Objective To investigate the association of paternal age at conception with the risk of offspring developing schizophrenia.
Design A population based cohort study.
Subjects 754 330 people born in Sweden between 1973 and 1980 and still alive and resident in Sweden at age 16 years.
Main outcome measures Hospital admission with schizophrenia or non-schizophrenic, non-affective psychosis.
Results After adjustment for birth related exposures, socioeconomic factors, family history of psychosis, and early parental death the overall hazard ratio for each 10 year increase in paternal age was 1.47 (95% confidence interval 1.23 to 1.76) for schizophrenia and 1.12 (0.98 to 1.29) for non-schizophrenic non-affective psychosis. This association between paternal age and schizophrenia was present in those with no family history of the disorder (hazard ratio for each 10 year increase in paternal age 1.60, 1.32 to 1.92), but not in those with a family history (0.91, 0.44 to 1.89) (P = 0.04 for interaction).
Conclusions Advancing paternal age is an important independent risk factor for schizophrenia. The stronger association between paternal age and schizophrenia in people without a family history provides further evidence that accumulation of de novo mutations in paternal sperm contributes to the overall risk of schizophrenia.
Objective To study the change in risk of suicide among patients with schizophrenia and related disorders.
Design Nested case-control design with linked data.
Setting 4 longitudinal Danish registers.
Participants 18 744 people aged up to 75 years who committed suicide in 1981-97 individually matched with 20 controls.
Results Over the time studied the reduction in suicide rate among patients with schizophrenia and schizophrenia spectrum disorder was similar to that seen in the general population (incidence rate ratio 1.00, 95% confidence interval 0.98 to 1.03). The reduction among patients with other psychosis in the schizophrenia spectrum was faster than the reduction seen in the general population. Among people admitted to hospital with schizophrenia the risk of suicide was highest in the first year after first admission, and the excess risk was largest in the younger age groups—that is, the risk decreased per year for every additional year of age.
Conclusion The suicide rate among patients with a diagnosis of schizophrenia and related disorders has fallen. This may be due to better psychiatric treatment, reduced access to means of suicide, or improvements in treatment after suicide attempts.
Clinic-based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non-affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non-affective psychosis.
A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non-affective psychosis, and 9,920 cases of bipolar disorder.
As in prior studies, there were a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first-degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non-affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain-Barré syndrome, Crohn’s disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder.
The familial relationship of schizophrenia to a range of autoimmune diseases extends to non-affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non-affective psychosis and bipolar disorder.
autoimmune disease; bipolar disorder; epidemiology; non-affective psychosis; register; schizophrenia
To examine prenatal and perinatal risk factors for subsequent development of schizophrenia and affective and reactive psychosis.
Three population based, case-control studies conducted within a Sweden-wide cohort of all children born during 1973-9. This was done by linking individual data from the Swedish birth register, which represents 99% of all births in Sweden, to the Swedish inpatient register.
Patients listed in inpatient register as having been first admitted to hospital aged 15-21 years with a main diagnosis of schizophrenia (n=167), affective psychosis (n=198), or reactive psychosis (n=292). For each case, five controls were selected.
Main outcome measures
Risks of schizophrenia and affective and reactive psychosis in relation to pregnancy and perinatal characteristics.
Schizophrenia was positively associated with multiparity (odds ratio 2.0), maternal bleeding during pregnancy (odds ratio 3.5), and birth in late winter (odds ratio 1.4). Affective psychosis was associated with uterine atony (odds ratio 2.2) and late winter birth (odds ratio 1.5). Reactive psychosis was related to multiparity (odds ratio 2.1). An increased risk for schizophrenia was found in boys who were small for their gestational age at birth (odds ratio 3.2), who were number four or more in birth order (odds ratio 3.6), and whose mothers had had bleeding during late pregnancy (odds ratio 4.0).
A few specific pregnancy and perinatal factors were associated with the subsequent development of psychotic disorder, particularly schizophrenia, in early adult life. The association of small size for gestational age and bleeding during pregnancy with increased risk of early onset schizophrenia among males could reflect placental insufficiency.
