Clinical characteristics of familial and non-familial bipolar disorder

Objective: To explore the clinical characteristics of familial and non-familial bipolar disorder.

Method: Twenty subjects with bipolar disorder, who also had a family history of bipolar disorder in a first degree relative, were matched for current age, age of first onset of bipolar disorder and gender with 20 subjects with bipolar disorder who had no family history of any psychiatric disorders in first or second degree relatives.

Results: Fourteen subjects in each group were female. The mean age at interview was 45.2 years and the mean age at first admission was 26 years. Although familial and non-familial probands had an equivalent number of illness episodes, familial probands were significantly more likely to experience mixed states as compared to non-familial probands. The latter experienced significantly more depressive episodes and had significantly higher neuroticism (N) scores on the Eysenck Personality Inventory (EPI; Eysenck H, Eysenck S. Manual of the Eysenck Personality Inventory. London: University of London Press, 1964.).

Conclusions: If the results are replicated, they have important implications. For example, such data may aid decisions about the targeting of additional psychosocial interventions in high N score cases. Researchers will wish to investigate whether mixed states show a stronger association with early age of onset or family history of BD.     

An exploratory study on obsessive-compulsive disorder with and without a familial component: are there any phenomenological differences?

Familial studies on obsessive-compulsive disorders (OCD) have suggested that OCD is a heterogeneous condition, with some cases being familial and others being isolated cases in their families. Nevertheless, no studies evaluated whether there are clinical differences between OCD cases with and without a familial component. The current report presents data on the prevalence of OCD in first-degree relatives of OCD probands and compares phenomenological characteristics of familial and non-familial OCD types. The family study and the family history methods were used to estimate the prevalence of OCD in first-degree relatives of 74 OCD probands. A statistical comparison between OCD probands with and without familial loading was performed using Pearson's chi(2) test, Fisher's exact test, or Student's t test when appropriate. The rate of OCD was 3.5% in directly interviewed first-degree relatives. Eleven percent of the probands had at least one family member with OCD. There were no differences between the two types of OCD (familial vs. non-familial) except for life events prior to the onset of OCD, which were more common and more severe in non-familial OCD subtypes. In conclusion, our results (1) confirm that there is a familial component in the expression of some forms of OCD and (2) indicate that familial OCD patients are not characterized by peculiar clinical features, but appear to have a lower threshold for precipitating events.     

Do Women without a Family History of Schizophrenia Have a Later Onset of Schizophrenia ?

Abstract: The relation among age at onset of schizophrenia, sex and the presence or absence of first-degree relatives with schizophrenia was investigated in 2,417 inpatients meeting the DSM-111 criteria for schizophrenia. The mean age at onset of female schizophrenic patients without a family history of this illness was slightly later than that of any of the other three groups (male familial, female familial and male nonfamilial groups). The female nonfamilial group developed schizophrenia after the age of 25 and 30 more frequently than the male familial group and female familial or male nonfamilial group, respectively.     

Do women without a family history of schizophrenia have a later onset of schizophrenia?

The relation among age at onset of schizophrenia, sex and the presence or absence of first-degree relatives with schizophrenia was investigated in 2,417 inpatients meeting the DSM-III criteria for schizophrenia. The mean age at onset of female schizophrenic patients without a family history of this illness was slightly later than that of any of the other three groups (male familial, female familial and male nonfamilial groups). The female nonfamilial group developed schizophrenia after the age of 25 and 30 more frequently than the male familial group and female familial or male nonfamilial group, respectively.     

Heritability of cluster headache

We conducted a pedigree analysis in 222 patients with cluster headaches (CHs) in order to assess a familial predisposition to the disease. Heritability was determined by Falconer's index (from the incidence of CH among first degree relatives of probands compared with a control population), which varies between 0 and 1 (none or full genetic causation). A positive family history (I/II degree relatives) was found in 2.3% of our CH patients. Three generations were affected in one family and two generations in another two families. The calculated Falconer's heritability index was, however, only 0.26 ± 0.25 SD. Our study confirms a higher familial occurrence of CH, some families showing a pattern compatible with autosomal dominant inheritance with reduced penetrance. The low Falconer's index indicates, however, a large non-genetic causation in most cases of CH.     

