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PubMed1977

A study of predictive factors in depressive disorders of poor outcome.

A retrospective comparison was made between two groups, each consisting of 30 depressed patients, one in which the outcome following discharge had been good, the other where it had been poor. A previous psychiatric history, earlier admission for psychiatric illness, particularly for affective disorders and a poorer performance on routine intelligence tests were found in the poor prognosis group. In this group the duration of the index admission was longer and the condition of the patient was less improved at the time of discharge. Several symptom variables also discriminated between the groups. These findings are discussed.

Age Factors↗
PubMed2004

Behavioral and neuroendocrine changes during mental stress and repeated treatment with antidepressants in healthy men.

Excessive stress loadings in daily life are believed to play a role in the development of affective disorders. Our recent finding of enhanced neuroendocrine activation during stress of hypoglycemia after repeated antidepressant treatment in healthy men supports the hypothesis that the clinical effects of antidepressant treatment may be partly due to the adjustment of the stress response, which was reported to be blunted in depressive patients. The present double-blind placebo-controlled study investigated the effects of 6 days of treatment with the antidepressants citalopram or tianeptine on neuroendocrine activation during mental stress. Blood pressure, heart rate, and salivary cortisol values were measured. The stress procedure, lasting 17 min, consisted of a short intelligence test followed by the Stroop word-color interference test. Citalopram treatment was associated with a significant enhancement of stress-related increase in systolic and diastolic blood pressure. No differences were observed in the heart rates and salivary cortisol. Comparisons based on cluster analysis revealed that subjects with poor performance in the Stroop test displayed a significantly lower rise of systolic and diastolic blood pressure values after the stress procedure and lower prestress cortisol levels in saliva when compared to the good performing subjects. Our findings show that antidepressant treatment can enhance the neuroendocrine response also during mental stress, and suggest that mental performance during stress is related to the pattern of cardiovascular and adrenocortical activation.

Adult↗
PubMed1991

Comparison of neuropsychologic functioning and clinical indicators of neurotoxicity in long-term survivors of childhood leukemia given cranial radiation or parenteral methotrexate: a prospective study.

We prospectively compared neuropsychologic functioning and clinical indicators of neurotoxicity in 49 consecutive childhood leukemia patients in long-term continuous complete remission (CR) who had received two different regimens of CNS prophylaxis by random assignment. Twenty-three patients were treated with 1,800 cGy cranial radiation and intrathecal methotrexate (RT group) and 26 with parenteral methotrexate only (MTX group). Over half of the RT group had somnolence syndrome, and four developed cerebral calcifications late in their clinical course. Abnormal electroencephalograms (EEGs) were seen in 15 patients in the MTX group, and six had early, transient white-matter hypodensities apparent on computed tomographic (CT) scans. Mean scores on standard tests of intelligence and academic achievement, administered after remission induction and again at a median of 6 years after treatment cessation, did not differ significantly between the two groups. However, statistically significant decreases in overall and verbal intelligence quotients (IQs) and in arithmetic achievement were found within both treatment groups. Sixteen of 26 in the MTX group and 14 of the 23 in the RT group had clinically important decreases (greater than or equal to 15 points) on one or more neuropsychologic measures. These changes did not correlate with findings on CT scans, EEGs, or other clinical signs of neurotoxicity. We conclude that 1,800 cGy cranial radiation and parenteral methotrexate, as used in this study, are associated with comparable decreases in neuropsychologic function.

Adolescent↗
PubMed2006

Comparison of long-term neurocognitive outcomes in young children with acute lymphoblastic leukemia treated with cranial radiation or high-dose or very high-dose intravenous methotrexate.

PURPOSE: Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established. PATIENTS AND METHODS: Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m2 x 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m2 x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory. RESULTS: Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures. CONCLUSION: Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.

Antimetabolites, Antineoplastic↗
PubMed2003

Cerebral energy metabolism in phenylketonuria: findings by quantitative In vivo 31P MR spectroscopy.

