Athanasios Koukopoulos (1931–2013)

With the death of Athanasios Koukopoulos last year, psychiatry lost one of its most stimulating and scientifically influential representatives has been lost. His main scientific contributions are in the course of manic depressive illnesses and mixed affective states. Perhaps his most important contribution to modern psychiatry are his studies on the use of antidepressants in bipolar disorder. He was able to show that antidepressants attenuate the beneficial effects of lithium, can trigger mania, and can lead to cycle acceleration and rapid cycling.     

The diagnosis, symptomatology, and epidemiology of seasonal affective disorder

The operational criteria for seasonal affective disorder (SAD) have undergone several changes since first proposed in 1984. SAD is currently included as a specifier of either bipolar or recurrent major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The International Classification of Diseases, Tenth Edition has provisional diagnostic criteria for SAD. The most characteristic quality of SAD is that the symptoms usually present during winter and remit in the spring. Furthermore, the symptoms tend to remit when the patients are exposed to daylight or bright light therapy. The cognitive and emotional symptoms are as in other types of depression but the vegetative symptoms are the reverse of classic depressive vegetative symptoms, namely increased sleep and increased appetite. SAD is a common condition, but the exact prevalence rates vary between different studies and countries and is consistently found to be more common in women and in youth. SAD probably possibly occurs in children although not as commonly as in young adults. Some studies have found that certain ethnic groups who live at high northern latitudes may have adapted to the long arctic winter.     

Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects

Bright light therapy for seasonal affective disorder (SAD) has been investigated and applied for over 20 years. Physicians and clinicians are increasingly confident that bright light therapy is a potent, specifically active, nonpharmaceutical treatment modality. Indeed, the domain of light treatment is moving beyond SAD, to nonseasonal depression (unipolar and bipolar), seasonal flare-ups of bulimia nervosa, circadian sleep phase disorders, and more. Light therapy is simple to deliver to outpatients and inpatients alike, although the optimum dosing of light and treatment time of day requires individual adjustment. The side-effect profile is favorable in comparison with medications, although the clinician must remain vigilant about emergent hypomania and autonomic hyperactivation, especially during the first few days of treatment. Importantly, light therapy provides a compatible adjunct to antidepressant medication, which can result in accelerated improvement and fewer residual symptoms.     

Winter Depression Recurrence One Year After Cognitive-Behavioral Therapy, Light Therapy, or Combination Treatment

The central public health challenge in the management of seasonal affective disorder (SAD) is prevention of depression recurrence each fall/winter season. The need for time-limited treatments with enduring effects is underscored by questionable long-term compliance with clinical practice guidelines recommending daily light therapy during the symptomatic months each year. We previously developed a SAD-tailored group cognitive-behavioral therapy (CBT) and tested its acute efficacy in 2 pilot studies. Here, we report an intent-to-treat (ITT) analysis of outcomes during the subsequent winter season (i.e., approximately 1 year after acute treatment) using participants randomized to CBT, light therapy, and combination treatment across our pilot studies (N = 69). We used multiple imputation to estimate next winter outcomes for the 17 individuals who dropped out during treatment, were withdrawn from protocol, or were lost to follow-up. The CBT (7.0%) and combination treatment (5.5%) groups had significantly smaller proportions of winter depression recurrences than the light therapy group (36.7%). CBT alone, but not combination treatment, was also associated with significantly lower interviewer- and patient-rated depression severity at 1 year as compared to light therapy alone. Among completers who provided 1-year data, all statistically significant differences between the CBT and light therapy groups persisted after adjustment for ongoing treatment with light therapy, antidepressants, and psychotherapy. If these findings are replicated, CBT could represent a more effective, practical, and palatable approach to long-term SAD management than light therapy.     

Reactivity to a laboratory stressor among individuals with bipolar I disorder in full or partial remission

Strong links have been documented between life events and the course of bipolar disorder. Laboratory studies of stress provide an opportunity to understand the mechanisms involved in reactivity to stressors, but few such studies have been done in the bipolar field. In the current study, 28 people with bipolar I disorder in full or partial remission and 40 people with no history of a mood disorder were randomly assigned to 1 of 3 conditions involving different levels of failure feedback on a concept formation task. Confidence, affective reactions, and performance on a subsequent anagram task were assessed. Results provide tentative support for reactivity to the stressor among the bipolar group, although reactivity was limited to impaired anagram performance.     

Switching, induction of rapid cycling, and increased suicidality with antidepressants in bipolar patients: fact or overinterpretation?

Antidepressants constitute a central cornerstone in the treatment of depressive syndromes. In bipolar patients, however, there is an ongoing controversy about their usefulness for at least 3 decades. Early reports, mainly concerning tricyclic antidepressants, have repeatedly pointed toward unfavorable side effects on the course of the disorder, namely switching into (hypo)mania, induction of rapid cycling, and increased risk of suicide. Most evidence for both unfavorable and favorable effects has been deducted, thus far, from small studies with methodological flaws. More substantiated evidence only recently became available. From this it appears that, at least, the switch risk, and perhaps also the risk for rapid cycling and new-onset suicidality have been overinterpreted. At the same time, these new data raise doubt about the efficacy of antidepressants as a primary-treatment choice in bipolar depression.     

