Self-concept in adolescents with epilepsy: biological and social correlates

The purposes of this study were to (1) compare self-esteem in teens with epilepsy to the normative mean, and (2) identify which neurologic/epilepsy and social/familial variables are associated with self-esteem. Thirty-seven adolescents (aged 12-18 years) attending a pediatric neurology clinic completed the Piers-Harris 2 Self-Concept Scale, Family Assessment Measure III, Child Attitude to Illness Scale, and a brief questionnaire about current seizure status (frequency, severity, and number of antiepileptic drugs). Neurology clinic charts were reviewed for seizure types, etiology, age at diagnosis, and number of failed therapies. While Total Piers-Harris t score and most subscales did not differ significantly from the normative mean, teens with epilepsy had higher scores on Behavioral Adjustment (P < 0.04) and Physical Appearance and Attributes (P < 0.03). On univariate analysis, number of current antiepileptic drugs (P < 0.05) and Attitude to Illness and Family Function scores (P < 0.02 for both) were significantly associated with self-esteem. On linear regression analysis, only the Family Function score (P < 0.02) and number of antiepileptic drugs (P < 0.05) were associated with total self-concept. We conclude that self-concept in teens with epilepsy is most strongly associated with Family Function. With the exception of current number of antiepileptic drugs used, epilepsy-specific factors are of minimal importance.     

Depression and anxiety in children and adolescents with epilepsy: prevalence, risk factors, and treatment

Among the psychiatric comorbid conditions in children and adolescents with epilepsy, depression and anxiety disorders require further attention because they carry the risk of reduced quality of life and life-threatening complications (e.g., suicide). Research in recent years has shed light on both the prevalence of emotional problems in youth with epilepsy and the safety and efficacy of treatment options. A number of challenges exist in treating patients with epilepsy. This is particularly true when seizures are difficult to control and medication regimens are more complex. Some pharmaceutical options may provide assistance with both seizures and emotional distress, but care is needed when considering such treatment approaches. In addition, integration of mental health professionals into the care of patients is necessary when cases are complicated and risk factors are high. Thorough methods to accurately diagnose emotional conditions and regular monitoring of symptoms can help prevent serious problems that can negatively affect the success of children and adolescents in everyday life. Collaboration between disciplines offers the best hope for early identification and treatment of these conditions.     

Genetic risk factors in schizophrenia

The high pathogenetic relevance of genetic factors in schizophrenia is beyond doubt based on the findings of epidemiological studies. By means of a complex mode of transmission, it is likely that several genes with weak to moderate effect jointly constitute a genetic basis for a vulnerability to schizophrenia that may well vary for different individuals. Other organic and psychosocial factors also play an individually different -- in some cases significant -- role in terms of pathogenesis, as a result of which an oligogenic/polygenic multifactor model is assumed from the standpoint of aetiopathogenetics. Molecular genetic methods consist in linkage analyses and association analyses. Positive linkage findings accumulate particularly for the chromosomes 1q, 6p, 8p, 13q and 22q. By themselves, individual mutations contribute little to the range of schizophrenic feature characteristics, it was not possible -- irrespective of some subtypes -- to replicate genes of major effect. From the large number of possible candidate genes, although studies on DRD3, DRD2 and HTR2A produced positive results, the magnitudes of effect were low. The findings for alleles of dysbindin, neuregulin 1, DAO, COMT, PRODH, ZDHHC and DISC are less clear. The search for schizophrenia-relevant mutations is hampered by the possibility of a heterogeneous phenotype of schizophrenia in case of a homogeneous genotype as much as by the possibility of inter-individually homogeneous phenotypical characteristics in case of schizophrenia-relevant heterotype in the genome. With the aid of the concept of endo-phenotypes, based on neurobiological phenomena, it might be possible to take a more direct approach that leads from relevant mutations to the risk of schizophrenias. However, replacing schizophrenic alienation with neurobiological aspects leads to difficulties in explaining these complex disorder profiles. Schizophrenic diseases require an explanatory approach that also incorporates personality and developmental psychological aspects from the outset, if the aim is not to restrict type of schizophrenic disease exclusively to loci of molecular genetic changes.     