Both severe impairments of brain development in untreated infants and acute reversible neurotoxic effects on brain function are clinical features of phenylketonuria (PKU). For determining whether impairments of cerebral energy metabolism play a role in the pathophysiology of PKU, quantitative in vivo 31P magnetic resonance spectroscopy (MRS) was performed in a supratentorial voxel of 11 adult PKU patients and controls. Peak areas of inorganic phosphate; phosphocreatine; alpha-, beta-, and gamma-ATP; NAD; phosphomonoesters; phosphodiesters; and a broad phospholipid signal were converted to millimolar concentrations. Mg2+, pH, ADP, the phosphorylation potential, and the relative velocity of oxidative metabolism V/Vmax were derived. Clinical evaluation included mutation analysis, neurologic investigation, intelligence testing, magnetic resonance imaging, and concurrent plasma and brain phenylalanine (Phe), the last by 1H-MRS. Phe loading was performed in five patients with an oral dose of 100 mg/kg body wt L-Phe monitored by spectral EEG analysis. Under steady-state conditions, 31P-MRS revealed normal values for ATP, phosphocreatine, NAD, phosphomonoesters, phosphodiesters, Mg2+, and pH in PKU. ADP (+11%) and the phosphorylation potential (+22%) were increased. Peak areas of inorganic phosphate (-22%) and phospholipid (-8%) were decreased. ADP correlated with concurrent plasma (r = 0.65) and brain (r = 0.55) Phe. During the Phe load, blood Phe levels increased steeply. EEG revealed slowing of background activity. The phosphorylation potential decreased, whereas ADP and V/Vmax increased. In vivo 31P-MRS demonstrated subtle abnormalities of cerebral energy metabolism in PKU in steady-state conditions that were accentuated by a Phe load, indicating a link between Phe neurotoxicity and imbalances of cerebral energy metabolism.

Adult↗
PubMed2002

Behavioral inhibition, self-regulation of motivation, and working memory in children with attention deficit hyperactivity disorder.

We examined 3 aspects of Barkley's (1997) recent model of Attention Deficit Hyperactivity Disorder (ADHD)--behavioral inhibition, self-regulation of motivation, and working memory utilizing 152 elementary school children ages 7 to 12. Seventy-six children with ADHD and 76 children without a psychiatric diagnosis completed the stop-signal task, a computerized Digit Span Task requiring concurrent storage and processing, and the Kaufman Brief Intelligence Test during a 1-hr testing session. Parent and teacher ratings were also obtained on the Conners Parent Rating Scale-Revised: Long Version (Conners, 1997), and the Conners Teacher Rating Scale-Revised: Long Version (Conners, 1997), respectively. Results indicated that children with ADHD had deficits in inhibitory control, working memory, and short-term memory relative to children without the disorder. Contrary to our prediction, the groups did not differ in their responsiveness to external reinforcement. In addition, children with and without ADHD had similar self-perceptions of their performances during the experimental session. Future directions for specifying childhood difficulties in inhibitory control and memory processes are discussed.

Arousal↗
PubMed2002

Cognitive development in school-age children with vertically transmitted HIV infection.

We examined a broad range of neuropsychological functioning in school-age children with vertically transmitted HIV infection and a control group made up of siblings of children with HIV infection. Fourteen children with HIV (2 asymptomatic, 8 mildly symptomatic, and 4 with AIDS) and 11 control children were administered a battery of neuropsychological tests assessing intelligence, receptive language, expressive language, visual and verbal memory, visual-motor speed and coordination, visual-motor and visual-spatial processing, fine motor skill, and academic achievement. Results revealed that school-age children with vertically transmitted HIV infection show many areas of cognitive function within the normal range. Despite normal cognitive development, subtle motor impairments were documented in children with vertically transmitted HIV infection. Our results are the first report of fine motor and motor strength deficits in school-age children with vertically transmitted HIV. Lastly, computed tomography (CT) results suggest that children with HIV who have documented structural anomalies in the brain may be at risk for deficits in visual-motor and visual-spatial processing. This finding should be explored with larger samples and other measures to determine its generalizability.

Adolescent↗
PubMed2002

The importance of head growth patterns in predicting the cognitive abilities and literacy skills of small-for-gestational-age children.

