Comorbid migraine with aura, anxiety, and depression is associated with dopamine D2 receptor (DRD2) NcoI alleles.

BACKGROUND: Unrelated individuals (n = 242) were interviewed directly for the presence of migraine, anxiety disorders, and major depression. MATERIALS AND METHODS: The data described in this study are derived from a clinical genetic relational database that was developed initially for the genetic analysis of migraine. Genotyping of the DRD2 NcoI C to T polymorphism located in exon 6 (His313His) was performed using previously described primers. RESULTS: A significantly increased incidence of migraine with aura (MWA), major depression, generalized anxiety disorder (GAD), panic attacks, and phobia was observed in individuals with the DRD2 NcoI C/C genotype compared with individuals with an DRD2 NcoI T allele. Specifically, 69% (91/131) of DRD2 NcoI C/C individuals in the present study met criteria for at least one of these neuropsychiatric disorders versus only 22% (4/18) of the DRD2 NcoI T/T individuals (Chi-square = 15.29; p < 0.00005). The DRD2 NcoI C allele frequency is significantly higher (Chi-square = 17.13; p < 0.00002) in individuals with MWA, anxiety disorders, and/or major depression (C allele frequency = 0.80) than in individuals who have none of these disorders (C allele frequency = 0.67). CONCLUSIONS: These data indicate that MWA, anxiety disorders, and major depression can be components of a distinct clinical syndrome associated with allelic variations within the DRD2 gene. Clinical recognition of this genetically based syndrome has significant diagnostic and therapeutic implications.     

Association between single nucleotide polymorphisms of TPH1 and TPH2 genes,and depressive disorders

Tryptophan catabolites pathway disorders are observed in patients with depression. Moreover, single nucleotide polymorphisms of tryptophan hydroxylase genes may modulate the risk of depression occurrence. The objective of our study was to confirm the association between the presence of polymorphic variants of TPH1 and TPH2 genes, and the development of depressive disorders. Six polymorphisms were selected: c.804‐7C>A (rs10488682), c.‐1668T>A (rs623580), c.803+221C>A (rs1800532), c.‐173A>T (rs1799913)—TPH1, c.‐1449C>A (rs7963803), and c.‐844G>T (rs4570625)—TPH2. A total of 510 DNA samples (230 controls and 280 patients) were genotyped using TaqMan probes. Among the studied polymoorphisms, the G/G genotype and G allele of c.804‐7C>A—TPH1, the T/T homozygote of c.803+221C>A—TPH1, the A/A genotype and A allele of c.1668T>A—TPH1, the G/G homozygote and G allele of c.‐844G>T—TPH2, and the C/A heterozygote and A allele of c.‐1449C>A—TPH2 were associated with the occurrence of depression. However, the T/T homozygote of c.‐1668T>A—TPH1, the G/T heterozygote and T allele of c.‐844G>T—TPH2, and the C/C homozygote and C allele of c.‐1449C>A—TPH2 decreased the risk of development of depressive disorders . Each of the studied polymorphisms modulated the risk of depression for selected genotypes and alleles. These results support the hypothesis regarding the involvement of the pathway in the pathogenesis of depression.     

Opioid peptides and immunodysfunction in patients with major depression and anxiety disorders

To assess cell-mediated immunity in depression and anxiety disorders and to elucidate whether immunodysfunction might be related to a high opioid activity, a prospective study of patients with major depression (n = 34) or anxiety disorders (n = 21) was performed. Cellular immunity tests, the in vitro effects of naloxone on monocytes, and beta-endorphin plasma levels were investigated. Peripheral blood mononuclear cells and some monocyte parameters were determined by flow cytometry. Natural killer (NK) cell activity was studied by cytotoxicity, gamma-interferon production by a standard bioassay, monocytic phagocytosis by ingestion of Candida albicans and latex, and blastogenesis by stimulation with phytohaemaglutinin. In major depression and anxiety: 1) a marked reduction in the number of monocytes that ingested particles and expressed cytoskeletal intermediate filaments and surface structures (CR1 receptors and HLA-DR antigens); 2) a monocytosis that was not able to normalize the count of functioning monocytes; 3) an in vitro correction of the monocyte dysfunction by naloxone; 4) a decrease in NK cell number and activity; and 6) an anergy to candidin and tuberculin and a diminished lectin-induced blastogenesis were observed. Some of these immune changes correlated closely with plasma beta-endorphin abnormally high in all the cases. In conclusion, a naloxone-reversible monocyte dysfunction, associated to decreased NK activity and cell-mediated hypersensitivity, was found together with high of beta-endorphin plasma levels. In addition, results suggest that these immunological alterations may be useful in the clinical management of patients with these psychiatric diseases.     