Key messagesThe role of prenatal and perinatal risk factors in the development of schizophrenia and affective and reactive psychosis in early adult life were investigated by linking individual data from the Swedish birth and inpatient registriesAdverse prenatal and perinatal factors were more common in patients with schizophrenia of early onset than in controls and seemed more important in the aetiology of schizophrenia than in that of affective and reactive psychosisMultiparity, bleeding during pregnancy, and small size for gestational age were associated with a threefold to fourfold increased risk for schizophrenia among malesThere was no support for previous claims that head circumference is small in preschizophrenic infantsLate winter birth was associated with increased risk of both schizophrenia and affective psychosis
Objectives: To clarify risk factors for the development of schizophrenia-like psychotic disorders following temporal lobectomy, and to explore the possibility that the early postoperative period is a time of high risk for the onset of such chronic psychotic disorders.
Methods: Patients who developed schizophrenia-like psychosis were identified from a series of 320 patients who had a temporal lobectomy for medically intractable epilepsy. The relationship of their disorders to both the operation and subsequent seizure activity was examined. Using a retrospective case–control design, risk factors for the development of schizophrenia-like psychosis were established.
Results: Eleven patients who developed schizophrenia-like psychosis postoperatively were identified and compared with 33 control subjects who remained free of psychosis postoperatively. The onset of de novo psychotic symptoms was typically in the first year following the operation. No clear relationship between postoperative seizure activity and fluctuations in psychotic symptoms emerged. Compared with the controls, patients who become psychotic had more preoperative bilateral electroencephalogram (EEG) abnormalities, pathologies other than mesial temporal sclerosis in the excised lobe and a smaller amygdala on the unoperated side.
Conclusions: Temporal lobectomy for medically intractable epilepsy may precipitate a schizophrenia-like psychosis. Patients with bilateral functional and structural abnormalities, particularly of the amygdala, may be at particular risk for the development of such psychoses.
Epilepsy affects an estimated 50 million people and accounts for approximately 1% of days lost to ill health globally, making it one of the most common, serious neurological disorders. While there are abundant global data on epilepsy incidence, prevalence and treatment, there is a paucity of Australian incidence data. There is also a general lack of information on the psychosocial impact and socioeconomic consequences of a new diagnosis of epilepsy on an individual, their family, household, and community which are often specific to the health and social system of each country.
The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) is an Australian population-based epilepsy incidence and outcome study that will recruit every newly diagnosed case of epilepsy in the Sydney South West Area Health Service to an epilepsy register. Multiple and overlapping sources of notification will be used to identify all new cases of epilepsy over a 24 month period in the Eastern Zone of the Sydney South West Area Health Service (SSWAHS) and follow up will occur over 12 months. SEISMIC will use the International League Against Epilepsy (ILAE) definitions and classifications for epidemiologic studies of epilepsy. The study will examine outcomes including mood, quality of life, employment, education performance, driving status, marital and social problems, medication use, health care usage, costs and stigma.
This study is designed to examine how clinical, psychological factors, socioeconomic circumstances, and healthcare delivery influence the experience of epilepsy for individuals and families allowing better targeting of specific services and informing policy makers and practitioners. In addition, the study will provide the basis for a longitudinal population-based cohort study and potentially inform qualitative sub-studies and randomised controlled trials of intervention strategies. The study has been registered on the Australia New Zealand Clinical Trial Registration database with ANZCTRN12609000059268.
Individuals with epilepsy are at increased risk of having psychotic symptoms that resemble those of schizophrenia. More controversial and less searched is if schizophrenia is a risk factor for epilepsy. Here we review overlapping epidemiological, clinical, neuropathological and neuroimaging features of these two diseases. We discuss the role of temporal and other brain areas in the development of schizophrenia-like psychosis of epilepsy. We underline the importance of ventricular enlargement in both conditions as a phenotypic manifestation of a shared biologic liability that might relate to abnormalities in neurodevelopment. We suggest that genes implicated in neurodevelopment may play a common role in both conditions and speculate that recently identified causative genes for partial complex seizures with auditory features might help explain the pathophysiology of schizophrenia. These particularly include the leucine-rich glioma inactivated (LGI) family gene loci overlap with genes of interest for psychiatric diseases like schizophrenia. Finally, we conclude that LGI genes associated with partial epilepsy with auditory features might also represent genes of interest for schizophrenia, especially among patients with prominent auditory hallucinations and formal thought disorder.
