The sociocommunicative deficit subgroup in anorexia nervosa: autism spectrum disorders and neurocognition in a community-based, longitudinal study.

BACKGROUND: A subgroup of persons with anorexia nervosa (AN) have been proposed to have sociocommunicative problems corresponding to autism spectrum disorders [ASDs, i.e. DSM-IV pervasive developmental disorders (PDDs): autistic disorder, Asperger's disorder, PDD not otherwise specified (NOS)]. Here, clinical problems, personality traits, cognitive test results and outcome are compared across 16 subjects (32%) with teenage-onset AN who meet or have met ASD criteria (AN+ASD), 34 ASD-negative AN subjects and matched controls from a longitudinal Swedish study including four waves of independent assessments from the teens to the early thirties. METHOD: The fourth wave included the Structured Clinical Interview for DSM-IV (SCID)-I and the SCID-II (cluster C, i.e. 'anxious' PDs) interviews, the Asperger Syndrome Diagnostic Interview, self-assessments by the Autism Spectrum Quotient and the Temperament and Character Inventory, neurocognitive tests by subscales from the Wechsler scales, continuous performance tests, Tower of London, and Happé's cartoons. RESULTS: The ASD assessments had substantial inter-rater reliability over time (Cohen's κ between 0.70 and 0.80 with previous assessments), even if only six subjects had been assigned a diagnosis of an ASD in all four waves of the study, including retrospective assessments of pre-AN neurodevelopmental problems. The AN+ASD group had the highest prevalence of personality disorders and the lowest Morgan-Russell scores. The non-ASD AN group also differed significantly from controls on personality traits related to poor interpersonal functioning and on neurocognitive tests. CONCLUSIONS: A subgroup of subjects with AN meet criteria for ASDs. They may represent the extreme of neurocognitive and personality problems to be found more generally in AN.

Borna disease in an adult alpaca stallion (Lama pacos).

Borna disease (BD) was diagnosed in a 2-year-old male alpaca with a history of chronic suppressed sexual desire and acute stretching convulsions. Microscopical examination of the central nervous system revealed non-purulent meningoencephalitis with mononuclear perivascular cuffing. The diagnosis was confirmed by immunohistochemistry, in-situ hybridization, polymerase chain reaction (PCR) and sequencing of PCR products and alignment with known Borna disease virus sequences. Serological screening of the herd was performed. This is the first detailed report of naturally occurring BD in alpacas.

Are stigma experiences among persons with mental illness, related to perceptions of self-esteem, empowerment and sense of coherence?

The aim of the study was to explore the relationship between stigmatizing rejection experiences and self-related variables. Our hypothesis was that rejection experiences would be negatively associated with perceptions of self-esteem, empowerment and sense of coherence. A cross-sectional study assessing rejection experiences, empowerment, sense of coherence and self-esteem was performed, including 200 persons in current or earlier contact with mental health services. The results showed that experiences of rejection were negatively associated with sense of coherence, empowerment and self-esteem. This exploratory investigation suggests that experiences of rejection might be a target for coping interventions. Mental health nurses are in a key position to identify patients' experiences of stigma and by that to understand what consequences of devaluation/discrimination can have for the afflicted.

Autistic disorders in Down syndrome: background factors and clinical correlates.

A study of a clinic-based sample of 25 individuals (12 females, 13 males; age at diagnosis 14.4 years, SD 7.4 years; age range 4 to 33 years) with Down syndrome (DS) and autism spectrum disorders, demonstrates that autism is by no means rare in DS. Results showed that there was a considerable delay in the diagnosis of autism as compared with children with autism who did not have DS. In 11 participants medical factors were identified that were likely to be of importance in contributing to the development of autism, and in four further participants there were factors of possible significance. Such factors include a history of autism or autism-related disorders in first- or second-degree relatives (n=5), infantile spasms (n=5), early hypothyroidism (n=3), evidence of brain injury after complicated heart surgery (n=2), or a combination of these factors. It is important that autism is recognised, identified, and fully assessed in individuals with DS in order for them to receive appropriate education and support.

The Asperger Syndrome (and high-functioning autism) Diagnostic Interview (ASDI): a preliminary study of a new structured clinical interview.

