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PubMed1991

Lack of beneficial effects of l-baclofen in affective disorder.

GABAB mechanisms have been implicated in the antinociceptive, but not anticonvulsant effects of carbamazepine. A variety of antidepressants have been reported to upregulate GABAB receptors after chronic administration. The GABAB agonist l-baclofen was studied in depressed patients based on two separate rationales. l-Baclofen, in doses ranging from 10-55 mg/day, was administered to five patients with primary affective disorder. No patient showed a positive clinical response, while three patients showed a pattern of increasing depression or cycling during treatment and improvement during withdrawal. These preliminary data suggest that GABAB agonism is unlikely to produce antidepressant effects and may be unrelated to the mechanism of carbamazepine's antidepressant action. These data, taken with a reinterpretation of other findings that antidepressant modalities upregulate GABAB receptors in brain following chronic administration, suggest that GABAB antagonism rather than agonism may be a fruitful clinical strategy to explore in depression.

Adult↗
PubMed1983

[Nonspecific antigenic suppression of the formation of immunologic memory to heteroerythrocytes].

Spleen cells (SC) of mice immunized with sheep red blood cells contain factor that suppresses primary immune response and the formation of immunologic memory. During studies of antigen-specific suppression of the immunogenesis, it has been discovered that suppressor factor of SC non-specifically blocks the development of immunologic memory for the other antigen (rat red cells) without affecting primary immune response to this antigen administration. It is assumed that at an early stage the cells responsible for the formation of immunologic memory are more sensitive to the non-specific effect of suppressor factor than those involved in the generation of primary immune response.

Animals↗
PubMed2006

Two different reorganization patterns after rehabilitative therapy: an exploratory study with fMRI and TMS.

We used two complementary methods to investigate cortical reorganization in chronic stroke patients during treatment with a defined motor rehabilitation program. BOLD ("blood oxygenation level dependent") sensitive functional magnetic resonance imaging (fMRI) and intracortical inhibition (ICI) and facilitation (ICF) measured with transcranial magnetic stimulation (TMS) via paired pulse stimulation were used to investigate cortical reorganization before and after "constraint-induced movement therapy" (CI). The motor hand function improved in all subjects after CI. BOLD signal intensity changes within affected primary sensorimotor cortex (SMC) before and after CI showed a close correlation with ICI (r = 0.93) and ICF (r = 0.76) difference before and after therapy. Difference in number of voxels and ICI difference before and after CI also showed a close correlation (r = 0.92) in the affected SMC over the time period of training. A single subject analysis revealed that patients with intact hand area of M1 ("the hand knob") and its descending motor fibers (these patients revealed normal motor evoked potentials [MEP] from the affected hand) showed decreasing ipsilesional SMC activation which was paralleled by an increase in intracortical excitability. This pattern putatively reflects increasing synaptic efficiency. When M1 or its descending pyramidal tract was lesioned (MEP from the affected hand was pathologic) ipsilesional SMC activation increased, accompanied by decreased intracortical excitability. We suggest that an increase in synaptic efficiency is not possible here, which leads to reorganization with extension, shift and recruitment of additional cortical areas of the sensorimotor network. The inverse dynamic process between both complementary methods (activation in fMRI and intracortical excitability determined by TMS) over the time period of CI illustrates the value of combining methods for understanding brain reorganization.

Aged↗
PubMed1980

Mood disorder in women professionals.

The lifetime prevalence of affective disorder in women with M.D.'s and Ph.D's was assessed by personal interview. The two groups were matched by age, race, and marital status. Thirty-nine percent of 111 white, women physicians and 30% of 103 white women Ph.D.'s were found to have primary affective disorder. There was no excess of depression in women psychiatrists or psychologists. Eleven percent of the first degree relatives of the depressed M.D.'s and 7% of similar relatives of depressed Ph.D's had affective disorder by family history compared to only 2% of the well M.D.'s and 2% of the well Ph.D's relatives. The study confirms that depression is an extremely common problem for professional women. By emphasizing its heritability, it raises the question of the self-selection for professional careers of women with affective disorder.