schizophrenia; epilepsy; temporal lobe; susceptibility; neurodevelopment; LGI genes
The goal of the present study was to examine the rate of cannabis use among participants in the Cognitive Assessment and Risk Evaluation (CARE) Program, a longitudinal program for individuals who are “at risk” for developing a psychotic disorder. Cannabis abuse was assessed in 48 individuals identified as “at risk” for schizophrenia based on subsyndromal psychotic symptoms and/or family history. At 1 year follow-up, 6 of the 48 (12.5%) at risk subjects had made the transition to psychosis. Of the 6 subjects who converted to psychosis at follow-up, 83.3% met criteria for cannabis abuse or dependence in remission. Of the 42 who had not converted to psychosis at 1 year, 26.2% met criteria for cannabis abuse or dependence in remission. Nicotine use was also found to be significantly associated with later conversion. The significant associations between cannabis and nicotine abuse and conversion to psychosis in individuals at risk for schizophrenia suggest that early identification and intervention programs should screen for and provide education about the deleterious effects of these substances.
Prodrome; Marijuana; Schizophrenia; Substance Use; At risk; Nicotine
Early detection and prospective evaluation of clinical high-risk
(CHR) individuals who may develop schizophrenia or other psychotic disorders
is critical for predicting psychosis onset and for testing preventive
To elucidate the neuropsychology of the CHR syndrome, to determine
the association of neuropsychological function with conversion to psychosis
and family history (FH) of psychosis, and to examine whether baseline
neuropsychological functioning predicts subsequent psychosis.
Design, Setting, and Participants
Longitudinal study with 2 1/2 years follow-up of 304 prospectively
identified CHR individuals meeting Structured Interview for Prodromal
Syndromes (SIPS) criteria, 52 non-CHR persons with a FH of psychosis in
first- or second-degree relatives (“family HR”/FHR), and 193
normal controls with neither a FH of psychosis nor a CHR syndrome, all of
whom had baseline neuropsychological evaluations, recruited across eight
centers as part of the North American Prodrome Longitudinal Study
A neurocognitive composite score, eight individual neuropsychological
measures, an IQ estimate, and HR status.
Global (“composite”) neuropsychological functioning
was comparably impaired in CHR and FHR groups compared to controls, but
profiles differed significantly between groups. Neuropsychological
functioning in the CHR group was significantly lower in persons who
progressed to psychosis than in those who did not, and worst in the subgroup
with a FH of psychosis. Tests of processing speed and verbal learning and
memory were most sensitive in discriminating CHR from controls, although
reductions were less severe than in established schizophrenia.
Neuropsychological functioning did not contribute uniquely to the prediction
of psychosis beyond clinical criteria, but worse verbal memory predicted
more rapid conversion.
These findings document that CHR individuals have significant
neuropsychological difficulties, particularly those who later develop
psychosis. This dysfunction is generally of moderate severity but less than
in first episode schizophrenia, suggesting that a further decline may occur
after baseline CHR assessment.
Phencyclidine (PCP), Ketamine (Special K) and MK-801 are non-competitive NMDA antagonists that produce acute psychosis in humans. The psychosis produced by these psychomimetic drugs is indistinguishable from schizophrenia and includes both positive and negative symptoms. This drug-induced psychosis occurs after puberty in humans. This brief review argues that this psychosis is an atypical form of limbic epilepsy based upon MK-801 induced spike-and-wave activity in rats and based upon increased blood flow and metabolism in brain of patients with psychosis caused by these psychomimetics. Moreover, there is a specific limbic thalamcortical psychosis circuit that mediates cell injury in limbic cortex of rodents and may mediate this PCP-induced psychosis in humans. It is proposed that this thalamocortical psychosis circuit develops at puberty and can mediate psychosis at puberty and in adulthood by PCP and ketamine-induced psychosis, and possibly in schizophrenia, bipolar disease and other psychotic states. Finally, based upon this developmentally regulated psychosis-epilepsy related thalamocortical circuitry, it is proposed that anti-epileptic drugs that promote GABAergic mechanisms might decrease the probability of episodic psychosis from any cause.