The development of the Asperger Syndrome (and high-functioning autism) Diagnostic Interview (ASDI) is described. Preliminary data from a clinical study suggest that inter-rater reliability and test-retest stability may be excellent, with kappas exceeding 0.90 in both instances. The validity appears to be relatively good. No attempt was made in the present study to validate the instrument as regards the distinction between Asperger syndrome and high-functioning autism.

Respiratory distress after intratracheal bleomycin: selective deficiency of surfactant proteins B and C.

Intratracheal bleomycin in rats is associated with respiratory distress of uncertain etiology. We investigated the expression of surfactant components in this model of lung injury. Maximum respiratory distress, determined by respiratory rate, occurred at 7 days, and surfactant dysfunction was confirmed by increased surface tension of the large-aggregate fraction of bronchoalveolar lavage (BAL). In injured animals, phospholipid content and composition were similar to those of controls, mature surfactant protein (SP) B was decreased 90%, and SP-A and SP-D contents were increased. In lung tissue, SP-B and SP-C mRNAs were decreased by 2 days and maximally at 4--7 days and recovered between 14 and 21 days after injury. Immunostaining of SP-B and proSP-C was decreased in type II epithelial cells but strong in macrophages. By electron microscopy, injured lungs had type II cells lacking lamellar bodies and macrophages with phagocytosed lamellar bodies. Surface activity of BAL phospholipids of injured animals was restored by addition of exogenous SP-B. We conclude that respiratory distress after bleomycin in rats results from surfactant dysfunction in part secondary to selective downregulation of SP-B and SP-C.

Ten-year follow-up of adolescent-onset anorexia nervosa: psychiatric disorders and overall functioning scales.

The aim of this study was to assess prospectively the long-term outcome in a representative sample of teenage-onset anorexia nervosa (AN) in respect of psychiatric disorders and overall outcome. Fifty-one AN cases, recruited by community screening, with a mean age of onset of 14 years, was contrasted with 51 matched comparison cases at a mean age of 24 years (10 years after AN onset). All 102 cases had been examined at ages 16 and 21 years. At 24 years all probands were interviewed regarding psychiatric disorders (SCID-I) and overall outcome (Morgan-Russell assessment schedule, the GAF). There were no deaths at 10-year follow-up. One in four in the AN group had a persisting eating disorder (ED), including three who still had anorexia nervosa. Lifetime diagnoses of affective disorders and obsessive-compulsive disorder were over-represented in the AN group. Outcome according to Morgan-Russell was poor in 27%, intermediate in 29%, and good in 43%. According to the GAF, half the AN group had a poor psychosocial functioning. These were subjects with either a persisting ED or lifelong problems with social interaction or obsessive-compulsive behaviour. Ten-year outcome of teenage-onset AN is favourable in the majority of cases; most individuals have recovered from their ED and have no other axis I disorder. However, half the AN group reported poor psychosocial outcome, in most cases explained by a persisting ED or chronic obsessive-compulsive behaviour/social interaction problems.

Autistic spectrum disorders in Möbius sequence: a comprehensive study of 25 individuals.

The prevalence of autistic disorder was analysed in 25 individuals with Möbius sequence, a disorder with brain-stem dysfunction. The sample consisted of 18 males and seven females (20 participants were aged 2 to 22 years, and five were aged 1, 19 and 23 months, and 55 years old). Participants were recruited after a nationwide call and were part of a multidisciplinary study of individuals with Möbius sequence. They were given a meticulous neuropsychiatric examination including standardized autism diagnostic interviews. Ten individuals had an autistic spectrum disorder. Six of these met all diagnostic criteria for autism. In 23 individuals cognitive development could be assessed. Eight of those 23 patients had clear learning disability and six individuals were functioning in the normal but subaverage range. Autistic spectrum disorder and learning disability occurred in more than a third of the examined patients. Considering the hospital-based nature of the sample, these findings may be overestimates. Nevertheless, awareness of this coexistence is important in the diagnosis and habilitation care of children with Möbius sequence. Moreover, the results provide further support for the notion of a subgroup of autistic spectrum disorders being caused by first trimester brain-stem damage.

Regional cerebral blood flow in weight-restored anorexia nervosa: a preliminary study.

