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Biomedical subjects

M H Teicher

Publications and source records attributed to M H Teicher.

At least 55 records · Page 3Linked to original sources

Seasonal mood disorders. Patterns of seasonal recurrence in mania and depression.

DSM-III-R criteria, applied retrospectively in a research-oriented psychiatric clinic, identified patients (N = 146) with a mood disorder and a seasonal pattern of recurrence (seasonal mood disorder). The seasonal mood disorder syndrome was not rare (10% of all mood disorders); diagnostic distribution was as follows: recurrent depression, 51%, and bipolar disorder, 49%, with 30% of the latter having mania (bipolar disorder type I) and 19% having hypomania (bipolar disorder type II). Most patients were women (71%); onset age averaged 29 years, with a mean of eight cycles in 12 years of illness; mean episode duration was 5.0 months. Mood disorder was found in a high proportion (68%) of the families. All but one patient followed one of two seasonal patterns in equal frequency: type A, fall-winter depression with or without spring-summer mania or hypomania; and type B, spring-summer depression with or without fall-winter mania or hypomania. Both types showed consistent times of onset and remission. These results emphasize that DSM-III-R seasonal mood disorder includes severe cases of recurrent depression and bipolar disorder and support a distinction between two seasonal subtypes.

Adult↗

Light visor treatment for seasonal affective disorder: a multicenter study.

The effectiveness of light therapy in seasonal affective disorder (SAD) was evaluated in 105 subjects across five centers. Three intensities of light (60 lux, 600 lux, and 3500 lux) were used in a 2-week randomized, parallel design. There was no significant difference in antidepressant efficacy of the three intensities of light. All three intensities produced a similar frequency of antidepressant response to each other and to that reported in previous studies. There were site differences in the severity of depression during light treatment, but diagnosis and medication status did not affect antidepressant response. These findings suggest that light therapy has an antidepressant action by a nonspecific effect or that light is biologically active in the treatment of SAD across a wide range of intensities.

Adult↗

Developmental differences in acute nigrostriatal and mesocorticolimbic system response to haloperidol.

Dose-dependent effects of haloperidol (2.66 nmol/kg to 79.8 mmol/kg, IP) on levels of dopamine, homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were assessed in the corpus striatum, nucleus accumbens, and medial prefrontal cortex (PFCTX) of 18-, 30-, and 110-day-old rats. Eighteen-day-old rats were 35% and 63% more sensitive than adults to the effects of haloperidol on striatal and accumbens turnover and had steeper dose-response curves. The dose-response function in the PFCTX was similar to striatum at 18 days, but became shallower and nonsigmoidal with age. Maximally effective doses of haloperidol produced, at all ages, a comparable percent rise in DOPAC levels in all regions. With maturation, the percent rise in HVA progressively outstripped DOPAC response in nucleus accumbens and striatum. Overall, prominent developmental differences emerged in these regions in their sensitivity and response to haloperidol, which are consistent with previously reported differences in behavioral sensitivity.

3,4-Dihydroxyphenylacetic Acid↗

Locomotor activity in depressed children and adolescents: I. Circadian dysregulation.

OBJECTIVE: To determine whether circadian activity rhythms were altered in pediatric patients with depression. Evidence was sought for a shift in the timing of the rhythm, blunting of circadian amplitude, or emergence of noncircadian periodicities. METHOD: Locomotor activity was quantified in 57 patients with major depressive mood disorders (mean age 12.4 years) and 16 normal controls (9.9 years). Activity was measured in 5-minute epochs during 72 hours using belt-worn electronic activity monitors. RESULTS: Patients with mood disorders displayed a 15% decrease in the amplitude of their circadian rhythm, and a 52% increase in the magnitude of their twice-daily (hemicircadian) rhythm. No significant difference emerged in the timing of the circadian rhythm. Depressed inpatients and outpatients displayed comparable disturbances, which were most marked in adolescents. CONCLUSIONS: Circadian activity rhythms were dysregulated in pediatric patients with major depression. These findings may have etiological and diagnostic significance.

Adolescent↗

Side effects of light therapy in seasonal affective disorder.

The authors report the frequency of side effects of light therapy in 105 patients with seasonal affective disorder treated with three intensities of light. Common symptoms to emerge during treatment were headache (19%), eyestrain (17%), and feeling "wired" (14%). There was no relationship between side effects and intensity of light used.

Female↗

Early childhood abuse and limbic system ratings in adult psychiatric outpatients.

The authors investigated the hypothesis that early abuse might affect the development of the limbic system. During initial psychiatric evaluation, 253 outpatients completed a self-report scale, the Limbic System Checklist-33 (LSCL-33), designed to measure somatic, sensory, behavioral, and memory symptoms suggestive of temporal lobe epilepsy, along with a questionnaire about physical or sexual abuse. Physical abuse was associated with a 38% increase in LSCL-33 scores (P < 0.01), sexual abuse with a 49% increase (P < 0.02), and combined abuse with a 113% increase (P < 0.0001). Physical or sexual abuse alone was associated with elevated LSCL-33 scores only if the abuse occurred before age 18.

