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Biomedical subjects

L T Young

Publications and source records attributed to L T Young.

At least 73 records · Page 4Linked to original sources
PubMed1996

Bipolar disorder, unipolar depression and the Five-Factor Model of personality.

We examined differences between personality characteristics of euthymic bipolar disorder patients (BD) (n = 34) and recovered unipolar depressed patients (UD) (n = 74) using the taxonomy of the Five-Factor Model of personality (FFM) as measured by composite scales derived from the NEO Personality Inventory (NEO PI) and the revised NEO PI (NEO PI-R). Euthymic BD patients scored significantly higher on the Openness (O) dimension and the Positive Emotions facet of the E dimension than did recovered UD patients. For O, euthymic BD patients scored higher on the Feelings facet. These results suggest not only that euthymic BD patients are more likely to experience positive affects than recovered UD patients, but also that euthymic BD patients are more receptive to their positive and negative feelings than are recovered UD patients.

Adult↗
PubMed1996

Mood stabilizers have differential effects on endogenous ADP ribosylation in C6 glioma cells.

Bipolar disorder is associated with increased levels and function of the G-protein, Gs alpha which may be normalized by treatment with mood stabilizing medications (i.e. lithium salts and the anticonvulsants, valproic acid and carbamazepine). In C6 glioma cells, endogenous ADP ribosylation was markedly increased by lithium chloride (+83%, P < 0.005), decreased by valproic acid (-48%, P = 0.07) whereas carbamazepine had no effect. Since ADP ribosylation of Gs alpha has been shown to increase turnover of this protein these results suggest a possible mechanism of action for lithium chloride. These results also suggest that lithium salts and the anticonvulsant mood stabilizers may have distinct mechanisms of action.

Adenosine Diphosphate Ribose↗
PubMed1996

Lack of effect of antidepressants on mononuclear leukocyte G-protein levels or function in depressed outpatients.

Evidence from studies in animal and cultured cell models suggests that antidepressants (ADs) may enhance postreceptor signalling through the G protein coupled adenylyl cyclase (AC) pathways. To test whether this also occurs in patients receiving AD treatment, G-protein-activated-AC activity and the levels of alpha s and alpha i were measured in mononuclear leukocytes (MNLs) from 12 subjects with major depressive disorder (MDD) at baseline and after a 5 week trial of AD treatment. Although no differences were found in GTP gamma S-and forskolin-stimulated AC activity or the levels of alpha s and alpha i in MDD subjects compared with age- and sex-matched healthy subjects, pretreatment basal AC activity was significantly lower in treatment responders compared with healthy subjects. No significant changes were evident in any of these biochemical measures following 5 weeks of AD treatment in the patient group as a whole or stratified by response. These findings do not support an effect of ADs on the G-protein AC pathway, at least in MNLs. Lower pretreatment basal AC activity in responders suggests some change(s) in post-receptor signalling processes may be associated with an increased likelihood of therapeutic response to ADs.

Adenylyl Cyclases↗
PubMed1996

Well-being and functioning in patients with bipolar disorder assessed using the MOS 20-ITEM short form (SF-20).

Sixty-eight euthymic outpatients diagnosed with bipolar disorder according to Research Diagnostic Criteria, based on structured assessment, completed the 20-item short form of the Medical Outcomes Study (MOS) questionnaire (SF-20). Patients' mean scores on the 6 SF-20 subscales fell within or below the range of mean scores reported for patients with chronic medical illness and major depression in the MOS. Thus, BD, even in clinical remission, is associated with marked reductions in self-reported functioning and well-being, confirming the importance of the disorder as a major public health problem, meriting substantial resources for research and treatment.

Activities of Daily Living↗
PubMed1996

Differential display PCR reveals increased expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase by lithium.

Differential display PCR was used to study the effects of lithium on gene expression. Four candidate genes were isolated and verified by Northern hybridization after 1 week treatment of C6 glioma cells with therapeutically relevant concentrations of LiCl (1 mM). Sequencing analysis revealed three previously unidentified cDNA fragments in addition to a sequence with 99% homology with the cDNA for 2',3'-cyclic nucleotide 3'-phosphodiesterase type II (CNPaseII). Since CNPaseII is important in myelinogenesis and possibly neuronal growth and repair, the present findings suggest that lithium treatment may regulate these processes.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1996

Stimulatory G-protein alpha-subunit mRNA levels are not increased in autopsied cerebral cortex from patients with bipolar disorder.

Increased alpha-subunit (alpha s) levels of both the 45- and 52-kDa isoforms of the stimulatory guanine nucleotide binding protein (G-protein), have been found in postmortem brain and mononuclear leukocytes from patients with bipolar disorder (BD). The pathophysiological mechanism responsible for increased alpha s protein levels is unknown, however, it may involve increased expression of the gene encoding this protein. To assess this possibility, alpha s mRNA levels were determined by RT-PCR in postmortem brain from 10 subjects with an antemortem diagnosis of BD and age- and sex-matched control subjects in whom we had previously reported increased alpha s protein levels. There were no significant differences in alpha s mRNA levels in frontal, temporal, or occipital cortex between BD and control subjects. Cerebral cortex alpha s mRNA levels did not correlate with age or postmortem interval. These findings do not support the notion that higher alpha s levels found in BD postmortem brain are a result of increased gene expression.

