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PubMed1995

Long-term treatment of mood disorders in schizophrenia.

Mood disorders in schizophrenia are common and are associated with a poor outcome, an increased risk of relapse and a high rate of suicide. Consequently, treatment strategies need to take mood disorders into account. In depressed and actively psychotic schizophrenic and schizoaffective patients, treatment with neuroleptic plus antidepressant may be less effective than neuroleptic alone. However, patients with post-psychotic depression on maintenance neuroleptics respond well to tricyclic antidepressants. Mood disorders can be caused by neuroleptics and if so will often improve if the dose is reduced or if the drug is changed. Anticholinergics may also help. In schizoaffective disorder, lithium is usually beneficial, especially for patients with classical affective disorder. Carbamazepine may be more effective in patients with schizoaffective and schizophreniform disorders. At doses comparable with those effective in schizophrenia, clozapine may be as good or better than conventional neuroleptics in schizophrenic patients with psychotic mood disorder or schizoaffective disorder. In patients with high BPRS anxiety/depression scores, risperidone (8 mg/day) was more effective than haloperidol (10 mg/day). Risperidone at a mean dose of 8.6 mg/day was also more effective than haloperidol (mean dose 9.2 mg/day) or levomepromazine (methotrimeprazine -- mean dose 125 mg/day) on the Psychotic Anxiety Scale. Mood-related symptoms are therefore amenable to treatment. Risperidone and clozapine appear to be good candidates for the long-term treatment of mood disorders in schizophrenia, although long-term, double-blind, controlled studies are needed to confirm this.

Affective Symptoms↗
PubMed2001

Emerging therapeutic targets in bipolar mood disorder.

Bipolar mood disorder is a chronic, severe and life-threatening psychiatric illness, whose underlying pathophysiology is still obscure. Lithium is the mainstay of treatment for this illness, with robust acute antimanic and long-term prophylactic effects. Over the past decade, valproate has been another medication shown to have possibly similar mood-stabilising properties to lithium, in double-blind controlled trials. Nonetheless, among patients suffering from bipolar disorder, a substantial percentage appears to respond poorly to currently available pharmacological therapies, including lithium, valproate, carbamazepine and other newer compounds, clearly demonstrating that there is a substantial need for improved therapeutic agents. Very significant effort has been made in the past several years to elucidate the cellular mechanisms by which lithium and valproate produce their therapeutic effects. The available evidence points to a modulatory action of these compounds over multiple neural biochemical pathways and most investigations have found relevant actions of mood stabilisers on intracellular signal transduction mechanisms. Moreover, it has been shown in recent years that lithium and valproate lead to long-term changes in neural plasticity, with eventual neurotrophic and neuroprotective effects. Although these actions are not fully understood, stimulation of transcription factors and effects on gene expression are potentially involved. The search for the mechanisms of action of well-established mood-stabilisers has helped to reveal promising molecular targets to test novel therapeutic approaches. This review will examine the current investigations on the diverse biochemical and molecular pathways regulated by either lithium or valproate and highlight the potential cellular targets for the development of novel mood stabilisers.

Journal Article↗
PubMed2001

Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders.

Velo-cardio-facial syndrome (VCFS) is a congenital malformation syndrome with variable phenotypic features that has been associated with chromosomal microdeletion 22q11.2. Psychiatric disorders have been reported to be highly prevalent in individuals with this syndrome, and the objective of this study was to assess the nature and extent of psychopathology among individuals with VCFS. We studied 20 children and adolescents with 22q11 deletions determined by fluorescence in situ hybridization (FISH). Control subjects were 11 nondeleted siblings who were the closest age match to the affected subjects. Both affected and control subjects were assessed using two standardized psychiatric research instruments. The results of this study confirmed the high rate of psychiatric disorders among VCFS subjects (60% of our subjects). Of the specific types of disorders, only mood disorders were significantly more common among VCFS subjects compared to sibling controls, with eight VCFS subjects having mood disorders compared with none of the control subjects (P<0.02). Three affected subjects had schizotypal traits comorbid with a mood disorder. In addition, disruptive behavior disorders were frequently diagnosed among VCFS subjects. Using a dimensional measure of psychopathology, significant differences between VCFS subjects and sibling controls were found on three scales: ADHD (P<0.02), separation anxiety (P<0.02), and depression (P<0.01). VCFS subjects were achieving significantly less well academically and requiring significantly more special educational assistance than sibling controls. Follow-up data were available on two subjects, both of whom had been diagnosed with schizophrenia. Further research on psychopathology in VCFS may provide a model of how a specific genetic defect can lead to the development of psychiatric disorders.

