Daniela Reginaldi

Episodes of Mood Disorders in 2,252 Pregnancies and Postpartum Periods

OBJECTIVE The risks of major affective episodes during pregnancy and during the postpartum period have rarely been compared in large samples across diagnoses. The authors hypothesized that perinatal episodes would mainly be depressive, would occur more in the postpartum than the prenatal period, and would be more prevalent with bipolar than unipolar depressive disorders. METHOD The authors pooled clinical information on 2,252 pregnancies of 1,162 women with clinically treated DSM-IV bipolar I disorder (479 pregnancies/283 women), bipolar II disorder (641/338), or recurrent major depressive disorder (1,132/541) to compare rates of affective episode types by diagnosis during pregnancy and the postpartum period and to identify risk factors. RESULTS Among women with bipolar disorder, 23% had illness episodes during pregnancy and 52% during the postpartum period. Among women with unipolar depression, 4.6% had illness episodes during pregnancy and 30% during the postpartum period. Based on exposure-adjusted risk per pregnancy, episodes were 3.5 times more prevalent during the postpartum period than during pregnancy, and the risk was consistently higher with bipolar disorder. Depression was the most frequent morbidity during and following pregnancy. In multivariate modeling, factors associated with affective episodes in pregnancy, in descending order, were younger age at onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Postpartum episodes were associated with younger age at onset, illness during pregnancy, bipolar disorder, fewer children, and more education. Moreover, pregnancy was less likely and perinatal episodes more likely if diagnosis preceded a first pregnancy. First lifetime episodes occurred in the perinatal period in 7.6% of cases. CONCLUSIONS Among women with major affective disorders, illness risk was much greater during the postpartum period than during pregnancy. Illness mainly involved depression and was strongly associated with younger age at illness onset, bipolar disorder, and high lifetime occurrence rates. The relative risk during pregnancy compared with nonpregnant periods remains uncertain.

Suicide in a large population of former psychiatric inpatients

Aims:  The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric inpatients receiving retrospective and prospective DSM‐IV diagnoses.

Antimanic and mood‐stabilizing effect of memantine as an augmenting agent in treatment‐resistant bipolar disorder

Memantine is a selective, uncompetitive N-methyl- D-aspartate (NMDA) receptor antagonist, currently used in the treatment of Alzheimers disease. Many clinical trials have demonstrated its tolerability and safety. We have suggested that antidepressants induce mania and rapid cycling by sensitizing dopamine D2 receptors and demonstrated that the sensitization induced by antidepressants requires the stimulation of NMDA receptors. It is tempting to suggest that the phenomenon of sensitization could underlie the spontaneous development and the course of mania as well.

Spontaneous length of depression and response to ECT

Electro-convulsive treatment (ECT) was therapeutically ineffective in 27 (20%) of 136 depressed patients. Failure to respond occurred in long-lasting depressions and in patients with a history of long-lasting depressions. In these cases the depression lasted at least 6 months. The hypothesis is proposed that ECT is effective only when given within 6 months of thespontaneous end of the depression. Clinical and nosological implications are discussed.

Depressive mixed states: A reappraisal of Koukopoulos'criteria

BACKGROUND Mixed states have been a fundamental part of Kraepelin׳s conceptualization of the manic-depressive illness. However, after Kraepelin, the study of mixed states was not of great interest, until the publication of the RDC criteria (1978) and then the DSM-III edition (1980), where criteria for mixed manic states were operationalized. The most notable victims of DSM nosology were depressive mixed states, in particular depression with flight of ideas and excited (agitated) depression. METHODS We briefly review the clinical work of Athanasios Koukopoulos on depressive mixed states (in particular agitated depression) pointing out the diagnostic and therapeutic contributions, especially in the lights of Koukopoulos׳ first description of depressive mixed syndrome in 1992. RESULTS The mixed depressive syndrome is not a transitory state but a state of long duration, which may last weeks or several months. The clinical picture is characterized by dysphoric mood, emotional lability, psychic and/or motor agitation, talkativeness, crowded and/or racing thoughts, rumination, initial or middle insomnia. Impulsive suicidal attempts may be frequent. The family observes incessant complaints, irritability, occasional verbal outbursts, occasional physical aggression, and occasional hypersexuality. Treatment with antipsychotics and ECT is very effective; antidepressants can worsen the clinical picture. LIMITATIONS Selective but not systematic review of the literature on depressive mixed states. Relatively little research data is currently available for validation of the criteria proposed by Koukopoulos. CONCLUSIONS Koukopoulos׳ proposal of mixed depression, besides its diagnostic implications, clearly identifying it as manifestations of bipolar disorder, allows for better clinical characterization of cases and improves treatment decisions.

Poor prophylactic lithium response due to antidepressants.

