Serum neurofilament light as a potential marker of illness duration in bipolar disorder.

INTRODUCTION: Investigation on specific biomarkers for diagnostic or prognostic usage in mental diseases and especially bipolar disorder BD seems to be one outstanding field in current research. Serum neurofilament light (sNfL), a marker for neuro-axonal injury, is increased in various acute and chronic neurological disorders, but also neuro-psychiatric conditions, including affective disorders. The aim of our study was to determine a potential relation between a neuron-specific marker like sNfL and different clinical states of BD. METHODS: In the current investigation, 51 patients with BD and 35 HC were included. Mood ratings with the Hamilton depression scale (HAMD) and the Young mania rating scale (YMRS) have been included. Illness duration was defined as the period from the time of diagnosis out of self-report and medical records. sNFL was quantified by a commercial ultrasensitive single molecule array (Simoa). RESULTS: There was a significant positive correlation between the number of manic episodes in the past and sNfL, controlled for age and duration of illness. (R = 0.49, p = 0.03) Depressive episodes were not associated to sNfL values. (R = 0.311, p = n.s.) Patients with >3 years of illness duration showed significantly higher levels of sNfL (M18.59; SD 11.89) than patients with shorter illness duration (M = 12.38, p = 0.03) and HC (M = 11.35, p = 0.02). Patients with <3 years of illness and HC did not differ significantly in sNfL levels. DISCUSSION: Interestingly, individuals with BD and HC did not differ in sNFL levels in general. Nevertheless, looking at the BD cohort more specifically, we found that individuals with BD with longer duration of illness (>3 years) had higher levels of sNfL than those with an illness duration below 3 years. Our results confirm previous reports on the relation of neuro-axonal injury as evidenced by sNfL and illness specific variables in bipolar disorder. Further studies are needed to clarify if sNfL may predict the disease course and/or indicated response to treatment regimes.

A one-year view on the association of metabolic syndrome and cognitive function in bipolar disorder - Preliminary data.

BACKGROUND: Individuals with bipolar disorder have a high prevalence of metabolic syndrome and an increased risk for cognitive deficits. The aim of this longitudinal study was to investigate the trajectory of cognitive decline in dependence of metabolic syndrome over a one-year interval. METHODS: 52 well-diagnosed individuals with bipolar disorder, euthymic at baseline and follow-up (n = 17 with metabolic syndrome vs. n = 35 without metabolic syndrome) were investigated with a comprehensive neurocognitive test battery (Trail Making Test A/B, Digit Symbol Test, California Verbal Leaning Test, or the Verbal Learning and Memory Test respectively) twice within the interval of one year. RESULTS: Patients with bipolar disorder and additional metabolic syndrome performed significantly worse in the domain of psychomotor and processing speed/attention than patients without metabolic syndrome at test point one. No deteriorating effects of metabolic syndrome on the cognitive domain scores and overall cognitive performance were found at the one-year follow up. However, no cognitive decline could be reported in both groups. LIMITATIONS: Time interval, small sample size and selection of metabolic syndrome affected patients were the major limitations of this study. CONCLUSION: There was no association of metabolic syndrome on the one-year trajectory of cognitive function in bipolar disorder. Future studies should expand the observation period and investigate larger samples.

Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls.

INTRODUCTION: Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression. METHODS: ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n = 81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression. RESULTS: ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta2= 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.). DISCUSSION: Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown.

Epidemiology and economic burden of fragility fractures in Austria.

