Autosomal recessive spinocerebellar ataxia and peripheral neuropathy with raised α-fetoprotein

We describe three patients from two families with progressive spinocerebellar ataxia, peripheral neuropathy, raised alpha-fetoprotein (AFP) and hypercholesterolaemia. Two siblings had identical clinical features, with late childhood onset of symptoms and slow progression, requiring crutches to walk at ages 37 and 38 years. Another patient developed ataxia aged 13 years and became wheel-chair bound by 20 years of age. Although they all had raised serum AFP levels, their clinical, immunological, biochemical, cytogenetic and molecular genetic studies failed to support a diagnosis of Ataxia Telangiectasia. Extensive investigation including imaging, biochemical and genetic studies excluded other known ataxias. Their clinical features most closely resemble the phenotype of a single consanguineous Japanese family with four individuals affected by spinocerebellar ataxia, peripheral neuropathy, raised AFP and hypercholesterolaemia. Homozygosity mapping has identified a locus in this Japanese family at 9q34. Haplotype analysis of our cases demonstrated possible linkage to 9q34, suggesting these may be the first Caucasian families described with this disorder.     

Life events and trauma in chronic negligent mothers

The present study examines more closely the chronic behaviors of maltreating mothers. Events that these mothers have experienced during childhood are examined, experiences including abuse, placement, separation, bereavement, rejection, neglect, lack of love and role reversal. Signs of unresolved trauma found in the discourse of mothers, such as dissociation, are also studied. It is proposed that negligent mothers from the chronic group will evoke more negative experiences and/or more intense negative experiences which occurred during childhood than the mothers from the transitory group. The chronic group will also show more signs of dissociation. From a six years follow-up study, a sample of 20 mothers was recruited from the Child Protection Services, including the cases of 10 chronic maltreating mothers and 10 transitory maltreating mothers. Two main measures were used: the Child Abuse Potential Inventory (CAPI) and the Adult Attachment Interview (AAI) (Main et Goldwyn, 1998). The experiences from childhood and complete discourse in AAI were analysed with the method used by Main et Goldwyn (1998). Non parametric analysis indicate that mothers from the chronic group evoke more negative and very negative childhood experiences than the mothers from the transitory group. Content analysis show that chronic maltreating mothers relate having gone through more potentially traumatic events such as foster care placements, separations and abuse. The analysis of the Adult Attachment Interview according to Main and Goldwyn's system demonstrate that the majority of the chronic maltreating mothers have two times more unresolved traumas.     

The psychosocial outcome of pregnancy in women with psychotic disorders

OBJECTIVE: To investigate the psychosocial outcome of pregnancies in women with a history of psychotic disorder in an epidemiologically representative sample and to determine the predictors of having a baby looked after by social services in the first year of life. METHOD: Historical matched controlled cohort study and nested case control study using the General Practice Research Database (GPRD), an anonymised primary care database, in women with a history of psychotic disorders who gave birth in 1996-1998 (199 cases and 787 controls). RESULTS: Twenty-seven percent of cases had a psychotic episode and a further 38% had nonpsychotic depression in the first year after birth. Women with nonaffective psychoses were at a significantly higher risk of postnatal depression compared with controls (adjusted rate ratio 2.07, 95% CI 1.45-2.96, p<0.001). Cases were well supported with 72% in a cohabiting relationship and only 38% on benefits. The only significant predictor of parenting difficulties was recent contact with psychiatric services. CONCLUSIONS: Women with a history of psychotic disorder are at high risk of psychiatric illness postpartum, particularly a twofold risk of postnatal depression, even if they have not been in contact with psychiatric services during pregnancy. However, this epidemiologically representative sample has better parenting outcomes than has been previously reported for specialist treated cases. Liaison between all professionals involved in the care of mothers with psychotic disorders during and after pregnancy is essential to optimise care for them and their families.     

A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction

OBJECTIVES: Even when euthymic bipolar disorder patients can have persistent deficits in working memory, but the neural basis of this deficit remains unclear. We undertook an functional magnetic resonance imaging investigation of euthymic bipolar disorder patients performing two working memory paradigms; the two-back and Sternberg tasks, selected to examine the central executive and the phonological loop respectively. We hypothesized that neuronal dysfunction would be specific to the network underlying the executive rather than the phonological loop component of working memory. METHODS: Twelve right-handed euthymic bipolar I males receiving lithium carbonate monotherapy were matched with 12 controls. The two-back task comprised a single working memory load contrasted with baseline vigilance condition. The Sternberg paradigm used a parametric design incorporating variable working memory load with fixed delay between presentation of an array of items to be remembered and a target item. Functional activation data were acquired during performance of the tasks and were analysed to produce brain activation maps representing significant group differences in activation (ANOVA). Load-response curves were derived from the Sternberg task data set. RESULTS: There were no significant between-group differences (t-test) in performance of the two-back task, or in 2 x 5 group by memory load ANOVA for the performance data from Sternberg task. In the two-back task, compared with controls bipolar disorder patients showed reductions in bilateral frontal, temporal and parietal activation, and increased activations with the left precentral, right medial frontal and left supramarginal gyri. No between-group differences were observed in the Sternberg task at any working memory load. CONCLUSIONS: Our findings support the notion that, in euthymic bipolar disorder, failure to engage fronto-executive function underpins the core neuropsychological deficits.     