50 manic-depressive patients with rapid cycles received lithium for more than 1 year, during depression they received antidepressant drugs. Response was poor in 36, partial in 6, and good in 8. 21 of the poor responders were persuaded to endure depression without antidepressants; anxiolytics were allowed, 15 stabilized after the end of the untreated depression or after a few milder, shorter episodes; 4 improved partially; 2 were unchanged. 15 other rapid cycle patients started on lithium and stopped antidepressants at the same time. Response was good in 13, partial in 1, and poor in 1. Patients with a course of depression-hypomania (or mania)-free interval also responded poorly to prophylactic lithium when the depression was treated with antidepressants. They responded well when antidepressants were withdrawn. Antidepressants often cause or accentuate a switch from depression to hypomania or mania, and temporary refractoriness to lithium of the hypomania or mania. In this way lithium fails to prevent depression.

Free Interval Duration: Clinical Evidence of the Primary Role of Excitement in Bipolar Disorder

Background: Cyclicity is the essential feature of Bipolar disorder, but the effect of different cycle patterns on the clinical features is poorly understood. Moreover, no studies investigated the relationship between mania and depression inside the manic-depressive cycle. Objective: The aim of this study is to verify the presence of a relationship between the manic and the depressive phase during the course of bipolar disorder. Method: 160 consecutive patients with BD type I were recruited and followed for a mean period of 10 years. During the follow-up period, four types of euthymic phases were collected: free intervals present between a depressive and a manic/hypomanic episode (D-M); free intervals present between a manic/hypomanic and a depressive episode (M-D); free intervals present between two depressive episodes (D-D); free intervals present between two manic/hypomanic episodes (M-M). One-way ANOVA using the groups as independent variable and the duration of the free intervals as dependent variables was used. Furthermore, ANOVA was followed by Fishers Protected Least Significant Difference post-hoc test to measure between-group differences. Results: M-D-free interval phases were shorter than D-M-free intervals. M-D intervals were the shortest ones, the D-D and D-M did not differ, and the M-M were the longest. Conclusion: The strict temporal link between manic and depressive phases supports the idea that the manic-depressive cycle usually begins with a manic episode, and that the subsequent depression is often the consequence of subsiding mania.

Child and Adolescent Clinical Features Preceding Adult Suicide Attempts.

The objective of this study was to identify the predictive value of juvenile factors for adult suicidal behavior. We reviewed clinical records to compare factors identified in childhood and adolescence between adult suicidal versus nonsuicidal major affective disorder subjects. Suicide attempts occurred in 23.1% of subjects. Age-at-first-symptom was 14.2 vs. 20.2 years among suicidal versus nonsuicidal subjects (p < 0.0001). More prevalent in suicidal versus non-suicidal subjects by multivariate analysis were: depressive symptoms, hyper-emotionality, younger-at-first-affective-episode, family suicide history, childhood mood-swings, and adolescence low self-esteem. Presence of one factor yielded a Bayesian sensitivity of 64%, specificity of 50%, and negative predictive power of 86%. Several juvenile factors were associated with adult suicidal behavior; their absence was strongly associated with a lack of adult suicidal behavior.

Transitions: Athanasios Koukopoulos [AθανάσιΟς κΟυκόπΟυλΟς], M.D. (1931–2013)

Athanasios Koukopoulos was born in Chaeronea, a village in the district of Boeotia in central Greece, on 23 November 1931 as the son of Konstantinos and Maria Koukopoulos. His father hoped that he would remain at home to manage the land they owned, but Athanasios preferred to study. His energetic and supportive mother fought for his education. At the end of World War II, following years of exposure to violence and privation, his family moved to Athens just before the Greek civil war of 1946 to 1949. In Athens, Koukopoulos continued his education while playing professional basketball with the prestigious Panatinaikos Sports Club of Athens, which later on presented him with the Golden Clover award. In 1951, he moved to Italy despite remaining hard feelings in Greece following the recent Greco-Italian war of 1940 to 1941 and the subsequent Balkan campaign of the Axis powers in World War II.

Psychopathological characteristics and adverse childhood events are differentially associated with suicidal ideation and suicidal acts in mood disorders

BACKGROUND Depression is an important risk factor for suicide. However, other dimensions may contribute to the suicidal risk and to the transition from ideas to acts. We aimed to test the relative involvement of hopelessness, temperament, childhood trauma, and aggression in suicide risk in a large sample of patients with mood disorders. METHODS We assessed 306 patients with major depressive and bipolar disorders for clinical characteristics including hopelessness, temperament, childhood trauma, and aggression. We tested their associations with suicidal ideation and acts using standard univariate/bivariate methods, followed by multivariate logistic regression models. RESULTS In multivariate analyses, the loss of expectations subscore of the hopelessness scale was associated with lifetime suicidal ideation but not suicide attempt. Childhood emotional abuse, severity of current depression, and female gender were associated with lifetime suicide attempts, whereas hyperthymic temperament was protective. Only hyperthymic temperament differentiated patients with a history of suicidal ideas vs. those with a history of suicide attempt. CONCLUSIONS Findings support the association of hopelessness with suicidal ideation and point to considering in suicidal acts not only depression, but also childhood emotional abuse, hyperthymic temperament, and gender.