Neurobehavioral disinhibition in childhood predicts early age at onset of substance use disorder

OBJECTIVE: This longitudinal study had three aims: 1) determine the extent to which boys at high average risk and low average risk for substance use disorder differ on a construct of neurobehavioral disinhibition, 2) evaluate the capacity of neurobehavioral disinhibition to predict substance use frequency at age 16, and 3) demonstrate the utility of neurobehavioral disinhibition in predicting substance use disorder. METHOD: The authors derived an index of neurobehavioral disinhibition from measures of affect, behavior, and cognition. The neurobehavioral disinhibition score was used to discriminate youth at high and low average risk for substance use disorder and to predict substance use frequency after 4-6 years and substance use disorder after 7-9 years. RESULTS: The neurobehavioral disorder score significantly discriminated boys at high average risk from those at low average risk at ages 10-12. Neurobehavioral disinhibition at age 16, in conjunction with substance use frequency and risk status group, predicted substance use disorder at age 19 with 85% accuracy and accounted for 50% of the variance in Drug Use Screening Inventory overall problem density score. Neurobehavioral disinhibition was a stronger predictor of substance use disorder (odds ratio=6.83) than substance consumption frequency (odds ratio=3.19). CONCLUSIONS: Cross-sectional and longitudinal analyses indicated that neurobehavioral disinhibition is a component of the liability to early age at onset of substance use disorder.     

Effects of alcohol dependence comorbidity and antipsychotic medication on volumes of the thalamus and pons in schizophrenia

OBJECTIVE: Postmortem and in vivo brain imaging studies have identified abnormalities in the thalamus and the pons in both schizophrenia and alcoholism. The authors sought to determine whether patients with both schizophrenia and alcohol dependence would manifest exaggerated volume deficits in either structure. METHOD: Volumetric measures of the left and right thalamus and the pons were derived from magnetic resonance imaging scans obtained from 27 patients with schizophrenia, 19 patients with schizophrenia and comorbid alcohol dependence, 25 patients with alcohol dependence without comorbid axis I disorders, and 51 healthy comparison subjects. RESULTS: The alcohol-dependent patients had significant volume deficits in both the thalamus and the pons. Among patients with schizophrenia, there were no differences in thalamus volumes between those with and without comorbid alcohol dependence. However, patients with schizophrenia who were taking atypical antipsychotic medications had bilateral thalamic deficits, whereas those taking typical neuroleptics did not. Patients with schizophrenia and comorbid alcohol dependence had deficits in the pons. CONCLUSIONS: Patients with schizophrenia and comorbid alcohol dependence are at risk for alcohol-related reduction of pontine structures that are not necessarily affected by schizophrenia per se. The effect of alcohol dependence on the thalamus in schizophrenic patients may be mitigated by the type of neuroleptic medication they receive.     

Mild disorders should not be eliminated from the DSM-V

BACKGROUND: High prevalence estimates in epidemiological surveys have led to concerns that the DSM system is overly inclusive and that mild cases should be excluded from future DSM editions. OBJECTIVE: To demonstrate that the DSM-III-R disorders in the baseline National Comorbidity Survey (NCS) can be placed on a severity gradient that has a dose-response relationship with outcomes assessed a decade later in the NCS follow-up survey (NCS-2) and that no inflection point exists at the mild severity level. METHODS: The NCS was a nationally representative household survey of DSM-III-R disorders in the 3-year time span 1990-1992. The NCS-2 is a follow-up survey of 4375 NCS respondents (76.6% conditional response rate) reinterviewed in 2000 through 2002. The NCS-2 outcomes include hospitalization for mental health or substance disorders, work disability due to these disorders, suicide attempts, and serious mental illness. RESULTS: Twelve-month NCS/DSM-III-R disorders were disaggregated into 3.2% severe, 3.2% serious, 8.7% moderate, and 16.0% mild case categories. All 4 case categories were associated with statistically significantly (P<.05, 2-sided tests) elevated risk of the NCS-2 outcomes compared with baseline noncases, with odds ratios of any outcome ranging monotonically from 2.4 (95% confidence interval, 1.6-3.4) to 15.1 (95% confidence interval, 10.0-22.9) for mild to severe cases. Odds ratios comparing mild to moderate cases were generally nonsignificant. CONCLUSIONS: There is a graded relationship between mental illness severity and later clinical outcomes. Retention of mild cases in the DSM is important to represent the fact that mental disorders (like physical disorders) vary in severity. Decisions about treating mild cases should be based on cost-effectiveness not current severity. Cost-effectiveness analysis should include recognition that treatment of mild cases might prevent a substantial proportion of future serious cases.     

Myelopathy due to copper deficiency following gastrointestinal surgery

BACKGROUND: Ataxic myelopathy due to copper deficiency has been described in ruminant animals and is called swayback. Neurological manifestations due to inherited copper deficiency secondary to the failure of intestinal copper absorption is well recognized as Menkes disease. The neurological consequences of acquired copper deficiency in humans are not well described. OBJECTIVE: To report 2 cases where patients developed a myelopathy with copper deficiency after gastrointestinal surgery.Patients Two patients developed a myelopathy many years after gastrointestinal surgery. Both had severe copper deficiency, which was the likely cause of the myelopathy. CONCLUSIONS: Acquired copper deficiency may present as a myelopathy. Gastrointestinal surgery and resulting decreased copper absorption may be causative.     

