Inositol reduces depressive-like behaviors in two different animal models of depression

  Rationale: Myo-inositol is an isomer of glucose that is a precursor in the phosphatidylinositol (PIP) cycle, a source of two second messengers: diacylglycerol (DAG) and inositol triphosphate (IP₃). Clinical studies have reported that inositol is effective in relieving symptoms of depression. Objective: The present study examined the effects of inositol on two animal models of depression: the Porsolt forced swim test, a behaviorally based model; and the reserpine-induced immobility model, a pharmacologically based model. Methods and results: Chronic inositol injections (daily for 14 days) of 1.2 g/kg (but not at lower doses) reduced immobility time and increased struggle time in the Porsolt test compared with control animals. The same dose and treatment schedule also reduced complete immobility time but did not affect ambulatory activity in the reserpine test compared with controls. Chronic oral treatment with inositol (10% in food for 14 days) had effects similar to IP inositol in the Porsolt test. Conclusions: The effect of inositol in animal models of depression supports its possible importance as a new treatment for the disorder, and permits research on its mechanisms of action. Received: 31 August 1998 / Final version: 18 November 1998     

Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test

Rationale: The forced swimming test (FST) is a behavioral test in rodents that predicts the clinical efficacy of many types of antidepressant treatments. Recently, a behavior sampling technique was developed that scores individual response categories, including swimming, climbing and immobility. Although all antidepressant drugs reduce immobility in the FST, at least two distinct active behavioral patterns are produced by pharmacologically selective antidepressant drugs. Serotonin-selective reuptake inhibitors increase swimming behavior, while drugs acting primarily to increase extracellular levels of norepinephrine or dopamine increase climbing behavior. Distinct patterns of active behaviors in the FST may be mediated by distinct neurotransmitters, but this has not been shown directly. Objectives: The present study examined the role of serotonin in mediating active behaviors in the forced swimming test after treatment with two antidepressant drugs, the selective serotonin reuptake inhibitor, fluoxetine and the selective norepinephrine reuptake inhibitor, desipramine. Methods: Endogenous serotonin was depleted by administering para-cholorophenylalanine (PCPA, 150 mg/kg, IP.) to rats 72 h and 48 h prior to the swim test. Fluoxetine (10 mg/kg, SC) or desipramine (10 mg/kg, SC) was given three times over a 24-h period prior to the FST. Behavioral responses, including immobility, swimming and climbing, were counted during the 5-min test. Results: Pretreatment with PCPA blocked fluoxetine-induced reduction in immobility and increase in swimming behavior during the FST. In contrast, PCPA pretreatment did not interfere with the ability of desipramine to reduce immobility and increase climbing behavior. Conclusions: Depletion of serotonin prevented the behavioral effects of the selective serotonin reuptake inhibitor fluoxetine in the rat FST. Furthermore, depletion of serotonin had no impact on the behavioral effects induced by the selective norepinephrine reuptake inhibitor, desipramine. The effects of antidepressant drugs on FST-induced immobility may be exerted by distinguishable contributions from different neurotransmitter systems. Received: 4 February 1999 / Final version: 2 June 1999     

Striatal dopamine transporter density in major depression

Rationale: There are no previous data available regarding [¹²³I]β-CIT binding to the dopamine transporter sites in the basal ganglia in depressed patients. Objective: The present study tested the hypothesis that the brain DAT density in depressed patients is lower than that in matched healthy controls. Methods: Fifteen drug-naive outpatients with major depression and 18 healthy controls were investigated using single photon emission computerized tomography (SPECT) with a high-affinity dopamine transporter specific radioligand, ¹²³I-labeled β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)-tropane). Results: We found a significantly higher [¹²³I]β-CIT uptake in both sides of the basal ganglia in patients with major depression than in the controls (Mann-Whitney U-test, P = 0.002 on the right and P = 0.003 on the left). Conclusions: The radioligand uptake reflecting the DAT density was significantly higher among the patients than in the controls. This finding is unexpected, since it is generally believed that monoaminergic neurotransmission is lower in depression, and therefore it could be assumed that a reduction in dopamine transmission would lead to secondary down-regulation of DAT density. However, it is possible that up-regulation of the DAT may be the primary alteration, which leads to lower intrasynaptic dopamine concentration and to lower dopamine neural transmission. Received: 20 October 1998/Final version: 25 January 1999     

