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W C Drevets

Publications and source records attributed to W C Drevets.

32 records · Page 2Linked to original sources

Functional neuroimaging studies of depression: the anatomy of melancholia.

Functional brain imaging techniques, which permit noninvasive measures of neurophysiology and neuroreceptor binding, are powerful and sensitive tools for research aimed at elucidating the pathophysiology of major depression. The application of these technologies in depression research has produced several studies of resting cerebral blood flow (BF) and glucose metabolism in subjects imaged during various phases of illness and treatment. This review examines these data and the principles relevant to their interpretation and discusses the insights they provide into the anatomical correlates of depression. Within the anatomical networks implicated in emotional processing by other types of evidence, these BF and metabolic data demonstrate that major depression is associated with reversible, mood state-dependent, neurophysiological abnormalities in some structures and irreversible, trait-like abnormalities in other structures. In some of the regions in which trait-like abnormalities appear, abnormal metabolic activity appears at least partly related to the anatomical abnormalities identified in magnetic resonance imaging (MRI) studies of depression.

Affect↗

Course of antidepressant treatment drug type, and prescriber's specialty.

OBJECTIVE: The study examined whether the relationship between the course of antidepressant treatment and the type of prescriber-psychiatrist or nonpsychiatrist-varied by whether a tricyclic antidepressant or a selective serotonin reuptake inhibitor (SSRI) was prescribed. METHODS: Pharmacy claims from a nationwide database were analyzed retrospectively. A total of 3,101 adults who did not have a prescription for antidepressants for nine months and who were then given a prescription for a tricyclic or an SSRI antidepressant were followed for 13 to 16 months after the initial prescription. Outcome measures were rates of treatment termination before one month and subtherapeutic dosing, defined as having received no prescribed daily dosages at or above commonly cited thresholds. RESULTS: Among tricyclic-treated patients, psychiatrists' patients were significantly more likely than nonpsychiatrists' patients to continue in treatment for more than one month (72 percent versus 62 percent). Among patients taking tricyclics for at least three months, those with at least one prescription from a psychiatrist had a significantly higher rate of therapeutic dosing than those with all prescriptions from a nonpsychiatrist (70 percent versus 25 percent). For SSRI-treated patients, rates of termination and therapeutic dosing did not differ significantly by prescriber type. In multivariate equations that controlled for selected differences, effects of drug type and prescriber type were independent when persistence in treatment was analyzed, and interactive when subtherapeutic dosing was analyzed. CONCLUSIONS: Policy making about antidepressant pharmacotherapy should include assessments of the relationships between drug selection and patient outcome across a variety of clinical settings.

Adult↗

Subgenual prefrontal cortex abnormalities in mood disorders.

Pathological disturbances of mood may follow a 'bipolar' course, in which normal moods alternate with both depression and mania, or a 'unipolar' course, in which only depression occurs. Both bipolar and unipolar disorders can be heritable illnesses associated with neurochemical, neuroendocrine and autonomic abnormalities. The neurobiological basis for these abnormalities has not been established. Using positron emission tomographic (PET) images of cerebral blood flow and rate of glucose metabolism to measure brain activity, we have now localized an area of abnormally decreased activity in the prefrontal cortex ventral to the genu of the corpus callosum in both familial bipolar depressives and familial unipolar depressives. This decrement in activity was at least partly explained by a corresponding reduction in cortical volume, as magnetic resonance imaging (MRI) demonstrated reductions in the mean grey matter volume in the same area of 39 and 48% in the bipolar and unipolar samples, respectively. This region has previously been implicated in the mediation of emotional and autonomic responses to socially significant or provocative stimuli, and in the modulation of the neurotransmitter systems targeted by antidepressant drugs.

Adult↗

Course of antidepressant treatment with tricyclic versus selective serotonin reuptake inhibitor agents: a comparison in managed care and fee-for-service environments.

We compared course of treatment with tricyclic antidepressant drugs (TCADs) and selective serotonin reuptake inhibitors (SSRIs) to assess interactive effects of antidepressant type with payer type and patient characteristics. A nationwide sampling of adults (n = 4,252) from approximately equal numbers of health maintenance organization (HMO) and indemnity enrollees were prescribed no antidepressants for 9 months, and thereafter prescribed a TCAD or SSRI. Using a retrospective analysis of prescription claims, these cohorts of TCAD and SSRI utilizers were followed for 13 to 16 months after their initial antidepressant prescription. Outcome measures included (1) termination of antidepressant treatment before 1 month; and (2) failure to receive at least one therapeutic dose during treatment lasting 3 months or more. Rates of premature termination and subtherapeutic dosing were significantly higher for TCAD-treated than SSRI-treated patients, and for HMO than indemnity enrollees. The interaction of HMO enrollment and TCAD use was associated with particularly high rates. Excluding patients terminating in the first month, the proportions of TCAD and SSRI utilizers remaining in treatment over time were not significantly different. We conclude that SSRIs may provide advantages in treatment adherence and therapeutic dosing, particularly in environments with limited prescriber time. The first month of treatment may be especially critical in determining compliance.

Adult↗

Blood flow changes in human somatosensory cortex during anticipated stimulation.

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

Adult↗

Geriatric depression: brain imaging correlates and pharmacologic considerations.