A family study on primary blepharospasm

BACKGROUND: Previous family studies provided evidence that blepharospasm (BSP) can aggregate in families but did not give accurate and reliable information on the characteristics and degree of familial clustering. AIM: To evaluate the proportion of familial and non-familial BSP cases, the clinical expression of dystonia within families, the inheritance pattern, and the extent of penetrance. METHODS: The study was based on the examination of the first degree relatives of 56 probands with primary BSP. RESULTS: The 56 families produced a potential population of 436 first degree relatives of whom 296 were alive and 233 were examined. The proportion of index patients with at least one first degree relative affected by BSP, or adult onset dystonia other than BSP, was 27%. There was a remarkable degree of phenotypic variability of dystonia within families. Similar segregation ratios were calculated for probands' siblings and children. Under the assumption of autosomal dominant transmission of adult onset dystonia, penetrance was about 20%. CONCLUSIONS: The findings of this family study are relevant for accurately counselling the families of patients with BSP and may help identify the most appropriate study design to explore genetic susceptibility in BSP.     

女性紧张性头痛及经期偏头痛影响因素的比较

目的比较女性紧张性头痛(TTH)及经期偏头痛(MM)的影响因素。方法收集104例女性TTH患者(TTH组)及91例MM患者(MM组)的临床资料。采用视觉模拟评分法(VAS)和头痛影响测评量表-6(HIT-6)对其头痛程度、生活质量进行评估,并采用汉密尔顿焦虑(HAMA)、抑郁量表(HAMD)对患者情绪障碍进行测定。结果 TTH组与经期相关19例,累积发病率18.3%;MM组与经期相关59例,累积发病率64.8%。与TTH组比较,MM组发病年龄显著降低,病程、家族史,焦虑、抑郁、重度疼痛、HIT-6(Ⅳ级)、共病的比率,以及HAMA、HAMD评分均显著升高(P0.05~0.01),而文化程度、吸烟、饮酒、职业差异无统计学意义(均P0.05)。无先兆的月经相关性偏头痛(MRM)、无先兆的单纯月经性偏头痛(PMM)及非月经性无先兆偏头痛患者发病年龄、家族史、VAS及HIT-6评分差异有统计学意义(P0.05~0.01)。结论与女性TTH比较,MM发病年龄更轻、病程更长,也更易合并焦虑、抑郁。在不同类型MM中,PMM发病年龄更早,有家族史的比率更高;而MRM的重度疼痛率及HIT-6评分最高。     

THE PROGNOSTIC CONSEQUENCES OF FAMILIAL PREDISPOSITION AND SEX IN EPILEPSY

A material of 193 patients with epilepsy, all of them followed for one year or more, was analysed retrospectively. 84 cases were assessed as symptomatic and 109 cases as cryptogenic. The cryptogenic group comprised 42 cases with and 67 cases without familial predisposition. The females were slightly over-represented, especially in the cryptogenic familial group. The males were over-represented in the symptomatic group. The interesting finding in this study was that the cryptogenic familial cases showed a significantly worse prognosis under treatment than did the non-familial cryptogenic cases. Analysing the cryptogenic familial and non-familial groups with regard to type of seizures, age at onset of the disease, and the duration of the disease, it could be shown that the prognostic difference between the familial and the non-familial cases was independent of these factors. When the prognosis in the two sex-groups was estimated, it was shown that the worse prognosis in the cryptogenic familial group was predominantly localized in the female members. The principal conclusion of this study was, then, that the poorer prognosis in the cryptogenic familial group had to be ascribed to the genetic trait. Further, it was concluded that females not only to a greater extent manifest the centrencephalic epileptic pattern in the EEG, as shown by other authors, but also to a greater extent than males develop epilepsy, and that the epilepsy in the female generally seems to take a more unfavourable course.     

Multicenter study of childhood headache

This multicenter study reports the results obtained between 1990 and 1991 by the Study Group for Childhood Headache of the Italian Neuropediatric Society. Standardized computerized case sheets were used in order to increase the number of young patients studied and obtain more homogeneous results. A clinical diagnosis of headache was made in 600 patients (314 female and 286 male) between 4 and 12 years of age, in accordance with the classification set down by the International Headache Society. Clinical symptoms and follow-up were more severe in children with migraine as opposed to headache. No sequence of associated neurological and neurovegetative symptoms was observed at onset of headache, and some (phono-photophobia, pallor, drowsiness, abdominal pains) were much more prevalent than others. Because of the patient's age we studied only the treatment of acute attack and did not take account of chronic treatment. In childhood the clinical course of primary headache tends to improve spontaneously, and we believe that prevention of headache attacks should be carried out only in very rare individual cases.     