This study evaluated the effects of head growth compromise beginning in utero and continuing, in some cases, through the first 9 months of life on the cognitive and literacy skills of school-age small-for-gestational-age (SGA) children. Seventy-one SGA children, aged 7 to 9 years (gestational ages, 24-41 weeks) and 16 full-term appropriate-for-gestational-age control children of comparable socioeconomic backgrounds and age at testing completed tests assessing intelligence, receptive language, working memory, problem solving, visual-motor integration, phonological awareness, reading, and spelling. SGA children were subdivided into head-growth pattern groups based on their head circumference at birth and at 9 months postterm. Analyses showed that SGA children with poor prenatal and postnatal head growth had the worst outcomes, followed by those with prenatal brain compromise, but good postnatal head growth. SGA children with preserved head growth in utero as well as good head growth after birth demonstrated the best outcomes, although spelling skills were deficient relative to full-term peers. The Verbal and Full Scale IQ ratings of the SGA children who had experienced brain compromise in utero declined significantly from 5 to 8 years of age. We conclude that mild intrauterine growth retardation (IUGR) has a minimal effect on the development of cognitive or academic abilities, providing that brain growth in utero is not affected. IUGR that slows brain growth in utero impairs the acquisition of some cognitive and academic abilities, even when followed by good catch-up head growth after birth, whereas poor brain growth in utero followed by little or no catch-up head growth results in widespread impairments. Findings highlight the limits to brain plasticity and emphasize the importance of optimal prenatal and postnatal brain growth.

Birth Weight↗
PubMed1990

Supplementary iodine fails to reverse hypothyroidism in adolescents and adults with endemic cretinism.

The efficacy of supplemental iodine in correcting hypothyroidism in adults and older children with endemic myxedematous cretinism is not known. To investigate this issue we administered im iodized oil (1.5 mL) to 28 hypothyroid endemic cretins (TSH, greater than 5 mIU/L) from western China, aged 14-52 yr (mean = 29 SD = 11 yr). Clinical examination, intelligence testing (Hiskey Nebraska Test of Learning Aptitude and the Griffiths Mental Development Scales), and thyroid function tests were performed before and 6 months after iodine supplementation. We found that signs of thyroid hormone deficiency, dwarfism, and delayed sexual maturity persisted after iodine supplementation. Further, mental disability and other clinical features of neurological damage were not altered by treatment. The mean serum concentration of total T4 before treatment was 75 nmol/L (SD = 40) and fell after iodized oil administration to 56 nmol/L (SD = 29; P less than 0.001). Mean serum levels of TSH before and after iodine showed a paradoxical fall [85 mIU/L (SD = 102) and 46 mIU/L (SD = 46), respectively]. Serum TSH levels decreased into the normal range (less than 5 mIU/L) in only 1 of 28 patients (4%). We conclude that iodine supplementation does not reverse thyroid hormone deficiency or its sequelae in adolescents and adults with endemic myxedematous cretinism. Iodized oil in this age group of patients with endemic cretinism does not appear to be beneficial and should be used with caution.

Adolescent↗
PubMed1995

Selective neuroanatomic abnormalities in Down's syndrome and their cognitive correlates: evidence from MRI morphometry.

We examined the pattern of neuroanatomic abnormalities in adults with Down's syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimer's disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hippocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefrontal white matter, the orbitofrontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimer's disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlation analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.

Adult↗
PubMed1991

[Effect on school performance of prenatal exposure to the Hiroshima atomic bomb].