psychosis; epilepsy; ketamine; PCP; phencyclidine; NMDA antagonists; anti-convulsants
Research suggests that first-degree relatives and individuals with schizophrenia spectrum personality disorders (SSPD) may represent nonpenetrant carriers of the genetic diathesis for schizophrenia. This study examined visuospatial working memory (SWM) as a cognitive endophenotype of schizophrenia by expanding the concept of risk for pathophysiological dysfunction beyond overt psychosis. Risk was thus defined by familial status and the presence or absence of SSPD. SWM was assessed in the following groups, in order of decreasing likelihood of genetic vulnerability: 23 patients with schizophrenia, 17 SSPD relatives of patients with schizophrenia, 23 non-SSPD relatives of patients with schizophrenia, 14 SSPD community members with no family history of psychosis, and 36 non-SSPD community members. SWM performance during a computer task was quantified by A-Prime. Relative risk ratios for SWM deficits were compared among the groups. Compared with community non-SSPD volunteers, relative risk (RR) of SWM deficits was significantly elevated in patients with schizophrenia (RR = 3.76, p = .002) and SSPD family members (RR = 2.97, p = .027), but not in the family non-SSPD (RR = 1.88, p = .241) or community SSPD (RR = 1.03, p = .971) groups. The pattern of SWM performance deficits reflected the proposed model of latent genetic liability, upholding SWM as a viable cognitive endophenotype. The results underscore the importance of including both familial liability and the schizophrenia spectrum when considering risk for schizophrenia and schizophrenia-related traits. This is particularly relevant for research efforts to identify pathophysiological components of the disease.
relative risk; genetics; schizotypy
Early intervention (EI) programs in schizophrenia and other psychoses are aimed at early detection (ED) of the disease; prevent conversion to manifested psychosis and phase-specific treatment to reduce development of chronic disabilities. EI strategies include targeting people at “high risk" for developing schizophrenia, intervening in prodromal phase of schizophrenia, and reducing the “duration of untreated psychosis" (DUP). Services are delivered by a specialized team and are usually resource intensive. Several strategies like treatment with antipsychotics, family interventions, and cognitive behavior therapy have been tried with modest success in prodromal patients. Significant ethical reservations exist regarding exposing prodromal patients to the stigma of labeling as “high risk for schizophrenia" and side effects of psychotropics in the absence of clear evidence of efficacy in favor of ED, intervention by specialist teams, and phase-specific interventions in prodrome of psychosis. More research is warranted to demonstrate the risk-benefit and cost-benefit of such interventions before these can be routinely recommended.
Duration of untreated psychosis; early intervention; early psychosis; prodrome; schizophrenia
There is a long history of research on the familial transmission of schizophrenia and other psychoses. However, few studies have investigated the specificity of the transmission of schizophrenia-psychosis spectrum (SPS) disorders and affective psychoses (APs) or observed high-risk offspring into mid-adulthood.
To investigate the transmission of psychoses from parents to their offspring and the specificity of transmission across psychosis subtypes.
High-risk follow-up study.
New England Family Study’s High-Risk Study, with population-based community sampling from Boston, Massachusetts, and Providence, Rhode Island.
A total of 203 high-risk offspring of 159 parents with diagnoses of psychoses (SPS and AP) and 147 control offspring of 114 control parents.
Main Outcome Measures
Systematically assessed research DSM-IV psychiatric diagnoses for adult offspring.
Compared with those of control parents, offspring of parents with SPS had a significant, almost 6-fold elevated risk of SPS disorders and a nonsignificant doubling of risk for AP. Offspring of parents with AP had a significant 14-fold elevated risk for AP compared with offspring of controls; for SPS disorders, the risk doubled but was not significant.
Having a parent with psychosis significantly increased the risk for psychosis among offspring and demonstrated specificity for the transmission of SPS disorders and APs within families.
