Kostas N. Fountoulakis

Towards a genetically validated new affective temperament scale: A delineation of the temperament ʻphenotype' of 5-HTTLPR using the TEMPS-A

BACKGROUND Although it has been described that affective temperaments are associated with the 5-HTTLPR, less attention was paid to the association between this polymorphism and subscales and items related to each affective temperament. The aim of our study was to investigate the association of affective temperament subscales and individual items with the s allele of the 5-HTTLPR. METHOD 138 psychiatrically healthy women completed the TEMPS-A questionnaire and were genotyped for 5-HTTLPR. Scores of subjects on the temperament scales, subscales and items in the three genotype and the two phenotype groups were compared using ANOVA. We selected items with significantly different mean scores between the three genotype groups and the two phenotype groups separately and performed item analysis. RESULTS Subjects in the different 5-HTTLPR genotype and phenotype groups have significantly different score on scales measuring depressive, cyclothymic, irritable and anxious temperaments, and several subscales composing these temperamental scales. Subjects in the three genotype groups scored significantly different on 11 items, 8 of these remained in a derived genotype scale after item analysis. Subjects in the two phenotype groups had significantly different scores on 12 items, 9 of them were retained in a derived phenotype scale after item analysis. LIMITATIONS Our sample was relatively small and included only women. CONCLUSIONS Our data provide support for the association of affective temperaments with the s allele. Although the cyclothymic temperament shows the strongest association, all temperaments within the depressive superfactor have a similar share in this association. The newly derived 5-HTTLPR Phenotype Scale shows strong association with 5-HTTLPR genotype and phenotype, therefore this scale should be further investigated in relation to psychiatric disorders, as well as psychological traits and temperaments.

A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression.

Despite the high morbidity and mortality associated with bipolar depression, the optimal treatment for this phase is still a matter of debate. The aim of the current review was to provide updated evidence about the efficacy and tolerability of anticonvulsants in the treatment of acute bipolar depression. A comprehensive review of randomized controlled trials (RCTs) evaluating the use of anticonvulsants for the treatment of acute bipolar depression up to June 2011 was conducted by means of the PubMed-Medline database. Eligibility criteria included active comparator-controlled or placebo-controlled randomized studies involving monotherapy or combination therapy. A total of 18 RCTs fulfilled the inclusion criteria. Studies supported the efficacy of divalproex as monotherapy in acute bipolar depression but small sample size was a common methodological limitation. Findings were inconclusive for lamotrigine and carbamazepine although overall lamotrigine may have a beneficial but modest effect. Negative results were found for levetiracetam and gabapentin but the evidence base on these agents is scant. All anticonvulsants were generally well tolerated. No double-blind RCTs were found for the use of other anticonvulsants such as oxcarbazepine, licarbazepine, zonisamide, retigabine, pregabalin, tiagabine, felbamate and vigabatrine in the acute treatment of bipolar depression. To sum up, taking into consideration the efficacy and tolerability profiles of anticonvulsants, current evidence supports the use of divalproex and lamotrigine in the treatment of acute bipolar depression. However, available data for most other anticonvulsants are inconclusive and further RCTs with larger sample sizes are needed before drawing firm conclusions.

General and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders: a report by the WPA section of pharmacopsychiatry

Current gold standard approaches to the treatment of depression include pharmacotherapeutic and psychotherapeutic interventions with social support. Due to current controversies concerning the efficacy of antidepressants in randomized controlled trials, the generalizability of study findings to wider clinical practice and the increasing importance of socioeconomic considerations, it seems timely to address the uncertainty of concerned patients and relatives, and their treating psychiatrists and general practitioners. We therefore discuss both the efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders. We explain and clarify useful measures for assessing clinically meaningful antidepressant treatment effects and the types of studies that are useful for addressing uncertainties. This includes considerations of methodological issues in randomized controlled studies, meta-analyses, and effectiveness studies. Furthermore, we summarize the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties, and differences between studies using antidepressants and/or psychotherapy. We also address the differential effectiveness of antidepressant drugs with differing modes of action and in varying subtypes of depressive disorder. After highlighting the clinical usefulness of treatment algorithms and the divergent biological, psychological, and clinical efforts to predict the effectiveness of antidepressant treatments, we conclude that the spectrum of different antidepressant treatments has broadened over the last few decades. The efficacy and clinical effectiveness of antidepressants is statistically significant, clinically relevant, and proven repeatedly. Further optimization of treatment can be helped by clearly structured treatment algorithms and the implementation of psychotherapeutic interventions. Modern individualized antidepressant treatment is in most cases a well-tolerated and efficacious approach to minimize the negative impact of otherwise potentially devastating and life-threatening outcomes in depressive disorders.

