Magnetic resonance spectroscopy. Bridging the neurochemistry and neuroanatomy of schizophrenia.
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Brain↗
Biomedical subjects
L Friedman
Publications and source records attributed to L Friedman.
A longitudinal study of apolipoprotein-E genotype and depressive symptoms in community-dwelling older adults.
The Apolipoprotein-E (APOE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD) and cognitive decline in older adults. Depression may also be a risk factor for dementia, and depression is important in the differential diagnosis of dementia. The authors performed a 5-year longitudinal study of APOE genotype and change in Geriatric Depression Scale scores in 113 community-dwelling older adults. No association was observed between APOE genotype and change in depressive symptoms. These results do not support the hypothesis that the APOE epsilon 4 allele is associated with depression. Important objections have been raised to APOE genotyping in the diagnosis of AD. However, the specificity of APOE genotyping in AD diagnosis would not appear to be compromised by an association with depression.
Age Factors↗
Identification of risk factors in hypertensive patients: contribution of randomized controlled trials through an individual patient database.
BACKGROUND: Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. METHODS AND RESULTS: Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. CONCLUSIONS: Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.
Age Factors↗
A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls.
The purpose of this study was to compare thalamic size in adolescent patients with either schizophrenia or bipolar disorder and healthy controls. T2-weighted axial magnetic resonance images were used to manually define the area of the thalamus for 20 schizophrenia patients, 15 bipolar patients and 16 normal control subjects, all of whom were adolescents. Two orthogonal planned contrasts were tested: Contrast 1, patients with schizophrenia vs. patients with bipolar disorder; and Contrast 2, both patient groups taken as a single group compared to controls. Contrast 1 was not statistically significant for right or left thalamic area. Contrast 2 was statistically significant and indicated reductions in thalamic area in the patients as compared to controls. The same pattern of results emerged after adjustment for total brain volume. Our results indicate that thalamic abnormalities reported in adult schizophrenic and bipolar patients are also observed in adolescent patients. Our findings also add to the evidence implicating the thalamus in the pathophysiology of schizophrenia and bipolar disorder.
Adolescent↗
An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects.
BACKGROUND: There are few imaging studies in adolescent patients with either schizophrenia or bipolar disorder. Such studies are of interest because adolescents may have a more severe illness and neurodevelopmental events may have a greater role in their pathophysiology. METHODS: We compared 20 patients with schizophrenia and 15 patients with bipolar disorder (10 to 18 years) to 16 normal adolescents on magnetic resonance imaging (MRI) measures of intracranial volume and ventricular and sulcal enlargement. Two planned comparison contrasts were employed, one comparing the two patient groups to each other (contrast 1), and one comparing both patient groups combined to control subjects (contrast 2). RESULTS: None of the contrast 1 comparisons (schizophrenia vs bipolar) were statistically significant. Contrast 2 comparisons (control subjects vs patients) were statistically significant for intracranial volume (reduced in patients) as well as frontal and temporal sulcal size (increased in patients). CONCLUSIONS: The patient groups were not statistically significantly different from each other on any measure. The combined patient groups were different from control subjects on intracranial volume and frontal and temporal sulcal size. Also, there was evidence for ventricular enlargement, after removal of a control subject with an extreme value. These findings indicate that the same abnormalities noted in adult populations are present in adolescents.
Adolescent↗
Meta-analysis of brain size in bipolar disorder.
A recent meta-analysis concluded that patients with schizophrenia have reduced cerebral volume, and this finding has been used to implicate neurodevelopmental events in the etiology of this disorder. Since bipolar-disorder patients and schizophrenia patients have some similar brain abnormalities, it was of interest to meta-analytically review the literature on brain size in bipolar disorder. Only seven studies met the inclusion/exclusion criteria for our meta-analysis, but none reported the brain size differences between the bipolar patients and the controls to be statistically significant. The composite effect size was a negligible 0.04 (95% CI: -0.17 to 0.25) and statistically not significantly different from 0.0 (no effect). Thus, it appears that bipolar disorder is not associated with the same cerebral volume reductions noted in schizophrenia. Implications for hypotheses regarding the etiology of the two disorders are discussed.
Bipolar Disorder↗
Cardiovascular screening of high school athletes.
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Adolescent↗
Three-dimensional magnetic resonance-based morphometrics and ventricular dysmorphology in schizophrenia.
BACKGROUND: Recent methodological refinements in magnetic resonance (MR) imaging have led to brain averaging and morphometric approaches that are sensitive to subtle anatomical distinctions in schizophrenia. METHODS: Using a novel morphometric technique for surface analysis, 48 selected landmarks of the rendered ventricular system were extracted and compared between the ventricles of 20 patients with schizophrenia and 20 normal subjects. RESULTS: There was no significant difference in ventricular shape between groups, but significant (p = .015) and highly localized shape deformity was detected at the foramen of Monro and at the proximal temporal horn of the lateral ventricle of male (but not female) patients relative to controls. CONCLUSIONS: Three-dimensional MR-based morphometrics complements established volumetric approaches and can detect minute shape deformities that may be associated with schizophrenia.
