Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.

Extracts of mulberry have been shown to reduce post-prandial glucose (PPG) and insulin (PPI) responses, but reliability of these effects and required doses and specifications are unclear. We previously found that 1·5 g of a specified mulberry fruit extract (MFE) significantly reduced PPG and PPI responses to 50 g carbohydrate as rice porridge, with no indications of intolerance. The trials reported here aimed to replicate that work and assess the efficacy of lower MFE doses, using boiled rice as the carbohydrate source. Two separate randomised controlled intervention studies were carried out with healthy Indian males and females aged 20–50 years (n 84 per trial), with PPG area under the curve over 2 h as the primary outcome. Trial 1 used doses of 0, 0·37, 0·75, 1·12 and 1·5 g MFE in boiled rice and 0 or 1·5 g MFE in rice porridge. Trial 2 used doses of 0, 0·04, 0·12, 0·37 g MFE in boiled rice. In trial 1, relative to control, all MFE doses significantly decreased PPG (–27·2 to −22·9 %; all P ≤ 0·02) and PPI (–34·6 to −14·0 %, all P < 0·01). Breath hydrogen was significantly increased only at 1·5 g MFE (in rice porridge), and self-reported gastrointestinal symptoms were uniformly low. In trial 2, only 0·37 g MFE significantly affected PPG (–20·4 %, P = 0·002) and PPI (–17·0 %, P < 0·001). Together, these trials show that MFE in doses as low as 0·37 g can reliably reduce PPG and PPI responses to a carbohydrate-rich meal, with no apparent adverse effects.

Aging can be described as the life-long accumulation of damage to the tissues, cells, and molecules of the body. One of the most widely used markers to study biological aging is telomere length. Telomeres are non-coding DNA structures located at the ends of chromosomes that become progressively shorter with age. Research in the past decade showed that persons with psychiatric disorders such as major depressive disorder, anxiety disorder or posttraumatic stress disorder on average have shorter telomeres, which might help explain the high levels of somatic morbidity in these patients. While telomere length is an elegant aging biomarker, reflecting a biological process in most living species, there are also some challenges. In human studies, the between-person variation is large and shortened telomeres showed not to be specific to psychiatric diagnosis but rather to a multitude of psychological and physiological stressors. Telomere length might therefore not be a diagnostic marker. It could, nonetheless, be an interesting target for pharmacological, psychological or exercise treatment. If persons with psychiatric disorders age biologically faster, to what extend can this be process be halted or even reversed with successful treatment? Other opportunities and obstacles of studying telomere length as a biological aging marker in psychiatry will be discussed in this session.

Velocardiofacial syndrome, nowadays called 22q11 deletion syndrome (22q11DS), involves a common hemizygous interstitial microdeletion at 22q11.2. The syndrome has a highly variable expression including congenital cardiac and vascular anomalies, endocrine dysfunctions, facial dysmorphisms and an increased risk for the occurrence of a specific psychopathological phenotype.

The patient is an 18-years-old female and only child from non consanguineous parents. She was referred because of anxious preoccupations with death. Her history mentioned postnatal feeding problems, surgical correction of septal defects aged 6 months, frequent upper airway infections during childhood, developmental delay and recurrent anxieties. Her somatic phenotype was characterized by nasal speech, minor facial dysmorphisms, bilateral hypoplasia of the thenar eminence. Neuropsychiatric examination demonstrated affective instability, severe anxieties accompanied with social withdrawal, ideas of reference, perseverations and paranoid ideation. Neuropsychological assessment demonstrated executive dysfunctions, attention deficits, low social and interpersonal skills and a disharmonic intelligence profile with limited verbal capacities. Total IQ was 81 indicating low intelligence level. Laboratory analyses and MRI scanning of the brain revealed no abnormalities. A provisional clinical diagnosis of 22q11 deletion syndrome was made. Treatment with 20mg citalopram daily for 2 years resulted in complete remission of anxiety symptoms.