Adolescent↗

Increased prevalence of electrophysiological abnormalities in children with psychological, physical, and sexual abuse.

This retrospective study examined the association between abuse history and neurological abnormalities in 115 consecutive patients admitted to a child and adolescent psychiatric inpatient unit. Increased electrophysiological abnormalities were found in abused patients compared with non-abused patients (54.4% vs. 26.9%, P = 0.021), predominantly in the left side of the frontal, temporal, or anterior region (P = 0.036). This may support the hypothesis that early abuse alters brain development, particularly limbic structures. However, a large-scale prospective longitudinal assessment study is needed to interpret this association. Possible clinical consequences of relatively preserved right frontal function are discussed.

Adolescent↗

Antidepressant drugs and the emergence of suicidal tendencies.

Although antidepressant medications represent the cornerstone of treatment for patients with moderate to severe clinical depression, they also carry serious risks. There is evidence which suggests that antidepressants can, in rare instances, induce or exacerbate suicidal tendencies. Nine clinical mechanisms have been proposed through which this may occur. These are: (a) energizing depressed patients to act on pre-existing suicidal ideation; (b) paradoxically worsening depression; (c) inducing akathisia with associated self-destructive or aggressive impulses; (d) inducing panic attacks; (e) switching patients into manic or mixed states; (f) producing severe insomnia or interfering with sleep architecture; (g) inducing an organic obsessional state; (h) producing an organic personality disorder with borderline features; and (i) exacerbating or inducing electroencephalogram (EEG) or other neurological disturbances. Epidemiological and controlled studies also provide data on the association between antidepressant drugs and suicidal ideation, attempts and fatalities. These include studies which: (a) suggest that electroconvulsive therapy may be more effective than antidepressant drugs in reducing the frequency of suicide attempts; (b) indicate that antidepressants may differ in their capacity to reduce the frequency of suicide attempts; (c) find that more overdose attempts were made by patients receiving maprotiline than placebo; and (d) suggest that fluoxetine may be associated with a greater risk of inducing de novo suicidal ideation. Evidence suggests that antidepressants may vary by at least 15-fold in the number of fatal overdoses per million prescriptions. Estimated overdose proclivity rates were derived after adjusting the fatal toxicity data by the therapeutic index of the drug. These rates were very consistent between agents with the same pharmacological properties, and correlated well with known overdose risk rates for amitriptyline, mianserin and maprotiline. Estimated overdose proclivity rates suggest that the highly selective noradrenaline (norepinephrine) uptake inhibitors (desipramine, nortriptyline, maprotiline) may be associated with a greater risk for overdose than more mixed uptake inhibitors and monoamine oxidase inhibitors (MAOIs). Antidepressants are not uniformly neutral in regard to suicidal ideation and attempts. Data clearly demonstrate that antidepressants ameliorate suicidal ideation more effectively than placebo in patients with depression. Although antidepressants diminish suicidal ideation in many recipients, about as many patients experience worsening suicidal ideation on active medication as they do on placebo. Furthermore, at least as many patients attempted suicide on fluoxetine and tricyclic antidepressants as on placebo, and more patients attempted to overdose on maprotiline than placebo. These observations suggest that antidepressants may redistribute suicide risk, attenuating risk in some patients who respond well, while possible enhancing risk in others who respond more poorly.(ABSTRACT TRUNCATED AT 400 WORDS)

Antidepressive Agents↗

Olfactory bulbectomy as a model for agitated hyposerotonergic depression.

Ablation of olfactory bulbs in rats reduced male sexual behavior, and altered the distribution of wheel-running activity between the light and dark phases of a 12:12 LD photoperiod. These effects were partially reversed by the tricyclic antidepressant amitriptyline. Olfactory bulbectomy also altered serotonin metabolism (5-HIAA/5-HT ratio) in the frontal cortex, nucleus accumbens, hippocampus and corpus striatum. These observations support the hypothesis that olfactory bulbectomy in rodents serves as a model of agitated hyposerotonergic depression.

Amitriptyline↗

Quantitative assessment of psychomotor activity in patients with neuroleptic-induced akathisia.

1. An ambulatory activity monitor with solid-state memory was employed to obtain 24-hour activity data in 29 neuroleptic-treated hospitalized patients and 9 normal controls. 2. The activity monitor is a piezoelectric device which was strapped to the non-dominant ankle. Activity was recorded in 5-minute epochs throughout the 24-hour period. 3. In contrast to patients with mania (N = 15) and schizophrenia (N = 4), depressed patients (N = 9) had higher clinical ratings of akathisia and lower levels of daytime activity. 4. Manic and depressed patients showed a delay of peak activity (= acrophase). 5. Quantifiable alterations in rest-activity rhythms may occur in neuroleptic-induced akathisia but measurement of activity may be complicated by the patient's psychiatric disorder.

