Secondary Affective Disorders Research Articles

Affective disorders in patients with epilepsy: primary process or consequence of paroxysmal activity?

The high prevalence of primary affective disorders in patients with epilepsy is beyond doubt. However, patients in this group are often identified as suffering from mood disorders that do not fulfil the criteria for primary mood disorders, such as recurrent depressive disorder and bipolar affective disorder. The aim of this paper is to analyze the classification and clinical picture of affective disorders in patients with epilepsy and differential diagnostic approaches to identify primary affective disorders and secondary affective disorders in epilepsy. A set of diagnostic signs for the differential assessment of affective disorders in patients with epilepsy is presented. Research of affective pathology in patients with epilepsy and the development of strategies for its successful treatment are still needed.

Anxiety disorders in clinical practice: from development mechanisms to differentiated therapy

Affective disorders represent an extremely topical issue in modern healthcare. Prevalence of anxiety disorders in clinical practice increased significantly since 2019 due to various situational causes, and the trend will probably continue in the coming years. Besides, due to aging of the population and significant growth of the number of patients with neurodegenerative diseases, so called secondary affective disorders also increase. These are linked to organic lesion of the zones strategically important for emotional process implementation, and damaging of the key neurotransmitter systems neurons often seen in neurodegenerative pathological process. Development of anxiety is chiefly based on the defect of the “threat-fear” bound, with the reaction developing in the organism not equivalent to the degree of danger. On pathophysiological level this can be explained by disruption of interaction between limbic system structures that provide “fight or flight” reflex response to the threat, and the neocortex responsible for cognitive processing and adaptation of out emotional reactions. Three key theories of anxiety development can be identified: insufficiency of control, generalization of fear, and hypersensibilization to threat. The first mechanism is most often linked to development of generalized anxiety disorder, the second theory reveals most fully the mechanisms of post-traumatic stress disorder development, while the hypersensibilization of prefrontal cortex best allows to explain sociophobia development. An important mechanism of development and chronification of various affective disorders is neuroinflammation, the role of which will also be highlighted in detail in this review. Understanding of the mechanisms of anxiety spectrum disorders development is important for differentiated drug and non-drug therapy and establishing the optimal strategy of treatment for such patients.

Dopamine receptor agonists: standard and non-standard applications in medicine

Dopamine receptor agonists (DRA) are a class of therapeutic drugs able to directly stimulate dopaminergic receptors facilitating a stronger effect of the endogenous dopamine, which is widely used in treatment of diseases that are accompanied with dopaminergic neurotransmission deficiency. A classical hypodopaminergic condition is Parkinson’s disease and DRA are traditionally associated with it. However, even the first DRA, Bromocriptine, widely adopted in PD treatment, was initially registered as a medication for treatment of prolactinaemia and associated pituitary adenomas and is still widely used in gynecology and endocrinology. In several countries DRA are used in treatment of diabetes, eating disorders, and addictions. Dopamine is the cardinal neurotransmitter of the emotional control and the main neurotransmitter of the reward system, and that defines the interest for researching the dopaminergic agents in treatment of primarily mental illnesses, as well as correction of secondary affective disorders. The experimental effectiveness of ADR in slowing down the rate of progression of the neurodegenerative process in severe incurable diseases, as well as potential neuroprotection in cerebrovascular insufficiency, will allow in the future to determine the criteria for the use of ADR in these non-standard situations, which may even lead to a change in clinical recommendations for the treatment of individual nosologies. Presented in this article are both traditional uses of DRA and an overview of non-standard applications of this class of medications with a discussion of recent studies. In the future, the likelihood of a rethinking of ADRs as a class of only antiparkinsonian drugs, with the expansion of their therapeutic indications.

Primary and secondary affective disorders in a sample of alcohol dependent inpatients: sociodemographic differences

Background Several studies indicate that patients with comorbid alcohol dependence and affective syndromes can be differentiated on the basis of the time of onset of mood symptoms relative to alcohol abuse. However, there are limited data on the underlying pathogenetic mechanisms and risk factors that differentiate between primary and secondary affective disorders (AD) in the context of alcohol dependence. In the present study we investigated the sociodemographic characteristics, family history and the course of illness in cases of comorbid alcohol dependence and AD.