Kraepelin-oriented research-diagnosable schizophrenia,mania, and depression in schneider-negative schizophrenics

Summary The rigorous neo-Kraepelinean research criteria of the St. Louis/ Iowa and Taylor groups were applied to case record data of 116 first admissions of Schneider-negative schizophrenics—that is, those without first-rank symptoms (FRSs)—hospitalized in a strongly Schneider-oriented German University Psychiatric Clinic from 1962 to 1971. This sample had a total of 45.7% (53 cases) of psychiatric illness diagnosable by research methods. Indeed, only 31% (36 cases) of Schneider-negative schizophrenics turned out to have research-positive Kraepelin-oriented schizophrenia; and of these, 21 fulfilled both sets of research criteria for schizophrenia. It is important that 14.6% (17 cases) of Schneider-negative schizophrenia consisted of research-diagnosable affective disorder, with mania making up 5.2% and depression 9.4% of this figure. The findings suggest that a sample of Schneider-oriented schizophrenia without FRSs as routinely diagnosed in Germany does not seem to represent a clear-cut homogeneous and uncontaminated group of schizophrenics.     

Response sensitization and depression following long-term amphetamine treatment in a self-stimulation paradigm

The effects of long-term amphetamine treatment were evaluated on responding supported by self-stimulation of the substantia nigra. Rats repeatedly treated with d-amphetamine, and tested with a low dose of the drug that ordinarily has no behavioral effect, showed higher response rates than animals repeatedly treated with saline and tested with the same dose of amphetamine. In contrast, a depression in responding was observed among animals that received long-term amphetamine administration and were tested with saline. The effects of long-term amphetamine treatment on self-stimulation could not be explained by the intrusion of drug-induced competitive behaviors such as locomotor activity and stereotypy. The results were attributed to changes in dopamine neurotransmission following prolonged exposure to amphetamine and were also discussed in terms of an animal model for amphetamine psychosis and postamphetamine depression in man.     

Psychopathometrie depressiver Verstimmungen bei chronischer Hämodialyse

Zusammenfassung 32 ambulante Hämodialyse-Patienten wurden über einen Zeitraum von 8 Tagen mehrfach täglich durch psychometrische Fremd- und Selbstbeurteilungsskalen in ihrer Befindlichkeit eingeschätzt. Ziel der Untersuchung war es, depressive Verstimmungen in ihrer Häufigkeit und Ausprägung bei Hämodialyse-Patienten zu erfassen. Es sollte zudem geprüft werden, inwieweit derartige depressive Verstimmungen zur Frage der biochemischen Determiniertheit von depressiven Syndromen beitragen können. Es fanden sich subjektiv erlebte kurzfristige depressive Stimmungsschwankungen in etwa 15% der Fälle, die in den psychometrischen Fremdbeurteilungen jedoch nicht zu objektivieren waren. Derartige depressive Verstimmungen sind somit als Modelldepression für die biologische Depressions-Forschung nicht geeignet. Geringe Häufigkeit und Schwere der depressiven Verstimmungen, sowie psychopathologischer Längs- und Querschnitts-befund lassen die Hämofiltration als wesentlichen Depressionsfaktor im Sinne der Katecholamin-/Indolamin-Mangel-Hypothese unwahrscheinlich erscheinen.     

