Biomedical subjects

Andrew H Miller

Publications and source records attributed to Andrew H Miller.

41 records · Page 3Linked to original sources

PubMed2002

Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.

We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-alpha (IFN-alpha) therapy can be reduced by pretreatment with the antidepressant, paroxetine. Using dimensional analyses, the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-alpha therapy. Forty patients with malignant melanoma eligible for IFN-alpha treatment were randomly assigned to receive either paroxetine or placebo in a double-blind design. Neuropsychiatric assessments were conducted at regular intervals during the first twelve weeks of IFN-alpha therapy and included the 21-item Hamilton Depression Rating Scale, the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale. Neurovegetative and somatic symptoms including anorexia, fatigue and pain appeared within two weeks of IFN-alpha therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-alpha treatment and more specifically in patients who met DSM-IV criteria for major depression. Symptoms of depression, anxiety, cognitive dysfunction and pain were more responsive, whereas symptoms of fatigue and anorexia were less responsive, to paroxetine treatment. These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-alpha, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced "sickness behavior."

Adult↗

PubMed2002

The phosphodiesterase type 4 inhibitor, rolipram, enhances glucocorticoid receptor function.

Previous studies have demonstrated that antidepressants can enhance glucocorticoid receptor (GR) translocation and function, possibly through activation of cAMP and downstream cAMP dependent protein kinases. Accordingly, we examined GR function in cells treated with rolipram, a phosphodiesterase (PDE) type 4 inhibitor that antagonizes cAMP breakdown. Compared with vehicle-treated cells, rolipram alone and in combination with dexamethasone significantly enhanced GR function as measured in both mouse L929 cells and rat C6 glioma cells stably transfected with reporter genes driven by upstream glucocorticoid response elements. Rolipram's facilitation of GR function was reversible by the GR antagonist, RU486, and was associated with reduced cytosloic GR binding, indicating rolipram enhancement of GR nuclear translocation. Finally, rolipram potently augmented GR enhancement by the antidepressant, desipramine. These findings broaden the potential pathways by which PDE type 4 inhibitors can influence cellular function and indicate that these agents may have special utility in disorders associated with impaired GR-mediated feedback inhibition.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2002

Increased early life stress and depressive symptoms in patients with comorbid substance abuse and schizophrenia.

Early adverse events have been associated with increased rates of substance abuse and depression. To investigate the association between early adverse events and comorbid substance abuse in schizophrenia patients, early life stress, depressive symptoms, positive and negative symptoms, anxiety, and cognitive function were measured in an age-, sex-, and race-matched sample of 40 schizophrenia patients with and without comorbid substance abuse. Compared to patients without substance abuse, patients with schizophrenia and a history of substance abuse had a significantly higher incidence of early life trauma, as well as significantly higher scores on the Modified Hamilton Rating Scale for Depression and the Psychiatric Epidemiology Research Interview Life Events Scale. No differences between groups were found in positive or negative symptoms, anxiety, or cognitive function. The results emphasize the importance of early life stress and affective symptoms and their potential relationship to substance abuse disorders in schizophrenia patients.

Adult↗

PubMed2002

Childhood trauma associated with smaller hippocampal volume in women with major depression.

OBJECTIVE: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. METHOD: Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses. RESULTS: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. CONCLUSIONS: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder.

Adult↗

PubMed2002

Antipsychotic-induced hyperprolactinemia and sexual dysfunction.

This overview of antipsychotic-induced hyperprolactinemia provides a summary of the current literature in relation to conventional antipsychotic agents and the five atypical antipsychotics currently available in the United States--clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. Dopaminergic antagonism within the tuberoinfundibular system causes elevation in plasma prolactin levels. Conventional antipsychotic medications and the atypical agent risperidone cause significant elevations in prolactin. Clozapine, olanzapine, quetiapine, and ziprasidone cause minimal effects on prolactin levels in adults, which may be due to a higher 5-HT2A:D2 binding ratio and differential effects on dopamine neurotransmission, with less interference in the tuberoinfundibular pathway. Antipsychotic-induced hyperprolactinemia presumably causes clinical side effects similar to those caused by other forms of hyperprolactinemia. Clinical and endocrinologic changes of hypogonadism also likely occur during chronic antipsychotic-induced hyperprolactinemia. Because hyperprolactinemia may cause clinically significant side effects in patients treated with antipsychotic medications, clinicians should be familiar with the evaluation and treatment of antipsychotic-induced hyperprolactinemia.

Animals↗