Adult↗
PubMed1996

The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain.

The function of the phosphoinositide second messenger system was assessed in occipital, temporal, and frontal cortex obtained postmortem from subjects with bipolar affective disorder and matched controls by measuring the hydrolysis of [3H]phosphatidylinositol ([3H]PI) incubated with membrane preparations and several different stimulatory agents. Phospholipase C activity, measured in the presence of 0.1 mM Ca2+ to stimulate the enzyme, was not different in bipolar and control samples. G proteins coupled to phospholipase C were concentration-dependently activated by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and by NaF. GTP gamma S-stimulated [3H]Pl hydrolysis was markedly lower (50%) at all tested concentrations (0.3-10 microM GTP gamma S) in occipital cortical membranes from bipolar compared with control subjects. Responses to GTP gamma S in temporal and frontal cortical membranes were similar in bipolars and controls, as were responses to NaF in all three regions. Brain lithium concentrations correlated directly with GTP gamma S-stimulated [3H]Pl hydrolysis in bipolar occipital, but not temporal or frontal, cortex. Carbachol, histamine, trans-1-aminocyclopentyl-1,3-dicarboxylic acid, serotonin, and ATP each activated [3H]Pl hydrolysis above that obtained with GTP gamma S alone, and these responses were similar in bipolars and controls except for deficits in the responses to carbachol and serotonin in the occipital cortex, which were equivalent to the deficit detected with GTP gamma S alone. Thus, among the three cortical regions examined there was a selective impairment in G protein-stimulated [3H]Pl hydrolysis in occipital cortical membranes from bipolar compared with control subjects. These results directly demonstrate decreased activity of the phosphoinositide signal transduction system in specific brain regions in bipolar affective disorder.

Adenosine Triphosphate↗
PubMed1996

Biological treatment of rapid-cycling bipolar disorder.

Rapid-cycling bipolar disorder (RCBD) is currently defined as the presence of at least four affective episodes per year. RCBD is often difficult to treat with standard therapies bipolar disorder (BD), thus dictating special treatment strategies. This is especially true for the treatment of RCBD with lithium, which has been described as insufficient to prevent the high-frequency episodes in up to 82% of cases. There are several other possibilities for the biological treatment of RCBD, including the mood-stabilizers carbamazepine (CBZ) and valproate, neuroleptics, antidepressants, calcium channel blockers, l-thyroxine, benzodiazepines. ECT, total sleep deprivation and several other less proven agents. The utility of these agents and treatment procedures in the acute and prophylactic treatment of RCBD is reviewed. Special emphasis is placed on the controversial discussion of the possible induction and worsening of RCBD by antidepressant treatment. Finally, a number of guidelines for the pharmacological management of RCBD are proposed.

Antidepressive Agents↗
PubMed1996

Serum Mg2+ and Ca2+/Mg2+ ratio in major depressive disorder.

Serum Mg2+ has been implicated in the symptom severity and pathophysiology of mood disorders. Furthermore, the recent findings of blunted signalling through the G-protein-coupled adenylyl cyclase (AC) pathway in major depressive disorder (MDD) and the importance of Mg2+ in G-protein/AC function led us to reexamine in a large sample whether serum Mg2+ concentrations were decreased in MDD patients. In 145 drug-free MDD patients compared with 2 control groups: (a) patients with bipolar disorder (n = 33) and (b) non-mood-disordered patients (n = 47), there were no differences in Mg2+ levels or Ca2+/Mg2+ ratios. Neither of these measures differed when comparing responders and nonresponders to antidepressant treatment.

Adult↗
PubMed1996

Response to an open trial of a second SSRI in major depression.

BACKGROUND: We evaluated the efficacy of a second serotonin selective reuptake inhibitor (SSRI) in patients who had failed to respond to the first SSRI used. METHOD: Fifty-five patients with major depression who had failed one of the SSRIs for their current depressive episode were included. After failing a trial of one SSRI, they received a second SSRI in an open clinical trial. RESULTS: On the basis of the Clinical Global Impression-Improvement scale, 28 of 55 patients had a marked or complete antidepressant response. CONCLUSION: These data provide preliminary clinical evidence that substituting a second SRI may be a useful clinical alternative in depressed patients who fail to respond to an adequate trial of an SSRI.

1-Naphthylamine↗
PubMed1995

A comparison of Tridimensional Personality Questionnaire dimensions in bipolar disorder and unipolar depression.

