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J E Alpert

Publications and source records attributed to J E Alpert.

48 records · Page 3Linked to original sources
PubMed1980

Effects of 6-hydroxydopamine and amphetamine on rat mothering behavior and offspring development.

Selective CNS dopamine depletion was produced in neonatal female rats by administration of 6-hydroxydopamine and desmethylimipramine. These rats were subsequently tested as adults for maternal behavior toward their own offspring and received d-amphetamine prior to half of these sessions. The effects of early, selective CNS dopamine depletion and its related developmental disruptions on later care of offspring and response to amphetamine were thereby assessed. Pup retrieval, nest building, crouching, and locomotor behaviors were studied in 6-OHDA + DMI treated mothers while offspring were examined with respect to weight, density of fur, age of eye opening, and shuttlebox avoidance learning. Depletion of brain dopamine to 30% of control concentrations was associated with increased crouching time but with no other differences in caregiving, offspring development, or response to amphetamine. Although profound neonatal depletion of dopamine leads to a variety of disturbances in early life, later maternal behavior is adequate and apparently enhanced. The possible role of compensatory brain mechanisms is discussed.

Amphetamine↗
PubMedDate not supplied

CCK-8 modulation of mesolimbic dopamine: antagonism of amphetamine-stimulated behaviors.

Rats (N = 15) were implanted with cannulae above the dopaminergic A10 ventral tegmental area (VTA). Two weeks later, four measures of open field behavior were quantified for 10 minutes commencing 30 minutes after parenteral d-amphetamine (1.5 mg/kg) and directly after bilateral infusion of 1.5 microliter of: (a) artificial CSF only (VEH), (b) 1.25 microgram desulfated CCK (DS-CCK), or (c) 1.25 microgram sulfated CCK (CCK). Additional rats with bilateral cannulae directed toward the A10 terminal zones of nucleus accumbens were similarly tested with either VEH (N = 2) or sulfated CCK (N = 2). With VTA infusions, both the number of occurrences and duration of rearing were significantly reduced in CCK rats, while neither the number of square crossings nor duration of forward locomotion were significantly modified from controls. With nuclei accumbens septi (NAS) infusions, CCK-8 reduced rearing behavior more than ambulatory behavior in this preliminary testing. With either VTA or NAS infusions, no significant differences from controls were found upon two derived measures of motoric performance, namely, "velocity" (number of squares crossed per second in locomotion) and "vertical stability" (seconds per rear). These results suggest a modulation of dopaminergically-mediated behavior by (sulfated) CCK-8 at the cell body region and terminal fields of the mesolimbic (A10) dopamine system.

Animals↗
PubMedDate not supplied

Anxiety disorders in major depression.

The prevalence and clinical impact of anxiety disorder comorbidity in major depression were studied in 255 depressed adult outpatients consecutively enrolled in our Depression Research Program. Comorbid anxiety disorder diagnoses were present in 50.6% of these patients and included social phobia (27.0%), simple phobia (16.9%), panic disorder (14.5%), generalized anxiety disorder ([GAD] 10.6%), obsessive-compulsive disorder ([OCD] 6.3%), and agoraphobia (5.5%). While both social phobia and generalized anxiety preceded the first episode of major depression in 65% and 63% of cases, respectively, panic disorder (21.6%) and agoraphobia (14.3%) were much less likely to precede the first episode of major depression than to emerge subsequently. Although comorbid groups were not distinguished by depression, anxiety, hostility, or somatic symptom scores at the time of study presentation, patients with comorbid anxiety disorders tended to be younger during the index episode and to have an earlier onset of the major depressive disorder (MDD) than patients with major depression alone. Our results support the distinction between anxiety symptoms secondary to depression and anxiety disorders comorbid with major depression, and provide further evidence for different temporal relationships with major depression among the several comorbid anxiety disorders.

Adult↗
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Hostility changes following antidepressant treatment: relationship to stress and negative thinking.