There is some evidence that childhood adversity may be associated with the expression of schizophrenia but whether genetic risk affects this finding is unknown. We investigated the history of early trauma in 194 subjects from 24 multiply affected families where schizophrenia was previously shown to be associated with a functional allele in the NOS1AP gene. In subjects with schizophrenia (n=79), only events prior to the onset of psychosis were considered. Generalized estimating equation models that adjusted for familial clustering were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Subjects with narrowly defined schizophrenia were more likely than their unaffected family members to have a history of early trauma (adjusted OR=4.17, 95% CI=1.52, 11.44). The results were similar after adjusting for the NOS1AP risk genotype (adjusted OR=3.57, 95% CI=1.32, 9.65) and for maternal or paternal history of schizophrenia (adjusted ORs=3.27, 95% CI=1.45, 7.38; 4.38, 95% CI=1.61, 11.91, respectively). The results suggest that childhood trauma is associated with expression of schizophrenia independent of measured genetic susceptibility and may be a candidate for gene-environment research using genetic variants.
PMID: 20541371 CAMSID: cams1808
Familial schizophrenia; Childhood adversity; Early trauma; Risk factor; Genetic predisposition
The neurodevelopmental model of schizophrenia, which posits that the illness is the end state of abnormal neurodevelopmental processes that started years before the illness onset, is widely accepted, and has long been dominant for childhood-onset neuropsychiatric disorders. This selective review updates our 2005 review of recent studies that have impacted, or have the greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis. New studies suggest that placental pathology could be a key measure in future prenatal high-risk studies. Both common and rare genetic variants have proved surprisingly diagnostically nonspecific, and copy number variants (CNVs) associated with schizophrenia are often also associated with autism, epilepsy and intellectual deficiency. Large post-mortem gene expression studies and prospective developmental multi-modal brain imaging studies are providing critical data for future clinical and high-risk developmental brain studies. Whether there can be greater molecular specificity for phenotypic characterization is a subject of current intense study and debate, as is the possibility of neuronal phenotyping using human pluripotent-inducible stem cells. Biological nonspecificity, such as in timing or nature of early brain development, carries the possibility of new targets for broad preventive treatments.
CNV; genetics; imaging; neurodevelopment; schizophrenia; placenta
Psychiatric manifestations after occurrence of epilepsy have often been noted. However, the association between newly diagnosed epilepsy and psychiatric disorders afterward is not completely understood. We conducted two longitudinal cohorts for patients with and without epilepsy to investigate the risk factors and hazard ratios of developing psychiatric disorders after patients were newly diagnosed with epilepsy.
We identified 938 patients with a new diagnosis of epilepsy and 518,748 participants without epilepsy from the National Health Insurance Research Database in 2000–2002 and tracked them until 2008. We compared the incidence of developing psychiatric disorders between the two cohorts, evaluated risk factors and measured the associated hazard ratios (HRs) and 95% confidence intervals (CIs) of developing psychiatric disorders.
The incidences of psychiatric disorders for people with and without epilepsy were 94.1 and 22.6 per 1000 person-years, respectively. After adjusting the covariates, the epilepsy cohort showed the highest risks in mental retardation (HR 31.5, 95% CI 18.9 to 52.4), bipolar disorder (HR 23.5, 95% CI 11.4 to 48.3) and alcohol or drug psychosis (HR 18.8, 95% CI 11.1 to 31.8) among psychiatric complications developed after newly diagnosed epilepsy. The risk increased with epileptic general seizure and frequency of outpatient visits for epilepsy, as well as with emergency room visits and hospitalizations for epilepsy, and with older age. Chronologically, the highest risk occurred in the first year after epilepsy diagnosis (HR 11.4, 95% CI 9.88 to 13.2).
Various psychiatric disorders were demonstrated after newly diagnosed epilepsy and closely related to general seizure and use of medical services for epilepsy. This shows a need for integrated psychiatric care for patients newly diagnosed with epilepsy, especially in the first year.
Prior studies suggest a higher incidence of symptoms of attention-deficit/hyperactivity disorder in children with epilepsy, but few have investigated epilepsy in children with attention-deficit/hyperactivity disorder. Our objective was to compare the incidence and characteristics of epilepsy among population-based, research identified cohorts of children with (N=358) and without attention-deficit/hyperactivity disorder (N=728), based on medical record review to age 20. Data abstracted included characteristics of seizures, testing, and treatment. Cases were 2.7 times more likely to have epilepsy than controls (95% confidence interval 0.94–7.76; p=0.066), had earlier seizure onset (median age 5.5 versus 15 years; p=0.020), and a trend toward more frequent seizures (more than monthly, 63% versus 17%). Among children with attention-deficit/hyperactivity disorder, those with epilepsy tended to be less likely to have received a clinical diagnosis of attention-deficit/hyperactivity disorder (63% versus 89%; p=0.052) or to be treated with stimulants (50% verses 85%; p=0.025). Our findings suggest a strong trend towards a higher incidence of epilepsy among children with attention-deficit/hyperactivity disorder compared to those without. Epilepsy in children with attention-deficit/hyperactivity disorder appears to be more severe than in those without. Finally, there appears to be a reluctance to diagnose and initiate treatment for attention-deficit/hyperactivity disorder in children with epilepsy.