偏头痛家族聚集性患者临床特点及其一级亲属患病风险因素分析

目的观察偏头痛家族聚集性患者的临床特征,分析其一级亲属的患病风险因素。方法收集资料完整的偏头痛患者72例,根据有无偏头痛家族史分为两组,有偏头痛家族史组及无偏头痛家族史组。利用问卷采集两组患者临床资料,单因素分析筛选出有统计学意义的变量后进行多因素logistic回归分析其一级亲属患病的危险因素。结果 72例中至少有1名一级亲属患有偏头痛者37例,家族史阳性率为51.4%。与家族史阴性的偏头痛先证者比较,家族史阳性的先证者在性别(P=0.675)、年龄(P=0.598)、病程(P=0.419)、先兆(P=0.669)、头痛程度(P=0.837)、发作频率(P=0.465)及头痛伴随症状、头痛部位、头痛性质方面差异无统计学意义;与家族史阴性的头痛先证者比较,家族史阳性的先证者在起病年龄早(16岁)方面的差异(48.6%vs.22.9%,χ~2=5.186,P=0.023)及在头痛发作持续时间长(≥24 h)方面的差异(35.1%vs.14.3%,χ~2=4.170,P=0.041)有统计学意义(P0.05)。多因素回归发现,发病年龄早(OR=2.986,95%CI:1.621~5.503)、头痛发作持续时间长(OR=2.320,95%CI:1.219~4.415)的先证者,其一级亲属患病风险高(P0.05)。结论起病年龄早及头痛持续时间长的偏头痛患者,其一级亲属患偏头痛的风险更高。     

Benign infantile seizures and paroxysmal dyskinesia: A well-defined familial syndrome

The aim of this study was to analyze the electroclinical features and evolution in patients with benign infantile seizures (BIS) associated with paroxysmal dyskinesia (PD).

Patients and methods

Among 198 patients with BIS (78 of whom were familial cases), we evaluated 12 unrelated patients with BIS and PD seen at two pediatric neurology departments from January 1990 to February 2009.

Results

The patients were eight boys and four girls, one of whom was not a familial case. The time of follow-up was between 6 and 19 years. Median age at onset of epilepsy was 7 months (R: 5–18 m). Seizures were brief, focal, with or without secondary generalization, and occurred in clusters in 58% of the cases. Seven of 12 patients with BIS and 13 family members had PD. The age at onset of PD was between 5 and 18 years and it was characterized by choreoathetosis in 12 and dystonia in 8. PD was kinesigenic in all cases.As to family history, BIS was found in mothers in two patients, in fathers in five, in a grandfather in one, in grand-uncle in one, in uncles in four, in brothers in three, and in sisters in three other patients. PD was found in fathers in four patients, in the mother in one, in a brother in one, in a cousin in three, in an uncle in one, in an aunt in one, and in grandfathers in two. During follow-up, one patient and a relative with BIS from two different families presented Rolandic epilepsy. The father of the case with BIS and Rolandic epilepsy also had BIS and benign focal seizures of adolescence.

Conclusions

BIS and PD syndrome is a well-defined familial syndrome. BIS had the similar features described in patients with familial and non-familial BIS. The patient with non-familial BIS who developed PD later, suggests that non-familial forms may have a genetic cause and may be caused by de novo mutations.     

A typological model of schizophrenia based on age at onset,sex and familial morbidity

We investigated the age at onset distributions of schizophrenia in men and women and the relationship of age at onset and sex to the familial rates of schizophrenia and manic-depression in data from a Swedish family study of 270 schizophrenic probands. On the logarithmic scale, the age at onset distribution of schizophrenia in both male and female relatives was bimodal, suggesting that broadly defined schizophrenia may be a mixture of 2 (probably related) disorders. The risk of schizophrenia in relatives decreased as a function of the age at onset of the proband, irrespective of the sex of the proband or relative. In contrast, the risk of manic-depression was significantly higher in relatives of female probands with an age at onset in the twenties than in relatives of female probands with earlier or later onset, or in relatives of male probands. This suggests a third disorder related to affective psychosis, with an intermediate age at onset and female preponderance.     

Inheritance of frontotemporal dementia.