Adult↗
PubMed1998

Clinical consequences of sensitisation in affective disorder: a case register study.

Clinically derived measures of the initial course of episodes might reflect a process of sensitisation in affective disorder. However, the clinical consequences of such measures have not been investigated. The predictive effect of measures of the initial course of episodes was investigated in relation to the subsequent risk of alcoholism, dementia, death and suicidal attempts/suicide in a case register study including all hospital admissions with primary affective disorder in Denmark from 1971 to 1993. A total of 8737 patients with more than one episode were included in the analyses. A short period between initial episodes of the illness, reflecting a great intensity of illness, predicted increased risk of subsequent development of dementia, and for unipolar patients, decreased risk of subsequent alcoholism. Surprisingly, a progressive course, with decreasing intervals between initial episodes of the illness, had no predictive effect. Similarly, no predictive effects on the risk of death or suicidal acts could be demonstrated with any measure of the initial course of episodes.

Aged↗
PubMed1998

Recurrence in affective disorder. II. Effect of age and gender.

BACKGROUND: The risk of recurrence in affective disorder has been found to increase with each new episode. It is unclear whether it is universal without regard to gender, age and type of disorder. METHOD: Survival analysis was used to estimate the risk of recurrence in a case-register study including all hospital admissions with primary affective disorder in Denmark from 1971-1993. In this period 20,350 first-admission patients had been discharged with a diagnosis of affective disorder, depressive or manic/cyclic type. RESULTS: The risk of recurrence increased with the number of previous episodes regardless of the combination of gender, age and type of disorder. Initially in the course of illness, unipolar and bipolar women experienced an equal greater risk of recurrence than men. The risk of recurrence after the first episode was increased for middle-aged and older unipolar women compared with the risk for younger women, while after all other episodes younger age at first episode increased the risk of recurrence. CONCLUSIONS: The course of severe unipolar and bipolar disorder seems to be progressive in nature irrespective of gender, age and type of disorder.

Adult↗
PubMed2004

Major method-specific differences in the measurement of intact parathyroid hormone: studies in patients with and without chronic renal failure.

BACKGROUND: Following the introduction of two-site immunometric assays for parathyroid hormone (PTH), the expectation of good inter-assay agreement has not been fulfilled. The reasons for this may include differences in standardization as well as fragment recognition between the assays. METHODS: PTH values for healthy individuals, patients with renal failure and patients with normal renal function and elevated parathyroid hormone (hPTH) were compared using two commercial two-site immunochemiluminometric assays (Bayer Magic-lite and DPC Immulite 2000). RESULTS: Immulite results had a mean value 50.4% greater than the corresponding Magic-lite values for the whole study population with individual values ranging from 17.5% below to 118.3% above the corresponding Magic-lite value. There was no significant difference in inter-assay bias between patients with renal failure and those with normal renal function, suggesting that variable cross-reactivity with circulating disease-specific PTH fragments was not the primary cause of the observed discrepancy. Cross-reactivity with the synthetic fragment hPTH (7-84) was 34+/-5% for Magic-lite and 62+/-2% for Immulite. We also studied the stability of synthetic hPTH on storage. CONCLUSION: The instability of synthetic hPTH over extended storage periods may affect primary standard material. The consistent inter-assay differences and the over-recovery observed in external quality assessment programmes for the Immulite assay may have best been explained by differences in calibration and the relative cross-reactivities and/or kinetics of the two assay systems for specific parathyroid fragments.

Humans↗
PubMed2004

Course of illness in depressive and bipolar disorders. Naturalistic study, 1994-1999.