Adolescent↗
Clozapine and other 5-hydroxytryptamine-2A receptor antagonists alter the subcellular distribution of 5-hydroxytryptamine-2A receptors in vitro and in vivo.
In this study, we demonstrate that clozapine and other atypical antipsychotic drugs induce a paradoxical internalization of 5-hydroxytryptamine-2A receptors in vitro and a redistribution of 5-hydroxytryptamine-2A receptors in vivo. We discovered that clozapine, olanzapine, risperidone and the putative atypical antipsychotic drug MDL 100,907 all induced 5-hydroxytryptamine-2A receptor internalization in fibroblasts stably expressing the 5-hydroxytryptamine-2A receptor in vitro. Two 5-hydroxytryptamine-2A antagonists (mianserin and ritanserin), which have been demonstrated to reduce negative symptoms in schizophrenia, also caused 5-hydroxytryptamine-2A receptor internalization. Four different drugs, each devoid of 5-hydroxytryptamine-2A antagonist activity, had no effect on the subcellular distribution of 5-hydroxytryptamine-2A receptors in vitro. Treatment of rats for seven days with clozapine induced an increase in intracellular 5-hydroxytryptamine-2A receptor-like immunoreactivity in pyramidal neurons, while causing a decrease in labeling of apical dendrites in the medial prefrontal cortex. This redistribution of 5-hydroxytryptamine-2A receptors in pyramidal neurons was also seen when rats were chronically treated with another atypical antipsychotic drug, olanzapine. The typical antipsychotic drug haloperidol, however, did not induce a redistribution of 5-hydroxytryptamine-2A receptors in pyramidal neurons in the medial prefrontal cortex. Taken together, these results demonstrate that several atypical antipsychotic drugs with high 5-hydroxytryptamine-2A receptor affinities induce a redistribution of 5-hydroxytryptamine-2A receptors both in vivo and in vitro. It is conceivable that the loss of 5-hydroxytryptamine-2A receptors from the apical dendrites of pyramidal neurons is important for the beneficial effects of atypical antipsychotic drugs and other 5-hydroxytryptamine-2A antagonists in schizophrenia.
3T3 Cells↗
Mnemonic training in older adults: effects of age, length of training, and type of cognitive pretraining.
OBJECTIVES: To improve performance with mnemonic techniques for remembering words and proper names. DESIGN: For word recall, a 2 x 2 factorial in which type of pretraining and length of training were between-subjects manipulations. For proper name recall, a two-group design in which type of pretraining was manipulated between subjects. SETTING: Community. PARTICIPANTS: 268 community-dwelling adults over the age of 55 years who wished to improve their memory. MEASUREMENTS: Recall of words and proper names both before and after training in mnemonics. INTERVENTION: Participants received a 2-week training course on two mnemonic techniques, the method of loci for words and a name association technique for proper names. RESULTS: There was no effect of the pretraining manipulation on proper name recall. For word recall, however, a multiple regression that included age indicated that the older-old participants benefited more from a combination of comprehensive pretraining and extended mnemonic training than did the younger-old. CONCLUSIONS: Increased training time coupled with a comprehensive pretraining regimen can improve the performance of the older-old in using mnemonics; this improved performance cannot be attributed solely to enhanced knowledge of the mnemonic.
Age Factors↗
Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture for drug users in methadone maintenance.
BACKGROUND: Tuberculosis is common in drug users, although compliance with therapy may be difficult in this population. OBJECTIVE: To evaluate an approach to enhancing compliance with tuberculosis chemoprophylaxis in drug users enrolled on methadone maintenance utilizing an isoniazid (INH)-methadone admixture. DESIGN: A prospective cohort study. SETTING: A drug treatment program in New Haven, Connecticut, USA. PATIENTS: Opioid-dependent drug users enrolled in methadone maintenance. INTERVENTION: Liquid isoniazid was mixed into subjects' daily dose of methadone. Vitamin B6 was given to subjects for self-administration. MEASUREMENTS AND MAIN RESULTS: Number of eligible subjects, reasons for not starting therapy, number starting therapy, proportion completing therapy and median duration of INH therapy were calculated. Thirty-nine subjects were eligible for INH chemoprophylaxis: 34 (87%) received INH mixed directly in their methadone and five (13%) had their INH consumption supervised by a nurse. Among these subjects, 72% (28/39) completed therapy. Among the 11 subjects who discontinued INH, discharge from the methadone maintenance program was the most common reason--73% (8/11). Thus, among the 31 subjects who were not discharged from methadone maintenance, 90% (28/31) successfully completed INH prophylaxis. The median duration of therapy was 182 days. CONCLUSIONS: Tuberculosis chemoprophylaxis using a liquid isoniazid-methadone admixture appears to be an effective approach to enhancing compliance with this therapy in methadone-maintained drug users.
Antitubercular Agents↗
Geriatric performance on the Benton Visual Retention Test: demographic and diagnostic considerations.