Routine cytogenetic investigation demonstrated a normal 46XX karyotype, and no fragile X. 22q11.2 FISH analysis showed no deletions nor did subsequent MLPA subtelomere deletion testing. SNP array analysis demonstrated a 738,8 kb distal deletion in 22q11.21q11.22.

This report demonstrates the importance of testing for 22q11.2 distal deletions in patients with a mild phenotypical presentation, etiologically suggestive for 22q11DS.

A 30-year-old female patient with moderate mental retardation and minor dysmorphisms was referred for neuropsychiatric examination because of psychotic and autistic symptoms and impulsivity. She was born dysmaturally after an uncomplicated pregnancy. Postnatally, she developed cyanosis, feeding problems and recurrent urinary tract infections. Her developmental trajectory showed delayed milestones, speech retardation and restricted peer interactions resulting in special education from age 9. Behavioural problems because of sensory impairments induced paranoid ideation due to social misinterpretations, increasing from age 18.

At referral, physical investigation revealed mild dysmorphisms, severe hearing loss and visual impairment, oestrogen deficiency, kyphoscoliosis, mild hypotonia and hyperlaxity of joints. Neuropsychological examination disclosed a disharmonic intellectual and social cognitive profile (total IQ: 50) with adequate performal capacities and marked cognitive alexithymia. No formal psychiatric diagnosis could be established. Karyotyping showed a de novo ring chromosome 21: 46,XX,der(21)r(21)(p11q22.3). High resolution array analysis of chromosome 21 demonstrated one interstitial duplication, two interstitial deletions and one terminal deletion.

Ring chromosome 21 syndrome is a rare condition that may occur on a de novo basis or via parental transmission. Major characteristics of the phenotype are vulnerability to infections, mild facial dysmorphisms, infertility and kyphosis. In addition there may be congenital malformations of nearly all organ systems.

The current case report demonstrates the importance of targeted high resolution micro array analysis in order to substantiate the genotype-phenotype correlation in patients with r(21) and stresses the importance of cognitive alexithymia as a potential cause for behavioural problems and psychiatric symptoms in patients with mental retardation.

Treatment with psychotropic drugs is frequently associated with obesity, dislipidemia, hyperglycaemia and hypertension, resulting in the development of the metabolic syndrome which in turn is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. The atypical antipsychotics clozapine and olanzapine have the most pronounced effect on metabolic parameters. Over the past years, several studies using the definitions of the so called Third Adult Treatment Panel (ATP-III) of the National Cholesterol Education Program, demonstrated a high prevalence of metabolic syndrome in schizophrenic patients treated with atypical antipsychotics.

The present study includes a total of 96 clozapine-treated inpatients. A total of 34 patients had to be excluded because of refusal tot participate (n=23) or not meeting the DSM-IV criteria for psychotic disorders (n=11). Finally, 62 patients (male: 46; female: 16; mean age: 49 ± 14.2 years; mean duration of clozapine treatment: 9.2 years; current dose: 331.5mg daily) were evaluated according to ATP-III criteria. Other parameters that were collected comprised co-medication, smoking status and alcohol use.

Metabolic syndrome was found in 60% of the patients and was associated with female gender. No association was found between metabolic syndrome and duration of clozapine treatment. Frequencies of the individual components were 92% for dyslipidemia, 43% for obesity, 36% for hypertension, 18% for impaired fasting glucose and 18% for diabetes mellitus type 2.

Metabolic syndrome is highly prevalent among patients with psychotic disorders who are treated with clozapine. Additional factors like unhealthy life stile, inactivity and co-medication, emerge as major treatment targets.

A male patient aged 49 was referred for evaluation of an acute paranoid psychotic state followed by an apathy syndrome. Since his history, apart from hypertension, did not mention any somatic complaints or psychiatric symptoms, and he had been involved in an adequate professional career as metalworker and welder, MRI- scanning of the brain was performed. There appeared to be bilateral hyperdensity of the globus pallidus, suggestive for chronic manganese (Mn) intoxication. Subsequently, a Mn plasma level of 31 nmol/l (range: 7-20nmol/l) that confirmed the diagnosis.