Fragility fractures are a frequent and costly event. In Austria, 92,835 fragility fractures occurred in patients aged ≥ 50 years in 2018, accruing direct costs of > 157 million €. Due to demographic aging, the number of fragility fractures and their associated costs are expected to increase even further. INTRODUCTION: Fragility fractures are frequently associated with long hospital stays, loss of independence, and increased need for care in the elderly, with consequences often leading to premature death. The aim of this study was to estimate the number of fragility fractures and associated healthcare costs in Austria in 2018. METHODS: The number of in-patient cases with relevant ICD-10 diagnoses in all Austrian public hospitals was derived from discharge documentation of diagnoses and procedures covering all public hospitals in Austria. Fractures resulting from falls from standing height in patients aged ≥ 50 years were used as a proxy for fragility fractures, and the number of in-patient and out-patient cases was estimated. The direct costs of these cases were calculated using the average cost of the corresponding in-patient hospital stay and the average cost for the out-patient stay. RESULTS: The present study estimated the number of fragility fractures (pelvis, thoracic and lumbar vertebra, hip, humerus, rib, forearm, and tibia) for 2018 at 92,835 or just over half of all fractures in patients aged ≥ 50 years, corresponding to a prevalence of 2,600 per 100,000 inhabitants of this age group. A constant increase in the proportion of fragility fractures among all fractures was observed with increasing age in both men and women. These fractures amounted to direct costs of > 157 million €. CONCLUSION: Fragility fractures are a frequent and costly event in Austria. Due to the aging of the population, the number of fragility fractures and their associated costs is expected to increase even further.

Sex differences in zonulin in affective disorders and associations with current mood symptoms.

INTRODUCTION: The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. METHODS: In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. RESULTS: Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. DISCUSSION: Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.

The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder.

INTRODUCTION: Altered levels of acute-phase proteins are often described in different conditions in BD. Nevertheless, data on the association between lithium treatment and inflammatory markers in the long-term course of BD are still missing. The aim of the study was to examine the long-term course of BD concerning long-term lithium treatment, chronic inflammatory processes and symptom progression. Furthermore, the association between duration of lithium treatment and levels of hsCRP was explored. METHODS: 267 individuals (males= 139, females= 128) with BD were included. Duration of lithium treatment as well as symptom progression, defined as the increase in severity of symptoms, number of episodes a year and duration of episodes within a period of 1.5 years in the past and hsCRP were evaluated. RESULTS: Male individuals with symptom progression over time had significantly lower duration of lithium treatment compared to individuals without symptoms progression (U= 47.4, p=.037). There were significantly higher levels of hsCRP in male individuals with symptom progression compared to males without symptom progression (U= 47.5, p=.027). Further, there was a significant negative correlation between the duration of lithium treatment and hsCRP levels in the whole sample (r= -.276, p<.05). CONCLUSION: Our results show that an altered inflammatory state may be associated with a more severe illness course in BD. Further, a longer duration of lithium treatment may be associated with lower symptom progression. The shown association between hsCRP-levels and lithium treatment duration suggests a potential anti-inflammatory effect of lithium as a mediator of its significant positive outcome effect in BD.

The relationship between "Eyes Reading" ability and verbal memory in bipolar disorder.

In psychiatric disorders, neurocognitive impairments are prevalent and have been associated with poor outcome. Deficits in Theory of Mind (ToM, "mentalising") have also been observed in bipolar disorder (BD); however, the literature shows inconsistent data. The aim of this study was to explore ToM performance in a well-characterized sample of euthymic individuals with BD and its relationship with neurocognitive function. One hundred sixteen euthymic patients with BD between 18 and 74 years (mean age = 42.4, SD = 13.8) and 79 healthy controls (mean age = 39.8, SD = 16.5) were investigated with an extensive neurocognitive test battery (Trail Making Test A/B, d2 Test of Attention, Stroop Color-Word Test, California Verbal Learning Test, Multiple Choice Vocabulary Test). Additionally, all participants were given the Reading the Mind in the Eyes Test (RMET) to measure affective ToM, the ability to make assumptions about other people´s feelings. Overall, "Eyes Reading" performance was not impaired in individuals with BD compared with controls. However, a significant relationship between RMET and verbal memory in BD was shown, particularly in males. Data showed worse RMET performance in patients with memory deficits compared to patients without memory deficits and controls. Due to cross-sectional data, no conclusions can be made with respect to cause and effect.

Epigenetics of the molecular clock and bacterial diversity in bipolar disorder.