Attention-Deficit/Hyperactivity Disorder (ADHD); epilepsy; seizures; pediatric; epidemiology; stimulants
Pre-psychotic and early psychotic characteristics are investigated in the high-risk (HR) populations for psychosis. There are two different approaches based either on hereditary factors (genetic high risk, G-HR) or on the clinically manifested symptoms (clinical high risk, C-HR). Common features are an increased risk for development of psychosis and similar cognitive as well as structural and functional brain abnormalities.
We reviewed the existing literature on longitudinal structural, and on functional imaging studies, which included G-HR and/or C-HR individuals for psychosis, healthy controls (HC) and/or first episode of psychosis (FEP) or schizophrenia patients (SCZ).
With respect to structural brain abnormalities, vulnerability to psychosis was associated with deficits in frontal, temporal, and cingulate regions in HR, with additional insular and caudate deficits in C-HR population. Furthermore, C-HR had progressive prefrontal deficits related to the transition to psychosis.
With respect to functional brain abnormalities, vulnerability to psychosis was associated with prefrontal, cingulate and middle temporal abnormalities in HR, with additional parietal, superior temporal, and insular abnormalities in C-HR population. Transition-to-psychosis related differences emphasized prefrontal, hippocampal and striatal components, more often detectable in C-HR population.
Multimodal studies directly associated psychotic symptoms displayed in altered prefrontal and hippocampal activations with striatal dopamine and thalamic glutamate functions.
There is an evidence for similar structural and functional brain abnormalities within the whole HR population, with more pronounced deficits in the C-HR population. The most consistent evidence for abnormality in the prefrontal cortex reported in structural, functional and multimodal studies of HR population may underlie the complexity of higher cognitive functions that are impaired during HR mental state for psychosis.
Clinical high-risk for psychosis; Genetic high-risk for psychosis; At-risk mental state; functional MRI.
Major self-mutilation (MSM) is a rare but catastrophic complication of severe mental illness. Most people who inflict MSM have a psychotic disorder, usually a schizophrenia spectrum psychosis. It is not known when in the course of psychotic illness, MSM is most likely to occur. In this study, the proportion of patients in first episode of psychosis (FEP) was assessed using the results of a systematic review of published case reports. Histories of patients who had removed an eye or a testicle, severed their penis, or amputated a portion of a limb and were diagnosed with a schizophrenia spectrum psychosis were included. A psychotic illness was documented in 143 of 189 cases (75.6%) of MSM, of whom 119 of 143 (83.2%) were diagnosed with a schizophrenia spectrum psychosis. The treatment status of a schizophrenia spectrum psychosis could be ascertained in 101 of the case reports, of which 54 were in the FEP (53.5%, 95% confidence interval = 43.7%–63.2%). Patients who inflict MSM in FEP exhibited similar symptoms to those who inflict MSM later in their illness. Acute psychosis, in particular first-episode schizophrenia, appears to be the major cause of MSM. Although MSM is extremely uncommon, earlier treatment of psychotic illness may reduce the incidence of MSM.