BACKGROUND: Previous studies of families with fronto-temporal dementia (FTD) support an autosomal dominant inheritance pattern, but most studies have described genetic transmission in individual families specifically selected for the presence of multiple affected individuals. OBJECTIVE: To investigate the familial presentation and inheritance of FTD and related disorders among a large group of FTD index cases unselected for family history of dementia. DESIGN AND SETTING: We interviewed family members and reviewed medical records and autopsy reports at a university hospital and a university-affiliated hospital to determine the frequency of familial FTD and the most likely mode of inheritance. Characteristic families with the disorder are described, along with the history, clinical findings, and neuroimaging results in affected members of these families. PATIENTS AND PARTICIPANTS: The 42 index cases of FTD had a mean age of onset of 56.1 years (range, 40-69 years). Of these patients, 21 (50%) were women. All but one of the patients were white. Participants included male and female spouses and children of the index cases. family member with an FTD spectrum disorder and were considered familial cases. The majority (17 [89%]) of familial FTD cases showed a pattern consistent with dominant inheritance. If depression is excluded, familial cases decrease from 19 (45%) to 17 (40%), of which 15 (88%) showed a dominant transmission pattern. The initial presentations in the nonindex familial cases varied but most frequently consisted of personality and behavioral changes that preceded cognitive impairment (19 [43%]), followed by psychiatric illness (14 [33%]), dementia without behavioral change (5 [11%]), amyotrophic lateral sclerosis (5 [11%]), and parkinsonism (2[5%]). Two of the affected nonindex cases had dual presenting diagnoses. The average age of onset was 56.1 years and did not differ significantly between familial and nonfamilial cases. Onset of FTD-related symptoms occurred after the age of 65 years in only 4(10%) of 42 index cases and 3 (5%) of 60 affected relatives. CONCLUSIONS: Familial FTD is usually inherited in an autosomal dominant pattern. The initial onset is insidious, often consisting of mood and behavioral changes occurring in presenile years that are often erroneously attributed to other nonneurologic causes. Although the precise incidence of FTD in North America is not known, it is one of the most common presenile dementias.     

Schizophrenia: age at onset, gender and familial risk

In a family history study of 366 schizophrenic probands and their 1851 first-degree relatives, we found a relationship between age at onset of psychosis in the male probands and the risk for schizophrenia in their relatives. The relatives of male schizophrenic probands whose onset of psychosis occurred when they were younger than 17 years of age had an increased risk of schizophrenia when compared with the relatives of male probands with an age at onset greater than 17. We did not find an association between age at onset of psychosis in the female probands and familial risk. Cox proportional hazards models permitted us to examine the relationship between age at onset of psychosis in the probands and familial risk while controlling for possible confounding effects.     

Hypertension in headache patients? A clinical study

OBJECTIVES: The aim of the present study was to assess the prevalence of hypertension in patients with headache, coming to the observation of an Headache Center. MATERIALS AND METHODS: A total of 1486 consecutive outpatients were examined, and blood pressure was determined in all patients. RESULTS: Migraine without aura (MO) was the most common diagnosis, followed by migraine associated with tension-type headache, migraine with aura (MA), episodic tension-type headache (ETTH), chronic tension-type headache (CTTH), cluster headache (CH), and medication-overuse headache (MOH). Hypertension was present in 28% of the patients, and it was particularly common in MOH (60.6%), CTTH (55.3%), CH (35%), ETTH (31.4%), less common in MO (23%) and MA (16.9%). In all headache groups, the prevalence of hypertension was higher than in the general population, within all age groups. After adjustment for age and gender, hypertension was found to be more common in tension-type, and especially in CTTH, than in migraine. These findings could be affected by 'Berkson's bias': and should not be extrapolated to the general population, but apply only to the subpopulation of patients who come to the observation of an Headache Center, and who may have more disabling symptoms. CONCLUSION: Hypertension could be one of the factors leading to exacerbation of the frequency and severity of attacks, both in migraine and tension-type headache. Hypertension has important therapeutic implications and should be actively sought in headache patients, and more thoroughly investigated, with ad-hoc surveys in the general population.     

