Problem of item overlap between the Psychopathy Screening Device and attention deficit hyperactivity disorder, oppositional defiant disorder, and conduct disorder rating scales.

Content validity requires a clear definition of the construct of interest and the delineation of the construct from similar constructs. Content validity also requires that the items be representative of the construct as well as specific to the construct. An examination of the items on the Psychopathy Screening Device (PSD), a parent- and teacher-rating scale of childhood psychopathy, indicates significant overlap with the symptoms and associated features of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). The failure of the PSD to have unique items results in poor discriminant validity with ADHD ODD, and CD rating scales. More careful attention to content validation guidelines is required to develop a more useful measure of childhood psychopathy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

High presynaptic dopaminergic activity in children with Tourette's disorder

OBJECTIVE: Tourette's disorder is characterized by chronic fluctuating motor and vocal tics. Despite extensive investigation of the neuropathophysiology of the disorder by a wide array of methodologies, its neurobiochemical substrate is still unclear. Converging evidence, however, suggests a primary role of the dopaminergic system, particularly within the basal ganglia. METHOD: This study examined the integrity of presynaptic dopaminergic function in children with Tourette's disorder, using positron emission tomography and the tracer [18F]fluorodopa (FDOPA). Accumulation of FDOPA in synaptic terminals, a measure of DOPA decarboxylase activity, was quantified in caudate nucleus, putamen, frontal cortex, and midbrain (i.e., substantia nigra and ventral tegmentum). RESULTS: Subjects with Tourette's disorder showed higher FDOPA accumulation than controls in the left caudate nucleus (by 25%; p = .03) and right midbrain (by 53%; p = .08). CONCLUSION: These findings provide evidence of dopaminergic dysfunction in children with Tourette's disorder which affects both cell nuclei and nerve terminals. Based on the known regulation of DOPA decarboxylase activity by post- and presynaptic receptors, and by extracellular dopamine concentration, abnormal activity in this enzyme may reflect deficits in a variety of functional elements of the dopamine system. The precise mechanism underlying an up-regulation of DOPA decarboxylase activity needs to be identified in future studies.     

Is ADHD a disinhibitory disorder?

Attention deficit hyperactivity disorder (ADHD) is widely theorized to stem from dysfunctional inhibitory processes. However, the definition of inhibition is imprecisely distinguished across theories. To clarify the evidence for this conception, the author relies on a heuristic distinction between inhibition that is under executive control and inhibition that is under motivational control (anxiety or fear). It is argued that ADHD is unlikely to be due to a motivational inhibitory control deficit, although suggestions are made for additional studies that could overturn that conclusion. Evidence for a deficit in an executive motor inhibition process for the ADHD combined type is more compelling but is not equally strong for all forms of executive inhibitory control. Remaining issues include specificity to ADHD, whether inhibitory problems are primary or secondary in causing ADHD, role of comorbid anxiety and conduct disorder, and functional deficits in the inattentive ADHD subtype. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Obsessive-compulsive disorder in schizophrenia: epidemiologic and biologic overlap

AF64A (ethylcholine mustard aziridinium ion) was stereotaxically administered bilaterally (1 nmol/side) into rat lateral cerebral ventricles. Choline acetyltransferase (ChAT) activity and ChAT mRNA levels were measured at predetermined time points in the septo-hippocampal pathway and striatum, both well identified as rich in cholinergic neurons. AF64A caused a rapid but transient increase in ChAT mRNA (167%, P < 0.05) and ChAT activity (164%, P < 0.01) in the septum. By day 7 post treatment, there was a significant decrease in ChAT mRNA (42.5% of control, P < 0.05) in the septum although the ChAT activity still stayed high. This decreased ChAT mRNA level in the septum lasted for at least four weeks, and was paralleled by a long-lasting decrease in ChAT activity in the hippocampus. In the striatum, on the other hand, there were no observed changes in either ChAT activity or ChAT mRNA. These data suggest that the long term effect of AF64A on the septo-hippocampal cholinergic pathway may, at least in part, be due to an action of AF64A on gene expression in the cholinergic neuron. The difference in the response to AF64A between the septo-hippocampal and striatal cholinergic systems might be due to their difference in neuron types.     

Case study: worsening Tourette's disorder or withdrawal dystonia?

This case report focuses on withdrawal dystonia, a movement disorder associated with neuroleptics. Its occurrence in a patient with Tourette's disorder complicated the clinical picture. A misinterpretation of the symptoms led to ineffective management of the movement disorder. The presence of increased blinking with facial pain, dystonic movements, and other facial movements at each neuroleptic dose reduction pointed toward withdrawal dystonia rather than toward a worsening of Tourette's disorder. Implications for diagnosis and treatment are discussed.     

Attention deficit disorder and neuropsychological functioning in children with Tourette's syndrome.