Abnormalities, Multiple↗
PubMed2001

Multivariate logistic regression for familial aggregation of two disorders. II. Analysis of studies of eating and mood disorders.

Family studies have suggested that eating disorders and mood disorders may coaggregate within families. Previous studies, however, have been limited by use of univariate modeling techniques and failure to account for the correlation of observations within families. To provide a more efficient analysis and to illustrate multivariate logistic regression models for familial aggregation of two disorders, the authors analyzed pooled data from two previously published family studies (conducted in Massachusetts in 1984-1986 and 1986-1987) by using multivariate proband predictive and family predictive models. Both models demonstrated a significant familial aggregation of mood disorders and familial coaggregation of eating and mood disorders. The magnitude of the coaggregation between eating and mood disorders was similar to that of the aggregation of mood disorders. Similar results were obtained with alternative models, including a traditional univariate proband predictive model. In comparison with the univariate model, the multivariate models provided greater flexibility, improved precision, and wider generality for interpreting aggregation effects.

Family↗
PubMed1994

Social perceptions and borderline personality disorder: the relation to mood disorders.

We used the Structural Analysis of Social Behavior (SASB) to compare the social perceptions of borderline, unipolar, and bipolar-depressed inpatients. As predicted, borderline subjects differed from bipolar-depressed and unipolar subjects in their social perceptions. Borderline subjects viewed their relationships to their mother, hospital staff, and other patients as more hostile and autonomous than did mood disordered subjects. The results are discussed in terms of an integrative theory of borderline personality that considers the psychobiology of interpersonal relationships and attachment disruptions.

Adult↗
PubMed2007

Fluoxetine monotherapy in attention-deficit/hyperactivity disorder and comorbid non-bipolar mood disorders in children and adolescents.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for ADHD and comorbid non-bipolar mood disorders in a prospective, 6-12-week open-label, study of fluoxetine monotherapy. Fluoxetine was associated with significant decreases in the severity of depressive symptoms, and also, associated with significant decreases on subscales of inattention/overactivity and aggression/defiant symptoms-47% of participants were much or very much improved without observed adverse effects.

Adolescent↗
PubMed1994

A family study of anxiety disorders: familial transmission and relationship to mood disorder and psychoactive substance use disorder.

The prevalence of mental disorders in 76 first-degree relatives (parents and nontwin siblings) of 33 subjects with anxiety disorder was compared with the prevalence of mental disorders in 45 first-degree relatives of 20 subjects with mood disorder and 13 first-degree relatives of 6 subjects with psychoactive substance use disorder. All subjects were personally interviewed with the Structured Clinical Interview for DSM-III-R Axis I (SCID I). Interrater reliability was high for most diagnoses. Significantly more first-degree relatives of subjects with anxiety disorder had panic disorder and generalized anxiety disorder compared with relatives of probands with mood disorder. Significantly more female than male relatives of anxiety subjects suffered from anxiety disorders; there were no gender differences in the prevalence of anxiety disorders in relatives of mood and psychoactive substance use disorder (PSUD) subjects. The combination of anxiety and mood disorder was overrepresented in first-degree relatives of subjects with the same type of comorbidity. In relatives of subjects with mixed anxiety and psychoactive substance use disorder, but no mood disorder, there was an overrepresentation of PSUD; mainly alcohol abuse or dependence.

Adult↗
PubMed1999

Factors differentiating personality-disordered individuals with and without a history of unipolar mood disorder.

The relationship between mood disorders and personality disorders has been of longstanding interest to clinicians. Despite theoretical reasons to do so, virtually no studies have examined factors that discriminate personality-disordered subjects with a history of mood disorder (PD/HMD) from personality-disordered subjects without a history of mood disorder (PD). This study examined demographic variables, patterns of comorbidity, measures of life functioning, personality traits, and early life experiences differentiating PD/HMD (n = 83) from PD (n = 214). Diagnoses were assigned using structured clinical interviews and a best-estimate procedure. The results suggest that subjects with borderline personality disorder are more likely to have a life history of mood disorder than are subjects with other personality disorders. In addition, PD/HMDs are more likely to receive a diagnosis of anxiety disorder or alcoholism, to have lower Global Assessment of Functioning (GAF) scores, and to have sought treatment than PDs. On self-report measures of personality, PD/HMDs endorse higher levels of trait anxiety and affective lability (e.g., Harm Avoidance, Neuroticism) than do PDs. PD/HMDs are also more likely to report childhood physical and emotional abuse than are PDs, and to describe their parents as using affectionless control. No differences were found between Axis II clusters as a function of mood disorder history. The discussion suggests a potential model in which early environmental stress interacts with constitutional vulnerabilities to put individuals at an increased risk for both mood and anxiety disorders as well as personality disorders.