Relationship of stressful life events, anxiety and depression to hyperthyroidism in an asian population

BACKGROUND: Psychological disturbances are well-known disorders in patients with hyperthyroidism, with anxiety and depression being the most commonly described. Stressful life events may play an important role in the relationship of anxiety, depression and hyperthyroidism. We assessed the associations of these disorders by three-part rating scales, including the Hamilton Rating Scale for Anxiety (HAM-A) indicating anxiety, the Zung Self-Rating Depression Scale (Zung Scale) indicating depression and the Social Readjustment Rating Scale (SRRS) indicating external stress from life events in this study. METHODS: Eighty-six outpatients who visited an endocrine clinic with suspicion of thyroid disease and 18 healthy volunteers were enrolled in the study. In all of these individuals, thyroid functions were assessed and questionnaires were completed during an interview. RESULTS: The outpatients with hyperthyroidism (n = 39) had higher scores of HAM-A (15.7 +/- 1.1 vs. 8.0 +/- 0.8, p < 0.001), Zung scale (46.2 +/- 1.5 vs. 37.5 +/- 1.4, p < 0.001) and SRRS (92.9 +/- 13.5 vs. 56.9 +/- 8.4, p = 0.015) than those with euthyroidism (n = 47). The scores of the three-part rating scales were also higher in the outpatients with hyperthyroidism than in healthy volunteers (n = 18), with no significant differences between the outpatients with euthyroidism and healthy volunteers. CONCLUSION: In patients with hyperthyroidism, anxiety, depression and stressful life events were more severe than in those with normal thyroid function. There were no correlations between these psychological disorders and thyroid function tests of the subjects with hyperthyroidism. The role of psychotherapy in the development of hyperthyroidism deserves further investigations.     

The interaction between TPH2 promoter haplotypes and clinical-demographic risk factors in suicide victims with major psychoses

Tryptophan hydroxylase isoform 2 (TPH2) is a rate-limiting enzyme in the biosynthesis of serotonin (5-HT) and is predominantly localized in the brain. Previous studies have suggested that there is an association between serotonergic dysfunction in the brain and suicidality. This study was designed to examine whether the -473T > A and -8396G > C polymorphisms of the TPH2 gene may be associated with completed suicide in subjects with major psychoses from the Stanley Foundation Brain Bank sample. TPH2 genotypes were determined in 69 subjects with a diagnosis of schizophrenia or bipolar disorder, among which 22 died by suicide. Genomic DNA was amplified by polymerase chain reaction and typed by automated methods. Both markers were found to be in Hardy-Weinberg equilibrium and in strong linkage disequilibrium. No association with history of suicide was found for either polymorphism. Haplotype analysis with EHAP showed no association between completed suicide and haplotype distribution (chi2 = 1.877; 3 df; P = 0.598). Nor was there any association between suicide and these genetic markers even when clinical-demographic factors were considered as covariates in the haplotype analysis. These findings suggest that these 5' marker haplotypes in the TPH2 gene do not influence suicidal behaviour.     

The effects of depression,anxiety and sleep disturbances on cognitive impairment in patients with chronic obstructive pulmonary disease

The purpose of this study was to investigate the effects of depression, anxiety and sleep disturbances on cognitive functions in chronic obstructive pulmonary disease (COPD) patients. In this prospective case-control study, demographic data, smoking history, depression, anxiety, sleep quality and cognitive status of 48 COPD patients and 36 healthy volunteers aged 40–90 years were recorded. The Beck depression inventory (BDI), the Beck anxiety inventory (BAI), and Pittsburgh Sleep Quality Index (PSQI) were used to assess depression, anxiety and sleep quality, respectively in COPD patients. Cognitive performance was studied by the mini-mental state examination. The mean age of patients with COPD was 65.3 ± 9.4 years, and disease duration was 9.6 ± 7.8 years. Male sex ratio, smoking, BDI score, BAI score, total PSQI score, sleep latency, sleep duration, average use of sleep aids and sleep disturbances in patients with COPD were significantly higher than the control group (p < 0.05). When cognitive impairment was compared by age, FVC, FEV, FEV/FVC, PEF values and smoking, no statistically significant relationship was found (p > 0.05). A statistically significant relationship was established between cognitive impairment and severity of disease, presence of anxiety, presence of depression and sleep quality. In our study, we found that sleep disorders, depression and anxiety comorbid with COPD increased cognitive impairment as well as the severity of disease. We believe that this finding is important in terms of reducing the risk of cognitive impairment, preventing misdiagnosis and treatment of the aforementioned comorbid diseases.     