It is unclear whether changes in hostility following treatment are primarily related to improvement in depressive symptoms or are also closely associated with reductions in negative thinking or perceived stress. We evaluated 94 outpatients with major depression before and after eight weeks of fluoxetine treatment by administering the Symptom Questionnaire (SQ) Hostility Scale, the Hamilton Rating Scale for Depression (HAM-D), the Cognitions Questionnaire (CQ) and the Perceived Stress Scale (PSS). We observed significant elevations in scores on these questionnaires in depressed patients as compared to normal controls. Following treatment with fluoxetine, there was a statistically significant reduction in scores on all four questionnaires. We observed that changes in SQ Hostility were significantly positively related to changes in both depression severity and perceived stress, with these relationships remaining significant after adjusting for gender and baseline SQ Hostility. The relationship between SQ Hostility changes and reductions in negative thinking became significant only after adjusting for gender and baseline SQ hostility. Our results suggest that the marked decrease in hostility following antidepressant treatment is related to a reduction in depressive symptoms, stress levels and negative thinking.

Adult↗
PubMedDate not supplied

Role of endogenous substance P in stress-induced activation of mesocortical dopamine neurones.

The dopamine (DA) innervation to the forebrain arises from subpopulations of midbrain DA neurones broadly classified as nigrostriatal, mesolimbic and mesocortical. Significant differences in the autoregulatory mechanisms and neuronal inputs of these DA pathways may account for their differences in physiological and pharmacological responsiveness. For example, footshock stress can activate rat mesocortical DA cells but does not alter nigrostriatal DA turnover, while also decreasing substance P (SP) concentrations in the midbrain interpeduncular nucleus and in the adjacent ventral tegmental area (VTA), but not in the substantia nigra (SN). This suggested that the activation of the SP input to the VTA may mediate activation of certain DA systems by footshock stress; behavioural studies also had suggested an excitatory effect of SP on DA cells in the VTA. SP antagonists now available are neurotoxic and of questionable efficacy, we therefore used monoclonal antibody against SP. Antibody microinjected into the VTA prevented normal footshock-induced activation of mesocortical DA neurones, suggesting mediation by SP input to the VTA. The in vivo application of antibodies may prove valuable in studies of neuropeptides in the central nervous system (CNS).

3,4-Dihydroxyphenylacetic Acid↗
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Use of the five-factory inventory in characterizing patients with major depressive disorder.

Research on personality traits has suggested an association between depression and certain personality traits, such as neuroticism and extraversion. Costa and McCrae's five-factor personality inventory (NEO) has been shown to measure personality traits in a nonclinical population, but its use has not been fully explored in clinical populations. This study aims to compare NEO results in a sample of depressed outpatients with published test norms, and determine if different levels of neuroticism and extraversion are associated with differences in certain psychosocial and clinical characteristics. Seventy-six depressed outpatients participating in antidepressant clinical trials completed this self-report questionnaire before beginning pharmacological treatment. Diagnosis of major depressive disorder (MDD) was made using the Structured Clinical Interview for DSM-III-R or DSM-IV and the severity of depression was measured with the 17-item Hamilton Depression Rating Scale (HAM-D). The three analyses conducted were as follows: (1) NEO factor scores were compared with published normative means; (2) three groups, based on level of neuroticism, were compared on certain psychosocial and clinical characteristics; and (3) three groups, based on level of extraversion, were compared on the same psychosocial and clinical characteristics. Both the males and females obtained T score values for the Neuroticism Scale 1.5 SD above the mean, for the Extraversion Scale 1.5 SD below the mean, and for the Conscientiousness Scale 1.5 SD below the mean. No significant differences were found between subjects with different levels of neuroticism and extraversion, although a trend did exist indicating a positive relationship between neuroticism and severity of depression. Depressed outpatients experience frequent negative affects, have irrational thought processes, cope with stress poorly, have difficulty controlling impulses, prefer to be alone, and have difficulty carrying out tasks. Future studies should examine how such personality factors affect response to treatment and course of illness.

Adolescent↗
PubMedDate not supplied

Hypochondriacal concerns in depressed outpatients.