As a part of the continuing assessment of the effects on the developing embryonic and fetal brain of exposure to ionizing radiation, the school performance of prenatally exposed survivors of the atomic bombing of Hiroshima and a suitable comparison group have been studied. In this report, the changes in performance in seven school subjects according to dose are compared under the dosimetry system (DS86) instituted in 1986 at the Radiation Effects Research Foundation. The sample involves 929 children whose fetal absorbed dose are known and includes 14 severely mentally retarded persons. The findings can be summarized as follows: 1) Damage to the 8-15 week fetal brain appears to be linearly related to the absorbed dose, as judged by the simple regression of average school-performance score on dose. Damage to the fetus exposed at 16-25 weeks after fertilization appears similar to that seen in the 8-15 week group. Canonical and multiple correlations also show a highly significant relationship of exposure 8-15 weeks and 16-25 weeks after fertilization to achievement in school. This trend is stronger, however, in the earliest years of schooling. 2) In the group exposed within 0-7 weeks following fertilization, or 26 or more weeks after fertilization, there was no evidence of a radiation-related effect on scholastic performance. 3) These results parallel those previously found in prenatally exposed survivors with respect to achievement in standard intelligence tests in childhood and development of severe mental retardation.

Age Factors↗
PubMed2003

Neurologic outcomes of toxic oil syndrome patients 18 years after the epidemic.

Toxic oil syndrome (TOS) resulted from consumption of rapeseed oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to toxic oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to toxic oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neurotoxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to toxic oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to toxic oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women.

Adolescent↗
PubMed2003

Cognitive decline with immunologic and virologic stability in four children with human immunodeficiency virus disease.

This case series describes 4 children with vertically acquired human immunodeficiency virus (HIV) infection who exhibited immunologic, virologic, and clinical stability while on a protease inhibitor-containing highly active antiretroviral therapy (HAART) regimen, yet demonstrated significant cognitive decline as measured by standardized intelligence tests. A retrospective review of 107 patient records of children with HIV infection on HAART treatment protocols was conducted. Four patients were identified who responded to protease inhibitor-containing HAART therapy with sustained viral load suppression, and stable immunologic and medical parameters, yet demonstrated significant cognitive decline. Such discordance between biological and clinical markers previously has been reported in adults with HIV disease but not in children. This observed decline in neurocognitive functioning despite stable medical parameters suggests that HAART regimens that are effective for systemic disease may not be as effective for the central nervous system (CNS), perhaps because the antiretrovirals do not penetrate adequately into the CNS. Of note, 3 of these 4 patients did not have zidovudine (ZDV) included in their HAART regimen. The only patient who was treated with ZDV containing regimen received 90 mg/m(2) every 6 hours, which is at the lower end of the recommended ZDV pediatric full-dose range (90 mg/m(2) to 120 mg/m(2)). Two of the 4 patients began ZDV at 120 mg/m(2) every 6 hours following the decline in their cognitive test scores and subsequently showed improved or stable functioning as evidenced by the results of follow-up psychometric testing. Long-term prospective studies using both systemic and CNS measures are necessary to further investigate the effects of HAART in children with HIV disease. Longitudinal cognitive assessments of children receiving HAART appear indicated to identify cognitive decline and to provide appropriate therapeutic intervention when manifestations of HIV-related CNS disease progression occur.

Antiretroviral Therapy, Highly Active↗
PubMed1990

Intrinsic risk factors and athletic injuries.

The benefits of physical activity are widely known. However, the risk of a musculoskeletal injury is an unfavourable consequence in physical training. Age, gender, injury history, body size, local anatomy and biomechanics, aerobic fitness, muscle strength, imbalance and tightness, ligamentous laxity, central motor control, psychological and psychosocial factors as well as general mental ability are factors in the predisposition to injury. Junior (15 to 16 years) and senior athletes seem to be at a higher risk of injury in many types of sport. However, the relationship between age and injuries apparently depends on both the type and intensity of activity practiced. The majority of injured athletes in many studies have been males. Men are, however, more likely to participate in vigorous exercise and sport and it is not known if men are at a generally higher risk of injury when the exposure is taken into account. Certain lesions, such as sprains, strains and dislocations, tend to recur. Previous injuries may necessarily not cause a repetition of injury if treated adequately, but certain individuals may be at a higher risk of injury due to injury-prone biological characteristics. Excessive height and weight have been shown to predispose to stress injuries in physical training. Idiopathic or acquired abnormalities in the anatomy or biomechanics in any joint may lead to a local injury. However, physical requirements vary widely between different types of activity and predisposition to injury due to anatomical or biomechanical factors seems to be characteristic for each type of exercise. Lack of fitness, muscle weakness, joint looseness and poor general flexibility have been suggested as factors in the outcome of athletic injuries but no definite conclusions can be made on the basis of the existing literature. Long simple reaction times to visual stimuli and long choice reaction times to visual stimuli have recently been related to musculoskeletal injuries. No exceptional personality dimension in injury proneness as a whole has been found and the results from specific groups cannot be extrapolated generally. Accumulation of life stress apparently predisposes to an athletic injury. Musculoskeletal injuries seem to be more common in subjects with lower scores in intelligence tests but no causation has been shown yet. Altogether, a complex network of risk factors for athletic injuries has been found. However, no prospective study including all the recognised injury risk factors has been presented in the literature.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Psychological studies of aging: their origins, development and present challenge.