Objectives The gut microbiome harbors substantially more genetic material than our body cells and has an impact on a huge variety of physiological mechanisms including the production of neurotransmitters and the interaction with brain functions through the gut-brain-axis. Products of microbiota can affect methylation according to preclinical studies. The current investigation aimed at analyzing the correlation between gut microbiome diversity and the methylation of the clock gene ARNTL in individuals with Bipolar Disorder (BD). Methods Genomic DNA was isolated from fasting blood of study participants with BD (n = 32). The methylation analysis of the ARNTL CG site cg05733463 was performed by bisulfite treatment of genomic DNA with the Epitect kit, PCR and pyrosequencing. Additionally, DNA was extracted from stool samples and subjected to 16S rRNA sequencing. QIIME was used to analyze microbiome data. Results Methylation status of the ARNTL CpG position cg05733463 correlated significantly with bacterial diversity (Simpson index: r= -0.389, p = 0.0238) and evenness (Simpson evenness index: r= -0.358, p = 0.044). Furthermore, bacterial diversity differed significantly between euthymia and depression (F(1,30) = 4.695, p = 0.039). Discussion The results of our pilot study show that bacterial diversity differs between euthymia and depression. Interestingly, gut microbiome diversity and evenness correlate negatively with methylation of ARNTL, which is known to regulate monoamine oxidase A transcription. We propose that alterations in overall diversity of the gut microbiome represent an internal environmental factor that has an epigenetic impact on the clock gene ARNTL which is thought to be involved in BD pathogenesis.

Changes in the tryptophan-kynurenine axis in association to therapeutic response in clinically depressed patients undergoing psychiatric rehabilitation.

INTRODUCTION: In recent decades a number of studies have shown an association between the Tryptophan (Trp)-Kynurenine (Kyn) axis and neuropsychiatric disorders. However, the role of the Trp-Kyn pathway on the affective status in a general psychiatric cohort requires clarification. This study aimed to measure peripheral changes in Trp, Kyn and the Kyn/Trp-ratio as well as in the inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukine-6 (IL-6) in individuals undergoing a six-week course of intensive treatment program comparing subgroups of treatment responders and non-responders. METHODS: In this investigation 87 currently depressed individuals with a life-time history of depressive disorders were divided into treatment responders (n = 48) and non-responders (n = 39). The individuals were selected for an extreme group comparison out of 598 patients undergoing a 6-week psychiatric rehabilitation program in Austria. Responders were defined according to great changes in Becks Depression Inventory (BDI-II) between time of admission and discharge (BDI-II > 29 to BDI-II <14), while non-responders had no or minimal changes (BDI >20, max. 4 points change over time). Differences in the levels of Trp, Kyn, and the Kyn/Trp ratio as well as levels of hsCRP and IL-6, were compared between groups. Differences were analyzed at the time of admission as well as at discharge. RESULTS: A significant group x time interaction was found for Kyn [F(1.82) = 5.79; p = 0.018] and the Kyn/Trp ratio [F(1.85) = 4.01, p = 0.048]. Importantly, Kyn increased significantly in the non-responder group, while the Kyn/Trp ratio decreased significantly in the responder group over time. Furthermore, changes in Kyn as well as hsCRP levels correlated significantly with changes in the body mass index over time (Kyn: r=0.24, p = 0.030; hsCRP: r=0.25, p = 0.021). No significant interactions were found for Trp and hsCRP, although they increased significantly over time. DISCUSSION: Given the limitations of the study, we could show that the therapeutic response to a multimodal treatment in clinically depressed patients not receiving cytokine treatment is associated with changes in Kyn levels and the Kyn/Trp ratio as well as with hsCRP. However, it is too early to draw any causal conclusion. Future research should clarify relevant clinical and neurobiological parameters associated with changes in Kyn levels and Kyn/Trp ratio, especially in regard to clinical response.

The role of tryptophan metabolism and food craving in the relationship between obesity and bipolar disorder.