Estrogen receptor-alpha gene haplotype is associated with primary knee osteoarthritis in Korean population

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-alpha gene polymorphisms for its associations with primary knee OA, we conducted a case-control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-alpha gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-alpha gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01-1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, chi2 = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-alpha gene haplotype may be associated with primary knee OA, and genetic variations in the ER-alpha gene may be involved in OA.     

Dissociated deficits in attentional networks in social anxiety and depression

A critical cognitive symptom that is commonly involved in social anxiety and depression is attentional deficit. However, the functional relationship between attentional deficit and these two disorders remains poorly understood. Here, we behaviorally disentangled the three key attentional components(alerting, orienting, and executive control) using the established attentional network task(ANT) to investigate how social anxiety and depression are related to deficits in these attention components. We identified a double dissociation between the symptoms of social anxiety and depression and the attentional component deficits when processing non-emotional stimuli. While individuals vulnerable to social anxiety exhibited deficits in the orienting component, individuals vulnerable to depression were impaired in the executive control component. Our findings showed that social anxiety and depression were associated with deficits in different attentional components, which are not specific to emotional information.     

Serotonin transporter gene,childhood emotional abuse and cognitive vulnerability to depression

Meta‐analyses evaluating the association between the serotonin transporter polymorphism (5‐HTTLPR) with neuroticism and depression diagnosis as phenotypes have been inconclusive. We examined a gene–environment interaction on a cognitive vulnerability marker of depression, cognitive reactivity (CR) to sad mood. A total of 250 university students of European ancestry were genotyped for the 5‐HTTLPR, including SNP rs25531, a polymorphism of the long allele. Association analysis was performed for neuroticism, CR and depression diagnosis (using a self‐report measure). As an environmental pathogen, self‐reported history of childhood emotional abuse was measured because of its strong relationship with depression. Participants with the homozygous low expressing genotype had high CR if they had experienced childhood emotional maltreatment but low CR if they did not have such experience. This interaction was strongest on the Rumination subscale of the CR measure. The interaction was not significant with neuroticism or depression diagnosis as outcome measures. Our results show that 5‐HTTLPR is related to cognitive vulnerability to depression. Our findings provide evidence for a differential susceptibility genotype rather than a vulnerability genotype, possibly because of the relatively low levels of abuse in our sample. The selection of phenotype and environmental contributor is pivotal in investigating gene–environment interactions in psychiatric disorders.     

Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn's disease in a New Zealand Caucasian cohort

Polymorphisms in the organic cation transporter (OCTN) genes SLC22A4 (OCTN1; polymorphism 1672C/T) and SLC22A5 (OCTN2; polymorphism -207G/C) at the inflammatory bowel disease (IBD) 5 locus comprise a two-allele haplotype (SLC22A-TC) associated with increased risk for Crohn's disease (CD). In this study, we examined the contribution of the disease susceptibility haplotype SLC22A-TC to CD in a New Zealand Caucasian population. The frequencies of the gene polymorphisms 1672C/T and -207G/C were examined in 182 patients with CD and 188 ethnically matched controls by PCR-RFLP analysis. There was a significant difference in the allele frequency (0.444 vs 0.519; P = 0.041) of the 1672T polymorphism in the SLC22A4 gene between controls and patients with CD. In contrast, there was no significant difference (0.497 vs 0.552; P = 0.135) for the -207C polymorphism in the SLC22A5 gene. The homozygote SLC22A-TC diplotype was significantly associated with an increased risk for CD (odds ratio 2.19), and the SLC22A-TC haplotype was associated with increased risk (P = 0.0007) of ileocolonic involvement. The population-attributable risk for the SLC22A-TC haplotype is 15.1%. Thus, SLC22A-TC is associated with an increased risk of CD and disease phenotype in our New Zealand CD cohort.     