The Dental Cognitions Questionnaire in CBT for dental phobia in an adolescent with multiple phobias

A case of an adolescent boy with multiple phobias who was treated successfully for his dental phobia is described to illustrate the clinical utility of the Dental Cognitions Questionnaire (DCQ) in aiding effective cognitive-behavior therapy. The client showed drops in dental anxiety that coincided with the use of the DCQ in cognitive restructuring, and there was a close correlation between dental cognitions and degree of dental anxiety over the time-course of therapy and follow up.     

Antipsychotic drug interactions with specific [3H]ketanserin binding sites in membrane fragments derived from human prefrontal cortex and human amygdala

Two regions of the brain potentially significant for psychopathology in schizophrenia are the prefrontal cortex and the amygdala. Antipsychotic compounds bind at serotonin receptors in human prefrontal cortex. We hypothesized that the serotoninergic antagonist [3H]ketanserin would label similar sets of binding sites in these two brain regions. Further, we hypothesized that all antipsychotic compounds would show appreciable affinity for binding sites labeled by [3H]ketanserin in the prefrontal cortex. Our findings indicate some differences in [3H]ketanserin binding between prefrontal cortex and amygdala. We also observed that several antipsychotic compounds had very high affinity for the [3H]ketanserin binding sites in prefrontal cortex.     

Pyridoxine-dependent seizures and cognition in adulthood

A case report of neonatal onset pyridoxine-dependent seizures in a male patient with early diagnosis and treatment is presented. The patient's epilepsy was recognized and treated with pyridoxine (vitamin B6) within 8 hours of birth. Treatment has been nearly continuous since that time. This paper reports the results of a full neuropsychological evaluation at age 37 years and MRI completed at age 31 years. Consistent with other case reports in the literature, there was a significant Performance IQ (PIQ) advantage with decreased Verbal IQ (VIQ) and expressive language skills (Full-Scale IQ 71, VIQ 64, PIQ 85). MRI demonstrated characteristic thinning of the posterior corpus callosum. This report provides an example of early treatment that nonetheless results in a mild mental retardation. The similarity of the structural changes on MRI and the cognitive profile of this patient to those of others reported in the literature suggest that the underlying mechanism for both may be the same.     

Connexin immunoreactivity in glial cells of the rat retina

The rat retina contains two types of macroglial cells, Müller cells, radial glial cells that are the principal macroglial cells of vertebrate retinas, and astrocytes associated with the surface vasculature. In addition to the often-described gap-junctional coupling between astrocytes, coupling also occurs between astrocytes and Müller cells. Immunohistochemistry and confocal microscopy were used to identify connexins in the retinas of pigmented rats. Several antibodies directed against connexin43 stained astrocytes, identified using antibodies directed against glial fibrillary acidic protein (GFAP). In addition, two connexin43 antibodies stained Müller cells, identified with antibodies directed against S100 or glutamine synthetase. Connexin30-immunoreactive puncta were confined to the vitreal surface of the retina and colocalized with GFAP-immunoreactive astrocyte processes. Connexin45 immunoreactivity was associated with both astrocytes and Müller cells. We conclude that retinal glial cells express multiple connexins, and the patterns of immunostaining that we observe in this study are consistent with the expression of connexins30, -43, and possibly -45 by astrocytes and the expression of connexins43 and -45 by Müller cells. As gap-junction channels may be formed by both homotypic and heterotypic hemichannels, and the hemichannels may themselves be homomeric or heteromeric, there exists a multitude of possible gap-junction channels that could underlie the homotypic coupling between retinal astrocytes and the heterotypic coupling between astrocytes and Müller cells.     

Mercapturate metabolism of 4-hydroxy-2-nonenal in rat and human cerebrum

4-Hydroxy-2-nonenal (HNE), a potent toxin formed in the brain from oxidation of polyunsaturated fatty acids, is increased in Alzheimer disease (AD), where it is a proposed effector of amyloid beta peptide-mediated neurotoxicity. Detoxification of HNE via the mercapturic acid pathway (MAP) is the primary means by which other organs, such as liver, limit its toxic effects. Here we examined the distribution and activity of MAP detoxification for HNE in cerebrum. Our results showed that rat cerebral cortex and especially synaptosomes were less well equipped to detoxify HNE via the MAP than liver. Glutathione transferases (GSTs) catalyze the committed step in the MAP; GST-mu and GST-pi, but not OST-alpha, were detected in neurons and astrocytes in cerebrum from AD patients and controls. MAP activity in frontal cortex of AD patients was modestly but significantly increased compared to controls. These data suggest that lipid peroxidation may present a greater toxic burden to cerebrum than to other organs, and that a component of response to injury in late stage AD is a slight increase in MAP activity.     

Support for bereaved owners of pets

TOPIC: The bond that exists between people and their pets and its impact on physical and mental health. PURPOSE: To review the current literature and explore the clinical implications of bereavement related to pets. SOURCES: A comprehensive review of the bereavement, veterinarian, and agricultural literature related to attitudes and response patterns to pet and animal death. CONCLUSIONS: The death or loss of a beloved pet can be a life-changing event.