[A protocol for light therapy in bipolar disorder]. / Protocol voor lichttherapie bij bipolaire stoornis.

BACKGROUND: There is no national protocol for the use of light therapy in bipolar depression.
AIM: The chronotherapy collaboration group of the Foundation for Bipolar Disorders intended to write a protocol for light therapy in bipolar depressive episodes.
METHOD: Narrative review of several systematic reviews, two clinician's guides and deliberation with the sub-commission Guidelines of the Dutch Ophthalmologic Society.
RESULTS: The following indication was established: depressive episode, with or without seasonal features, in bipolar I or II disorder, including subsyndromal (depressive) seasonal complaints. The list of relative contra-indications (pre-existent retinal illnesses, systemic illnesses with effect on the retina and use of photosensitive medication) was shortened. In this case the medical professional discusses the possibility of an ophthalmologic consultation with the patient. Use of a mood stabilizer/antimanic medication in order to prevent mania or a mixed episode is only necessary in a depressive episode in bipolar I, but not in bipolar II disorder. Standard treatment is 10.000 lux white light during 30 minutes in the morning.
CONCLUSION: There is sufficient evidence to propose light therapy in a bipolar depressive episode with or without seasonal features.

Combined sleep deprivation and light therapy: Clinical treatment outcomes in patients with complex unipolar and bipolar depression.

BACKGROUND: The combination of sleep deprivation and light therapy, called combined chronotherapy, may yield positive short- and long-term results, even in patients with treatment resistant depression (TRD). The implementation of combined chronotherapy in daily clinical practice is rare. This study describes the implementation and the effectiveness in a clinical setting. METHODS: Twenty six depressed patients with unipolar or bipolar depression received combined chronotherapy consisting of three nights of sleep deprivation with alternating recovery nights, light therapy, and continuation of antidepressant medication. Inventory of Depressive Symptoms C (IDS-C) scores were determined before chronotherapy and at week 1, 2, and 4. Paired t-tests were used to compare the IDS-C scores over time. RESULTS: The mean pre-treatment IDS-C score was 39.3 ±â€¯9.6, the mean score in week 2 was 28.4 ±â€¯10.2, and 28.6 ±â€¯14.0 in week 4. A subsample of patients with psychiatric co-morbidities showed a reduction in depression severity from a mean score of 42.9 ±â€¯11.0 to a mean score of 34.9 ±â€¯13.0 after 4 weeks. The overall response rate was 34.6%, the remission rate 19.2%. LIMITATIONS: This open label case series has a relative small sample size and no control group CONCLUSION: In a clinical setting patients with major depressive disorder or bipolar disorder benefited significantly from combined chronotherapy. This chronotherapeutic intervention appears to have a rapid effect that lasts for at least several weeks, even in patients with psychiatric comorbidity or TRD. Indicating that chronotherapy can be a valuable treatment addition for depressed patients.

[The dysregulated brain - Consequences of spatial and temporal brain complexity for bipolar disorder pathophysiology and diagnosis]. / Het ontregelde brein; consequenties van ruimtelijke en temporele complexiteit van het brein voor pathofysiologie en diagnostiek van de bipolaire stoornis.

BACKGROUND: Despite the existence of several pathophysiological theories about bipolar disorder, it has so far been difficult to find diagnostic biomarkers and to develop new pharmacologic treatments based on the more novel theories. AIM: To reflect on the causes and consequences of problems that beset pathophysiological research into psychiatric disorders in general and bipolar disorder in particular. METHOD: In this essay we address the problems facing professionals engaged in research into bipolar disorder and we interpret these problem in the light of brain complexity. RESULTS: The complexity of the brain can be divided into two types: spatial complexity, which reflects the various physiological levels of the central nervous system (genetic, molecular, cellular, neuronal circuits and phenomenological levels), and temporal complexity, i.e. neurodevelopment. We discuss the consequences of these two types of complexity and make suggestions relating to clinical practice and pathophysiological psychiatric research. CONCLUSION: To achieve further progress in the field of brain research, we need to acquire a deeper understanding of the spatial and temporal complexity of the brain and consider the possible consequences of such knowledge for the pathophysiology and treatment of psychiatric illnesses such as bipolar disorder.

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls.

BACKGROUND: Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD: This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS: BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (ß = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (ß = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS: Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

The association between immune activation and manic symptoms in patients with a depressive disorder.

Although recent studies have shown that immunological processes play an important role in the pathophysiology of mood disorders, immune activation may only be present in specific subgroups of patients. Our study aimed to examine whether immune activation was associated with (a) the presence of manic symptoms and (b) the onset of manic symptoms during 2 years of follow-up in depressed patients. Patients with a depressive disorder at baseline (N=957) and healthy controls (N=430) were selected from the Netherlands Study of Depression and Anxiety. Assessments included lifetime manic symptoms at baseline and two-year follow up, as well as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) at baseline. Within depressed patients, immune activation was not related to the presence or absence of lifetime manic symptoms at baseline. However, CRP levels were strongly elevated in depressed men who developed manic symptoms compared with those who did not develop manic symptoms over 2 years (P<0.001, Cohen's d=0.89). IL-6 and TNF-α were also higher in depressed men with an onset of manic symptoms, but this association was not significant. However, we found that the onset of manic symptoms was particularly high in men with multiple elevated levels of inflammatory markers. Depressed men who developed manic symptoms during follow-up had increased immunological activity (especially CRP) compared with depressed men who did not develop manic symptoms. Further research should explore whether a treatment approach focusing on inflammatory processes may be more effective in this specific subgroup of depressed patients.

[Chronotherapy for affective disorders]. / Chronotherapie bij stemmingsstoornissen.

BACKGROUND: In the literature there is increasing interest in the chronobiology of affective disorders and in the most important chronotherapies for treating these disorders. AIM: To discuss the background to and the main features of the most important therapies for affective disorders. METHOD: Using PubMed, we performed a concise review of the literature on the use of chronotherapeutics in affective disorders and we also studied the standard textbooks on the subject. RESULTS: Light therapy is the type of chronotherapy that has been studied most. Chronotherapies show interesting and promising results in open label studies, but so far there have been no randomized double-blind placebo controlled trials. CONCLUSION: Chronotherapeutics provides a neurobiological model and a series of promising, possibly effective non-pharmacological therapies, particularly for affective disorders. Light therapy deserves to be included in the multidisciplinary treatment guidelines relating to affective disorders. However, more, better and longer trials are needed in order to evaluate the various types of chronotherapies.