Adolescent↗
PubMed2005

[The relationship between mood disorders and temperament, character and personality].

The terms temperament, character and personality have been used almost synonymously despite their different meanings. Hippocratic physicians conceptualized illness, including melancholia, in dimensional terms as an out-growth of premorbid characteristics. In modern times, full-scale application of this dimensional concept to psychiatric disorders led Kraepelin, Schneider and Kretschmer to hypothesize that the 'endogenous psychoses are nothing other than marked accentuation of normal types of temperament'. Akiskal's 'soft-bipolarity' and 'affective temperaments' concepts and Cloninger's psychobiological model of temperament and character, which includes four temperament and three character dimensions, are examples of this dimensional approach from the last two decades. Hypotheses concerning the relationship between personality disorders and mood disorders have been described, but it is likely that a single unitary model would not adequately capture the complexity inherent in the relationship between mood and personality disorders. The DSM multiaxial approach to diagnosis encourages the clinician to distinguish state (Axis I) from trait (Axis II) features of mental disorders. Categorical systems like DSM have been criticised because of their inability to mention temperament, character and personality features. In this review, examples of dimensional approaches to mood disorders are given and discussed under the influence of temperament, character and personality disorders. For this purpose, literature from 1980 to 2004 has been reviewed through Pub/med, using the following key words.

Character↗
PubMed1997

Temperament and personality features in panic disorder with or without comorbid mood disorders.

Personality and temperament features, assessed with the Structured Interview for DSM-III-R Personality Disorders-Revised (SIDP-R) and the Tridimensional Personality Questionnaire (TPQ), respectively, were evaluated in 62 patients affected by panic disorder with (PD + MD) (n = 22) or without comorbid mood disorder (PD) (n = 40). A significant difference in the prevalence of personality disorders (PD + MD, 86% vs. PD, 62%; P < 0.05), particularly dependent (PD + DM, 50% vs. PD, 17%; P < 0.01) and borderline (PD + DM, 9% vs. PD, 0%; P = 0.05) personality disorders, was observed between the groups. Moreover, patients in the PD + MD group had higher scores for harm avoidance (PD + MD, 22.2 +/- 5.6 vs. PD, 26.9 +/- 5.1; P < 0.05) than patients in the PD group. The harm avoidance score in PD patients was significantly related to personality disorder and not to MD, suggesting that harm avoidance is not associated with greater severity of the illness. Our data confirm the hypothesis that subjects with higher harm avoidance scores have a greater probability of being affected by cluster C personality disorders and comorbid mood and anxiety disorders.

Adult↗
PubMed2001

Premenstrual exacerbations of mood disorders.

Premenstrual exacerbation of mood disorders has received little attention, despite the recent interest in premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS). Differentiating between PMDD/PMS and other disorders, which worsen premenstrually, is a poorly understood diagnostic challenge. Controversy also focuses on a possible coexistence of PMDD and other mood disorders. This review discusses the differences between mood-disorder exacerbations and premenstrual disorders, evidence for premenstrual magnification of mood disorders, and possible mechanisms for these variations as well as clinical implications.

Adolescent↗
PubMed1991

Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia.

BACKGROUND: Although growing research indicates that the atypical antipsychotic agent clozapine is effective in patients with schizophrenia, little is known about the efficacy of clozapine in patients with schizoaffective disorder or psychotic mood disorders. The purpose of this study was to assess whether or not clozapine is effective in some patients with schizoaffective disorder or psychotic mood disorders. METHOD: By surveying treating clinicians and chart data, we assessed treatment response in 85 consecutive patients, including 39 with schizophrenia, 25 with schizoaffective disorder, and 14 with bipolar disorder with psychotic features, who received clozapine for at least 6 weeks at our center. RESULTS: All patients were either inadequately responsive to or unable to tolerate standard somatic therapies. Compared to patients with schizophrenia, patients with schizoaffective disorder and bipolar disorder with psychotic features displayed significantly higher response rates to clozapine. CONCLUSION: Clozapine may be a useful drug in the treatment of patients with schizoaffective disorder or psychotic mood disorders who are treatment resistant or intolerant of side effects.

Adult↗
PubMed2006

Reasons for substance use and vulnerability factors in patients with substance use disorder and anxiety or mood disorders.