Attentional bias in euthymic bipolar I disorder

Little is known about the nature of the relation between information-processing biases and affective traits in bipolar disorder. The present study was designed to investigate whether attentional biases are evident in persons diagnosed with bipolar disorder when they are in a positive mood state, and whether biases are related to indices of emotion regulation and to prior history of mood episodes. Ninety adults diagnosed with bipolar I disorder and 81 controls with no lifetime mood disorder underwent a positive mood induction and then completed an emotion face dot-probe task; participants in the bipolar disorder group also completed a self-report measure of responses to positive affect. Attentional bias was not related to a diagnosis of bipolar disorder or to symptom severity. Consistent with hypotheses, analyses within the bipolar group indicated that greater dampening of positive affect related to significantly less attention paid to the positively valenced faces. Discussion focuses on the potential role of affective traits in shaping attentional bias in bipolar disorder.     

Induced mood change and dysfunctional attitudes in remitted bipolar I affective disorder

This study investigated the possibility that, in remitted bipolar I affective disorder, dysfunctional attitudes are mood-state dependent. Participants were 120 individuals with remitted bipolar I disorder, remitted unipolar depression, or no history of affective disorder. The Dysfunctional Attitudes Scale (DAS; Weissman, 1979) was completed before and after positive or negative mood challenge. Following mood increase, the bipolar group changed significantly less in DAS total score than did the other 2 groups, and in goal-striving and achievement attitudes relative to the unipolar group. These findings did not provide clear support for the mood-state dependency theory in bipolar disorder, arguing instead for the presence in bipolar I disorder of dysfunctional cognitions that show characteristic resilience in the face of minor positive mood increase.     

Family transactions and relapse in bipolar disorder

This study examined whether patient symptoms and relatives' affective behavior, when expressed during directly observed family interactions, are associated with the short-term course of bipolar disorder. Twenty-seven bipolar patients and their relatives participated in two 10-minute family interactions when patients were discharged after a manic episode. Results indicated that patients who showed high levels of odd and grandiose thinking during the interactions were more likely to relapse during a 9-month followup period than patients who did not show these symptoms during the family discussions. Relapse was also associated with high rates of harshly critical and directly supportive statements by relatives. Patients' odd thinking and relatives' harsh criticism were significantly more likely to be correlated when patients relapsed (r = .53) than when they did not relapse (r = .12). Results suggest that bipolar patients who show increased signs of residual symptomatology during family transactions during the post-hospital period are at increased relapse risk. The data also suggest that relatives of relapsing patients cope with these symptoms by increasing both positive and negative affective behaviors. Moreover, a bidirectional, interactional relationship between patients' symptoms and relatives' coping style seems to capture best the role of the family in predicting relapse in bipolar disorder.     

Seasonal eating patterns in Norway: a non-clinical population study

Seasonal deviations in normal eating habits have been associated with seasonal affective disorder (SAD) and bulimia nervosa (BN). Two studies on seasonal variation in eating habits are reported in this paper. In Study 1, seasonal patterns of eating disturbances were measured cross-sectionally in 6313 participants using an eating disturbance scale (EDS-5) and a modified version of the Seasonal Pattern Assessment Questionnaire (SPAQ). Eating disturbance scores were predicted by seasonal sensitivity scores from the SPAQ, gender, age, and light. Study 2 used a longitudinal design in which 908 participants were given the EDS-5 every month from November 1993 to January 1995. Scores on the EDS-5 fluctuated with the season of the year, with higher EDS-5 scores in winter and lower in summer. The results suggest that seasonal fluctuations affect only a subset of the total population.     

Rapid Cycling

Rapid cycling is not a distinct disorder, but is a particularly severe form of bipolar disease. One in six patients with bipolar disease seen by psychiatrists either as an outpatient or as an inpatient suffers from four or more episodes per year. If at least four episodes occur within one year, this high-frequency phase is called ?rapid cycling“ (RC). Treatment for bipolar disorder with RC usually includes trialling mood stabilizers, such as lithium, anticonvulsants, and modern antipsychotics.In four out of five RC patients, treatment improves disease progression; however, some patients exhibit RC for many years.Specific studies have raised the suspicion that administering antidepressive therapy could facilitate an unfavorable course of bipolar affective disorder. The present case demonstrates disease progression and treatment attempts in a patient with distinct RC progression.     

