Regional homogeneity abnormalities in patients with interictal migraine without aura: a resting-state study

Previous studies have provided evidence of structural and task-related functional changes in the brains of patients with migraine without aura. Resting-state brain activity in patients with migraine provides clues to the pathophysiology of the disease. However, few studies have focused on the resting-state abnormalities in patients with migraine without aura. In the current study, we employed a data-driven method, regional homogeneity (ReHo), to analyze the local features of spontaneous brain activity in patients with migraine without aura during the resting state. Twenty-six patients with migraine without aura and 26 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, patients with migraine without aura showed a significant decrease in ReHo values in the right rostral anterior cingulate cortex (rACC), the prefrontal cortex (PFC), the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). In addition, we found that ReHo values were negatively correlated with the duration of disease in the right rACC and PFC. Our results suggest that the resting-state abnormalities of these regions may be associated with functional impairments in pain processing in patients with migraine without aura. We hope that our results will improve the understanding of migraine.     

Modulation of trigeminal reflex excitability in migraine: effects of attention and habituation on the blink reflex.

The modulation of trigeminal reflex excitability in migraine patients was evaluated during the asymptomatic phase by studying the effects of attention, habituation and preconditioning stimulus on the R2 and R3 components of the blink reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by migraine with aura and 35 sex- and age-matched controls were selected. In subgroups of migraine with-aura and without-aura patients, and normal controls, the blink reflex was elicited during different cognitive situations: (a) spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target numbers. In the remaining subjects, R2 and R3 habituation was evaluated by repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 recovery curves were also computed. A reduced R3 threshold with a normal pain threshold was found in migraine with-aura and without-aura patients; the R3 component was not significantly correlated with the pain thresholds in patients and controls. The R2 and R3 components were less influenced by the warning of the stimulus in migraine without-aura and migraine with-aura patients, in comparison with the control group. A slight increase of both R2 and R3 recovery after preconditioning stimulus was also observed in migraine patients, probably caused by a phenomenon of trigeminal hyperexcitability persisting after the last attack. The abnormal BR modulation by alerting expresses in migraine a dysfunction of adaptation capacity to environmental conditions, probably predisposing to migraine.     

Risk of peripheral artery disease and stroke in migraineurs with or without aura: a nationwide population-based cohort study

Background: Migraine is deemed a neurovascular disorder and there is growing evidence on the increased risk of cardiovascular disease, especially ischemic stroke, in patients with migraine. However the risk of peripheral artery disease (PAD) and stroke in migraineurs and the association between migraineurs with or without aura is still under debate. Our study aimed to identify the risk of PAD and stroke in migraineurs with or without aura.Methods: This was a population-based cohort study utilizing Taiwan Longitudinal Health Insurance Database (LHID2010). Patients with coding of migraine from 2002 to 2011 were enrolled and those with established cardiovascular disease defined as myocardial infarction, stroke, PAD, venous thromboembolism, atrial fibrillation and heart failure diagnosis before the index date were excluded. Participants were categorized into migraine group, migraine without aura group, and migraine with aura group respectively. The subjects in the three groups were propensity score-matched randomly to their counterparts without migraine. The study outcome was PAD and stroke. The Cox proportional hazard model was used to estimate the hazard ratios with 95% confidence interval (CI) for the association between migraine and the incident events of disease, after controlling for related variables.Results: The migraine, migraine without aura, and migraine with aura group included 5,173 patients, 942 patients and 479 patients respectively after propensity score-matching. The migraine group had an increased risk of PAD [adjusted hazard ratio (aHR): 1.93; 95% confidence interval (CI): 1.45-2.57; p < 0.001] and stroke (aHR: 1.55; 95% CI: 1.35-1.77; p < 0.001) compared to their non-migraine controls. Both the groups of migraine without aura and with aura had an increased risk of stroke (aHR: 1.49, 95% CI: 1.11-2.00; p = 0.008; aHR: 1.63, 95% CI: 1.10-2.43; p = 0.016). With regards to the outcome of PAD, the group of migraine with aura had a trend of an increased risk but did not reach statistical significance (aHR: 1.95, 95% CI: 0.86-4.40; p = 0.108).Conclusion: Migraineurs without established cardiovascular disease had a significantly increased risk of PAD and stroke, and the risk of stroke persists in migraineurs with or without aura, with an increased trend of PAD in migraineurs with aura. Our study result should remind clinical physicians of the risk of PAD in the future among migraineurs even without established cardiovascular disease currently, and screening for PAD and stroke may be needed in caring patients with migraine.     