We examined relationships between demographic and diagnostic variables and Benton Visual Retention Test performance in older adults aged 55 to 97 years. We derived extended geriatric norms for BVRT total number correct scores adjusted for variables that contributed significantly to the variance. We also investigated BVRT performance in two commonly presenting diagnostic groups: (1) normal adults with memory concerns, and (2) a group with mixed neurologic disorders. Age and education but not gender were significantly associated with BVRT performance in both normals and normals with memory concerns. Level of cognitive deficit was a moderating factor in that age and education also contributed significantly to the BVRT performance of no/low deficit neurologic patients but had no impact in patients whose cognitive deficits were moderate/severe.
Adult↗
Why is reality a troubling concept?
Many psychoanalysts assume that modern philosophy has revealed that objective reality is an illusion, and they take that as their starting point for discussing psychic reality and the direction of treatment. However, the philosophical argument for the antiobjectivist position, far from being a final truth, can be seen as a late echo of the age-old debate over whether it is possible to match unchanging general descriptions to the changing individuals in the world. It is but one of two competing philosophical positions (postulating either a world of incomparable individuals or a world of abstract properties), neither of which can definitively vanquish its rival without violating common sense. The underlying, specifically psychoanalytic problem that stirs these recent debates is not the philosophical problem of reality, but rather the question of what it can mean to say that someone is realistic in regard to the world of human values, roles, and relationships. Analytic tradition begins the inquiry by suggesting that realisticness about human meaning is a matter of feeling out the potentialities of the human world by multiple affective attachments. Many questions remain to be answered.
Humans↗
Syringe disposal options for injection drug users: a community-based perspective.
This study was a qualitative exploration of syringe disposal interventions for injection drug users (IDUs). Data were collected through in-depth interviews with 26 community members who injected drugs and 32 noninjecting community members in Atlanta, Georgia. Both groups supported syringe exchange programs as syringe disposal interventions, while noninjecting community members favored a one-way drop box. IDUs identified fear of arrest for possession of syringes as the most salient barrier to safe syringe disposal, revealing the negative consequences of drug paraphernalia laws.
Acquired Immunodeficiency Syndrome↗
How to drastically reduce priming in word stem completion--and still present the words.
This paper describes a series of experiments in which we demonstrated that "dysphonemic" word stems, which are likely not pronounced in isolation as they are within a word (e.g., MUS in MUSHROOM or LEG in LEGEND), showed less priming than did "phonemic stems" (e.g., MUS in MUSTARD or LEG in LEGACY). Furthermore, words with either dysphonemic or phonemic three-letter stems gave rise to equivalent levels of priming when test cues were four-letter stems (LEGE) or word fragments (L_G_ND). Moreover, the difference between phonemic and dysphonemic stems persisted when nonpresented completion rates were matched. A final cued-recall experiment revealed that performance was greater for phonemic stems than for dysphonemic stems and that this difference was greater for older participants than for younger ones. These results are not readily accounted for by extant theoretical approaches and point to important methodological issues regarding stem completion.
Adult↗
A profile of bereaved caregivers following provision of terminal care.
Caregivers are often overwhelmed by the strain of terminal caregiving. We wished to better understand the needs of terminal caregivers and to supply a basis for tailoring interventions to them during caregiving and early bereavement. This report provides a profile of 124 bereaved caregivers interviewed within three months of their patient's death. Three quarters were female and married to the patient. Four major areas were assessed: psycho-spiritual, personal-social, health status, and financial status. Caregivers reported higher than average depressive symptomatology (mean CES-D = 17.6), moderate levels of positive outlook, low negative reactions to caring, and relatively high levels of spirituality. Caregivers were highly involved in their patient's activities of daily living, providing an average of 10.8 hours/day of direct care and 8.9 hours/day of companionship. Caregivers reported low utilization of health services and relatively high personal health status. 45% of the sample reported lower income since the patient's death and 44% reported out-of-pocket expenses not covered by insurance. Suggestions for interventions that target emotional, physical, and financial concerns are discussed.
Adult↗
Serotonergic antagonist effects on trafficking of serotonin 5-HT2A receptors in vitro and in vivo.
The mechanism by which antagonists down-regulate 5-HT2A receptors in unknown. We here report that a variety of 5-HT2A antagonists induce a change in the subcellular distribution of 5-HT2A receptors both in vitro and in vivo. In a stably transfected NIH 3T3 cell-line, brief exposure to 1 muM clozapine caused a 2.5-fold increase in intracellular 5-HT2A-like immunoreactivity, as measured by confocal microscopy. Confirmatory studies utilizing a biotin-trap technique, demonstrated that the increase in intracellular immunoreactivity results from internalization of receptor from the cell surface. Exposure of transfected cells to other 5-HT2A receptor antagonists produced similar increases in intracellular 5-HT2A-like immunoreactivity. In vivo administration of clozapine (20 mg/kg, sc, X 7 days) caused a greater than twofold increase in intracellular immunoreactivity in cell bodies of cortical pyramidal neurons. Additionally, chronic clozapine administration was associated with decrease in labeling of apical dendrites on pyramidal cells. These results show that clozapine causes a change in subcellular distribution of 5-HT2A receptors in vitro and in vivo.
3T3 Cells↗
Fifty years of death certificates: the Framingham Heart Study.
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Coronary Disease↗