The CBCL Bipolar Profile and Attention,Mood, and Behavior Dysregulation

Biederman and colleagues reported that a CBCL profile identified youngsters who were diagnosed with bipolar disorder. Some studies found that this CBCL profile does not reliably identify children who present with bipolar disorder, but nonetheless this CBCL does identify youngsters with severe dysfunction. However, the nature of the impairment of youngsters who fit this profile is unclear. The goal of this study was to describe the clinical characteristics of youngsters who fit this CBCL profile. The sample included 310 youngsters referred to an outpatient psychopharmacology clinic. There were 55 youngsters who fit the CBCL profile. These youngsters were compared to 255 youngsters who did not fit the CBCL profile. Measures included the CBCL, standardized measures of aggression and ADHD symptoms, youngsters’ self-reported depression, DSM-IV diagnoses, and child and adolescent psychiatrists’ ratings of impairment and functioning. Compared to youngsters who did not fit the CBCL bipolar disorder profile, youngsters who fit the profile had significantly higher scores on all but one CBCL scale and significantly higher levels of aggression. Youngsters who fit the CBCL profile also had greater psychosocial impairment and more DSM-IV diagnoses than youngsters who did not fit the profile. Youngsters who fit the CBCL profile exhibit severe dysregulation across multiple domains of functioning including attention, affective, and behavioral dysregulation that are not easily nor efficiently captured by extant DSM-IV diagnoses. These youngsters are not uncommon and comprise slightly less than 1 in 5 referrals to a child psychiatry clinic.     

双相障碍及其社会-心理治疗的研究现状

双相障碍是以起伏性躁狂或抑郁为特征的慢性周期性精神疾病。近年来,社会-心理疗法作为药物治疗的辅助手段被引入到该类疾病的治疗过程中。本文基于近期关于双相障碍的病因学的研究,评述了各种不同形式的社会-心理疗法在双相障碍治疗中的应用及其疗效,指出今后的研究需要进行严格的临床设计,以保证不同研究间的可比性和可重复性;应尽可能延长追踪观察的时间,并进行大样本多变量研究,以保证研究结果的普遍性。     

Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.     

The contemporary face of bipolar illness: complex diagnostic and therapeutic challenges

Manic depression, or bipolar disorder, is a multifaceted illness with an inevitably complex treatment. The current article summarizes the current status of our knowledge and practice concerning its diagnosis and treatment. While the prototypic clinical picture concerns the "classic" bipolar disorder, today mixed episodes with incomplete recovery and significant psychosocial impairment are more frequent. The clinical picture of these mixed episodes is variable, eludes contemporary classification systems, and possibly includes a constellation of mental syndromes currently classified elsewhere. Treatment includes the careful combination of lithium, antiepileptics, atypical antipsychotics, and antidepressants, but not all of the agents in these broad categories are effective for the treatment of bipolar disorder.     

Genetic linkage in bipolar disorder

Bipolar disorder is an etiologically complex syndrome that is clearly heritable. Multiple genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the last few decades. However, specific causal genetic mutations for bipolar disorder have not been identified. Both candidate gene studies and complete genome screens have been conducted. They have provided compelling evidence for several potential bipolar disorder susceptibility loci in several regions of the genome. The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21. Other regions of interest, including those on chromosomes 5 and 8, are also under investigation. New approaches, such as the use of genetically isolated populations and the use of endophenotypes for bipolar disorder, hold promise for continued advancement in the search to identify specific bipolar disorder genes.     

Creativity and Affective Temperament in Artistic and Non-artistic Students: Different Temperaments are Related to Different Aspects of Creativity

The relationship between creativity and temperament has been well documented in studies with professional artists. This also pertains to affective temperaments which constitute the vulnerability to affective disorders. However, less is known about the contribution of particular temperaments to specific components of creativity, for example, ideational fluency, or originality of thinking. The aim of the present study was to assess affective temperaments and creativity in artistic and non-artistic students. Ninety (39 artistic and 51 non-artistic) students were enrolled in the study. Affective temperaments were evaluated by means of TEMPS-A questionnaire. Creativity was measured with BWAS test assessing the originality of thinking and a sample of tasks derived from BIS battery, assessing ideational fluency. Artistic students showed higher rates of cyclothymic temperament. They also outperformed non-artistic students in both domains of creativity. The originality of thinking correlated positively with the level of cyclothymic temperament, whereas ideational fluency was positively related to hyperthymic temperament. Ideational fluency also correlated with the level of parental education. Results indicate that creativity is related to temperaments underlying predisposition to bipolar affective disorder; however, different temperaments are related to different aspects of creativity.     

Functional magnetic resonance imaging studies in bipolar disorder

Abnormalities in brain activation using functional magnetic resonance imaging (fMRI) during cognitive and emotional tasks have been identified in bipolar disorder patients, in frontal, subcortical and limbic regions. Several studies also indicate that mood state may be differentiated by lateralization of brain activation in fronto-limbic regions. The interpretation of fMRI studies in bipolar disorder is limited by the choice of regions of interest, medication effects, comorbidity, and task performance. These studies suggest that there is a complex alteration in regions important for neural networks underlying cognition and emotional processing in bipolar disorder. However, measuring changes in specific brain regions does not identify how these neural networks are affected. New analytical techniques of fMRI data are needed in order to resolve some of these issues and identify how changes in neural networks relate to cognitive and emotional processing in bipolar disorder.     

Treatment-resistant posttraumatic stress disorder: strategies for intervention

The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. To date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment-refractory PTSD.