Neuropsychological deficits in Tourette's syndrome (TS) may result from comorbid psychiatric disorders. This study compared the neuropsychological performance of TS children with and without attention deficit disorder (ADD). Participants were 82 children between 6 and 18 yrs of age with TS, 36 of whom had ADD. ADD children did not differ from non-ADD children in age or in onset or duration of TS but did display more severe complex tics and obsessive-compulsive symptoms. After statistical control for these characteristics, ADD children demonstrated significant deficits in various elements of attention, including encoding, sustaining, and focusing/ executing, and in academic achievement. They did not differ in IQ, non-attentional cognitive skills, or sensorimotor functions. The comorbid psychiatric disorders associated with TS yield distinct patterns of neuropsychological functioning that may reflect overlapping neuroanatomic substrates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical features distinguishing patients with Tourette's syndrome and obsessive-compulsive disorder from patients with obsessive-compulsive disorder without tics

OBJECTIVE: It is not clear whether obsessive-compulsive disorder (OCD) in the context of Tourette's syndrome (TS) is the same as that disorder found in patients with OCD alone. This study evaluated the severity and characteristics of the obsessive-compulsive symptoms in adult patients with OCD and TS compared to adult patients with OCD alone. METHOD: Thirteen subjects with both DSM-III-R TS and OCD and 13 subjects with OCD alone were recruited. Obsessive-compulsive severity was determined by using the Yale-Brown Obsessive Compulsive Scale. The Tourette Syndrome Association Unified Tic Rating Scale was administered to determine tic severity, and the adult version of the Attention Deficit and Hyperactivity Checklist was used to detect a history of childhood attention-deficit hyperactivity disorder (ADHD). RESULTS: Subjects with OCD alone had very few obsessions and compulsions that were not also experienced by subjects with both TS and OCD. In contrast, subjects with TS and OCD were significantly more likely to report obsessions involving nonviolent images, excessive concern with appearance, and need for symmetry. Touching, blinking or staring, and counting compulsions were also significantly more common in this group. Eight subjects with OCD and TS had a childhood history of ADHD, compared to none of the pure OCD subjects. CONCLUSION: There are subtle but definite differences in symptomatology of subjects with pure OCD compared to those with OCD and TS consistent with putative differences in pathophysiology between the 2 groups, i.e., abnormalities in the serotonergic system in OCD patients and serotonergic and dopaminergic abnormalities in those with OCD and TS. These observations may be consistent with genetic heterogeneity within both OCD and TS.     

Visuospatial priming and latent inhibition in children and adults with Tourette's disorder.

Evidence suggests that there are deficits in cognitive inhibition in patients with Tourette's disorder (TD). The pathophysiology of TD includes abnormalities in basal ganglia structure and function. The authors assessed 2 measures of central inhibition—visuospatial priming (VSP) and latent inhibition—in TD patients and in age- and sex-matched controls that are believed to be regulated by brain regions that include the basal ganglia. Among children, TD patients exhibited reduced inhibitory priming and increased facilitatory priming in the VSP paradigm. In comparison with controls, both children and adult TD patients exhibited significantly reduced inhibition in relation to facilitation: this pattern paralleled the pattern of differences between control children and adults. Latent inhibition was intact in control and TD children and adults. Central inhibitory deficits in TD patients appear to be task specific and are not fixed across the life span. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tourette's disorder: Genetic update, neurological correlates, and evidence-based interventions.

This article provides an update of the search for genetic markers related to Tourette's Disorder. The probable neurophysiology of the disorder is reviewed. Frequently prescribed medications are related to the probable biological bases of the disorder. Behavioral interventions and assessment tools are examined. It is concluded that evidence based studies of behavioral treatments are sorely needed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disentangling the prospective relations between maladaptive cognitions and depressive symptoms.

In a four-wave, cohort-longitudinal design with a community sample of 515 children and adolescents (grades 2 through 9), this study examined the longitudinal structure of and prospective interrelations between maladaptive cognitions and depressive symptoms. Multigroup structural equation modeling generated four major findings. First, the longitudinal structures of maladaptive cognitions and depressive symptoms consist of a single time-invariant factor and a series of time-varying factors. Second, evidence supported a model in which depressive symptoms predicted negative cognitions but not the reverse. Third, the time-invariant components of cognition and depression were highly correlated. Fourth, the strength of the depression-to-cognition relation increased with age. Implications regarding the mechanisms underlying clinical interventions with depressed children are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Disentangling the adult attention-deficit hyperactivity disorder endophenotype: Parametric measurement of attention.

Attention deficit hyperactivity disorder (ADHD) persists frequently into adulthood. The decomposition of endophenotypes by means of experimental neuro-cognitive assessment has the potential to improve diagnostic assessment, evaluation of treatment response, and disentanglement of genetic and environmental influences. We assessed four parameters of attentional capacity and selectivity derived from simple psychophysical tasks (verbal report of briefly presented letter displays) and based on a “theory of visual attention.” These parameters are mathematically independent, quantitative measures, and previous studies have shown that they are highly sensitive for subtle attention deficits. Potential reductions of attentional capacity, that is, of perceptual processing speed and working memory storage capacity, were assessed with a whole report paradigm. Furthermore, possible pathologies of attentional selectivity, that is, selection of task-relevant information and bias in the spatial distribution of attention, were measured with a partial report paradigm. A group of 30 unmedicated adult ADHD patients and a group of 30 demographically matched healthy controls were tested. ADHD patients showed significant reductions of working memory storage capacity of a moderate to large effect size. Perceptual processing speed, task-based, and spatial selection were unaffected. The results imply a working memory deficit as an important source of behavioral impairments. The theory of visual attention parameter working memory storage capacity might constitute a quantifiable and testable endophenotype of ADHD. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Brain morphometry in Tourette's syndrome: the influence of comorbid attention-deficit/hyperactivity disorder