BACKGROUND: Newer antidepressants have increasingly been used during the past decade. These drugs may increase compliance and reduce the risk of cycle acceleration in affective disorders. AIMS: To investigate the naturalistic longitudinal course of illness in patients with depressive or bipolar disorder following the use of recently introduced drugs. METHOD: The rates of relapse leading to hospitalisation after successive episodes were calculated in a case register study including all hospital admissions of patients with primary affective disorder in Denmark during 1994-1999. Altogether, 9417 patients had a diagnosis of depressive disorder and 1106 patients had a diagnosis of mania or bipolar disorder, at first-ever discharge. RESULTS: The rate of relapse leading to hospitalisation increased with the number of previous episodes in both depressive and bipolar disorders. However, the effect of episodes was not significant for men. The rate of relapse did not decline during the study period. CONCLUSIONS: The course of severe depressive and bipolar disorders has remained roughly the same despite introduction of new treatments.

Adult↗
PubMed2005

[Fibromyalgia and facial expression].

QUESTION: Do female inpatients with fibromyalgia (FM) differ from healthy women in their nonverbal affective behavior? METHODS: The data culled from 15 interviews with female FM inpatients and 15 interviews with healthy women were analyzed and the analyses of facial expression were subsequently correlated with gaze behavior. RESULTS: FM patients exhibited neither a reduction of total activity of facial expression nor of absolute frequency of primary affects in comparison to healthy subjects who did (also in eye contact) however exhibit a significantly higher proportion of "genuine joy" and lower proportion of "contempt." CONCLUSION: The absence of reduced total activity of facial expression is in contrast to the elaborate descriptions of symptoms provided by the patients, but detailed analyses show that elements which stabilize relationships are lacking and that dissociative elements are implanted in the interactions.

Emotions↗
PubMed2000

Disparate intracellular processing of human IL-12 preprotein subunits: atypical processing of the P35 signal peptide.

IL-12 is a heterodimeric cytokine produced by APC that critically regulates cell-mediated immunity. Because of its crucial function during immune responses, IL-12 production is stringently regulated, in part through transcriptional control of its p35 subunit, which requires the differentiative effects of IFN-gamma for expression. To determine whether post-transcriptional aspects of IL-12 production might be regulated, we examined intracellular protein processing of each subunit. We report here that p40 and p35 subunits are processed by disparate pathways. Whereas processing of p40 conforms to the cotranslational model of signal peptide removal concomitant with translocation into the endoplasmic reticulum (ER), processing of p35 does not. Translocation of the p35 preprotein into the ER was not accompanied by cleavage of the signal peptide; rather, removal of the p35 signal peptide occurred via two sequential cleavages. The first cleavage took place within the ER, and the cleavage site localized to the middle of the hydrophobic region of the signal peptide. Although the preprotein was glycosylated upon entry into the ER, its glycosylation status did not affect primary cleavage. Subsequently, the remaining portion of the p35 signal peptide was removed by a second cleavage, possibly involving a metalloprotease, concomitant with additional glycosylation and secretion. Secretion could be inhibited by mutation of the second cleavage site or by inhibition of glycosylation with tunicamycin. In contrast, p40 secretion was not affected by inhibition of glycosylation. Our findings demonstrate that IL-12 subunits are processed by disparate pathways and suggest new modalities for regulation of IL-12 production.

Amino Acid Sequence↗
PubMed1981

Neurochemical abnormalities in anorexia nervosa: similarities to affective disorders.

Certain investigators have asserted that the illness of anorexia nervosa is a form of hypothalamic disturbance. The relationship between 24-hr urine 3-methoxy-4-hydroxyphenylglycol (MHPG) and dexamethasone suppression tests was examined in 13 female patients with AN diagnosed by RDC. Patients showed a consistent association between low urine MHPG and failure to suppress to dexamethasone. In addition, family histories of index cases showed a high percentage of relatives with either primary affective disorder or alcoholism. These results are evidence in support of an hypothesis of hypothalamic dysfunction in AN. Furthermore, these biochemical parameters are also found to be abnormal in PAD. These data, coupled with the genetic material, suggest a link between AN and PAD.