HLA-DRB1 genotyping in Italian migraine patients

We examined the distribution of HLA-DRB1 alleles in a cohort 255 Italian migraine patients and in a control group of 325 healthy subjects. 214 patients fulfilled the ICHD-II criteria for migraine without aura and 41 patients the criteria for migraine with aura. The frequency of DRB1*16 allele was found to be significantly increased in migraine without aura patients (p=0.02; OR 1.97, 95% CI: 1.10-3.54) than in healthy controls. The frequencies of HLA-DRB1 alleles were not significantly different between migraine with aura patients and controls. We did not detect any effect of DRB1 alleles on age at onset, duration of the disease, frequency and duration of migraine attacks. Our data suggest the presence of a genetic susceptibility factor for migraine without aura within the HLA region.     

Electrophysiological evidence for trigeminal neuron sensitization in patients with migraine.

The electrically elicited corneal reflex is a useful tool for exploring the trigeminal system in humans and it may provide additional evidence pointing to a dysfunction of this system in migrainous patients. Tactile perception, corneal reflex and pain thresholds were studied in 48 migraine without aura patients during pain-free periods and compared with those observed in 24 controls. Twenty-eight of the patients had strictly unilateral headache, while the other 20 had bilateral or side-shifting pain during attacks. Both migraine subgroups (bilateral and unilateral) showed significantly lower thresholds compared with controls. The lowest values were observed on the symptomatic side of unilateral migraine patients. These findings suggest that sensorimotor mechanisms and/or pain control systems at the trigeminal level are impaired in migraine. The bilateral location of these abnormalities seems to point to a centrally located dysfunction.     

Apolipoprotein E gene polymorphisms in patients with migraine.

To investigate the role of apolipoprotein E (APOE) polymorphisms in migraine, we analyzed the APOE genotypes of 241 migraine patients and 587 controls. The results of a Chi-square analysis indicated that APOE alleles were similarly distributed (chi(2)=2.89, P=0.24) between cases and controls. However, we found a significant (P<0.001) increase of the varepsilon2-varepsilon4 genotype in the group of migraine patients. Patients were divided into three subgroups: migraine with aura; migraine without aura; and mixed headaches (migraine associated with tension-type headache). Subgroup analysis showed that the varepsilon2-varepsilon4 genotype was significantly increased only in patients with mixed headaches. The stratification of patients by APOE status did not reveal significant associations with the clinical features of the disease. In conclusion, we observed no significant association between APOE polymorphisms and migraine. The association between the APOE varepsilon2-varepsilon4 genotype and the tension-type headache deserves further evaluation.     

Effects of experimental hypercapnia on hippocampal long-term potentiation in anesthetized rats

Neuronal voltage-dependent P/Q Ca2+ channels are genetically abnormal in many cases of familial hemiplegic migraine and possibly associated with the more common forms of migraine with and without aura. Besides the brain, these channels are found in motor nerve endings where they control stimulation-induced acetylcholine release. Using single fiber EMG recordings we were able to demonstrate subclinical abnormalities of neuromuscular transmission in a subgroup of patients suffering from migraine with aura. This could be related to genetic abnormalities of P/Q Ca2+ channels in certain patients suffering from migraine with aura, which needs to be explored by proper genetic analyses.     

High harm avoidance and low self-directedness in euthymic young adults with recurrent, early-onset depression

BACKGROUND: The personality dimensions of harm avoidance (HA) and self-directedness (SD), as measured by the Temperament and Character Inventory (TCI), have been widely associated with depression and there is preliminary evidence that they may represent trait markers for depression. However, many studies in this area are limited by the use of heterogeneous samples of depressed patients and by the confounding effect of depressed mood during personality testing. The current study compares TCI personality dimension scores in a group of euthymic young adults with recurrent early-onset major depressive disorder (RE-MDD) to well-matched euthymic controls. METHODS: Fifty-two young adults with a past history of RE-MDD were recruited from consecutive referrals to a psychiatric clinic at a university health service. Eighty nine controls were also recruited. Euthymia was established in patients by a score of less than 9 on the Hamilton Rating Scale for Depression (HRSD) and in controls by a Becks Depression Inventory (BDI) score of less than 10. All participants completed the TCI-125. RESULTS: Patients and controls were well matched in terms of sociodemographic profile. Euthymic RE-MDD patients scored significantly higher than controls on the temperament dimension of harm avoidance (HA; mean score 14.5 versus 7.8, p<0.0001) and significantly lower than controls on the character dimension of self-directedness (SD; mean score 14.1 versus 19.9, p<0.0001). Covariance analysis suggested that both HA and SD contributed independently to the familial risk of depression. LIMITATIONS: Subjects and controls all came from relatively affluent social backgrounds-these findings may not generalise to more socioeconomically diverse populations. The possibility of a 'scarring effect' of depressive episodes on self-reported personality dimension scores cannot be excluded. CONCLUSIONS: High HA and low SD represent trait markers for liability to recurrent major depressive disorder in young adults. Further research is needed to replicate these findings and to assess the contribution that the experience of depressive episodes makes to self-reported personality dimension scores.     