BACKGROUND & AIMS: Individuals with bipolar disorder (BD) have a significantly increased risk of obesity-related conditions. The imbalance between food intake and energy expenditure is assumed to be a major risk factor for obesity in BD. This study analyzed food craving in relation to anthropometric, metabolic, and neurobiological parameters in a well-characterized cohort of euthymic individuals with BD. METHODS: One-hundred-thirty-five patients completed the Food-Craving Inventory assessing four categories of food craving (fat, fast-food, sweets and carbohydrate craving). Additionally, clinical, metabolic and anthropometric parameters were assessed. RESULTS: Higher levels of fat craving were observed in males, versus females, with BD. High levels of carbohydrate craving positively correlated with kynurenine and the kynurenine-to-tryptophan ratio. Higher serum nitrite and neopterin levels were related to fat craving. Parameters of fat metabolism (triglycerides, high-density lipoprotein) were associated with fat and fast-food craving. Anthropometric measures of obesity (e.g. body mass index, waist-to-hip-ratio) were not related to food craving. CONCLUSIONS: Overweight/obese individuals with BD show an increased driving of tryptophan down the kynurenine pathways, as indicated by an increase in the serum kynurenine-to-tryptophan ratio. The driving of tryptophan down the kynurenine pathway is mediated by immune-inflammatory activity and stress. The correlation of increased kynurenine with food craving, especially carbohydrate craving, probably indicates a regulatory deficit in the maintenance of chronic inflammatory processes in obesity and BD. Food craving seems to be of clinical importance in the treatment of metabolic disturbances in BD, although not associated with anthropometric measures of obesity. Rather, food craving correlates with blood metabolic parameters and an increased activation of the kynurenine pathway, both of which are linked to higher affective symptomatology and the development of cardiovascular diseases.

Gender differences in the association between physical activity and cognitive function in individuals with bipolar disorder.

INTRODUCTION: Bipolar disorder (BD) is accompanied by a high number of comorbidities and associated with an overall increased mortality. Especially obesity, systemic inflammatory processes and cognitive deficits are highly prevalent and increase with the course of illness. Physical activity (PA) is associated with beneficial effects on somatic comorbidities such as obesity or cardiovascular disease in individuals without psychiatric disorder. Furthermore, PA might increase neurocognitive performance and reduce systemic inflammation. OBJECTIVE: The aim of the study was to investigate the association between PA and neurocognitive function in euthymic individuals suffering from BD. METHODS AND PARTICIPANTS: 120 individuals with BD, euthymic at test time, completed the self-reported International Physical Activity Questionnaire (IPAQ) assessing PA of the past seven days and were accordingly assigned to a specific activity category (low, moderate or vigorous). Furthermore, clinical parameters were gathered and cognitive tests analysing verbal-dependent intelligence, attention, executive functioning as well as memory were administered. RESULTS: Female individuals in the vigorous PA group performed significantly higher in most of the cognitive domains compared to females with moderate or low PA. In males, we only found a significant difference in one test for attention between moderate/vigorous and the low activity group. CONCLUSION: Differences between PA groups in cognitive performance in female individuals with BD were obvious in almost all cognitive domains. As cognitive deficits are strongly associated with a worse course of disease and outcome, PA might offer a concomitant therapy targeting not only somatic comorbidities such as obesity and cardiovascular disease, but also neurocognition.

Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals.

OBJECTIVES: Overweight/obesity has been implicated to play a role in cognitive deficits in bipolar disorder (BD). This study aims to identify the relationship between body fat distribution and different domains of cognition in BD during euthymia. METHODS: A sample of 100 euthymic individuals with BD was measured with a cognitive test battery (i.e., Trail Making Test-A-B/TM-A/B, d2 Test of Attention, Stroop test, California Verbal Learning Test/CVLT) and an anthropometric measures set (body mass index, waist circumference, hip circumference, waist-to-hip-ratio, waist-to-height-ratio, and lipometry). Patient data were compared with a healthy control group (n = 64). RESULTS: Results show that overweight patients with BD exhibit lower performance in the TMT-A/B as well as in the free recall performance of the CVLT compared to normal-weight patients with BD and controls. In bipolar individuals, (abdominal) obesity was significantly associated with a poor cognitive performance. In bipolar females, associations with measures of verbal learning and memory were found; in bipolar males, associations with poor performance in the TMT-A/B and in the Stroop interference task were demonstrated. In controls, no associations were found. CONCLUSIONS: There are several possible pathways moderating the association between obesity and cognition in BD. Anthropometric and lipometry data underline the substantial mediating impact of body fat distribution on cognition in BD.

Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.

INTRODUCTION: Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS). METHODS: Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS. RESULTS: The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28). CONCLUSION: Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.