Mn is a trace element that regulates many enzymes and is essential for normal development and body function. Chronic Mn intoxication has an insidious and progressive course and usually starts with complaints of headache, fatigue, sleep disturbances, irritability and emotional instability. Later, several organ systems may be affected leading to increased heart rate and/or blood pressure, elevated total cholesterol levels, and lowered fertility in males. With respect to neurotoxicity, Mn primarily affects the globus pallidus and the striatum of the basal ganglia, and induces damage to the dopaminergic system. This may ultimately lead to dystonic movements and a parkinsonian syndrome that is dominated by generalized bradykinesia and rigidity.

As to neuropsychiatry, an array of symptoms may develop up to 30 years after intoxication of which gait and speech abnormalities, cognitive and motor slowing, mood changes and hallucinations are the most common. Psychotic phenomena are rarely reported.

In conclusion, subacute psychotic symptoms in the absence of a psychiatric history, may point towards rare occupational diseases.

The influence of subsyndromal mood symptoms (SSMS) on cognition and psychosocial functioning of euthymic bipolar patients remains unclear. Viewpoints vary from minor to major influence of SSMS, but seem to be dependent on the methodological choices of the respective researchers. The present study evaluates the relationship between SSMS and cognitive or psychosocial functioning. 16 euthymic patients with bipolar (I: n= 10; II: n= 6) disorder according to DSM-IV criteria were included. SSMS were measured using the MOODS-SR. Cognitive functioning was measured using STROOP, Trail Making Task, WMS-R visual memory subtests, CVLT, WCST, BADS, NART, amongst others. Psychosocial functioning was determined using the GVSG-45, and the Rand-36. Number of bipolar mood symptoms significantly predicted psychosocial functioning. Post-hoc analyses revealed this effect was greatest for the number of depressive symptoms. To our surprise, cognitive functioning had no significant relation to number of mood symptoms or psychosocial functioning. Although the study has several limitations, our results may imply careful detection of subsyndromal depressive mood symptoms in recovered bipolar patients, as these symptoms may typically be responsible for lowered psychosocial functioning and well-being.

Specific types of cognitions and mental processes may lead to greater stress arousal and may subsequently impact cell longevity. The study of telomeres and telomere-related molecular systems may provide a pathway for exploring the link between psychological domains and cell physiology. Based on findings emerging from clinical and preclinical data, we hypothesize that the telomere-telomerase system contributes to explain certain biological underpinnings of psychological interventions.

In this symposium we’ll present the preliminary evidence on the complex translational relationships between specific psychological domains (i.e. childhood adversities, stressful life events, mindfulness-based interventions and perceived distress), the telomere-telomerase system and clinical outcomes. Further, we’ll discuss preliminary data on the effect of mindfulness- and meditation-based interventions on cellular ageing and disease-associated molecular phenotypes.

Many psychiatric disorders have been associated with increased risk of mortality and various aging-related somatic diseases. In addition to unhealthy lifestyles, also various stress-related physiological processes likely play a role in explaining these detrimental health consequences of psychiatric disorders. The impact could be visible at the cellular level, with psychiatric patients presenting more signals of physiological aging for instance as determined by measuring telomere length. In this talk we will first highlight the current state-of-the art evidence that various psychiatric conditions, including e.g. depression, anxiety and PTSD, are associated with shorter telomere length. Second, we will provide results from the Netherlands Study of depression and anxiety (n = 2981) that tested longitudinal associations using 6 year data on psychiatric status and telomere length. These results indicate that the association between depressive and anxiety disorders with telomere length is stable over time, and doesn’t show many dynamic associations. Finally, in the same study we have also tested to what extent lifestyle and dysregulations of physiological stress systems such as the immune, HPA-axis and autonomic nervous systems are partly responsible for the observed shorter telomere length in depressed or anxious patients. Results indicate that especially smoking behavior and systemic inflammation partly contribute to the shorter telomere length, but can’t completely explain found associations.

In sum, this talk will highlight the current state-of-evidence for an association between various psychiatric conditions with shorter telomere length, and will provide insights into its dynamics and its contributing mechanisms.