self-mutilation; schizophrenia; first-episode psychosis
The authors evaluated the association between gestational age, birth weight, intrauterine growth and epilepsy in a population-based cohort of 1.4 million singletons born in Denmark (1979-2002). A total of 14,334 individuals were registered with epilepsy in the Danish National Hospital Register as inpatients (1979-2002) and outpatients (1995-2002). Information on gestational age and birth weight was obtained from Danish Medical Birth Registry. Children small at birth were identified through two methods: 1) sex-, birth order-, and gestational-age-specific z-score, and 2) deviation from the expected birth weight estimated based on the birth weight of an older sibling. The incidence rates of epilepsy increased consistently with decreasing gestational age and birth weight. The incidence rate ratios (IRR) for epilepsy in the first year of life were more than five-fold in children born at 22-32 weeks compared with children born at 39-41 weeks, and in children with a birth weight <2,000 grams compared with children of 3,000-3,999 grams. The IRRs decreased with age, but remained elevated into early adulthood. Children identified as growth-restricted according to either of the two methods had increased IRRs for epilepsy, even among children with a ‘normal’ birth weight of 3,500-3,999 grams. Low gestational age at birth and low birth weight are associated with an increased risk of epilepsy throughout childhood and persisting into puberty. Intrauterine growth restriction is associated with an increased risk of epilepsy, even among children with a birth weight in a normal range.
Although schizophrenia is characterized by gray matter (GM) abnormalities, particularly in the prefrontal and temporal cortices, it is unclear whether cerebral cortical GM is abnormal in individuals at ultra-high-risk (UHR) for psychosis. We addressed this issue by studying cortical thickness in this group with magnetic resonance imaging (MRI). We measured cortical thickness of 29 individuals with no family history of psychosis at UHR, 31 patients with schizophrenia, and 29 healthy matched control subjects using automated surface-based analysis of structural MRI data. Hemispheric mean and regional cortical thickness were significantly different according to the stage of the disease. Significant cortical differences across these 3 groups were found in the distributed area of cerebral cortices. UHR group showed significant cortical thinning in the prefrontal cortex, anterior cingulate cortex, inferior parietal cortex, parahippocampal cortex, and superior temporal gyrus compared with healthy control subjects. Significant cortical thinning in schizophrenia group relative to UHR group was found in all the regions described above in addition with posterior cingulate cortex, insular cortex, and precentral cortex. These changes were more pronounced in the schizophrenia group compared with the control subjects. These findings suggest that UHR is associated with cortical thinning in regions that correspond to the structural abnormalities found in schizophrenia. These structural abnormalities might reflect functional decline at the prodromal stage of schizophrenia, and there may be progressive thinning of GM cortex over time.
MRI; gray matter; cortical thinning; surface-based analysis
Individuals with 22q11.2 deletion syndrome are known to be at high risk of developing schizophrenia. Previous imaging studies have provided limited data on the relation of schizophrenia expression in 22q11.2 deletion syndrome to specific regional brain volumetric changes. The authors hypothesized that the main structural brain finding associated with schizophrenia expression in 22q11.2 deletion syndrome, as for schizophrenia in the general population, would be gray matter volumetric deficits, especially in the temporal lobes.
MR brain images from 29 patients with 22q11.2 deletion syndrome and schizophrenia and 34 comparison subjects with 22q11.2 deletion syndrome and no history of psychosis were analyzed using a voxel-based morphometry method that also yielded volumes for related region-of-interest analyses. The authors compared data from the two groups using an analysis of covariance model correcting for total intracranial volume, age, sex, IQ, and history of congenital cardiac defects. The false discovery rate threshold was set at 0.05 to account for multiple comparisons.
Voxel-based morphometry analyses identified significant gray matter reductions in the left superior temporal gyrus (Brodmann’s area 22) in the schizophrenia group. There were no significant between-group differences in white matter or CSF volumes. Region-of-interest analyses showed significant bilateral gray matter volume reductions in the temporal lobes and superior temporal gyri in the schizophrenia group.
The structural brain expression of schizophrenia associated with the highly penetrant 22q11.2 deletion involves lower gray matter volumes in temporal lobe regions. These structural MRI findings in a 22q11.2 deletion syndrome form of schizophrenia are consistent with those from studies involving schizophrenia samples from the general population. The results provide further support for 22q11.2 deletion syndrome as a genetic subtype and as a useful neurodevelopmental model of schizophrenia.
PMID: 21362743 CAMSID: cams2144
People with epilepsy are at increased risk for sudden death. The most prevalent cause of sudden death in the general population is sudden cardiac arrest (SCA) due to ventricular fibrillation (VF). SCA may contribute to the increased incidence of sudden death in people with epilepsy. We assessed whether the risk for SCA is increased in epilepsy by determining the risk for SCA among people with active epilepsy in a community-based study.