Cardiovascular risk factors and homocysteine in epilepsy

Epidemiological studies have found the risk for heart disease and stroke are increased in persons with epilepsy. Anti-epileptic drugs (AEDs) have varying effects on serum lipids and homocysteine-an independent risk factor for coronary disease. The prevalence of cardiovascular risk factors (high cholesterol, hypertension, diabetes, obesity and smoking) and homocysteine were investigated in a multiethnic epilepsy population. Data included demographics, clinical factors, lab assessments and supplementation patterns. Mean age was 45 years (71 males and 94 females)-75 were African American, 27 Latino and 60 Caucasian. Fifty-two percent of participants had two or more cardiovascular risk factors when compared with rates for the general population of 28%. The Framingham risk score (FRS) assessment was also used to compare risk levels. Twenty-nine percent of men and 1% of women had a FRS indicating >5% level of risk, only 7% had a FRS>10%. Cardiovascular screening and primary preventative recommendations based on the American Heart Association and supplementation should be suggested for the adult epilepsy population when appropriate.     

Intractable epilepsy: etiology, risk factors and treatment

The data emerging from our study are the following: the presence of an identifiable cause is important: complications like tuberous sclerosis or signs of marked cerebral damage represent an adverse risk factor for IE. The presence of epilepsy among relatives, evidence of pre- or perinatal cerebral damage, mental retardation, and early onset, long periods of uncontrolled seizures before starting an adequate therapy and frequency of seizures appear to be indicative of an adverse prognosis, since differences between the two groups of responsive or unresponsive patients are statistically significant. On the contrary, the occurrence of febrile convulsions in the past history does not seem to have an adverse prognosis. Temporal lobe epilepsy and IS bear the worst prognosis. ME, CPS, GTCS, SPS, LGS and PM have a progressively better outcome in responsiveness to AEDs. Concerning therapy in patients with IE, studies indicate the results of high dose monotherapy appear to be equal or better than with polypharmacy. Because of the gravity of the situation, trials with unconventional drugs have been performed, but it is too early to draw definite conclusions about the long-term usefulness of most of them. In conclusion, our data indicate that the appearance of an IE can be predicted utilizing the above mentioned criteria, considered either alone or in combination. The issue of IE remains undoubtedly an important one among the group of convulsive disorders. Further studies considering a greater number of patients and new therpeutic strategies are to be recommended.     

Juvenile myoclonic epilepsy: Long-term prognosis and risk factors

ObjectiveOur goal was to investigate the long-term clinical course of juvenile myoclonic epilepsy (JME) in a cohort of patients and to identify prognostic factors for refractoriness and seizure relapse after anti-seizure medications (ASMs) withdrawal. A literature review is also presented to consolidate and compare our findings with the previously reported cases.MethodsWe retrospectively studied a series of patients diagnosed with JME with 15 years or more of evolution. We collected clinical, neurophysiological and neuroimaging data from patients who met defined inclusion and exclusion criteria.ResultsStudy involved 61 patients (65.5% female) with mean age at study of 37.6 years, and mean age at its outset of 14.8 years. Median follow-up was 31.0 years (mean 28.9, range 15–53). They presented more frequently with a combination of myoclonic and generalized tonic-clonic seizures (GTCS) (65.6%). Sixty-five percent of patients (n = 40) had a 5-year terminal remission with a mean age at last seizure of 27.4 years. Thirty-two percent of seizure-free patients (n = 13) withdrew ASMs: 6 out of 13 had a recurrence of the seizures while 7 remained seizure-free (mean age at ASMs withdrawal 21.0 versus 35.7 years, p < 0.05). In the multivariate model, a high GTCS frequency at onset (p = 0.026) was a prognostic factor of drug resistance.ConclusionJME is often regarded as a benign epileptic syndrome, although a quarter of the individuals have refractory epilepsy. The possibility of withdrawing ASMs in patients who have been free of seizures over an extended time seems feasible.     