This cross-sectional study examined the reasons for substance use and the presence of vulnerability factors such as substance sensitivity, sensation seeking, and symptoms related to the attention deficit hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) and comorbid mood and anxiety disorders by using the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS), a novel instrument designed to explore the spectrum of substance use and its clinical correlates. Study participants included 61 patients with SUD and mood or anxiety disorder, and two comparison groups including 35 patients with SUD only and 50 controls not in treatment for mental disorders or SUD. We found that patients with co-morbid mood or anxiety disorder had significantly higher scores on the SCI-SUBS domains 'substance sensitivity' and 'self-medication' as compared to those with SUD only. Scores on 'sensation seeking' and 'ADHD' domains were similar between both groups of patients and higher than in controls. Patients with comorbid mood or anxiety disorders showed a higher sensitivity to substances and were more prone to self-medication than those with SUD only. These characteristics should be taken into account in the diagnostic assessment and in long-term treatment to decrease the risk of relapse.

Adult↗
PubMed2003

[Posttraumatic stress disorder and bipolar mood disorder].

Bipolar disorder (BD) is not only an endogenous condition. Severe negative life events have been shown to influence the development of the first episode and lifetime course of BD. Posttraumatic stress disorder (PTSD) is a severe and incapacitating mental condition that affect a significant proportion of the general population at some time in their lives. The concomitant presence of BD and PTSD has been shown to be more frequent than previously suggested and psychotic patients with trauma histories have a tendency to present more severe symptoms and are more proned to present substance use disorders. Trauma-related intrusive memories and nightmares of PTSD have been associated with mood changes. Also, kindling and behavioral sensitization have been proposed to explain the etiology and course of both disorders. Pharmacological approaches for this comorbidity are still based on empirical or not controlled approaches. In this article, we critically review the current literature regarding this co morbid condition, and highlight some aspects related to epidemiology, etiology, course and pharmacological treatment of both disorders. Overall, our review emphasizes the importance of systematically evaluate trauma histories in patients with BD.

Bipolar Disorder↗
PubMed1997

Mood Disorders Secondary to Stroke.

Mood disorders associated with stroke have been recognized by clinicians for over 100 years. Recent studies, however, have begun to distinguish whether these mood disorders represent primary disorders or are a secondary consequence of the cerebral infarction. Although poststroke mood disorders share similarities with primary mood disorders in their clinical phenomenology, longitudinal course, and response to treatment, clinical-pathologic correlations during the acute poststroke period have provided a strong argument that these disorders are frequently etiologically linked to the cerebral ischemia. Major depression during the acute stroke period was associated with left frontal and left basal ganglia lesions, while mania was associated with right orbital frontal, basotemporal, basal ganglia, or thalamic lesions. Identification of the mechanism of these disorders will ultimately establish their "secondariness" as well as development of more focused treament strategies.

Journal Article↗
PubMed2006

Mood disorders in the elderly.

Mood disorders in the elderly are a growing source of morbidity and mortality. Unfortunately, mood disorders in later life frequently are not diagnosed and treated. Appropriate, prompt diagnosis and treatment of late-life mood disorders can significantly improve the quality of life of patients and families and may prove life saving. Current treatments can help most older adults with mood disorders. Future treatments are promising, particularly for those with treatment-resistant depression.

Aged↗
PubMed1993

Depressive symptoms and family history in seasonal and nonseasonal mood disorders.

OBJECTIVE: The authors' goal was to compare the symptoms and family history of seasonal affective disorder with those of nonseasonal mood disorders. METHOD: From a subspecialty mood disorders clinic, 34 patients with major depression, seasonal pattern (seasonal affective disorder), diagnosed with DSM-III-R criteria, were matched in age, sex, and diagnostic subtype (recurrent unipolar, bipolar I, or bipolar II) to 34 patients with nonseasonal mood disorders. Data on symptoms during the most recent depressive episode were obtained by chart review and compared by using chi-square tests. Family history data for first-degree relatives of patients with seasonal and nonseasonal mood disorders were gathered by using the family history method, and diagnoses were based on Family History Research Diagnostic Criteria. RESULTS: Patients with seasonal affective disorder reported significantly more hypersomnia, hyperphagia, and weight gain and reported less suicidal ideation and morning worsening of mood than the patients with nonseasonal mood disorders. No differences were found in family histories of mood disorders, other psychiatric disorders, and any psychiatric disorder between the groups with seasonal versus nonseasonal mood disorders. Alcoholism was found more frequently in the relatives of the patients with seasonal affective disorder. CONCLUSIONS: Differences in symptoms between seasonal and nonseasonal mood disorders provide some support for seasonal affective disorder as a diagnostic subtype of mood disorders. However, the genetic loading for mood disorders (of unspecified seasonality), as determined by the family history method, is similar for seasonal and nonseasonal mood disorders.

Adult↗