Game-based biofeedback for paediatric anxiety and depression

Twenty-four children and adolescents aged 9-17 who were referred for treatment for anxiety were assigned to either a game-based biofeedback group or a waiting list comparison group. The eight-session biofeedback intervention included psychoeducation, identification of triggers and signs of anxiety, and in vivo practice. The intervention used computer-based gaming technology to teach and practise relaxation. Analyses using ANCOVA revealed significant differences in post-test scores of anxiety and depression measures between the two groups. The intervention group reduced anxiety and depression scores on standardised tests. Findings suggest that biofeedback-assisted relaxation training can be useful in decreasing anxiety and depressive symptoms in anxious youths.     

Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder

Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and allelic variations at the TPH1 locus have been implicated in the pathophysiology of depression. Using 1.5-Tesla functional magnetic resonance imaging, we investigated the possible relationship between TPH1 A218C polymorphism and amygdala response to negative facial stimuli in 26 right-handed female subjects with major depressive disorder (MDD). Genotyping was performed with the polymerase chain reaction. We found a significant association between A allele of the TPH1 A218C polymorphism and neural activations in response to negative facial stimuli. Subjects with the A allele of the TPH1 A218C polymorphism showed greater brain activity in the bilateral amygdala under the sad vs. the neutral condition compared with subjects homozygous for the C allele. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of amygdala activity in patients with MDD.     

Impaired attribution of emotion to facial expressions in anxiety and major depression

Background

Recognition of others'' emotions is an important aspect of interpersonal communication. In major depression, a significant emotion recognition impairment has been reported. It remains unclear whether the ability to recognize emotion from facial expressions is also impaired in anxiety disorders. There is a need to review and integrate the published literature on emotional expression recognition in anxiety disorders and major depression.

Methodology/Principal Findings

A detailed literature search was used to identify studies on explicit emotion recognition in patients with anxiety disorders and major depression compared to healthy participants. Eighteen studies provided sufficient information to be included. The differences on emotion recognition impairment between patients and controls (Cohen''s d) with corresponding confidence intervals were computed for each study. Over all studies, adults with anxiety disorders had a significant impairment in emotion recognition (d = −0.35). In children with anxiety disorders no significant impairment of emotion recognition was found (d = −0.03). Major depression was associated with an even larger impairment in recognition of facial expressions of emotion (d = −0.58).

Conclusions/Significance

Results from the current analysis support the hypothesis that adults with anxiety disorders or major depression both have a deficit in recognizing facial expression of emotions, and that this deficit is more pronounced in major depression than in anxiety.     

Tryptophan hydroxylase 1 gene haplotypes modify the effect of a hostile childhood environment on adulthood harm avoidance

We conducted a series of tests to determine whether there is any association between tryptophan hydroxylase 1 (TPH1) and temperament in adulthood. In addition to testing for main effects, we investigated whether TPH1 gene variation modifies the influence of childhood environment on temperament in adulthood. The subjects were 341 healthy adults whose childhood environment was assessed by their mothers in 1980 and who self-rated their temperaments twice, in 1997 and 2001. We found no association between the TPH1 gene and temperament; however, among women, the TPH1 gene modified a relationship between adverse childhood environment and harm avoidance in adulthood. This finding was confirmed in the same sample in another test setting 4 years later. The presence of the A/A haplotype of the TPH1 intron 7 A218A and A779C polymorphism predicted a high level of adulthood harm avoidance in the presence of a hostile childhood environment as defined in terms of emotional rejection, maternal neglect and harsh and inconsistent discipline. In addition, the findings suggest a gene-environment correlation for novelty seeking in men.     