The clinical approach to geriatric major depression involves a variety of special etiopathophysiologic, pharmacokinetic, and pharmacodynamic considerations. In regard to pathophysiology, modern brain imaging and postmortem assessments are elucidating neuropathologic changes in elderly depressives that challenge the notion that geriatric depression is simply a functional brain disorder. These data suggest (but do not yet establish) that many patients who experience depression onset at a late age may acquire affective disease on an arteriosclerotic basis. In contrast, elderly depressives who experience depression onset at an early age are more likely to have acquired depression due to genetic factors but may nevertheless develop degenerative neuropathologic changes over time. The presence of these neuropathologic changes appears to increase elderly patients' risk for developing the adverse central nervous system (CNS) effects of antidepressant treatments. They thereby add another level of complexity to the management of an age group in which pharmacokinetic and pharmacodynamic changes already contribute to the likelihood of adverse drug reactions. Fortunately, the last decade of antidepressant drug development has produced several new agents (including the serotonin selective reuptake inhibitors and more recently, venlafaxine and nefazodone) with substantially reduced CNS and cardiovascular toxicity that facilitate effective treatment of geriatric depression.

Age Factors↗

Buspirone in the treatment of tardive dyskinesia.

Eight patients with mild to severe tardive dyskinesia (TD) were treated for 12 weeks with buspirone in dosages of up to 180 mg/day in an open-label study. Changes in TD severity were assessed by the Abnormal Involuntary Movement Scale. The rater was blind to buspirone dosage. Buspirone was well tolerated by most subjects. A within-subjects comparison of pretreatment and post-treatment Abnormal Involuntary Movement Scale scores revealed a mean improvement of 4.4 (p < 0.01). Improvement was also observed in neuroleptic-induced extrapyramidal side effects such as parkinsonism and akathisia. Scores on the Hamilton Rating Scale for Anxiety and the Brief Psychiatric Rating Scale did not change during the 12-week study. The results of this open-label pilot study suggest that relatively high doses of buspirone may be efficacious in the treatment of TD.

Adult↗

Neuroanatomical circuits in depression: implications for treatment mechanisms.

We previously investigated the functional neuroanatomy of familial pure depressive disease (FPDD) using positron emission tomography (PET) measurements of regional blood flow and obtained evidence that flow is increased in the left prefrontal cortex, amygdala, and medial thalamus and is decreased in the medial caudate. These data along with other evidence suggested that circuits involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus are involved in the pathophysiology of FPDD. One of these circuits, the limbic-thalamo-cortical circuit, which includes the amygdala, the medio-dorsal thalamus, and parts of the ventral and medial prefrontal cortex, may be engaged in abnormal reverberatory activity that maintains the cognitive and emotional set of depression. Using this hypothesis as a neural model to investigate antidepressant treatment mechanisms, we review evidence that the changes in dopaminergic, serotonergic, and noradrenergic function induced by somatic antidepressant therapies may yield modulatory effects on limbic-thalamo-cortical activity. We also discuss preliminary findings of treatment-associated changes in this circuit in studies comparing PET images acquired before and during antidepressant treatment.

Depressive Disorder↗

A functional anatomical study of unipolar depression.

The functional neuroanatomy of unipolar major depression was investigated using positron emission tomography to measure differences in regional cerebral blood flow (BF). A relatively homogeneous subject group was obtained using criteria for familial pure depressive disease (FPDD), which are based upon family history as well as upon symptoms and course. Because of the absence of certain knowledge about the pathophysiology of mood disorders and their underlying functional neuroanatomy, we used data obtained from the subtraction of composite images from one-half of depressed and control subjects to identify candidate regions of interest. The major cortical region defined in this manner was statistically tested on a second set of subjects. Using this strategy, we found increased BF in an area that extended from the left ventrolateral prefrontal cortex onto the medial prefrontal cortical surface. Based upon the connectivity between these portions of the prefrontal cortex and the amygdala and evidence that the amygdala is involved in emotional modulation, activity was measured in the left amygdala and found to be significantly increased in the depressed group. A separate group of subjects with FPDD who were currently asymptomatic were also imaged to determine whether these findings represented abnormalities associated with the depressed state, or with a trait difference that might underlie the tendency to become depressed. Only the depressed group had increased activity in the left prefrontal cortex, suggesting that this abnormality represents a state marker of FPDD. Both the depressed and the remitted groups demonstrated increased activity in the left amygdala, though this difference achieved significance only in the depressed group. This suggests that the abnormality involving the left amygdala may represent a trait marker of FPDD, though further assessment in a larger sample size is necessary to establish this. These data along with other evidence suggest that a circuit involving the prefrontal cortex, amygdala, and related parts of the striatum, pallidum, and medial thalamus is involved in the functional neuroanatomy of depression.

Adult↗

Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type.

Delusions, misidentifications and hallucinations occur frequently throughout the course of senile dementia of the Alzheimer type (SDAT). Rates of psychosis among subjects with moderate to severe SDAT range from 42% to 84% in our study group; at least half of persons with SDAT with no prior psychiatric history will display psychosis at some point during the course of dementia. Furthermore, psychotic symptoms are associated with accelerated cognitive deterioration, but not with increased mortality.

Aged↗

The nature of psychotic symptoms in senile dementia of the Alzheimer type.

The Alzheimer Disease Research Center at Washington University's medical school has gathered a large sample of subjects with senile dementia of the Alzheimer type (SDAT) who are free of other potentially complicating medical, neurologic and psychiatric disorders. Using this homogeneous population, we have characterized psychotic symptoms associated with SDAT. Three groups of symptoms occur commonly: paranoid delusions, misidentification syndromes, and hallucinations. The nature and frequency of these syndromes are discussed.

Aged↗

Erotomania and senile dementia of Alzheimer type.

A case of erotomania in a 75-year-old female with senile dementia of Alzheimer type (SDAT) is described. This case demonstrates the presence of an elaborately systematised delusion in SDAT, and the influence of the progression of SDAT on this delusion.

Aged↗