Three separate groups, using MRI, have reported basal ganglia abnormalities in Tourette's syndrome (TS). We found similar abnormalities in boys with attention-deficit/hyperactivity disorder (ADHD). Because TS and ADHD are frequently comorbid, we contrasted ADHD boys with and without TS along with control subjects. As expected, we found a significant loss of the normal globus pallidus asymmetry in the patients, but presence or absence of TS did not differentiate the ADHD groups. We conclude that accounting for ADHD comorbidity will be important in future TS morphometric studies.     

Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): Gender, psychiatric comorbidity, and maternal ADHD.

The authors examined the siblings of 140 attention-deficit hyperactivity disorder (ADHD) and 120 control probands and classified families as antisocial if the proband had conduct disorder or a parent had antisocial personality. Partial support was found for the hypothesis that the ADHD gender effect would be limited to antisocial families. Boys had an increased risk for ADHD compared with girls, but only among siblings from antisocial families. The effect size for predicting ADHD in siblings of probands was greater for maternal compared with paternal ADHD, but only for families exhibiting antisocial disorders. Strong support was found for the hypothesis that, compared with siblings from nonantisocial families, those from antisocial families would have more psychopathology (ADHD, depression, substance use, and conduct disorders). The presence of antisocial disorders signals a distinct subtype of ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recent developments in the pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD).

In comparison to other mental health disorders in pediatric populations, there seems to be compelling evidence-based support for both the efficacy of stimulant medication for children and adolescents with attention deficit/hyperactivity disorder (ADHD) and associated symptoms. Tricyclic antidepressants provide an alternative when stimulants are found to be ineffective or associated with too many adverse effects, particularly for children who have comorbid conditions including anxiety and depression. Finally, the alpha-adrenergic agents, although not approved for the management of ADHD, have been widely employed clinically, particularly for the treatment of impulsivity, overactivity, and aggression. Behavior therapy has been demonstrated to be effective for many of the functional impairments associated with ADHD. Research efforts are needed to examine these therapies either alone or in combination on the long-term outcome of children with ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conduct disorder with and without mania in a referred sample of ADHD children

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.     

Reversal of a visuoconstructional disorder by weak electromagnetic fields in a child with Tourette's syndrome

Tourette's syndrome (TS), a chronic familial neuropsychiatric disorder of unknown etiology, is characterized clinically by the occurrence of motor and vocal tics and by the presence of a variety of neurobehavioral and neurocognitive abnormalities including hyperactivity, self-mutilatory behavior, obsessive-compulsive behavior, learning disabilities, and conduct disorder. Cognitive deficits related to right hemispheric dysfunction are common in TS patients accounting for decrements in visuospatial, visuoconstructional and visuomotor skills. An 11 year old boy with a 5 years history of TS exhibited during a routine neuropsychological assessment an unusual visuoconstructional disorder which previously has been observed in dyslexic children. Specifically, when instructed to draw a bicycle from memory, he drew spontaneously a design executed from the perspective of a bird's eye view. After receiving a 20 minute treatment session with picotesla range electromagnetic fields (EMFs) applied extracranially, this visuocontructional disorder was spontaneously reversed and he drew an elaborate and detailed bicycle positioned in profile. A placebo EMF treatment, which was administered prior to magnetic therapy, had no effect on this child's visuoconstructional disorder. During the ensuing week there was a marked reduction in the child's hyperactive behavior with attentuation of motor tics. Spontaneous drawing of a bicycle a week after the administration of magnetic therapy was executed in profile although some elements were presented from a bird's eye view. This case demonstrates the potential impact of treatment with picotesla EMFs in reversing specific cognitive deficits in TS related to right posterior hemispheric dysfunction.     

Genetic and phenotypic overlap between autophagy and the cytoplasm to vacuole protein targeting pathway

We have explored the phenotypic and genetic overlap between autophagocytosis and cytoplasm to vacuole targeting in the yeast Saccharomyces cerevisiae. Complementation analysis was performed with mutants in each of these groups (aut and cvt, respectively), and three complementation groups were found to overlap. Also, most of the unique aut mutants accumulated precursor aminopeptidase I in the cytoplasm, while maintaining wild type kinetics and maturation of proteins targeted to the vacuole via the secretory pathway. The majority of the non-overlapping cvt mutants were found to be at least partially defective in autophagy. Some mutants in each group, however, appear to be only marginally affected in the other phenotype, implying that these pathways only partially overlap. We propose that import of aminopeptidase I into the vacuole shares a number of components required for bulk autophagocytosis, but is made specific, saturable, and constitutive by the presence of a receptor or other interacting protein(s).