Muscle tension and physiologic hyperarousal,performance, and state affectivity: assessing the independence of effects in frequent headache and depression

Anxiety, depression, and frequent headache are closely associated. The comorbidity may be due to selection bias (such as inherent in treatment seeking), shared environmental or genetic factors, or a common underlying process. In this study, comorbidity is considered an alternative explanation for correlates of frequent headache found in earlier work. This study addressed whether EMG, peripheral temperature, performance measures, and measures of affect were independently attributable to depression or headache proneness, after control of trait anxiety. Headache state was evaluated in parallel analysis. Seventy-two participants, comprising four groups, were tested: depressedt/ptheadache-prone, depressed/headache-resistant, not depressed/headache-prone, and not depressed/headache-resistant. Participants completed a performance task that allowed assessment of ambition and performance accuracy while measures of affect, headache state, EMG, and peripheral temperature were obtained. Headache proneness, independently of depression and trait anxiety, was related to heightened EMG. Depression was related to EMG, ambition, and performance accuracy independently of headache proneness and trait anxiety. Headache state was associated only with negative affect, independently of depression and anxiety. These results suggest that headache states during assessment, as well as comorbid depression and anxiety, are not primarily responsible for the heightened EMG found in headache-prone individuals. Negative affect often reported in the headache prone, however, may be due to concommitant anxiety. Other analyses address a variety of issues surrounding distinctions among these variables raised in previous research.     

Report on the Molecular Approaches to Osteoarthritis Symposium,Imperial College London,UK, 18–20 April 2004

Estrogen and estrogen receptors (ERs) are known to play important roles in the pathophysiology of osteoarthritis (OA). To investigate ER-α gene polymorphisms for its associations with primary knee OA, we conducted a case–control association study in patients with primary knee OA (n = 151) and healthy individuals (n = 397) in the Korean population. Haplotyping analysis was used to determine the relationship between three polymorphisms in the ER-α gene (intron 1 T/C, intron 1 A/G and exon 8 G/A) and primary knee OA. Genotypes of the ER-α gene polymorphism were determined by PCR followed by restriction enzyme digestion (PvuII for intron 1 T/C, XbaI for intron 1 A/G, and BtgI for exon 8 G/A polymorphism). There was no significant difference between primary knee OA patients and healthy control individuals in the distribution of any of the genotypes evaluated. However, we found that the allele frequency for the exon 8 G/A BtgI polymorphism (codon 594) was significantly different between primary knee OA patients and control individuals (odds ratio = 1.38, 95% confidence interval = 1.01–1.88; P = 0.044). In haplotype frequency estimation analysis, there was a significant difference between primary knee OA patients and control individuals (degrees of freedom = 7, χ² = 21.48; P = 0.003). Although the number OA patients studied is small, the present study shows that ER-α gene haplotype may be associated with primary knee OA, and genetic variations in the ER-α gene may be involved in OA.     

The complex roles of neurosteroids in depression and anxiety disorders

The role of neurosteroids in neuropsychiatric disorders has been thoroughly investigated in many research studies that have stressed their significant pathophysiological function in neuropsychiatry. In this review, we will focus mainly on the steroids active on the GABA(A) receptors studied in anxiety and depression. The aim is to discuss the controversial results reported in research on anxiety and depressive disorders. We suggest the combined use of biological parameters linked to psychopathological dimensions to make more homogeneous diagnoses and to develop more precise therapies for the treatment of depression and anxiety disorders. We discuss the role of neurosteroids in the pathophysiology and therapy of anxiety and depression. Finally, we consider the possibility of using quantification of mRNA expression of steroidogenic enzymes from peripheral sources in neuropsychiatry.     

Clinical presentation of depression among Malaysian women in Penang Island

Objectives To identify the aetiology and clinical presentation of depression among Malaysian women.Methods A cross-sectional study was conducted at the Psychiatry Clinic, Public Hospital, Pulau Penang, Malaysia. Retrospective evaluations of records were conducted between January 2002 and December 2007. The data were analysed using the statistical software, SPSS v. 131®.Results Ninety-six (56.8%) of the patients were Chinese, the mean (± SD) age of the patients was 45 ± 17.8 years, with a majority (72; 42.6%) aged over 50 years. The incidence of depression with comorbid hypertension and comorbid diabetes mellitus was significant among women aged over 50 (P < 0.001 (hypertension) P < 0.015 (diabetes mellitus)). Marital and relationship problems were found to significantly affect Chinese women aged 15–30 years (P = 0.019). In terms of the clinical presentation of depression among Malaysian women, suicidal ideation and somatic symptoms like reduced energy/being easily fatigued were more frequent among Chinese.Conclusion Symptoms of being short-tempered, crying, restless and doubtful/distracted should not be neglected in primary care because of the possibility of mental health disorders. The timely evaluation of diabetic and hypertensive patients is an ideal strategy to prevent mental health disorders.