Adolescent↗
PubMedDate not supplied

Predictors of recurrence in affective disorder--analyses accounting for individual heterogeneity.

BACKGROUND: Previous studies suggest that gender, age at onset, and marital status act as risk factors for further recurrence initially during the course of affective disorder but not at a later stage. These studies did, however, not take the individual liability to recurrence into account. METHOD: The effect of predictors of recurrence was estimated with the use of generalised linear mixed models in a case register study including a random sample of all patients admitted with primary affective disorder in Denmark during 1971-1993. RESULTS: In total, 7047 first admission patients with a diagnosis of affective disorder, depressive or manic/circular type were included in the analyses. The study confirmed that the effect of the type of disorder, age at first admission, and never being married decreased during the course of illness even when the individual liability to recurrence was taken into account. No differences in the effect of gender and in the effect of a recent divorce were found between early and later episodes and the effect of a recent death of a spouse seemed to increase during the course of illness. The risk of recurrence increased with every new episode for all sub-groups of patients. CONCLUSION: The effect of some, but not all, predictors of recurrence decline during the course of affective illness. The number of previous episodes predicts recurrence in most subgroups of patients. LIMITATION: The data relate to re-admissions rather than recurrence. CLINICAL RELEVANCE: The study underscores the importance of the illness process itself.

Adult↗
PubMed1989

Depression, learning disability, and school behavior problems.

It is possible that recurrent depression (primary affective illness) is the most significant variable related to school problems of a behavioral nature in children manifesting developmental specific learning disabilities. The association of school problems and depression was investigated at a private school for children with developmental specific learning disabilities. These children were of normal intelligence and were free of primary conduct or thought disturbances. Prior to entering school, 95% of the students fulfilled criteria for developmental specific learning disabilities and 64% for depression with or without hyperactivity. Students manifesting no diagnosable behavioral condition prior to entrance continued to be relatively free of behavioral problems during their stay at school. Students with both depression and hyperactivity showed the most problematic behavior followed by students with depression without hyperactivity.

Adolescent↗
PubMed1977

A contrast of the three more common illnesses with the ten less common in a study and 18-month follow-up of 314 psychiatric emergency room patients. II. Characteristics of patients with the three more common illnesses.

The three more common illnesses diagnosed in the sample of 314 emergency room patients were (in order of frequency) affective disorder (N = 135), alcoholism (N = 112), and antisocial personality (N = 57). This study describes the occurrence and frequency of affective disorders and evaluates the relative usefulness of three separate sets of diagnostic criteria for the depressive phase of the illness, which are considered in three self-evident, mutually exclusive groups, the definition of which depends on chronology of onset in relation to other diagnoses. Findings show a 3:2 ratio of primary affective disorder to secondary affective disorder. The 112 diagnoses of alcoholism were based on defined criteria that separated "definite" (N = 102) from probable (N = 10) alcoholism. A high incidence of secondary affective disorder (38%) in patients with a first diagnosis of alcoholism is noted. The third most common diagnosis, antisocial personality, was based on defined criteria requiring a specified number of manifestations both before and after age 15 years. Only 11% of the antisocial personality patients received a single diagnosis of antisocial personality. An additional diagnosis of alcoholism occurred in 61%. Besides antisocial symptoms, the 57 patients reported 74 different nonantisocial symptoms, supporting the conclusion that antisocial personality patients may be as susceptible to neurotic and psychotic symptoms as other patients.

Adolescent↗
PubMed2002

Angiostatin potentiates cyclophosphamide treatment of metastatic disease.