Personality traits and stress sensitivity in migraine patients

A review of the literature on migraine and personality yielded strong evidence for secondary neuroticism and increased sensitivity to stress in patients with migraine. This study focused on the identification of specific stressful situations and coping strategies in such patients. We conducted a psychodiagnostic study of 30 migraine patients in accordance with the criteria of the Headache Classification Committee of the International Headache Society and 30 healthy control subjects matched for age, sex, and social status. All participants completed the Minnesota Multiphasic Personality Inventory (MMPI) and special questionnaires on stressful situations and coping strategies. The migraine patients had higher neuroticism and introversion scores on the MMPI than the healthy subjects. There was a positive correlation between the neuroticism score and headache duration (number of hours per week). The patients used coping strategies characterized by the development of physical symptoms, social isolation, and preoccupation with stress. They rated themselves as less calm, less capable of relaxing, and more irritable than did the healthy controls subjects, and they responded more often with internal tension, especially in work and other achievement situations. Questionnaires that measure constructs dealing with stress yield information that is more relevant for the treatment of migraines than do global personality tests.     

Cerebral blood flow in migraine with aura.

Pathognomonic changes in regional cerebral blood flow (rCBF) have gradually been described during the last decade. They support spreading cortical depression as the mechanism underlying the migraine aura but are not the direct cause of pain since they are absent in migraine without aura and are present in migraine aura without pain. Dilatation of intra- and extracranial arteries, on the other hand, takes place in both forms of migraine and seem closely associated to the pain. Dilatation and perivascular nociceptor sensitization may, very likely, be caused by neuropeptides and monoamines released from perivascular nerves and/or mast cells.     

Stress, personality and depressive symptoms in a 6.5 year follow-up of subjects at familial risk for affective disorders and controls

BACKGROUND: The aim of the study was to identify risk factors in subjects at risk for depressive disorders and controls. METHODS: In a 6.5 year follow-up study we examined the effects of personality (neuroticism, frustration intolerance, rigidity, melancholic type), adverse life events and chronic difficulties on depressive symptoms in 89 high-risk subjects (HRS, siblings and children of patients suffering from an affective disorder), without any mental illness at wave 1 (T1), and 49 controls without any personal and family history of psychiatric disorder at T1. To this end, regression analysis and path analysis using a structural equation model (only for HRS) were performed. RESULTS: Risk factors for depressive symptoms at wave 2 (T2) in HRS comprised acute adverse life events, frustration intolerance (T1) and depressive symptoms (T1). Risk factors for depressive symptoms in controls included chronic difficulties, neuroticism and rigidity. HRS had less stressful life events and the same risk for chronic difficulties, but perceived adverse events as more stressful. LIMITATION: The sample size of the control group is too small for identifying slight effects. CONCLUSION: Our results indicate that the impact on the emergence of depressive symptoms of various risk factors is different in high-risk subjects and controls. High-risk subjects are more sensitive to the depressogenic effects of acute stress and thus avoid potential stressful changes in their life to a higher extent. On the other hand, the influence of persistent factors such as personality traits (neuroticism, rigidity) and chronic difficulties on subsequent depressive symptoms was less pronounced in HRS as compared to controls.     

Use of the Coping Inventory for Stressful Situations in a clinically depressed sample: factor structure,personality correlates,and prediction of distress

The Coping Inventory for Stressful Situations (CISS; Endler & Parker, 1990) is a self-report measure of Emotion-, Task-, and Avoidance-oriented coping. The psychometric properties of the CISS were evaluated in a large sample of outpatients with major depressive disorder (N = 298). The CISS scales demonstrated good reliability and support for their factorial validity was obtained. Relationships between the CISS scales and the broad personality domains from the five-factor model of personality, as well as two measures of emotional distress, were examined. Less-adaptive coping strategies (i.e., Emotion-oriented coping) were associated with less-adaptive personality traits (i.e., Neuroticism) and with psychological distress (i.e., Depression), whereas the reverse was found regarding adaptive coping strategies (i.e., Task-orientated coping). The incremental validity of the CISS was demonstrated by multiple-regression analyses that found two CISS scales accounted for significant variance in psychological distress beyond that contributed by the demographic and personality variables.     