Twenty-one individuals (19 females, two males) with teenage-onset anorexia nervosa (AN), 19 of whom were weight restored, were assessed using single-photon emission computed tomography (SPECT) 7 years after onset of AN, at a mean age of 22 years. For comparison we recruited a younger group without neuropsychiatric disorder (mean age 9:8 years; five females, four males) who underwent SPECT at follow-up after an operation for coarctation of the aorta or because of lymphatic leukaemia. Ethical considerations precluded the study of regional cerebral blood flow (rCBF) in participants with completely normal development. The group with AN showed marked hypoperfusion of temporal, parietal, occipital, and orbitofrontal lobes compared to the contrast group. rCBF was not correlated to body mass index in any of the groups. Results suggest that, even long after re-feeding has occurred, AN may be associated with moderate to severe cerebral blood flow hypoperfusion in the temporoparietal (or temporoparietooccipital) region and in the orbitofrontal region. A limitation of the study is that the young contrast group in this study could be expected to have a higher global rCBF than the group with AN. However, this should not significantly affect the relative values used in this study.

Depressive disorders in teenage-onset anorexia nervosa: a controlled longitudinal, partly community-based study.

The study objective was to examine the prevalence and course of depressive disorders (DDs) in teenage-onset anorexia nervosa (AN) over a period of 10 years. Fifty-one adolescents with AN and a sex- and age-matched control group (n = 51) were assessed at ages 16, 21, and 24 years. Probands and controls were examined in depth using semistructured and structured interviews. Their parents were interviewed on the occasion of the first examination. DDs were assessed using DSM-III-R criteria. Subjects with AN had a greatly increased rate of DDs (85%) of all kinds and at all ages as compared with control subjects. The risk of DD during the follow-up period from 21 up to and including 24 years could be predicted by diagnostic group status and the presence of DD during the period from 16 to 21 years, while the risk of DD during the follow-up period from 16 up to and including 21 years was solely predicted by the presence of AN at age 16 years. Long-term resolution of the eating disorder (ED) was associated with the absence of mood disorder or vice versa. Bipolar disorder (BP) occurred at roughly the expected rate (11%) among subjects (probands and controls) with major depression (MDD). In conclusion, depression is a very common comorbid problem in AN: more than four of five individuals with teenage-onset AN had at least one episode of DSM-III-R depression (MD or dysthymia [DT]) within 10 years after onset of the ED. AN appears to trigger the first episode of depression, but once it is manifest, depression predicts further depressive episodes.

Ten-year follow-up of adolescent-onset anorexia nervosa: physical health and neurodevelopment.

To study the development of physical health and some neuromotor functions in anorexia nervosa (AN) 51 individuals (48 females, three males) with a mean AN onset of 14 years, recruited after community screening, were followed prospectively together with 51 age-, sex-, and school-matched individuals without AN (controls). About 10 years after AN onset, all individuals were examined in respect of physical health and neurodevelopment. There were no deaths. Weight and height had normalised, except in three participants with persistent AN. Significantly more participants with AN had a physical complaint/disorder, including hirsutism. This might be a long-term complication in weight restored AN. Dysdiadochokinesis occurred almost exclusively among individuals with former AN in accordance with our previous studies.

Acetaminophen alters estrogenic responses in vitro: inhibition of estrogen-dependent vitellogenin production in trout liver cells.

The purpose of this study was to determine if acetaminophen altered estrogen-dependent vitellogenin production in isolated trout liver cells. Estrogen-induced vitellogenesis was studied in liver cells isolated from male trout and cultured in defined medium; vitellogenin secreted into culture medium was quantitated using immunological procedures. Vitellogenin production was absolutely dependent on the addition of estradiol (10(-6) M) to liver cells from male trout. Acetaminophen produced a dose-dependent inhibition of vitellogenin production; approximately 50% inhibition was achieved with 0.05 mM acetaminophen, while 0.3 mM acetaminophen inhibited secreted vitellogenin to undetectable levels. In contrast, these concentrations of acetaminophen (< or = 1 mM) did not significantly alter the production of secreted albumin, determined immunologically, or cause detectable toxicity. Higher doses of acetaminophen were toxic, but did not induce DNA fragmentation in the trout liver cells. Acetaminophen reduction of estradiol-induced vitellogenin production was accompanied by a dose-dependent decrease in vitellogenin mRNA, indicating acetaminophen inhibited a step prior to, or during, formation of vitellogenin mRNA. Estrogen receptor-binding assays demonstrated that acetaminophen did not reduce binding of [3H]-estradiol to trout liver estrogen receptor. In addition, catabolism of estradiol to water-soluble metabolites was not significantly altered by acetaminophen. These studies indicate that non-toxic concentrations of acetaminophen specifically inhibit estrogen-dependent vitellogenin synthesis and suggest that this commonly used drug may alter estrogen-regulated processes.