Differentiation of Secondary From Primary Mood Disorders: Controversies and Consensus.

The separation of primary and secondary affective disorders is an important clinical and research diagnostic issue. The characteristics and current hypotheses about the pathophysiology of secondary affective disorders are reviewed. The difficulties inherent in the separation of primary from secondary affective disorders are discussed and guidelines are given to help in this process. In contemporary practice, the affective disorder is not treated significantly differently if found to be a secondary disorder. Areas for further research are suggested.

Clinical EEG findings in mania.

Clinical EEG findings from 202 hospitalized manic patients repeated during 131 recurrences of mania were described. Results were considered in the light of current issues in the literature including the incidence of EEG abnormalities and minor variations, relationships between EEG and family history, EEG lateralization and longitudinal course of illness. The majority of patients had normal EEGs or mild nonspecific deviations compatible with effects of psychoactive medications. More definitive EEG abnormalities were observed in 16-percent. Microsleep occurred in 19 percent and small sharp spikes were found in 17 percent of those who drowsed, with lower incidences of 14 and 6 positive bursts and 6 Hz spike-and-slow-waves. Significant relationships between moderate or severe EEG abnormalities and negative familial loading were identified. Lateralized EEG abnormalities appeared in 9 percent of cases, involving the left side significantly more often than the right. With one exception EEG recordings during subsequent episodes did not suggest structural brain changes. Clinical EEG studies are useful in discriminating between primary and secondary affective disorders. They are also sensitive to effects of lithium and other psychoactive medications. The significance of EEG variations including microsleep and other atypical features continues to be elusive. Issues relating to heritability, hemispheric dysfunction and longitudinal course of illness merit further investigation.

Baclofen administration for the treatment of affective disorders in alcoholic patients

Ninety alcoholic patients with the secondary affective disorders (anxiety, depression) were divided into four groups. Patients in the first group received GABAB receptor ligands (baclofen), those in the second group, diazepam, those in the third group, amitriptyline and those in the fourth group, placebo. The results of clinical, psychological (tests of Spielberger, Zung and MMPI), and electrophysiological (superslow ω-potential) investigations showed that baclofen is an effective drug for affective disturbances in alcoholic patients, with efficacy superior to placebo and equal to diazepam and amitriptyline. At the same time baclofen does not have the side-effects and complications of the latter. Significant changes in platelet MAO Bactivity and the dopamine, serotonin and GABA concentrations in blood after treatment were not found in the four patient groups. The peripheral matabolism of GABA and monoamines do not seem to be related to the development of secondary affective disorders in alcoholic patients. This investigation encourages the search for drugs acting on the affective psychopathology of GABA B receptor ligands.

Neuroanatomical Studies of Major Affective Disorders

Interest in the long-neglected neuropathology of major affective disorders has recently been rekindled, partly because of the emergence of brain-imaging techniques. We review the literature suggesting that attention be given to the neuroanatomy and neuropathology of primary and secondary affective disorders. Computerised tomography studies show that patients with affective disorders tend to be similar to schizophrenic patients and significantly different from normal control subjects in ventricle:brain ratio, sulcal widening, and cerebellar vermian atrophy. As yet, there are few neuropathological investigations of the brains of patients with primary affective disorders. Suggestions for further research in the neuropathology of affective disorders are offered.

Primary and secondary affective disorders: baseline charactristics of unipolar patients

We studied 569 patients with RDC non-bipolar major depressive disorder from the clinical portion of the NIMH Program on the Psychobiology of Depression. Primary ( n = 327; never had a non-affective disorder), secondary ( n = 191; had a non-affective disorder before ever having a major depressive episode), and ‘complicated’ ( n = 51; had at least one depressive episode before and another since developing a non-affective condition) patients were compared on demographic variables, past episodes of depression, past treatments received, and symptoms seen in the index episode. For most characteristics, the groups fell in the order primary, secondary, complicated, such that complicated cases had the earliest onset, the longest duration and the greatest severity in the index episode. These data do not discriminate between two hypotheses: that secondary and complicated depressions are basically depressions which happen to occur in a non-affectively ill person, or that they are different disorders which are distinguished clinically by characteristics related to severity.