Methods and Results
This investigation was part of the Amsterdam Resuscitation Studies (ARREST) in the Netherlands. It was designed to assess SCA risk in the general population. All SCA cases in the study area were identified and matched to controls (by age, sex, and SCA date). A diagnosis of active epilepsy was ascertained in all cases and controls. Relative risk for SCA was estimated by calculating the adjusted odds ratios using conditional logistic regression (adjustment was made for known risk factors for SCA). We identified 1019 cases of SCA with ECG-documented VF, and matched them to 2834 controls. There were 12 people with active epilepsy among cases and 12 among controls. Epilepsy was associated with a three-fold increased risk for SCA (adjusted OR 2.9 [95%CI 1.1–8.0.], p = 0.034). The risk for SCA in epilepsy was particularly increased in young and females.
Epilepsy in the general population seems to be associated with an increased risk for SCA.
Background: Prior studies of common disorders in community-dwelling adults identified internalizing and externalizing spectra of mental illness. We investigated the placement of schizophrenia and schizotypal personality disorder in this framework and tested the validity of the resulting organization in a clinical population. Methods: The data came from the Suffolk County Mental Health Project cohort (N = 628), which consists of first-admission patients with psychosis recruited from inpatient units throughout Suffolk County, NY (72% response rate). The sample was reassessed multiple times over the following 10 years. Complete diagnostic data were available for 469 participants. Mental health professionals diagnosed 11 target conditions based on semistructured clinical interviews, review of medical records, and reports of significant others. Two validators were included: family history of schizophrenia and 10-year illness course. Results: Confirmatory factor analysis revealed that the The Diagnostic and Statistical Manual of Mental Disorders-IV grouping of conditions fit the data poorly. The best alternative classification consisted of three clusters: internalizing, externalizing, and schizophrenic. Both validators supported the coherence and distinctiveness of the schizophrenic cluster. Conclusions: We replicated internalizing and externalizing spectra in a clinical population, identified a schizophrenic spectrum, and provided initial evidence of its validity. These findings suggest that schizotypal personality disorder may be better placed with schizophrenia, antisocial conditions with substance use disorders, and major depression with anxiety disorders.
nosology; classification; DSM; confirmatory factor analysis; validation
The Belgian shepherd Groenendael and Tervueren is believed to be at higher risk of developing epilepsy than dogs of the common population. This epidemiological study was designed to estimate the prevalence of epilepsy in the Danish population of Groenendael and Tervueren born between 1995 and 2004. Furthermore, it was the intention to describe the clinical manifestation (seizure types and phenomenology) of epilepsy and to identify risk factors for euthanasia once the dog was diagnosed as having epilepsy.
All owners of Groenendael and Tervueren dogs born between January 1995 and December 2004 and registered in the Danish Kennel Club (1,248 dogs) were contacted and asked to answer a mailed questionnaire concerning epilepsy. Positive responders were subsequently validated in a follow-up interview conducted by telephone using a standardized questionnaire. Owners were questioned about age at first seizure, seizure frequency, seizure duration, a detailed description of seizure phenomenology, post-ictal signs and if a veterinarian had diagnosed the dog with epilepsy.
Prevalence of epilepsy was estimated at 9.5%. Mean age of epilepsy debut was 3.3 years (range 0.5–8.0 years). There was an almost equal number of Groenendael (25) and Tervueren (24). The distribution of females and males was 31 and 18 respectively. Twenty-five per cent experienced focal seizures, 53% experienced focal seizures with secondary generalization and 18% experienced primary generalized seizures. In four percent seizures were unclassifiable. The most commonly reported focal seizure phenomenology included ataxia, crawling, swaying, fearful behavior, salivation, excessive attention seeking and disorientation. In 16% of the cases, epilepsy led to euthanasia. Intact dogs with epilepsy had a significantly increased risk of being euthanized because of epilepsy compared to neutered dogs with epilepsy. In 22% of the cases the owners reported that anxiety/hyperactivity/stress could act as a seizure provoking factor.
A high prevalence of epilepsy appears to be present in the Danish Groenendael and Tervueren population. The relatively late debut age of epilepsy in this breed contributes greatly to the increased prevalence of epileptic individuals, because dogs developing epilepsy late in life are used for breeding unintended.