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

BACKGROUND The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS Recall bias for onset and family history data. CONCLUSIONS A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Influence of light exposure during early life on the age of onset of bipolar disorder

BACKGROUND Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Executive summary of the report by the WPA section on pharmacopsychiatry on general and comparative efficacy and effectiveness of antidepressants in the acute treatment of depressive disorders

Current gold standard in the treatment of depression includes pharmacotherapeutic and psychotherapeutic strategies together with social support. Due to the actually discussed controversies concerning the differential efficacy of antidepressants, a contribution to a comprehensive clarification seems to be necessary to avert further deterioration and uncertainty from patients, relatives, and their treating psychiatrists and general practitioners. Both efficacy and clinical effectiveness of antidepressants in the treatment of depressive disorders can be confirmed. Clinically meaningful antidepressant treatment effects were confirmed in different types of studies. Methodological issues of randomized controlled studies, meta-analyses, and effectiveness studies will be discussed. Furthermore, actual data about the differential efficacy and effectiveness of antidepressants with distinct pharmacodynamic properties and about outcome differences in studies using antidepressants and/or psychotherapy are discussed. This is followed by a clinically oriented depiction—the differential clinical effectiveness of different pharmacodynamic modes of action of antidepressants in different subtypes of depressive disorders. It can be summarized that the spectrum of different antidepressant treatments has broadened during the last decades. The efficacy and clinical effectiveness of antidepressants is statistically significant and clinically relevant and proven repeatedly. For further optimizing antidepressant treatment plans, clearly structured treatment algorithms and the implementation of psychotherapy seem to be useful. A modern individualized antidepressant treatment in most cases is a well-tolerated and efficacious tool to minimize the negative impact of the otherwise devastating and life-threatening outcome of depressive disorders.

Classification and Epidemiology

The principle of classification is that it is a reductionist process by which complex phenomena can be grouped into categories on the basis of objective and stringent criteria. Often the criteria are less reliable and valid than expected or needed; however, many researchers follow the opinion of Claude Levi-Strauss (1908–2009) that ‘any classification is better than no classification at all’. On the other hand, classification itself has an impact on nosology since it often gives birth to interest groups of experts and followers and it might trigger vicious circles concerning their survival. Once classification follows a specific path, a radical change is often difficult if not impossible and this is evident from the way modern classification systems move on from previous to the next edition.

Arguments against the Cognitive Dysmetria Hypothesis of Schizophrenia

Recently, the ‘cognitive dysmetria’ theory for schizophrenia has been formulated. According to this theory. a primary neurocognitive dysfunction is the core of schizophrenia and underlies symptom formation, The suggested perceptual fragmentation of external stimuli and inability to connect such perceptions with internal schemata is suggested to lead to positive symptoms, while defensive self-restriction and the exhaustion of the mental apparatus lead to negative symptomatology. Objections to this theory include observations (i) that patients with dominant positive symptoms, e.g., delusions, hallucinations, manifest better neurocognitive function and (ii) that typically antipsychotics significantly reduce positive symptoms and thus improve both the clinical picture and the functioning (to the extent it is reduced with positive symptoms) of the patients, yet have little or no effect on negative, e.g., loss of volition, emotional blunting, and neurocognitive symptomatology, e.g., attentional and memory deficit. The literature suggests that neurocognitive symptoms group independently of other symptomatology. It is suggested that there is currently more evidence against than in favor of the ‘cognitive dysmetria’ theory.

Psychosocial Treatment and Interventions

It has been solidly shown that BD has an unfavourable outcome in a considerable number of patients, in spite of the recent advances in its pharmacological treatment. Many BD patients eventually suffer from chronic mood symptoms with significant global disability and burden, not only for themselves but also for their family and the society. The overall functional outcome can be captured mainly by two dimensions representing clinical severity and cognitive dysfunction. Unfortunately, symptomatic remission does not imply functional recovery which is absent in a significant number of clinically and symptomatically remitted patients.

Long-Term Course

Historically, the first note on polarity was made in the early 1960s when Leonhard reported that 17.9 % of patients had a manic and 25.6 % had a depressive predominant polarity, while the rest of the patients had similar occurrence of the two poles. However, the concept was formulated by Jules Angst.