The relationship between hypochondriacal concerns, as assessed by the Illness Attitude Scales, and depressive symptoms was examined in a sample of 100 drug-free outpatients with major depressive disorder. These patients were treated with fluoxetine for 8 weeks, and the effect of treatment on hypochondriacal symptoms was examined. All patients were administered the Structured Clinical Interview for DSM-III-R, the Hamilton Depression Rating Scale, the Symptom Questionnaire, and the Personality Disorders Questionnaire-Revised. We found little relationship between severity of depressive symptoms and hypochondriacal concerns. Measures of anxiety, somatic symptoms, and psychological distress were more consistently related to these concerns. Similarly, patients with either histrionic personality disorder or a lifetime history of panic disorder had greater hypochondriacal concerns than patients without these diagnoses. After open treatment with fluoxetine, the degree of hypochondriacal concerns showed statistically significant decreases, which were only partly related to the degree of change in depression and anxiety severity. Our findings suggest that the presence of hypochondriacal concerns among depressed outpatients is more closely related to the presence of anxiety than depressive symptoms. The relatively small impact of an acute course of antidepressant treatment on hypochondriacal concerns in our sample suggests that these concerns may be enduring characteristics modulated only to a limited extent by short term pharmacological alterations of affective state.

Adult↗
PubMedDate not supplied

Outcome definitions and predictors in depression.

BACKGROUND: The definition of outcome in antidepressant treatment studies may be a crucial factor influencing the relationship between possible treatment variables and treatment response. We therefore wanted to investigate possible relationships between baseline severity of depression and anxiety, and different definitions of outcome among outpatients with major depressive disorder undergoing antidepressant treatment. METHODS: Two hundred and forty-eight patients diagnosed with major depression with the Structured Clinical Interview for DSM-III-R Diagnosis - Patient Edition were treated with fluoxetine 20 mg/day for 8 weeks. Patients were evaluated both pretreatment and posttreatment with the 17-item Hamilton Rating Scale for Depression (Ham-D-17), the Clinical Global Impressions Scales for Severity (CGI-S) and Improvement (CGI-I). We chose four continuous definitions of response using a linear regression method to analyze the relationship to baseline anxiety and depression. We used a logistic regression analysis for the relationship between seven categorical definitions of response and baseline severity of depression and anxiety. RESULTS: Greater endpoint severity was significantly positively related to greater baseline severity of depression and anxiety. Lesser baseline severity of depression or anxiety predicted a greater degree of response on either the endpoint CGI-I score (with lower scores indicating greater improvement) or the percent change in HAM-D-17 score (with higher percent change indicating greater improvement). For all seven categorical definitions of response, lower baseline scores were significantly related to the probability of being a responder. CONCLUSIONS: These findings support the impression that how outcome is defined affects the strength and direction of observed relationships with predictive variables. Methodological implications are discussed.

Adult↗
PubMedDate not supplied

Management of major depression in the primary care setting.

BACKGROUND: Patients treated in community clinics, particularly those of minority status, may rely more heavily on primary care physicians (PCPs) for the diagnosis and management of depression. We wished to determine how PCPs in a community clinic setting initially manage patients newly diagnosed with major depression. METHODS: 698 patients were screened for major depression by the Structural Clinical Interview for DSM-III-R in a community-based primary care health center. Forty outpatients (29 Hispanic) were found to suffer from major depression. A letter explaining positive findings was sent to the patients' PCPs. Medical record charts were reviewed 3 months later to determine the PCP's management following the diagnosis. RESULTS: Of the 38 patients who remained in the study at 3 months, 20 (53%) received no intervention from the PCP by the end of 3 months after diagnosis, and of these, 14 were Hispanic. Five (13%) were prescribed an antidepressant by the PCP. Nine (24%) were referred to mental health services for medication, psychotherapy or combination treatment. Four (11%) were prescribed an antidepressant and then referred to mental health services. Differences between management of Hispanic and non-Hispanic patients were not statistically significant. CONCLUSIONS: Independent screening by psychiatrists in primary care settings may not be adequate enough to ensure appropriate management of depression by PCPs. Possible explanations may include time constraints during primary care visits, patient and/or physician reticence, and insufficient education of PCPs about depression.

Adult↗