No preferential parent of origin for the isochromosome 17q in childhood primitive neuroectodermal tumor (medulloblastoma).

We have shown that an i(17q) is the most frequent abnormality in central nervous system primitive neuroectodermal tumors (PNETs; medulloblastoma), implicating the presence of a tumor suppressor gene which maps to 17p. In the present study, we investigated whether the deletion of chromosome arm 17p that results from the formation of the i(17q) is preferentially of maternal or paternal origin. Eight cases of primary PNETs of the posterior fossa were examined at five polymorphic loci which map to 17p13. Two or three informative loci were detected in each family. Of the eight cases, four tumors evidenced loss of the paternal allele for loci on 17p13 and four tumors demonstrated maternal deletions. Although the number of cases is relatively small, these studies do not implicate the loss of an imprinted gene as a mechanism for tumorigenesis in children with central nervous system PNETs/medulloblastoma.

Acetaminophen toxicity in cultured trout liver cells. I. Morphological alterations and effects on cytochrome P450 1A1.

To better characterize the hepatotoxicity of acetaminophen, the effects of this drug were investigated on isolated liver cells from a species relatively resistant to acetaminophen toxicity, rainbow trout. At high concentrations of acetaminophen (2-10 mM), pathologic effects were detected, including loss of lactate dehydrogenase from cells, disruption of cell-cell aggregation, cell death, and distinctive alterations in cell morphology, as demonstrated by light and electron microscopic examination. Most striking was the acetaminophen-induced rearrangement of mitochondria, which were clustered adjacent to the nucleus and rarely seen at cell periphery. The endoplasmic reticulum was also altered by acetaminophen treatment. In the middle portion of the cytoplasm, parallel arrays of endoplasmic reticulum cisternae were abundant; however, the peripheral cytoplasm was restricted to vesicular profiles of endoplasmic reticulum. Although nuclei in acetaminophen-treated cells displayed peripheral heterochromatin aggregation, acetaminophen did not produce detectable DNA fragmentation, in contrast to effects reported for mouse liver cells. Thus DNA fragmentation does not appear to be required for acetaminophen to manifest cytotoxic effects. In addition, immunohistochemical studies indicated that toxic concentrations of acetaminophen which altered the endoplasmic reticulum helped maintain cytochrome P450 1A1 in liver cells from beta-naphthoflavone-induced trout.

Obesity-induced hypertension in the dog.

To study the relationship between body weight and blood pressure, we have developed an animal model of obesity-induced hypertension. Nine adult mongrel dogs were chronically instrumented with aortic and vena caval catheters. After a 2-week control period, all dogs were made to gain weight by adding 2 lb/day of beef fat to their diet for 5 weeks. Blood pressure, heart rate, and body weight were measured daily before the addition of dietary fat, during the 5 weeks of the high fat diet, and for 6 weeks after the fat supplement was stopped. Plasma volume and cardiac output were measured prior to and after 5 weeks of the fat diet. During the 5-week high fat diet, the dogs' body weight increased from 22.2 +/- 2.1 to 27.4 +/- 3 kg (p less than 0.001); mean blood pressure increased from 90 +/- 5 to 112 +/- 6 mm Hg (p less than 0.01); and heart rate increased from 70 +/- 7 to 85 +/- 5 beats/min (p less than 0.05). Blood pressure, heart rate, and body weight returned to near control values after the fat diet was stopped. Over the 5-week fat diet, the dogs' plasma volume increased from 920 +/- 130 to 1059 +/- 195 ml (p less than 0.05); cardiac output increased from 2.5 +/- 0.4 to 3.1 +/- 0.3 L/min (p less than 0.05); and systemic vascular resistance increased from 35.3 +/- 8 to 38.9 +/- 9 mm Hg/L/min (p less than 0.1). Weight gain in the dogs was also associated with hyperinsulinemia and insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)