Present day psychological studies of aging had their origins in attempts to study, in fundamental terms, performances of people in later middle-age relevant to capacity for industrial work. From these beginnings fundamental psychological knowledge of aging has expanded rapidly during the last forty years. Application of this knowledge to practical problems presents a challenge and a wide field of opportunity. Needs and potentialities for application are considered in the areas of: Industrial and other work, Clinical assessment and intelligence testing, Assessment of attitudes, and Coping with everyday problems in old age and with interpersonal relationships, especially in old people's communities and between old people and caregivers.

Activities of Daily Living↗
PubMed2005

[Autoimmune thyroid disease and brain].

Changes of the affective and cognitive function are usually associated with thyroid gland dysfunction. In autoimmune thyroid disease, these changes can be caused by thyroid dysfunction (hypo- or hyperthyroidism) or associated with the presence of antithyroid antibodies. Even a small change in thyroid hormone concentration is associated with change of cognitive function. In euthyroid older males, variation of total and free thyroxin accounts for about 10% of Wechsler adult intelligence test variance. In euthyroid females, lower cognitive function, measured by Mini Mental test, also correlates with blood thyroxin. Short-term (4 weeks) hypothyroidism induces clinically significant cognitivedysfunction, which is reversible by thyroid hormone substitution. Mild hypothyroidism (TSH less than 10) also induces reversible cognitive dysfunction. In hypothyroidism, PET scanning shows global reduction of brain blood flow and glucose metabolism. Hashimoto's encephalopathy is characterized by corticosteroid reversible encephalopathy associated with the presence of antithyroid antibodies. Encephalopathy can be manifested as multiple stroke-like episodes (vasculitis like), or as diffuse, progressive type characterized by dementia and psychiatric symptoms. In euthyroid patients with Hashimoto's thyroiditis and no evidence of neurological disease, SPECT showed brain perfusion abnormalities. Post mortem and brain biopsy findings can be normal or show perivascular lymphocytic infiltration. Recently, presence of antineuronal antibodies has been found in patients with Hashimoto's thyroiditis. Specific high reactivity against human alpha-enolase was high in patients with Hashimoto's encephalopathy, but absent in patients with other neurological disorders and healthy subjects. Specific antineural antibodies were found in another group of Hashimoto's encephalopathy patients. Furthermore, Ferracci et al, found antithyroid antibodies in the CSF of patients with Hashimoto's encephalopathy.

Autoimmune Diseases↗
PubMed1997

Long lasting blindness, availability of resources, and early aging.

The present paper studied the influence of long lasting blindness on processes of aging. It addressed the broader issue of the effects of familiarity with and earlier experience of stress on the capacity of individuals to deal successfully with similar stressful situations at a later point of development. 75 chronically blind men and women, aged 45 to 65, were compared with 75 sighted individuals (matched by age, sex, and cultural origin) on scores on the Shanan Sentence Completion Technique, an interview designed to assess perception of change in various areas of everyday living, and on scores on the Wechsler-Bellevue Intelligence Test. Blind subjects showed less psychological and less social engagement with the outer world. Availability of resources, education, and assistance considerably reduced differences between the nonsighted and sighted subjects. These findings were interpreted as pointing to a potentially preventable process of premature aging.

Adaptation, Psychological↗