[Rapid cycling--finally stable but obese--target acquired?]. / Rapid Cycling--Endlich stabil aber adipös--Ziel erreicht?

Overweight and obesity are common in patients with bipolar disorder. Rates of up to 70% are described in scientific publications. There is sufficient evidence that these conditions are associated with a worse course of the disease (more episodes, higher suicide and hospitality rates, worse response to lithium, somatic comorbidities). Most of the mood stabilisers lead to weight gain. This is also true for clozapine, which can be effective in therapy-refractory courses of bipolar disorder. This case report demonstrates the complexity of the treatment of bipolar disorder. A young patient in depressive stupor following a severe suicide attempt after 5 months of hospital treatment was sent to our department to perform ECT. This was not possible because of the severity of his injuries. We were able to cure the acute condition and interrupt the course of rapid cycling with a combination of clomipramine, lithium and clozapine. A stable course of four years under this medication and psychoeducation has been achieved. In this period the patient was able to lower his body mass index from 38 to 26 because of a consequent lifestyle modification.

[Pediatric bipolar disorder - case report of a bipolar patient with disease onset in childhood and adolescence: implications for diagnosis and therapy]. / Pädiatrische Bipolare Störung - Kasuistik eines bipolaren Patienten mit Krankheitsbeginn im Kindes- und Jugendalter: Diagnostische und therapeutische Implikationen.

In recent years, intense controversies have evolved about the existence and exact diagnostic criteria of pediatric bipolar affective disorder. The present study aims to discuss pediatric bipolar affective disorder based on the current literature focussing on the diagnostic prospects. Based on a case study, a process of bipolar disorder developed in childhood is depicted exemplarily. Because of the high comorbidity and overlapping symptoms of paediatric bipolar affective disorder and other psychiatric disorders, the major impact of the differential diagnosis has to be stressed. An early diagnosis and the treatment possibilities are discussed.

[Oxidative stress in bipolar affective disorder]. / Oxidativer Stress bei bipolar affektiver Störung. (corrected).

The results of mortality studies have indicated that medical conditions, such as cardiovascular disease, obesity and diabetes are the most important causes of mortality among patients with bipolar disorder. The reasons for the increased incidence and mortality are not fully understood. Oxidative stress and an inadequate antioxidative system might be one missing link and could also help to further elucidate the pathophysiological basis of bipolar disorder. This article provides a comprehensive review of oxidative stress in general and about the existing data for bipolar disorder. In addition information is given about possible therapeutic strategies to reduce oxidative stress and the use in bipolar disorder.

[Poststroke-bipolar affective disorder]. / Poststroke-Bipolar affektive Erkrankung.

A few weeks after suffering from a basal ganglia infarction (globus pallidus) with left-sided hemiplegia, a 23-year-old woman exhibited for the first time a pronounced mania with self-endangerment. The use of oral contraceptives was the only determinable risk factor. During the further course, the mother also developed a depressive disorder. Thus a certain genetic predisposition for affective disorders may be relevant, although this would not explain the outbreak by itself. An association between the right-sided basal ganglia infarction and the occurrence of a bipolar affective disorder has been described in the literature. Vascular or, respectively, inflammatory risk factors in synopsis with the aetiopathogenesis of bipolar affective disorders are also discussed in depth in this case report.

[Bipolar disorder and compliance]. / Bipolar affektive Störung und Compliance.

According to literature data the lack of compliance is a massive problem in up to 50 % of the patients with bipolar affective disorders and can lead to severe long-term complications in the further course of the diseases. In this case report we present various strategies that are intended to improve compliance.

Highly directional emission from photonic crystal waveguides of subwavelength width.

Recently it has been shown that it is possible to achieve directional emission out of a subwavelength aperture in a periodically corrugated metallic thin film. We report on theoretical and experimental studies of a related phenomenon concerning light emitted from photonic crystal waveguides that are less than a wavelength wide. We find that the termination of the photonic crystal end facets and an appropriate choice of the wavelength are instrumental in achieving very low numerical apertures. Our results hold promise for the combination of photonic crystal waveguides with conventional optical systems such as fibers, waveguides, and freely propagating light beams.