Neuronal nitric oxide synthase expression in cerebellar mutant mice

Nitric oxide (NO) is a diffusible, multifunctional signaling molecule found in many areas of the brain. NO signaling is involved in a wide array of neurophysiological functions including synaptogenesis, modulation of neurotransmitter release, synaptic plasticity, central nervous system blood flow and cell death. NO synthase (NOS) activity regulates the production of NO and the cerebellum expresses high levels of nitric oxide synthase (NOS) in granule, stellate and basket cells. Cerebellar mutant mice provide excellent opportunities to study changes of NO/NOS concentrations and activities to gain a greater understanding of the roles of NO and NOS in cerebellar function. Here, we have reviewed the current understanding of the functional roles of NO and NOS in the cerebellum and present NO/NOS activities that have been described in various cerebellar mutant mice and NOS knockout mice. NO appears to exert neuroprotective effects at low to moderate concentrations, whereas NO becomes neurotoxic as the concentration increases. Excessive NO production can cause oxidative stress to neurons, ultimately impairing neuronal function and result in neuronal cell death. Based on their genetics and cerebellar histopathology, some of cerebellar mutant mice display similarities with human neurological conditions and may prove to be valuable models to study several human neurological disorders, such as autism and schizophrenia.     

Spinal muscular atrophy

Spinal muscular atrophy is a common genetic disease of the motor neuron (frequency of eight cases per 100,000 live births) with a high mortality during infancy and no known treatment. Death is caused by severe and progressive restrictive lung disease. New information regarding the nature and function of the SMN protein and the availability of new pharmacologic agents now make it possible to consider clinical trials in this disease. Rehabilitation and proper management of medical complications have improved both the quality and duration of life for children with spinal muscular atrophy.     

Clinical efficacy of metal stents for the treatment of focal abdominal aortic stenosis

Seven patients (four women and three men) who underwent primary stenting of infrarenal abdominal aortic stenosis over a 4-year period are reported. The patients ranged between 44 and 77 years of age. All were referred for treatment of disabling claudication. Self-expanding stents with balloon assistance were used. A single complication, a retroperitoneal haematoma, requiring surgical intervention occurred in one patient. Patients had either complete resolution of symptoms (five of seven) or a substantial decrease in their claudication symptoms. Primary stenting is a safe and effective treatment for severe abdominal aortic stenosis.     

Improving access to geriatric mental health services: a randomized trial comparing treatment engagement with integrated versus enhanced referral care for depression, anxiety, and at-risk alcohol use

OBJECTIVE: The authors sought to determine whether integrated mental health services or enhanced referral to specialty mental health clinics results in greater engagement in mental health/substance abuse services by older primary care patients. METHOD: This multisite randomized trial included 10 sites consisting of primary care and specialty mental health/substance abuse clinics. Primary care patients 65 years old or older (N=24,930) were screened. The final study group consisted of 2,022 patients (mean age=73.5 years; 26% female; 48% ethnic minority) with depression (N=1,390), anxiety (N=70), at-risk alcohol use (N=414), or dual diagnosis (N=148) who were randomly assigned to integrated care (mental health and substance abuse providers co-located in primary care; N=999) or enhanced referral to specialty mental health/substance abuse clinics (i.e., facilitated scheduling, transportation, payment; N=1,023). RESULTS: Seventy-one percent of patients engaged in treatment in the integrated model compared with 49% in the enhanced referral model. Integrated care was associated with more mental health and substance abuse visits per patient (mean=3.04) relative to enhanced referral (mean=1.91). Overall, greater engagement was predicted by integrated care and higher mental distress. For depression, greater engagement was predicted by integrated care and more severe depression. For at-risk alcohol users, greater engagement was predicted by integrated care and more severe problem drinking. For all conditions, greater engagement was associated with closer proximity of mental health/substance abuse services to primary care. CONCLUSIONS: Older primary care patients are more likely to accept collaborative mental health treatment within primary care than in mental health/substance abuse clinics. These results suggest that integrated service arrangements improve access to mental health and substance abuse services for older adults who underuse these services.     

Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior

BACKGROUND: Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability. Attempts at rehabilitation have had circumscribed effects on cognition, without concurrent improvement in broad aspects of behavior and adjustment. OBJECTIVE: To determine the differential effects of cognitive enhancement therapy (a recovery-phase intervention) on cognition and behavior compared with state-of-the-art enriched supportive therapy. DESIGN: A 2-year, randomized controlled trial with neuropsychological and behavioral assessments completed at baseline and at 12 and 24 months. SETTING: An outpatient research clinic housed in a medical center's comprehensive care service for patients with severe mental illness. PATIENTS: A total of 121 symptomatically stable, non-substance-abusing but cognitively disabled and chronically ill patients with schizophrenia or schizoaffective disorder. INTERVENTIONS: Cognitive enhancement therapy is a multidimensional, developmental approach that integrates computer-assisted training in neurocognition with social cognitive group exercises. Enriched supportive therapy fosters illness management through applied coping strategies and education. MAIN OUTCOME MEASURES: Six highly reliable summary measures--Processing Speed, Neurocognition, Cognitive Style, Social Cognition, Social Adjustment and Symptoms--were tested using analysis of covariance and linear trend analysis. RESULTS: At 12 months, robust cognitive enhancement therapy effects were observed on the Neurocognition and Processing Speed composites (P<.003), with marginal effects observed on the behavioral composites. By 24 months, differential cognitive enhancement therapy effects were again observed for the 2 neuropsychological composites and for Cognitive Style (P=.001), Social Cognition (P=.001), and Social Adjustment (P=.01). As expected, no differences were observed on the residual Symptoms composite. Effects were unrelated to the type of antipsychotic medication received. Enriched supportive therapy also demonstrated statistically significant within-group effect sizes, suggesting that supportive psychotherapy can also have positive, although more modest, effects on cognitive deficits. CONCLUSION: Many cognitive deficits and related behaviors of patients with stable schizophrenia are improved when sufficient exposure to relevant rehabilitation is provided.