Adolescent↗

Dopamine D1 autoreceptor function: possible expression in developing rat prefrontal cortex and striatum.

Synthesis-modulating dopamine (DA) autoreceptor function was studied in vivo using gamma-butyrolactone (GBL) to block propagation along DA axons. DA synthesis was measured by the accumulation of L-3,4-dihydroxyphenylalanine (L-DOPA) after inhibition of aromatic L-amino acid decarboxylase. GBL treatment markedly increased DOPA accumulation in both the striatum and prefrontal cortex of developing rats. The selective DA partial D1 agonist SKF-38393 inhibited this GBL-induced rise in DA synthesis in both the striatum and prefrontal cortex of 15- and 22-day-old rats, but not in adults. The effects of SKF-38393 in developing rats were mimicked by the non-catechol D1 partial agonist CY-208-243, and were blocked by the D1 antagonist SCH-23390, suggesting receptor mediation. The mixed D2/D3 agonist quinpirole attenuated DA synthesis in striatum of both two-week-old and adult rats, but failed to inhibit the GBL-induced increase in DA synthesis in the developing prefrontal cortex. These findings suggest that synthesis-modulating D1-like receptor function may emerge transiently in the developing mammalian forebrain. In the adult striatum these functions appear to be subsumed by D2-like receptors, whereas all synthesis-modulating DA receptor function in prefrontal cortex appears to be essentially lost with maturation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Circadian locomotor activity rhythms in Alzheimer's disease.

Circadian motor activity rhythms in 19 severely demented, institutionalized patients with Alzheimer's disease (AD) were evaluated with small, waist-worn electronic monitors which recorded 5-minute epochs for 48 to 72 hours. Controls were eight normal subjects of the same age (71 to 73 years) in a similar environment. As expected, computer-assisted analysis indicated more than twofold average increases in nocturnal activity and in the proportion of nocturnal to total daily activity in the AD patients. In patients (n = 8) with virtually constant pacing, daytime activity was markedly increased over that of normal controls; these "pacers" also had a significantly decreased amplitude of the circadian activity rhythm compared with controls. Moreover, AD patients showed a marked phase-delay, with individual afternoon maxima (acrophases) averaging 2.1 hours later than in controls (p less than 0.005). These findings quantitatively document clinical observations that AD patients, and especially a subgroup with pacing behavior, have markedly disturbed levels and modulation of daily locomotor activity. They accord with reports of altered circadian rhythms of endocrine and other physiologic parameters in such patients. Activity monitoring may represent a relatively simple, objective measure with which to characterize demented patients and to assess responses to treatment.

Aged↗

Dopamine D1 receptor development depends on endogenous dopamine.

Profound depletion of forebrain dopamine by 6-hydroxydopamine in neonatal rats (day 3) was associated with up to 82% loss of D1 receptor sites labeled with [3H]SCH-23390 at day 21. Administration of the selective D1 agonist SKF-38393 (days 6-18) abolished the correlation between D1 receptor density and DA concentrations, even with greater than 99% depletion of DA. In intact control animals, there was an inverse correlation between spontaneous variation in levels of DA and D1 receptor site density in forebrain tissue (r = -0.79) which also was abolished by treatment with the D1 agonist. Thus, D1 receptor density may be regulated by reciprocal regulatory processes during normal development, but may fail to develop in the absence of an adequate level of stimulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Olfactory bulb control of circadian activity rhythm in mice.

Ablation of mouse olfactory bulbs lengthened the circadian period of wheel-running activity by 43 min and delayed the onset of entrained activity by 108 min. A transient increase in activity during the light phase of the 12:12 h light-dark photoperiod also occurred following surgery. These disruptions suggest that olfactory systems can modulate mammalian circadian rhythms.

Animals↗

COSIFIT: an interactive program for simultaneous multioscillator cosinor analysis of time-series data.

A BASIC program for the Macintosh family of computers has been developed that provides an iterative nonlinear least-squares analysis of biological rhythm data using Marquardt's modification of the Gauss-Newton algorithm. A cosinor model is used, and multiple cosine functions can be fit simultaneously to any equi- or unequispaced time-series data. The program computes optimal frequency, mesor, amplitude, and phase, with standard errors of measurement and both parametric and nonparametric estimates of goodness-of-fit. Multiple time-series can be analyzed simultaneously, allowing one to test for shared characteristics between series. Statistical differences between parameter values of select curves are ascertained by ANOVA. The program is interactive and designed to be user-friendly for the scientist or clinician.

Adult↗

Emergence of intense suicidal preoccupation during fluoxetine treatment.

Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupation after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these patients had ever experienced a similar state during treatment with any other psychotropic drug.

Adult↗