Temperament and personality in bipolar I patients with and without mixed episodes

BACKGROUND: Personality and temperament are supposed to have an impact on the clinical expression and course of an affective disorder. There is some indication, that mixed episodes result from an admixture of inverse temperamental factors to a manic syndrome. In a preliminary report [Brieger, P., Roettig, S., Ehrt, U., Wenzel, A., Bloink, R., Marneros, A., 2003. TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits. J. Affect. Disord. 73, 99-104] we reported support for this assumption. The present study completes the preliminary results and compares patients with and without mixed episodes with respect to personality and personality disorders in addition. METHODS: Patients who had been hospitalized for bipolar I disorder were reassessed after 4.8 years. We examined temperament (TEMPS-A), personality (NEO-FFI) and frequency of personality disorders (SCID-II). Furthermore, illness-related parameters like age at first treatment, depressive and manic symptomatology, frequency and type of episodes and level of functioning were obtained and patients with and without mixed episodes were compared. RESULTS: Patients with (n=49) and without mixed episodes (n=86) did not differ significantly with regard to the illness-related parameters and personality dimensions. The frequency of personality disorders was significantly higher in patients with prior mixed episodes. With respect to temperament, scores of the depressive, cyclothymic, irritable and anxious temperament were significantly higher in patients with mixed episodes. LIMITATIONS: We were not able to assess premorbid temperament and premorbid personality. CONCLUSIONS: The findings of the present study support the assumption of Akiskal [Akiskal, H.S., 1992b. The distinctive mixed states of bipolar I, II, and III. Clin. Neuropharmacol. 15 Suppl 1 Pt A, 632-633.] that mixed episodes are more frequent in subjects with inverse temperament.     

抑郁症患者的家庭暴力及因素分析

目的:研究家庭暴力与抑郁症个性特点、社会支持、应对方式的关系,针对心理十预提供理论依据。方法:采用自行设计的家庭暴力调查表、汉密尔顿抑郁量表(HAMD)、社会支持评定量表、特质应对方式问卷和艾森克人格问卷(EPQ),对72例抑郁症患者进行评定和比较。结果:有家庭内暴力者38例(男16例,女22例),家庭暴力与抑郁症患者HAMD 抑郁总分呈正相关;有家庭暴力组男性的主观支持分、总社会支持分低于无家庭暴力组(18.8±4.9,22.6±3.4;33.7±8.2,39.6±6.4,P<0.05),消极应对分高于无家庭暴力组(34.9±4.7,30.1±6.5,P<0.05);有家庭暴力组女性的支持利用度分低于无家庭暴力组(6.1±2.0,8.1±2.0,P<0.05), EPQ的神经质评分高于无家庭暴力组(64.2±7.4,56.5±10.3,P<0.05)。结论:抑郁症患者的家庭暴力事件应予以重视,家庭暴力与男性抑郁症患者的绝望感、主观支持、总社会支持及消极应对方式相关;家庭暴力与女性的支持利用度和神经质个性相关。     

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.     

Can personality traits predict increases in manic and depressive symptoms?

BACKGROUND: There has been limited research investigating personality traits as predictors of manic and depressive symptoms in bipolar individuals. The present study investigated the relation between personality traits and the course of bipolar disorder. The purpose of this study was to identify specific personality traits that predict the course of manic and depressive symptoms experienced by bipolar individuals. METHODS: The sample consisted of 39 participants with bipolar I disorder assessed by the Structured Clinical Interview for DSM-IV. Personality was assessed using the NEO Five-Factor Inventory. The Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale were used to assess symptom severity on a monthly basis. RESULTS: Consistent with previous research on unipolar depression, high Neuroticism predicted increases in depressive symptoms across time while controlling for baseline symptoms. Additionally, high Conscientiousness, particularly the Achievement Striving facet, predicted increases in manic symptoms across time. LIMITATIONS: The current study was limited by the small number of participants, the reliance on a shortened version of a self-report personality measure, and the potential state-dependency of the personality measures. CONCLUSIONS: Specific personality traits may assist in predicting bipolar symptoms across time. Further studies are needed to tease apart the state-dependency of personality.     