PURPOSE: We examined the interaction between cyclophosphamide (CPA) and angiostatin (AS) on the growth of primary Lewis lung carcinoma (LLC) tumors and on the development of LLC pulmonary metastases. We studied the effects of AS and CPA on the stages of angiogenesis employing in vitro assays. METHODS: Primary tumor growth and pulmonary metastases were measured to evaluate the effects of treatment with AS alone, CPA alone or the combination of CPA and AS. We examined the effects of CPA plus AS on endothelial cell (HUVEC) survival, migration and tube formation. RESULTS: Combined treatment with CPA and AS did not significantly affect primary tumor growth when compared with CPA treatment alone. However, a significant decrease in the number of pulmonary metastases was observed following CPA plus AS treatment when compared with CPA treatment alone ( P<0.001). AS did not enhance CPA-mediated HUVEC cytotoxicity, and CPA failed to enhance AS-mediated inhibition of migration. However, tube formation was inhibited following combined treatment with CPA and AS when compared with either treatment alone. CONCLUSIONS: AS enhanced the antimetastatic effects of CPA without significantly influencing the effects of CPA on primary tumor growth. CPA plus AS inhibited tube formation, suggesting that interrupting specific steps in the angiogenesis process might be an effective approach to the treatment of subclinical distant metastases.

Angiogenesis Inhibitors↗
PubMed1976

Electroencephalographic sleep diagnosis of primary depression.

Studies of severely depressed hospitalized patients suggest a shortened rapid eye movement (REM) latency as a specific biological marker for primary affective disease. To assess the validity of these findings, 40 outpatients referred to our Electroencephalographic Sleep Center for evaluation of depressive symptoms were studied. Concurrent with the all night EEG sleep studies, all patients received a brief clinical interview and a battery of self-rating scales. The entire sample was then subdivided into primary and secondary depressives on the basis of follow-up diagnoses. While there were no significant differences between groups on self-ratings of depressive symptoms, the group of primary depressives had significantly shorter REM latencies and higher measures of phasic REM than the secondary depressives. Furthermore, in this patient group, the delineation of primary vs secondary depression was greater than 80% on the basis of only two nights of EEG sleep. Such objective biological measures, if replicated, could provide a method for increasing the accuracy of differential diagnosis among depressed populations in clinical research.

Adult↗
PubMed1979

Plasma and erythrocyte cations in affective illness.

Plasma and erythrocyte cations (sodium and magnesium) were studied in groups of patients with an affective disorder and in normal subjects. Baseline determinations were obtained before initiation of treatment for mania or depression. In a subgroup of patients, sequential measurements of cations were made during treatment with lithium carbonate. No differences were found in intraerythrocyte sodium or magnesium among any of the patient groups and controls. Patients with a primary affective disorder had significantly higher plasma sodium than control subjects. Neither baseline cation concentrations nor changes in cation concentration during treatment with lithium correlated with treatment response. Gender was shown to be a significant variable affecting intraerythrocyte cation concentrations.

Bipolar Disorder↗
PubMed1986

Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder.

The brains of 232 patients with a case-note diagnosis of schizophrenia or affective disorder who died in one mental hospital over a period of 22 years were weighed, and were assessed in a coronal section at the level of the interventricular foramina. From this sample were eliminated the brains of patients whose illnesses did not meet the Washington University criteria for a diagnosis of definite schizophrenia or primary affective disorder and those brains that showed significant histopathologic evidence of Alzheimer's-type change or cerebrovascular disease. This left a sample of 41 patients with schizophrenia and 29 patients with affective disorder. With age, sex, and year of birth controlled for, the brains of the patients with schizophrenia were 6% lighter, had lateral ventricles that were larger in the anterior (by 19%), and particularly in the temporal, (by 97%) horn cross section, and had significantly thinner parahippocampal cortices (by 11%). The findings provide postmortem confirmation of reports of ventricular enlargement in radiological studies and suggest that such enlargement is associated with tissue loss in the temporal lobe. The changes in schizophrenia were of a lesser degree than those seen in a sample of brains of patients with Alzheimer's-type dementia and Huntington's chorea.

Aged↗