Gender aspects in schizophrenia: bridging the border between social and biological psychiatry

OBJECTIVE: This paper tries to show that gender differences in mental diseases are a valuable paradigm for research into the interplay between biological and psychosocial factors--not only regarding pathogenetic mechanisms, but also concerning therapeutic approaches. METHOD: Based on relevant literature, this topic is highlighted using schizophrenia as an example. RESULTS: Schizophrenic disorders show a later age of onset in women and a slightly better course, especially in young women. As to pathogenesis, there is some evidence that the age difference might be due at least partly to the female sex hormone oestradiol being a protective factor. Differences in course might also have to do with this biological factor, but at the same time with the psychosocial advantages of a higher age of onset and other psychosocial factors. Concerning therapy, these gender differences have important implications for pharmacotherapy, but also psychotherapy and social measures. CONCLUSION: A gender-sensitive approach in psychiatry improves our understanding of mental illness and our therapeutic strategies and at the same time illustrates that comprehensive psychiatry cannot be practised in artificially separated 'drawers' called 'biological psychiatry', on one hand, and 'social psychiatry' on the other.     

Depression in postpartum and non-postpartum women: prevalence and risk factors

OBJECTIVE: The aim of the study was to assess the prevalence of depression in postpartum women as compared with non-postpartum women, and to identify risk factors of depression in both groups. METHOD: A population based questionnaire study was performed among women 18-40 years in two municipalities in Norway in 1998-1999. A total of 2,730 women were included, of whom 416 were in the postpartum period. RESULTS: The prevalence of depression was higher in non-postpartum as compared with postpartum women. High scores on the life event scale, a history of depression and a poor relationship to the partner were associated with depression in both postpartum and non-postpartum women. When controlling for the identified risk factors of depression the odds-ratio for depression in the postpartum period was 1.6 (95% CI: 1.0-2.6). CONCLUSION: The risk for depression was increased in the postpartum period, when controlling for the uneven distribution of risk factors.     

The causes of schizophrenia: neurodevelopment and other risk factors

Understanding the etiology of schizophrenia has been a considerable challenge. The neurodevelopmental hypothesis has held sway in recent years, focusing our attention on biological causes acting in early life. Much evidence supports this hypothesis and risk factors operating in early life (e.g., obstetric complications) have been shown to be associated with the later development of schizophrenia. Indicators of abnormal neurodevelopment that characterize individuals vulnerable to later developing schizophrenia have also been identified. For example, as a group, children who will later develop schizophrenia subtly differ from their peers in terms of their motor, cognitive, and social functioning. However, there is much that cannot be explained in purely neurodevelopmental terms. There is growing evidence of associations between the risk of schizophrenia and factors such as drug misuse, ethnicity/migration, life events, and urbanicity. A multifactorial model of causation that encompasses biological, social, and psychological elements is arguably both a better representation of current research findings and a more appropriate model for clinical practice.     

Depression in older adults with schizophrenia spectrum disorders: prevalence and associated factors.

RATIONALE: Although depression is common in older adults with schizophrenia, it has not been well studied. The authors examine those factors that are related to depression in a multiracial urban sample of older persons with schizophrenia. METHODS: The schizophrenia group consisted of 198 persons aged 55 or older who lived in the community and developed schizophrenia before age 45. Persons with substantial cognitive impairment were excluded from the study. A community comparison group (N = 113) was recruited using randomly selected census tract data. The authors adapted George's Social Antecedent Model of Depression, which consists of six categories comprising 16 independent variables, and used a dichotomous dependent variable based on a Center for Epidemiologic Studies Depression Scale cutoff score of > or = 16. RESULTS: The schizophrenia group had significantly more persons with clinical depression than the community comparison group (32% versus 11%, respectively; chi(2) = 28.23, df = 1, p = 0.001). Bivariate analysis revealed that eight of the 16 variables were significantly related to clinical depression in the schizophrenia group. In logistic regression, six variables retained significance: physical illness (odds ratio [OR] = 1.60, 95% confidence interval [CI], 1.17-2.18), quality of life (OR = 0.84, 95% CI, 0.76-0.93), presence of positive symptoms (OR = 1.12, 95% CI, 1.02-1.21), proportion of confidants (OR = 0.03, 95% CI, 0.01-0.39), copes by using medications (OR = 2.12, 95% CI, 1.08-4.13), and copes with conflicts by keeping calm (OR = 1.34, 95% CI, 1.03-1.74). CONCLUSION: Consistent with earlier studies of schizophrenia in older persons, the authors found physical health, positive symptoms, and several nonclinical variables to be associated with depression. Potential points for intervention include strengthening social supports, improving physical well-being, more aggressive treatment of positive symptoms, and increasing the recognition and treatment of depression.     

