Intensified testing for attention-deficit hyperactivity disorder (ADHD) in girls should reduce depression and smoking in adult females and the prevalence of ADHD in the longterm.

Attention-deficit hyperactivity disorder (ADHD) is the most common neurobehavioral disorder in youth. About a third to one-half of the affected subjects continue to have symptoms in adulthood. Remarkably, the prevalence numbers published for adult females are higher than for girls. The differences in the epidemiological data between the age groups clearly point to underdiagnosed ADHD in girls. Major depression, the most frequent psychiatric condition worldwide in adulthood, is twice as common in female as in male adults. Anxiety and depression are also among the most common comorbidities in adults with ADHD. Therefore, an undiagnosed ADHD may often underlie the psychopathology in depressive women. Another possibly associated phenomenon is the increased frequency of smoking in adult females. Since nicotine indirectly enhances the intrasynaptic dopamine level which presumably is too low both in ADHD and in depression, smoking might be used as a self-medication in women with untreated ADHD and consecutive depression. Furthermore, smoking during pregnancy is a major risk factor for ADHD in the offspring, so the vicious circle is complete. Depression in mothers of children with ADHD is associated with a higher rate of comorbidity in the children. Improved screening for ADHD in girls and treatment in childhood might thus reduce the rate of depression and smoking in adult females. We hypothesize that earlier identification and interventions might not only improve the lives of millions of girls and women but might also reduce the prevalence rates in future generations or at least moderate the deviant behaviour in this highly heritable disorder in which the development and severity of symptoms and the functional impairment depend to a high degree on epigenetic factors.

Spastin related hereditary spastic paraplegia with dysplastic corpus callosum.

Thin corpus callosum has been recently observed in two patients with an autosomal dominant trait of hereditary spastic paraplegia (HSP) linked to a novel mutation in the spastin gene (SPG4). In the same two patients cerebellar atrophy has been found. Reportedly, in other members of the same family, there has been a variable presence of mental retardation. We report on the clinical and genetic investigation of an Austrian family with a novel mutation in the spastin gene. Genetic analysis of the SPG4 locus revealed a mutation (C1120A) and a known intronic polymorphism (996-47G>A) of the spastin gene. In one affected family member, previously undescribed dysplasia of the corpus callosum (CC) was found in conjunction with otherwise uncomplicated HSP. Dysplastic CC was not paralleled with cortical atrophy, cognitive impairment or other phenotypic variations. Two further affected family members showed the same mutation and polymorphism, but no evidence of CC abnormalities. We conclude that apparently pure HSP may present with MRI features of dysplastic CC. This finding extended the spastin-related phenotype which is distinct from previous reports of thin CC in HSP.

X-linked bulbospinal neuronopathy: Kennedy disease.

OBJECTIVE: To characterize the earliest symptoms of X-linked bulbospinal neuronopathy (Kennedy disease [KD]) during the course of the disease, including a definition of the age of onset. METHODS: We describe the earliest symptoms, signs on clinical investigation, electrophysiological and muscle biopsy specimen findings, and creatine kinase levels in 34 patients with KD. Correlations were made among the CAG-repeat length and clinical symptoms, age at onset, and the presence of electrophysiological and laboratory findings. RESULTS: Our findings indicate that the age at onset of KD is in adolescence which is earlier than previously thought. Most frequently early symptoms are gynecomastia, muscle pain, and premature muscular exhaustion. Weakness is not a typical initial symptom and is frequently found in distal limbs if present early. We found a correlation between the of number of CAG repeats and the age at onset of weakness but not to the age at onset of KD. Furthermore, no correlations were found between the occurrence of gynecomastia, tremor, increased creatine kinase levels, and additional myopathic changes in muscle biopsy specimens. CONCLUSIONS: Our data show that KD is a multisystem disorder with onset in adolescence. Because of the heterogeneity of clinical presentation and no correlation between the number of CAG repeats and most of the clinical hallmarks of KD, we suggest that other environmental or genetic factors contribute to the manifestation of specific organ systems in KD.

Variable reduction of caveolin-3 in patients with LGMD2B/MM.

Mutations in the human dysferlin gene ( DYSF) cause autosomal recessive muscular dystrophies characterized by degeneration and weakness of proximal and/or distal muscles: limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Recently, an interaction between caveolin-3 and dysferlin in normal and dystrophic muscle (primary caveolin-3 deficiency; LGMD1C) was shown. In this study, clinical,morphological and genetic analysis was carried out in four independent LGMD2B/MM patients. All patients presented with an adult-onset, slowly progressive muscular dystrophy with variable involvement of proximal and distal muscles. We found complete lack of dysferlin in the four LGMD2B/MM patients. Secondary reduction of caveolin-3 was detected in three out of the four patients. Regular caveolae were detected along the basal lamina in two patients by electron microscopy. We provide further evidence that dysferlin and caveolin-3 interact in human skeletal muscle. It remains to be elucidated whether the loss of this interaction contributes to pathogenic events in muscular dystrophy.

Neural hyporesponsiveness and hyperresponsiveness during immediate and delayed reward processing in adult attention-deficit/hyperactivity disorder.

BACKGROUND: Dysfunctional reward processing, accompanied by a limited ability to tolerate reward delays, has been proposed as an important feature in attention-deficit/hyperactivity disorder (ADHD). METHODS: Using functional magnetic resonance imaging (fMRI), brain activation in adult patients with ADHD (n=14) and healthy control subjects (n=12) was examined during a series of choices between two monetary reward options that varied by delay to delivery. RESULTS: Compared with healthy control subjects, hyporesponsiveness of the ventral-striatal reward system was replicated in patients with ADHD and was evident for both immediate and delayed rewards. In contrast, delayed rewards evoked hyperactivation in dorsal caudate nucleus and amygdala of ADHD patients. In both structures, neural activity toward delayed rewards was significantly correlated with self-rated ADHD symptom severity. CONCLUSIONS: The finding of ventral-striatal hyporesponsiveness during immediate and delayed reward processing in patients with ADHD further strengthens the concept of a diminished neural processing of rewards in ADHD. Hyperactivation during delayed reward processing, gradually increasing along the ventral-to-dorsal extension of the caudate nucleus, and especially the concomitant hyperactivation of the amygdala are in accordance with predictions of the delay aversion hypothesis.