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Biomedical subjects

J E Alpert

Publications and source records attributed to J E Alpert.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nutrition and depression: the role of folate.

A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways. Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15-38% of adults diagnosed with depressive disorders. Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified.

Adult↗
PubMed1997

Folate, vitamin B12, and homocysteine in major depressive disorder.

OBJECTIVE: The authors examined the relationships between levels of three metabolites (folate, vitamin B12, and homocysteine) and both depressive subtype and response to fluoxetine treatment in depressed patients. METHOD: Fluoxetine, 20 mg/day for 8 weeks, was given to 213 outpatients with major depressive disorder. At baseline, depressive subtypes were assessed, and a blood sample was collected from each patient. Serum metabolite levels were assayed. Response to treatment was determined by percentage change in score on the 17-item Hamilton Depression Rating Scale. RESULTS: Subjects with low folate levels were more likely to have melancholic depression and were significantly less likely to respond to fluoxetine. Homocysteine and B12 levels were not associated with depressive subtype or treatment response. CONCLUSIONS: Overall, the results are consistent with findings linking low folate levels to poorer response to antidepressant treatment. Folate levels might be considered in the evaluation of depressed patients who do not respond to antidepressant treatment.

Adolescent↗
PubMed1996

Attention deficit hyperactivity disorder in childhood among adults with major depression.

The prevalence of attention deficit hyperactivity disorder (ADHD) with childhood onset and its relationship to course and treatment outcome of major depressive disorder (MDD) in adults was studied in 116 patients (ages 18-65) consecutively enrolled for treatment of MDD. Sixteen percent of the patient were found to meet full or subthreshold criteria for the DSM-III-R diagnosis of childhood ADHD. Twelve percent endorsed persistence of ADHD symptoms into adulthood. Depressed adults meeting criteria for childhood ADHD did not differ significantly from other depressed adults on any measures related to the chronicity or severity of the mood disorder, Axis I comorbidity, or response to acute antidepressant treatment. Our results are clinically important as they suggest that clinicians need to be aware of the possibility that a substantial proportion of patients with MDD may suffer from comorbid ADHD and that treatments need to include the targeting of possible residual ADHD symptoms in addition to those of depression.

Adolescent↗
PubMed1996

Patterns of personality disorder comorbidity in early-onset versus late-onset major depression.

OBJECTIVE: This study tested the hypothesis that in a population of adult outpatients with major depression, those with an early onset of depression would have a greater prevalence of personality disorders than those with a late onset of depression. METHOD: The 404 subjects were patients participating in depression treatment studies at the Massachusetts General Hospital. They were administered the Structured Clinical Interview for DSM-III-R-Patient Version to assess the current presence of major depression and the age at onset of the initial depressive episode. The subjects were then divided into two groups: those with early onset (before 18 years of age) and those with late onset (at age 18 or later). The prevalence of personality disorders was determined through use of the physician-rated Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II) and the patient-rated Personality Diagnostic Questionnaire-Revised (PDQ-R). RESULTS: The patients with early onset of major depression had a significantly higher prevalence of avoidant, histrionic, narcissistic, and borderline personality disorders according to the SCID-II. The PDQ-R scores indicated that avoidant, dependent, passive-aggressive, histrionic, narcissistic, borderline, and antisocial personality disorders were significantly more prevalent among the patients with early onset of major depression. CONCLUSIONS: Overall, the results are consistent with the view that early-onset depressive illness is distinguished from late-onset major depression by more frequent association with persistent disturbances in behaviors and attitudes.

Adolescent↗
PubMed1995

The Mini-Mental State Examination among adult outpatients with major depressive disorder.

One hundred forty-eight patients, ages 18-65, with major depression were administered the Mini-Mental State Examination (MMSE) prior to 8 weeks of treatment with fluoxetine; 75 of these patients were readministered the MMSE following treatment. MMSE scores were not related to pretreatment severity of depression or to reported concentration problems and were not predictive of antidepressant response. Non- and partial responders had lower posttreatment MMSE scores than responders, men had lower posttreatment scores than women, and subjects over 50 had lower pretreatment scores than younger subjects, although in all cases, the magnitude of the differences was small and unlikely to be clinically important. Our results suggest that while the MMSE has been shown to be useful among geriatric and other depressed inpatients, it is not a sensitive indicator of depression severity, concentration problems, or likelihood of treatment response among otherwise healthy adults with major depression in an outpatient setting.

Adolescent↗
PubMed1995

Early nonresponse to fluoxetine as a predictor of poor 8-week outcome.

