrial outer membrane permeabilisation (MOMP), but this does not confer long-term protection because caspase-independent death pathways emerge. Here, we describe a novel mechanism of mitochondrial self-destruction in caspase-inhibited cells, whose hallmark is the degradation of Tim23, the essential pore-forming component of the TIM23 inner membrane translocase. We show that Tim23 degradation occurs in cycling and post-mitotic cells, it is caspase-independent but Bax/Bak dependent, and it follows cytochrome c release. The proteolytic degradation of Tim23 is induced by MOMP and is mitochondrion-autonomous, as it also occurs in isolated mitochondria undergoing permeability transition. Degradation of Tim23 is selective, as expression of several other inner membrane proteins that regulate respiratory chain function is unaffected, and is not autophagic, as it occurs similarly in autophagy-proficient and -deficient (Atg-5 knockout) cells. Depleting Tim23 with siRNA is sufficient to inhibit cell proliferation and prevent long-term survival, while expression of degradation-resistant Tim23-GFP in mitochondria delays caspase-independent cell death. Thus, mitochondrial autodigestion of Tim23 joins the array of processes contributing to caspase-independent cell death. Because mitochondrial biogenesis requires a functional protein-import machinery, preventing Tim23 degradation might, therefore, be essential for repairing damaged mitochondria in chronic degenerative diseases.