Family structure and risk factors for schizophrenia: case-sibling study

Background  

Several family structure-related factors, such as birth order, family size, parental age, and age differences to siblings, have been suggested as risk factors for schizophrenia. We examined how family-structure-related variables modified the risk of schizophrenia in Finnish families with at least one child with schizophrenia born from 1950 to 1976.     

Depression in schizophrenia

Depressive syndromes that occur during the course of schizophrenia are not clearly understood but have important implications for the treatment of the schizophrenic patient. In this review of the literature on depression secondary to schizophrenia, the author notes that lack of tested diagnostic criteria has led to a misunderstanding of its relatively high frequency and its association with poor outcome features such as impaired psychosocial functioning, schizophrenic relapse, and suicide. Differential diagnosis, including ruling out akinetic depression, is essential, he believes, partly because the concept of schizophrenic depression as postpsychotic is not supported by evidence. Clinical management must address such increased risk factors as relapse and suicide, but evidence indicates that secondary depression in schizophrenia does not respond to antidepressant medication.     

Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia.

OBJECTIVE: The aim of this study was to investigate when social consequences in schizophrenia emerge, and what conditions give rise to the social disadvantage evident in people suffering from schizophrenia. METHOD: Early course in schizophrenia was studied in a population-based sample of 232 first illness-episode cases retrospectively from onset to first admission, and in a representative subsample of 115 patients prospectively at six cross-sections over a period of 5 years. Data on non-specific and negative symptomatology and social development was compared with data from an age- and sex-matched control group drawn from the normal population. RESULTS: In total, 73% of the patients showed a prodromal phase of several years. First signs were depressive and negative symptoms. In 57% of cases social disability emerged 2 to 4 years before first admission. Social consequences depended on the level of social development at onset. An early onset involved social stagnation, and a late onset was associated with social decline. Men's poorer social outcome was determined by their lower level of social development at onset and socially adverse illness behaviour. The 5-year symptom-related course showed no gender difference. At 81% the lifetime prevalence of depressive mood until first admission was several times higher in schizophrenics than in healthy controls. Early depression predicted a lower subsequent score for affective flattening. Suicide indicators were predicted by lack of self-confidence and feelings of guilt early in the illness. CONCLUSION: Taking into account a prodromal phase of several years on average before first hospital admission, early detection, case identification and intervention are urgently needed. The intervention must be targeted at syndromes such as early depression, negative symptoms and certain forms of cognitive and social impairment.     

Paternal factors and schizophrenia risk: de novo mutations and imprinting

There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, because advancing paternal age is the major source of new mutations in humans. This review describes several neurodevelopmental disorders that have been associated with de novo mutations in the paternal germ line and reviews data linking increased schizophrenia risk with older fathers. Several genetic mechanisms that could explain this association are proposed, including paternal germ line mutations, trinucleotide repeat expansions, and alterations in genetic imprinting in one or several genes involved in neurodevelopment. Animal models may be useful in exploring these and other explanations for the paternal age effect and they may provide a novel approach for gene identification. Finally, it is proposed that environmental exposures of the father, as well as those of the mother and developing fetus, may be relevant to the etiology of schizophrenia.     

Sudden unexpected death in epilepsy: a search for risk factors

Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Of the 6140 patients registered with the Epilepsy Unit at the Western Infirmary in Glasgow between 1982 and 2005, 529 had died, 62 (11.7%) of whom succumbed to SUDEP. All but 2 deaths occurred at home; 3 were witnessed. Two living controls were matched with each SUDEP case for year of birth, gender, and syndromic classification. Mean duration of epilepsy was significantly longer in cases compared with controls (P=0.001). More people succumbing to SUDEP had had a seizure within the previous year (P=0.007). There were no significant associations between SUDEP and a history of generalized tonic-clonic seizures, drug polytherapy, and current use of carbamazepine. There is an urgent need for a large-scale, prospective, international, community-based study of SUDEP to explore more closely the risk factors to plan preventive strategies.     