OBJECTIVE: The purpose of this study was to quantify the proportion of patients who show no response to a fixed dose of fluoxetine after 2, 4, and 6 weeks of treatment and then respond by week 8. METHOD: In an open trial, 143 outpatients who met DSM-III-R criteria for major depressive disorder were treated with a regimen of fluoxetine, 20 mg/day. The authors analyzed the proportion of patients who had less than a 20% decrease from baseline in their scores on the Hamilton Rating Scale for Depression after 2, 4, and 6 weeks and who went on to have a 50% or greater reduction by week 8. A last-observation-carried-forward strategy was used to calculate conditional probabilities of 8-week response. Kaplan-Meier survival analysis was used to estimate probabilities of response at week 8 given degrees of response at week 2. RESULTS: Eighty-two subjects (57.3%) who started the trial responded by week 8. Of those subjects who showed no improvement at weeks 2, 4, and 6, the proportions of responders at week 8 were 36.4%, 18.9%, and 6.5%, respectively. The Kaplan-Meier estimate of 8-week response given nonresponse at week 2 was 0.45. CONCLUSIONS: The proportion of patients with no response to antidepressant treatment by 4 or 6 weeks who responded by week 8 was substantially less than that for subjects who had at least a partial response. Nonresponse as early as week 2 predicted 8-week outcome.

Adult↗
PubMed1995

Relapse in patients on long-term fluoxetine treatment: response to increased fluoxetine dose.

BACKGROUND: Although several studies have examined the long-term efficacy of antidepressants, relatively little attention has been paid to the management of relapses or recurrences during continued antidepressant treatment. This study examined whether depressed patients who had recovered and then relapsed on fluoxetine 20 mg/day would benefit from an increase in fluoxetine dose. METHOD: Eighteen patients who relapsed on fluoxetine 20 mg/day during long-term treatment with fluoxetine as part of a placebo-controlled study had their fluoxetine dose raised to 40 mg/day and were followed for at least 1 month (mean time = 4.7 months). RESULTS: Twelve (67%) were full responders, 3 (17%) partial responders, and 3 (17%) dropped out because of side effects (e.g., insomnia and agitation). Of those patients who had either full or partial response (N = 15; 83%), 3 complete responders had a recurrence on 40 mg/day after a mean of 5.8 months and 1 partial responder had a recurrence 11 months later. Overall, 11 (61%) of 18 patients maintained their response during their follow-up while taking the higher dose of fluoxetine. CONCLUSION: An increase in dose of fluoxetine to 40 mg/day appears to be an effective strategy in the treatment of relapse among depressed patients who had initially responded to fluoxetine 20 mg/day.

Adult↗
PubMed1994

Childhood psychopathology retrospectively assessed among adults with early onset major depression.

Prevalence and impact of comorbidity in early onset major depressive disorder were studied in 116 depressed adult outpatients whose onset of first major depressive episode occurred by age 18. Eighty-eight percent of these patients had at least one additional comorbid Axis I lifetime diagnosis including: social phobia (28%), simple phobia (16%), alcohol (17%) and cannabis (13%) abuse/dependence, and bulimia nervosa (8%). Comorbid anxiety disorders preceded the onset of major depression in two-thirds of individuals while comorbid substance abuse/dependence followed the onset of major depression in two-thirds and predicted more frequent occurrences into adulthood. In contrast to frequency of episodes, severity and duration of an index episode of major depression were not influenced by comorbidity.

1-Naphthylamine↗
PubMed1986

Selective activation of mesolimbic and mesocortical dopamine metabolism in rat brain by infusion of a stable substance P analogue into the ventral tegmental area.

Microinfusion of the metabolically stable substance P (SP) agonist, [pGlu5,MePhe8,Sar9]-SP5-11 (DiMe-C7), into the ventral tegmental area (VTA) of rat brain increased levels of the dopamine (DA) metabolite dihydroxyphenylacetic acid in the prefrontal cortex (+ 120%) and nucleus accumbens (+30%) but not in other regions of forebrain. In contrast, infusions of DiMe-C7 or SP into the lateral ventricles or microinfusions of SP into VTA failed to elicit increases in DOPAC levels in forebrain. DA levels were unaffected by SP or DiMe-C7 regardless of the route of administration. These data and previous studies suggest a role for endogenous SP in the modulation of mesocortical and mesolimbic DA neurones.

Animals↗
PubMed1985

Aversive effects of subcutaneously injected vasopressin in the rat: independence of the ascending dorsal noradrenergic bundle.