Primary and secondary affective disorders: Unipolar patients compared on familial aggregation

We examined rates of mental disorders in relatives of 569 unipolar depressed patients. Probands were divided into three groups: primary depression (never secondary; N = 327), secondary depression (never primary; N = 191), and complicated depression (both primary and secondary episodes of depression; N = 51). We obtained blind family study diagnoses (direct interview) for 1,152 relatives and family history diagnoses (information from proband, with or without information from another relative) for 3,617 relatives. There was no increase in risk for major affective disorder in relatives of probands with primary depression as compared to the other two groups. The risks for several nonaffective diagnoses were increased in the families of patients with secondary depression (as were the risks for secondary depression). The family data for patients with complicated depressions were similar to those with secondary depression. We may conclude that secondary depression is a common finding in patients with nonaffective mental disorders, and shows no increased familial aggregation except increased frequency of nonaffective disorders which themselves are associated with secondary depression.

Abnormal beta-endorphin and beta-lipotropin responses to TRH and LRH administration in primary and secondary affective disorders.

Anomalous anterior pituitary hormone responses to acute administration of TRH and LRH have previously been observed in patients with primary affective disorders (PAD), with TRH eliciting GH, FSH and LH rises, and LRH eliciting GH and Prl rises. We examined whether the same unusual responses were present also for beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in 15 PAD patients, in 9 patients with secondary affective disorders (SAD), and in 7 controls. TRH (500 micrograms iv) elicited rises of beta-EP plasma levels in 5 PAD and 2 SAD patients, and of beta-LPH in 4 PAD and 3 SAD patients. LRH (150 micrograms iv) elicited rises of plasma beta-EP levels in 2 PAD and 2 SAD patients, and of beta-LPH in 5 PAD and 2 SAD patients. No rises of beta-EP and beta-LPH plasma levels were observed in PAD patients after saline administration, nor in the controls after TRH, LRH or saline administration.

Primary and secondary affective disorders in adolescents and young adults.

The concepts of primary and secondary affective disorders have become widely accepted by researchers of adult psychiatric disorders. They are based on the chronological development of certain specified major affective disorders in relation to diagnosable, nonaffective psychiatric disorders. Despite potential etiological implications, little data are currently available on the primary-secondary classification applied to cases with early onset adolescent and young adulthood affective disorders. This study reports on the application and clinical implications of the primary-secondary classification in a sample of 65 adolescent and young adult inpatients who meet Research Diagnostic Criteria (RDC) for an index episode of Major Depressive Disorder.

Serum creatine phosphokinase levels in patients meeting the St. Louis research diagnostic criteria for schizophrenia.

In this study 18 patients with a research diagnostic criteria diagnosis of schizophrenia had a mean initial serum creatine phosphokinase level significantly higher than that of 36 control subjects with other RDC diagnoses. There were no corresponding elevations in the serum levels of nondrinking alcoholics or patients with primary or secondary affective disorders. The authors suggest that increased creatine phosphokinase levels in schizophrenic patients may be due to a sudden increase in the substance in the dopaminergic or limbic system due to increased muscle membrane permeability or to sympathetic nervous system or adrenergic dominance.

The distinction of primary and secondary affective disorders: Clinical implications

We studied a sample of 26 primary depressives and 18 secondary depressives for a number of demographic, family history, and clinical variables and prospectively followed them over one hospitalisation to assess short-term differences in outcome. The Hamilton rating scale for depression and the Zung self-rating depression scale were administered at admission and discharge. While both groups received similar treatments, the primary depressives exhibited a statistically significantly greater degree of recovery than the secondary depressives as measured by these scales. The secondary depressives had more prior suicide attempts (if psychiatrically or medically non-serious attempts are included), a longer duration of current episode of depression and a higher proportion of relatives with alcoholism than the primary depressives.