High social class and suicide in persons at risk for schizophrenia

Objective: The relationship between suicide and social class has been equivocal. While some authors have reported that higher social class is related to higher rates of suicide, most other studies report that lower social class is associated with higher rates of suicide. Our study attempted to resolve these inconsistencies by using a High Risk for schizophrenia method. Method: Children of women with severe schizophrenia were assessed in 1962. In 2005, when subjects were a mean age of 58 years, we identified those who had committed suicide. Results: A higher rate of suicide was associated with risk for schizophrenia in the High‐Risk sample. Higher social class origin was associated with suicide in persons at risk for mental illness. Conclusion: Higher social class origin was associated with suicide in subjects at genetic risk for schizophrenia (but not those without risk).     

Toxoplasma gondii and other risk factors for schizophrenia: an update

The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors. In a previous study, antibodies to Toxoplasma gondii were found to be elevated in 23 studies of schizophrenia (OR 2.73; 95% CI 2.10-3.60). The current study replicates this finding with 15 additional studies (OR 2.71; 95% CI 1.93-3.80) and compares this with other identified schizophrenia risk factors. The highest risk factors are having an affected mother (relative risks [RR] 9.31; 95% CI 7.24-11.96), father (RR 7.20; 95% CI 5.10-10.16), or sibling (RR 6.99; 95% CI 5.38-9.08) or being the offspring of immigrants from selected countries (RR 4.5; 95% CI 1.5-13.1). Intermediate risk factors, in addition to infection with T. gondii, include being an immigrant from and to selected countries (RR 2.7; 95% CI 2.3-3.2), being born in (RR 2.24; 95% CI 1.92-2.61) or raised in (RR 2.75; 95% CI 2.31-3.28) an urban area, cannabis use (OR 2.10-2.93; 95% CI 1.08-6.13), having minor physical anomalies (OR 2.23; 95% CI 1.42-3.58), or having a father 55 or older (OR 2.21-5.92; 95% CI 1.46-17.02). Low-risk factors include a history of traumatic brain injury (OR 1.65; 95% CI 1.17-2.32), sex abuse in childhood (OR 1.46; 95% CI 0.84-2.52), obstetrical complications (OR 1.29-1.38; 95% CI 1.00-1.84), having a father 45 or older (OR 1.21-1.66; 95% CI 1.09-2.01), specific genetic polymorphisms (OR 1.09-1.24; 95% CI 1.06-1.45), birth seasonality (OR 1.07-1.95; 95% CI 1.05-2.91), maternal exposure to influenza (RR 1.05; 95% CI 0.98-1.12), or prenatal stress (RR 0.98-1.00; 95% CI 0.85-1.16).     

Understanding putative risk factors for schizophrenia: retrospective and prospective studies

This paper describes a research program intended to provide a better understanding of the influence of several putative risk factors for schizophrenia on child development and psychosis. Two related components of the overall program are described: the retrospective EnviroGen projects, which use a variety of putative risk factors to explain variance in several dimensions of schizophrenia and in psychotic symptoms in community controls, and Project Ice Storm, which prospectively examines the effects of prenatal maternal stress in the children of women who were exposed to the 1998 Quebec ice storm during their pregnancies. The EnviroGen projects have been successful in explaining variance in several dimensions of illness, including premorbid adjustment and severity of dissociative symptoms. Project Ice Storm has demonstrated the noxious effects of prenatal stress on cognitive and language development in children. We have also found that "ice storm children" exposed in specific weeks of gestation show greater dermatoglyphic asymmetry, as has been reported for samples of patients with schizophrenia. In both studies, prenatal maternal stress has been associated with more severe childhood behaviour problems. The combination of retrospective and prospective studies is a rich source of triangulated results providing information about developmental psychopathology.