Desmethylimipramine attenuates cocaine withdrawal in rats

Depression and anhedonia are two major symptoms of cocaine withdrawal in humans. Hence, pharmacological treatments effective in depression might also alleviate the symptoms of cocaine withdrawal. In the present study, the effects of acute and repeated administration of a tricyclic antidepressant, desmethylimipramine (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model of cocaine withdrawal was used that employs the elevation in intracranial self-stimulation (ICSS) thresholds following the termination of prolonged periods of cocaine self-administration as a measure of an animal's anhedonic state. The influence of chronic DMI treatment on-adrenergic receptor binding and affinity was also correlated with the behavioral signs of cocaine withdrawal. Neither acute nor repeated DMI treatment influenced reward functions in rats that were not undergoing cocaine withdrawal. However, repeated DMI treatment significantly down-regulated-adrenergic receptors, and shortened the duration of the post-cocaine anhedonia (elevation in thresholds). Furthermore, the magnitude of the-adrenergic receptor down-regulation correlated significantly with the degree of effectiveness of DMI treatment in reversing the post-cocaine anhedonia. However, chronic DMI treatment did reduce the amount of cocaine self-administered by the animals. The reversal of the post-cocaine anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment demonstrates the potential usefulness of the model in identifying new pharmacotherapies for cocaine withdrawal. In addition, the results indicate that tricyclic antidepressants may be able to ameliorate some of the symptoms of cocaine withdrawal.     

Neue Untersuchungen zur Typus-melancholicus-Struktur bei Migränikern

In an earlier published study [16, 17, 18], it was demonstrated that migraine sufferers have personality traits significantly more strongly associated with the typus melancholicus than healthy individuals and patients with other mental and physical illnesses. They display a fixation on tidiness which manifests itself in an excessive striving for quality and quantity in performance-oriented situations. The main features of their social relationships are excessive helpfulness combined with an exaggerated tendency towards guilt avoidance and symbiotic attachment to their own families. They do not differ from unipolar depressives in these respects. The major aim of the new study is to examine whether the concept of the typus melancholicus in relation to migraine sufferers as proposed in the first study is adaptable to explaining the personality characteristics of migraine sufferers ("typus migraenicus"). Age-matched samples of 42 female migraine sufferers, 40 female patients with unipolar depression, and 41 female control subjects took part in the new study. The test instruments used were von Zerssen's Munich Personality Test (MPT) and a questionnaire specially designed by the first author for assessing the typus migraenicus (German "Fragebogen zur Erfassung des Typus migraenicus," or FETM). The results obtained using univariate and multivariate analyses demonstrate a confirmation of the typus migraenicus concept, although to a less pronounced degree than the previous study. This can be seen as supporting evidence that, independently of the study sample and the investigators, migraine sufferers display with higher random frequency a personality profile very similar to the premorbid personality structure in unipolar depressives.     

A Competency-based Model of Child Depression: A Longitudinal Study of Peer, Parent, Teacher, and Self-evaluations

In a two-wave longitudinal study of third and sixth graders ( N = 617), we obtained self-reports of depression and peer, teacher, parent, and self-reports of competence in five domains: academic, social, attractiveness, conduct, and athletic. Competency evaluations by others predicted change in self-perceived competence over time for girls, but not for boys. Depression predicted change in self-perceived competence over time for boys but not for girls. Among girls, the relative importance of parent, teacher, and peer appraisals shifted from third to sixth grade. For both boys and girls, self-perceptions of competence predicted change in depression scores over time. Furthermore, self-perceived competencies mediated the relation between competency appraisals by others and children's self-reported depression. Results are interpreted in light of a competency-based model of child depression.     

An Investigation of Adolescents' Substance Use Behaviors, Depressed Affect, and Suicidal Behaviors

Data from a four-wave panel design of 975 adolescents were used to study inter-relationships among suicidal behaviors, depressive symptoms, and substance use behaviors. Persistently high levels of problem drinking and depressive symptoms were associated with higher levels of suicidal thoughts and attempts. Higher levels of depressive symptoms and greater cigarette and illicit drug use distinguished suicidal ideators from attempters. Adolescents attempting suicide reported lower levels of family social support, a greater use of substances to cope with stressors, and a higher density of substance-using peers. Implications of the findings for preventive interventions with high-risk teens are discussed.