β-endorphin and β-lipotropin plasma levels in chronic schizophrenia, primary affective disorders and secondary affective disorders

Plasma levels of β-endorphin (β-EP), β-lipotropin (β-LPH) and ACTH were assayed in 15 chronic schizophrenics, nine patients with primary affective disorders (PAD) and seven patients with secondary affective disorders (SAD). Patients received no therapy for 10 days prior to study. All subjects were studied once; eight schizophrenics were studied again after 10 days of Haloperidol therapy, at a dose of 0.1 mg/kg body weight. β-LPH levels were significantly higher in the schizophrenics without hallucinations and in the PAD and SAD patients in comparison to the controls; β-EP levels were higher in the schizophrenics and SAD patients compared to the controls; and ACTH concentrations were significantly lower in the SAD than in the PAD patients. Haloperidol therapy failed to induce significant changes in β-LPH, β-EP or ACTH plasma levels. Statistical evaluation by multiple linear regression confirmed the significant positive correlations among β-LPH, β-EP and ACTH in the controls, schizophrenics with hallucinations, and PAD and SAD patients, while inverse correlations between β-LPH and the other two peptides were found in the schizophrenics without hallucinations. The same analysis revealed that, while in the PAD patients equimolar amounts of the three peptides occurred, the SAD patients were characterized by ACTH/β-LPH and ACTH/β-EP molar ratios of 0.5. Although these results are preliminary, they seem to indicate that β-LPH, β-EP and ACTH secretion patterns in chronic schizophrenia, PAD and SAD may help in revealing specific groups of patients with different biochemical substrates.

Primary and secondary affective disorder. 1. Past social history and current episodes in 92 depressed inpatients

Patients with a clinically significant depressive syndrome are divided into those with another preexisting psychiatric illness (secondary affective disorder) and those whose depression antedates any other diagnosable psychiatric illness (primary affective disorder). Ninety-two randomly selected patients with primary and secondary affective disorder were followed throughout their hospitalization. The current paper reports differences between the two groups in the following areas: past social history; recent psychiatric history including suicidal behavior, type of onset of symptoms and reason for admission; drinking patterns; and certain areas of current symptomatology. Patients with secondary affective disorders have been shown to have a greater disturbance in practically every area.

N-methylnicotinamide excretion and affective disorders.

N-Methylnicotinamide urinary output is examined in 38 healthy volunteers, 52 patients with secondary affective disorders (SAD), 55 patients with primary affective disorders (PAD) and 46 healthy first-degree relatives of PAD patients. The results indicate (1) that in PAD patients and their first-degree relatives the frequency of low N1-MN excretion was significantly higher (P less than 0-001) than in healthy controls and in patients with secondary affective disorders, and (2) that PAD patients have a consistently low N1-MN output, at all times constant and independent of the clinical phases of the disease. These findings provide evidence that the low N1-MN levels may represent an index of a biological background linked to a high morbidity risk for primary affective disorders. The theoretical implications deriving from these data are briefly discussed.

The significance of psychotic affective disorders.

A study of 253 patients with primary and secondary affective disorders disclosed that psychotic features were more frequent among bipolar patients. Except for more frequent psychiatric hospitalization among unipolar patients with psychotic features, no demographic, family history, or parental home variable was found to distinguish between those with and without psychotic features. Chance variation probably accounted for the few symptoms whose frequencies were different depending on the presence or absence of psychotic features. The results failed to support the validity of a classification of affective disorders based on the presence or absence of psychotic features.

Sleep EEG and Motor Activity as Indicators in Affective States

This report reviews a number of studies which support our current classification schema for affective disorders. This classification differentiates between an anxious-hyperactive type and an anergic-hypoactive type which are then further subdivided into primary and secondary affective disorders. While the motor and activity measurements are for the most part limited to patients suffering from primary affective disease, current studies under way indicate that secondary affective disorders may also have characteristic biologic changes. EEG sleep and motor activity parameters provide useful pointers for differential diagnosis and treatment while having the added advantage of diminishing the clinician's almost exclusive dependency on amnestic data and the psychological observations made on the patient's behavior.

The natural history of affective disorders—I. Symptoms of 72 patients at the time of index hospital admission

Fifty-four patients hospitalized with primary affective disorder (depression) were compared with eighteen patients hospitalized with secondary affective disorder (depression). Primary affective disorder was defined as an affective illness occurring in a patient who had no previous psychiatric history other than that compatible with affective illness. Secondary affective disorder was defined as a depression occurring in a patient with a pre-existing, non-affective, psychiatric illness. The distribution and prevalence of affective symptoms in the current episode of illness was found to be the same among the two groups. This investigation indicates that the cross-sectional picture does not serve to distinguish primary from secondary affective disorders among hospitalized patients.