Showing papers by "L. Trevor Young published in 2004"

Impact of comorbid anxiety disorders on outcome in a cohort of patients with bipolar disorder.

Abstract: Background: High rates of comorbid anxiety disorders have been described in individuals with bipolar disorder. Although it is well recognized that anxiety disorders often co-occur with bipolar disorder, few studies have examined the impact of more than 1 anxiety disorder on long-term outcome in patients with bipolar disorder. Method: The rates of DSM-IV generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder were determined using structured clinical interviews in 138 patients with bipolar disorder who presented consecutively between 1994 and 1999. Patients were then followed for up to 3 years with longitudinal clinical surveillance. The impact of 1 or more comorbid anxiety disorders on mood symptoms and general function was evaluated. Results: In our sample, 55.8% of the patients had at least 1 comorbid anxiety disorder, and 31.8% had 2 or more anxiety disorder diagnoses. The most common anxiety disorder was generalized anxiety disorder, followed by panic disorder. The presence of an anxiety disorder led to significantly (p <.05) worse outcome on global as well as specific illness measures, including illness severity, proportion of patients characterized as euthymic, and proportion of the year spent ill. Number of anxiety disorders was less important than type, with generalized anxiety disorder and social phobia having the most negative impact on outcome. Conclusion: Our data suggested that multiple anxiety disorder comorbidities were not infrequent in bipolar disorder and that generalized anxiety disorder and social phobia were more likely to be associated with poor outcome. We discuss some potential mechanisms and implications in our findings.

Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

Abstract: Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders.

Abstract: Background: There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive. This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospectively for an average of three years. Method: Detailed life-charting data were obtained from 138 patients with bipolar disorder. Mood states were characterized as euthymic, subsyndromal, minor or major affective episodes based on rigorously defined criteria. The amount of time spent in these mood states during follow-up was examined. Results: Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic. The remainder of the time was spent in varying severity of mood states. However, the majority of time was spent with minor and subsyndromal symptoms, both manic and depressive. Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal, minor and manic symptoms. There was no difference in time spent with depressive symptoms between the two groups. Conclusions: Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal. Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder.

Glutathione S-transferase is a novel target for mood stabilizing drugs in primary cultured neurons

Abstract: Oligonucleotide microarray technology was used to analyze gene expression profiles after chronic treatment with the mood stabilizing drug valproate at a therapeutically relevant concentration in primary cultured rat cerebral cortical cells We discovered that valproate regulates expression of 28 genes, including three isoenzymes (M1, A3 and A4) of glutathione S-transferase (GST), an important protective factor against oxidative stress Because previous studies in our laboratory found that chronic valproate treatment protected cultured neurons against oxidative stress, further experiments on the regulation of GST were performed Regulation of GST M1, GST A3 and GST A4 was verified using northern blotting hybridization Chronic valproate treatment increased mRNA levels of M1 and A4, but decreased the A3 mRNA level dose-dependently, indicating further complexities in the regulation of GST by valproate The level of GST M1 protein and GST activity were also increased by chronic valproate treatment In addition, chronic treatment with lithium, another commonly prescribed mood stabilizer, also increased levels of GST M1 mRNA and protein The present findings suggest that regulation of GST M1, and possibly GST A4, may mediate the anti-oxidative effects of valproate treatment, and regulation of GST may be involved in the mood stabilizing effect of valproate and lithium

A pilot study of visual backward masking performance among affected versus unaffected offspring of parents with bipolar disorder

Abstract: Background: Cognitive dysfunction is evident in some euthymic patients with established bipolar disorder (BD), including deficits in visual backward masking (VBM) tasks which map to a specific neural pathway. A high-risk paradigm would clarify the temporal relation of cognitive dysfunction to clinical course. Method: We compared euthymic offspring (age range: 18–32 years) of lithium-responsive bipolar parents with and without a previous lifetime history of psychiatric illness to healthy comparison subjects with a negative family history, on a VBM task that requires target location. Results: High-risk offspring with no lifetime psychiatric history performed the VBM task at levels of healthy controls. High-risk offspring with a previous history of a mood disorder, in complete remission, made significantly more errors at short target-mask intervals than control or never ill offspring. These higher error rates were not a consequence of faster response times. Conclusions: There is preliminary evidence of specific cognitive dysfunction early in the course of illness in affected offspring of parents with lithium responsive BD. VBM is ideal for future longitudinal studies addressing whether cognitive dysfunction in BD is a trait marker or a consequence of illness manifestation.