The unconditioned stimulus properties of subcutaneously administered arginine vasopressin (AVP) were examined using place and taste conditioning paradigms. Evidence for an aversive effect of the peptide was found, in general agreement with a previous report, although a high dose of AVP (10 micrograms) was required. Also investigated was the possible role of the dorsal noradrenergic bundle (DNAB) in conditioned taste aversion established by AVP. Although the DNAB has been proposed as one of the central pathways through which AVP exerts a facilitatory effect on conditioned behaviour, destruction of this pontine-forebrain projection with 6-hydroxydopamine did not appear to alter the aversiveness of the drug in the present study. These results replicate the finding that AVP can serve as an aversive stimulus but also indicate that the aversive properties of the peptide may prove to be dissociable from its ability to enhance the retention of learned behaviour.

Animals↗
PubMed1984

Impairment in T-maze reinforced alternation performance following nucleus basalis magnocellularis lesions in rats.

Rats were trained on a reinforced alternation paradigm using an elevated T-maze. After pre-surgical training subjects received either ibotenic acid (4 micrograms/0.4 microliter) or vehicle (pH 7.4, 0.4 microliter) bilaterally into the region of the nucleus basalis magnocellularis--an important source of neocortical acetylcholine projections. Acetylcholinesterase staining of sectioned brains revealed a loss of neocortical, but not hippocampal staining in lesioned animals. On the T-maze task, lesioned rats showed significantly impaired choice performance relative to controls. They also demonstrated significant side biases, the degree of which was correlated with choice performance deficit.

Acetylcholine↗
PubMed1984

Dopamine denervation of frontal cortex or nucleus accumbens does not affect ACTH-induced grooming behaviour.

Studies with dopamine (DA) receptor antagonists have implicated brain DA systems in the increased grooming behaviour elicited by intracerebroventricular (i.c.v.) administration of ACTH or exposure to a novel environment. To evaluate the potential contributions of DA terminals innervating frontal cortex and nucleus accumbens, stereotaxically guided injections of 6-hydroxydopamine (6-OHDA) were made into these regions of rat brain following peripheral administration of desmethylimipramine and pargyline. Despite an 88% mean reduction of DA, and 68% mean reduction of noradrenaline in frontal cortex, the amount of grooming behaviour observed either in a novel cage, or after i.c.v. injection of ACTH1-24 was not detectably altered. The lesions also did not affect locomotor activity measured during the scoring of grooming, in an open field, in photocell cages, or in a running wheel, even in the animals most severely depleted of DA. Following nucleus accumbens 6-OHDA infusions, depletions of DA as great as 99% were obtained. Animals with accumbens depletions greater than 90% showed the expected attenuation of amphetamine-stimulated locomotor activity. Nevertheless, they exhibited normal grooming scores in a novel cage, and in response to i.c.v. ACTH1-24. It is concluded that dopaminergic terminals in nucleus accumbens and probably those in frontal cortex are not necessary for the expression of novelty- or ACTH-induced grooming.

Adrenocorticotropic Hormone↗
PubMed1983

The effects of central catecholamine depletions on spatial learning in rats.

The role of forebrain catecholamine systems in spatial learning was assessed using a recently described place navigation task. Rats were required to learn the spatial location of a platform hidden 1 cm below the surface in order to escape from a large pool filled with opaque water. Circumscribed destruction of dopamine or noradrenaline neurones was achieved with bilateral stereotaxic injections of 6-hydroxydopamine. Rats with neostriatal dopamine depletions showed regulatory impairments, mild akinesia and increased latencies to escape during training on both the spatial task and on a non-spatial control task. However their normal transfer test performance indicated that their deficit was not due to impaired spatial learning. Similarly, spatial learning and transfer test performance were unimpaired by mesocorticolimbic dopamine depletions or by extensive noradrenaline loss in cortex and hippocampus following dorsal noradrenergic bundle lesions. These findings suggest that considerable spatial learning can occur in the absence of each of the major telencephalic catecholamine systems.

Afferent Pathways↗
PubMed1980

Amphetamine and maternal behavior: dose response relationships.

Primiparous rats received 0.05, 0.25, 0.50, or 1.50 mg d-amphetamine/kg body weight, injected IP, when offspring reached 3-4 and 10-11 days of age. A multidimensional analysis of their maternal behavior revealed that at doses as low as 0.25 mg/kg, amphetamine had a disruptive effect on mother-pup intercontact interval, retrieval latency, inter-retrieval interval, number of pup retrieved and number of corners to which they were retrieved, time nest building, number of paper strips used, nursing time, time in motion, and number of squares entered. Disruption was dose-dependent for all the preceding except number of corners and time nest building. Amphetamine had no effect on the rate of maternal locomotion. The impact of amphetamine on nursing was significantly greater at pup ages of 3-4 days than at 10-11 days. Drug-induced augmentation of arousal exceeding optimal levels for adequate care-giving and locomotor stimulation incompatible with elements of maternal behavior may account for dose-dependent impairment in the range of 0.25 to 1.50 mg/kg d-amphetamine.

Aging↗