Personality and object relations in patients with affective disorders: idiographic research by means of the repertory grid technique

BACKGROUND: This paper presents an idiographic approach to evaluate the self concept and the self-object-relationship of patients suffering from affective disorders. METHODS: Significant dimensions of the personality and the object relations of 127 depressive patients and 34 orthopaedic patients were investigated with the repertory grid-technique. The self concept and the object relations were compared by means of nomothetically used idiographic results after recovery from manifest depression. RESULTS: 'Low self esteem' was frequently found in patients with a long lasting course of illness and the ICD-10-diagnoses of 'bipolar affective disorder' and 'dysthymia'. The object relations of the depressive sample were characterised by the dimension 'symbiotic near'; 'ambivalent' and 'indifferent' partnership relationships were found much more frequently in the controls. CONCLUSIONS: The idiographic results help to differentiate the spectrum of affective disorders. They underline the importance of the interpersonal dimension of depression and may be used as a basis of a therapeutic appraisal. LIMITATIONS: The repertory grid-technique may not be used as a diagnostic instrument. However, the combination of idiographic results with further clinical informations enables the multidimensional assessment of the self concept and psychosocial coping mechanisms.     

Capsaicin failed in suppressing cortical processing of CO2 laser pain in migraine patients

The aim of this study was to compare the properties of the nociceptive system in eight migraine without aura patients in the pain-free phase with 10 healthy controls, by evaluating the topography and the source of the CO2 laser-evoked potentials (LEPs) obtained by the right supraorbital skin, during and after capsaicin topical application. In healthy subjects the acute cutaneous pain induced by capsaicin reduced the amplitude of the vertex LEPs and induced a posterior shifting of the P2 wave dipolar source within the anterior cingulate cortex. These functional changes seemed significantly reduced in migraine patients, for a disturbed pattern of pain modulation at the cortical level, which may subtend the onset and persistence of migraine.     

Major depressive disorder, serotonin transporter, and personality traits: why patients use suboptimal decision-making strategies?

BACKGROUND: Patients with major depressive disorder (MDD) show suboptimal decision-making strategy in experimental game situations. The influence of personality traits and genetic variations on decision-making is not known. METHODS: Contingency learning based on the cumulative effect of reward and punishment was assessed in 124 patients with unipolar MDD using the ABCD (reward sensitivity) and EFGH (punishment sensitivity) versions of the Iowa Gambling Test. All patients were genotyped for serotonin transporter promoter polymorphism (5-HTTLPR) and received the Temperament and Character Inventory (TCI). RESULTS: Patients with the ll genotype achieved higher persistence scores and used more optimal decision-making strategy on the ABCD task compared with patients with the ss genotype. Higher persistence was associated with better performance on the ABCD task, and higher harm-avoidance was associated with worse performance on the EFGH task. LIMITATIONS: Healthy control volunteers were not included. Personality traits and decision-making were not assessed with multiple questionnaires and tasks. Type I errors cannot be excluded. CONCLUSIONS: Decision-making strategy is influenced by personality traits and genetic variations in patients with MDD. Patients carrying the ss variant of the 5-HTTLPR show less persistence and tend to be influenced by high immediate reward.     

Structural and functional abnormalities in migraine patients without aura

Migraine is a primary headache disorder characterized by recurrent attacks of throbbing pain associated with neurological, gastrointestinal and autonomic symptoms. Previous studies have detected structural deficits and functional impairments in migraine patients. However, researchers have failed to investigate the functional connectivity alterations of regions with structural deficits during the resting state. Twenty‐one migraine patients without aura and 21 age‐ and gender‐matched healthy controls participated in our study. Voxel‐based morphometric (VBM) analysis and functional connectivity were employed to investigate the abnormal structural and resting‐state properties, respectively, in migraine patients without aura. Relative to healthy comparison subjects, migraine patients showed significantly decreased gray matter volume in five brain regions: the left medial prefrontal cortex (MPFC), dorsal anterior cingulate cortex (dACC), right occipital lobe, cerebellum and brainstem. The gray matter volume of the dACC was correlated with the duration of disease in migraine patients, and thus we chose this region as the seeding area for resting‐state analysis. We found that migraine patients showed increased functional connectivity between several regions and the left dACC, i.e. the bilateral middle temporal lobe, orbitofrontal cortex (OFC) and left dorsolateral prefrontal cortex (DLPFC). Furthermore, the functional connectivity between the dACC and two regions (i.e. DLPFC and OFC) was correlated with the duration of disease in migraine patients. We suggest that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex, and these changes may explain the functional impairments in migraine patients. Copyright © 2012 John Wiley & Sons, Ltd.