The harm avoidance (HA) personality dimension has been hypothesized to be a vulnerability factor for unipolar depression (UD) but not for bipolar disorder (BD). The reported difference on HA scores between these diagnostic groups may have been compromised by the assessment of BD patients who had not fully recovered. To test the diagnostic specificity of elevated HA scores and to elucidate whether assumptions about differences between patients with UD or BD might be attributed to the lingering effects of mood state, the Tridimensional Personality Questionnaire (TPQ) was administered to recovered patients with either BD or UD and a nonpatient comparison group. Both patient groups scored higher on the HA dimension than the nonpatient comparison group, but the patient groups did not differ from one another on this dimension. Moreover, novelty seeking (NS) scores were elevated in subjects with BD compared with both UD patients and nonpatient subjects. These results suggest that high HA scores may be associated with a mood disorder diagnosis, whereas high NS scores may be associated with the BD subtype.

Adult↗
PubMed1994

Reduced brain 5-HT and elevated NE turnover and metabolites in bipolar affective disorder.

Levels of norepinephrine (NE), serotonin (5-HT), dopamine (DA), and their major metabolites were determined in postmortem brain obtained from nine subjects with antemortem histories meeting DSM-III-R criteria for bipolar affective disorder. Compared with controls, no statistically significant differences were found in mean levels of NE, 5-HT, or DA in any brain area of bipolar subjects. NE turnover as estimated by the ratio of the major NE metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) to NE was increased in frontal (+107%), temporal (+103%), and occipital (+64%) cortex and thalamus (+83%). Significant decreases were found in the major 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA), in frontal (-54%) and parietal cortex (-64%), and in 5-HIAA/5-HT ratio in temporal cortex (-55%), with a trend for decreases in both measures in caudate nucleus. In addition, levels of the major DA metabolite, homovanillic acid (HVA) were significantly decreased (-46%) in parietal cortex and HVA/DA ratios were significantly reduced (-66%) in occipital cortex obtained from bipolar compared to control subjects. Our data, taken together with previous findings regarding monoamines in postmortem brain of depressed and suicide subjects, suggest that decreased 5-HT metabolite levels and turnover may be common to all mood disorders. Increased cortical NE turnover, however, may be a more important component in the pathophysiology of bipolar disorder.

Adult↗
PubMed1994

Cerebral cortex beta-adrenoceptor binding in bipolar affective disorder.

Beta-Adrenoceptor density was measured in cerebral cortex membranes obtained postmortem from age-matched controls and subjects with bipolar disorder (BD). [125I]Iodopindolol (PIN) binding performed using a single point concentration was not different in frontal, occipital or temporal cortex in BD. Scatchard analysis of [125I]PIN binding in temporal cortex confirmed the lack of differences in binding density and no changes in KD between these two subject groups. These findings do not support alterations in the density or affinity of beta-adrenoceptor binding in cerebral cortex in BD.

Adrenergic beta-Antagonists↗
PubMed1994

The thyroid and mixed affective states.

The relationship between Grade II subclinical hypothyroidism and mixed affective states were examined in a cohort of 66 patients with bipolar affective disorder. The overall frequency of Grade II subclinical hypothyroidism was 20%. There was no difference in frequency of subclinical hypothyroidism or in mean thyroid hormone levels between the mixed state and non-mixed-state group.

Adult↗
PubMed1994

Mononuclear leukocyte levels of G proteins in depressed patients with bipolar disorder or major depressive disorder.

Stimulatory (Gs) and inhibitory (G(i)) guanine nucleotide binding protein alpha subunit levels were measured in mononuclear leukocytes from 22 drug-free depressed patients (eight with bipolar disorder, 14 with major depressive disorder) and a comparison group of 17 age- and sex-matched healthy subjects. The levels of Gs alpha and G(i) alpha were significantly higher (160% and 114%, respectively) in the bipolar patients, but not the patients with major depressive disorder, than in the healthy subjects. These data add to the evidence for abnormalities in G protein levels and function in the pathophysiology of bipolar disorder.

Adult↗
PubMed1993

Effects of chronic lithium and carbamazepine treatment on G-protein subunit expression in rat cerebral cortex.

Although lithium and carbamazepine (CBZ) are effective in the treatment of bipolar affective disorder, their mechanism of action is still unknown. Recent evidence suggests that lithium and CBZ might exert their therapeutic effects by modulating the function of guanosine triphosphate (GTP)-regulatory (G) proteins associated with central nervous system second messenger systems. In the present study, we showed that chronic lithium administration decreases G alpha s, G alpha i1, and G alpha i2 messenger RNA (mRNA) abundance by 25%-30% in rat cerebral cortex. However, the levels of G alpha s, G alpha i1, and G alpha i2 mRNA were unaffected by chronic CBZ treatment. The effects of lithium on G alpha s, G alpha i1, and G alpha i2 mRNA levels appear to be selective, as the mRNA levels of G alpha o, G alpha x, G beta 1, G beta 2, and G beta 3 subunits remained unchanged. Two days after terminating chronic lithium treatment, changes in G alpha s, G alpha i1, and G alpha i2 mRNA levels were not demonstrable. Short-term administration of lithium (2 days), however, reduced only the G alpha i2 mRNA levels. Surprisingly, there was no significant difference in the amount of immunologically detectable G alpha s-s, G alpha s-1, G alpha i(1 + 2), G alpha 0, and G beta (1 + 2) in the cortex of rats chronically treated with lithium or CBZ, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