Family studies in insomnia

OBJECTIVE: Several predisposing factors to insomnia have been hypothesized, including a familial component; however, few studies have focused on this topic. The aim of this study is to evaluate the prevalence of insomnia among first-degree relatives of chronic insomniacs and to compare the symptoms between sporadic and familial insomnia. METHODS: Two hundred fifty-six consecutive chronic insomniacs completed a clinical interview, psychometric questionnaires, a questionnaire on the family history of insomnia and, when indicated, a polysomnography. A control group was performed to estimate a base-rate incidence of insomnia in their families. RESULTS: Patients with primary (n=77) and psychiatric (n=104) insomnia were definitely included. Of those with primary insomnia, 72.7% reported familial insomnia compared with 24.1% in the noninsomnia control group. Among the psychiatric insomniacs, 43.3% reported familial insomnia. The mother was the relative most frequently affected. Comparisons between the family prevalence rates of insomnia assessed by the probands and by first-degree relatives show high concordance. A tendency to a younger age at onset was observed in familial and primary insomnia. CONCLUSION: This study reports a significant increase of familial aggregation of insomnia, warranting further genetic studies in primary insomnia with early age at onset.     

原发性低颅压头痛15例临床分析

目的：探讨原发性低颅压性头痛的临床特点。方法：回顾性分析15例原发性低颅压性头痛的临床资料。结果：15例患者中,急性发病12例,慢性发病3例;女性9例,发病年龄28～56岁。93.33%患者有体位性头痛,恶心和呕吐是主要伴随症状。腰穿脑脊液平均压力（41.2±30.85）mmH2O,女性患者明显低于男性患者（P〈0.05）。影像学检查和脑池显影均未见明显异常。全部患者均保守治疗后症状明显好转。结论：典型体位性头痛,腰穿脑脊液压力〈60mmH2O为原发性低颅压性头痛的主要特点,预后良好。     

The clinical phenotype of familial and sporadic late onset Alzheimer's disease

BACKGROUND: Familial factors are clearly associated with an increased risk of developing late onset Alzheimer's disease (LOAD). However, there is emerging evidence to suggest that familial factors may also influence clinical phenotype. To date, most studies have focussed on familial influences upon age of onset or duration of illness and few studies have compared the frequency of non-cognitive symptoms between familial and sporadic LOAD. OBJECTIVE: To describe the clinical phenotype, with an emphasis on non-cognitive symptoms, of patients with LOAD and to explore familial differences. METHOD: 374 patients with LOAD were recruited from the community based Camberwell Dementia Case Register and a comparison made of the clinical phenotype of patients with and without a first degree family history of dementia. RESULTS: A first degree family history of dementia was found in 27% of fully ascertained cases. An earlier age of onset was found in familial cases (77.2 years compared to 78.3 years, p<0.05). However, no other differences in clinical phenotype, including the rate of cognitive decline, duration or the frequency of non-cognitive symptoms, were found between familial and sporadic cases. CONCLUSIONS: Apart from an earlier age of onset, patients with familial LOAD, as a group, do not have major differences in their clinical phenotype compared to patients with sporadic LOAD.     

Postdural puncture headache leads to clinical worsening of pre-existing chronic headache

The incidence of postdural puncture headache (PDPH) in relation to pre-existing chronic headache (CH) was assessed, as was the clinical course of CH, at one, three, and six months after PDPH.The study was conducted as a single center cohort prospective study that included 252 patients (105 men and 147 women), average age of 47.3 ± 15.0 years, on whom lumbar puncture (LP) was performed.PDPH was reported in 133 (52.8%) patients; CH was reported in 82 (32.5%) patients. Patients with CH were more likely to have PDPH (p = 0.003). The individual clinical type of CH did not have an effect on the incidence of PDPH (p = 0.128). Patients with PDPH had a clinical deterioration of CH three and six months after LP (p = 0.047, p = 0.027, respectively) in terms of increased headache days per month and/or incomplete efficacy of performed therapy in relation to baseline values. Six months after LP, the worsening of CH was more common in women with PDPH (OR 5,687 [95% CI: 1526–21,200], p = 0.010) and patients with a longer history of CH (OR 1064 [95% CI: 1007–1124], p = 0.027). Multivariate analysis confirmed the direct association of female sex and duration of CH and its worsening six months after PDPH (OR 4478 [95% CI: 1149–17,452], p = 0.031; OR 1448 [95% CI: 1292–1808], p = 0.022).The presented results could be significant for the prediction/differential diagnosis of PDPH in patients with CH and for the prediction/prevention of CH clinical worsening after PDPH.