Annabel Vreeker

Cigarette smoking and cannabis use are equally strongly associated with psychotic-like experiences: a cross-sectional study in 1929 young adults.

BACKGROUND Cannabis use is associated with increased risk for psychotic-like experiences (PLEs) and psychotic disorders. It remains unclear whether this relationship is causal or due to confounding. METHOD A total of 1929 young adults aged 18-30 years participated in a nationwide internet-based survey in The Netherlands and gave information on demographics, substance use and parental psychiatric illness and completed the Community Assessment of Psychic Experiences (CAPE). RESULTS Cigarette smoking and cannabis use were equally strongly associated with the frequency of PLEs in a fully adjusted model (β = 0.098 and 0.079 respectively, p < 0.05). Cannabis use was associated with distress from PLEs in a model adjusted for an elaborate set of confounders excluding smoking (β = 0.082, p < 0.05). However, when cigarette smoking was included in the model, cannabis use was not a significant predictor of distress from PLEs. Cigarette smoking remained associated with distress from PLEs in a fully adjusted model (β = 0.107, p < 0.001). CONCLUSIONS Smoking is an equally strong independent predictor of frequency of PLEs as monthly cannabis use. Our results suggest that the association between moderate cannabis use and PLEs is confounded by cigarette smoking.

Cognitive enhancing agents in schizophrenia and bipolar disorder

Cognitive dysfunction is a core feature of schizophrenia and is also present in bipolar disorder (BD). Whereas decreased intelligence precedes the onset of psychosis in schizophrenia and remains relatively stable thereafter; high intelligence is a risk factor for bipolar illness but cognitive function decreases after onset of symptoms. While in schizophrenia, many studies have been conducted on the development of cognitive enhancing agents; in BD such studies are almost non-existent. This review focuses on the pharmacological agents with putative effects on cognition in both schizophrenia and bipolar illness; specifically agents targeting the dopaminergic, cholinergic and glutamatergic neurotransmitter pathways in schizophrenia and the cognitive effects of lithium, anticonvulsants and antipsychotics in BD. In the final analysis we conclude that cognitive enhancing agents have not yet been produced convincingly for schizophrenia and have hardly been studied in BD. Importantly, studies should focus on other phases of the illness. To be able to treat cognitive deficits effectively in schizophrenia, patients in the very early stages of the illness, or even before - in the ultra-high risk stages - should be targeted. In contrast, cognitive deficits occur later in BD, and therefore drugs should be tested in BD after the onset of illness. Hopefully, we will then find effective drugs for the incapacitating effects of cognitive deficits in these patients.

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls

BACKGROUND Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (β = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (β = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

Brain network analysis reveals affected connectome structure in bipolar I disorder

The notion that healthy brain function emerges from coordinated neural activity constrained by the brains network of anatomical connections—i.e., the connectome—suggests that alterations in the connectomes wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected “rich club” organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brains network. We find that bipolar I disorder patients exhibit reduced global efficiency (−4.4%, P =0.002) and that this deficit relates (r = 0.56, P < 0.001) to reduced connectivity strength of interhemispheric connections (−13.0%, P = 0.001). Bipolar disorder patients were found not to show predominant alterations in the strength of brain hub connections in general, or of connections spanning brain hubs (i.e., “rich club” connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central “rich club” system appears not to be particularly affected. Hum Brain Mapp 37:122–134, 2016.

Change in cannabis use in the general population: A longitudinal study on the impact on psychotic experiences

OBJECTIVE To prospectively assess the relationship between cannabis use and psychotic experiences over time. METHOD In a longitudinal design, young adults aged 18-27years (N=705) gave online information on cannabis use and completed the Community Assessment of Psychic Experiences (CAPE). These measures were repeated after an interval ranging from six months to five years. RESULTS A decrease in cannabis use was associated with a decrease in total psychotic experiences (β=-0.096, p=0.01) after adjustment for a range of potential confounders. An increase in cannabis use was associated with increased positive symptoms at follow-up (β=0.07, p=0.02), but was not significantly associated with increases in Negative and Depression symptom scores, nor with the total number of psychotic experiences. CONCLUSION In the first study to the association of change in cannabis use and psychotic experiences over time in the general population, we found an association between changes in cannabis use and changes in the frequency of psychotic experiences. While this does not prove a causal relationship between cannabis use and psychosis, our findings are consistent with studies suggesting that cessation of cannabis use may be beneficial in terms of reducing psychotic experiences.

The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder

There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium.

BDNF Val66Met homozygosity does not influence plasma BDNF levels in healthy human subjects

A putative pathway by which the BDNF Val66Met polymorphism (rs6265) leads to aberrant phenotypes is its influence on plasma BDNF. Research into the impact of rs6265 on plasma BDNF has given rise to conflicting results. Moreover, most such studies have compared Met-carriers with Val-homozygous subjects. We therefore genotyped subjects from a population-based cohort (the Utrecht Health Project, N=2743) and assessed whether plasma BDNF differs between rs6265 homozygous groups. We maximized the number of Met-homozygous subjects in whom we measured plasma BDNF, resulting in plasma BDNF being available for 19 Met-homozygous and 42 matched Val-homozygous subjects. Mean concentrations (S.D.) were 1963.1 (750.1) and 2133.2 pg/ml (1164.3) for the Val/Val and Met/Met groups, respectively. Using ANOVA, no differences in plasma BDNF between the two groups were detected. In conclusion, these results add to a growing body of evidence indicating that allelic variation at rs6265 does not have medium to large effects on plasma BDNF concentrations.

Advanced paternal age and vulnerability to psychotic-like experiences in the offspring

OBJECTIVE To investigate whether advanced paternal age is associated with increased psychotic-like experiences (PLEs) and increased sensitivity to Cannabis in the offspring. METHODS A cross-sectional population-based study in 1684 participants aged 18 to 25. RESULTS We found no association of paternal age with PLEs. Only the positive dimension subscale was associated to paternal age, but that could be largely contributed to outliers. Also no increased sensitivity to Cannabis smoking was apparent. CONCLUSION In the general population, we did not find robust support for an association between paternal age and vulnerability to PLEs in 18-25year old offspring.

The relationship between brain volumes and intelligence in bipolar disorder

OBJECTIVES Bipolar disorder type-I (BD-I) patients show a lower Intelligence Quotient (IQ) and smaller brain volumes as compared with healthy controls. Considering that in healthy individuals lower IQ is related to smaller total brain volume, it is of interest to investigate whether IQ deficits in BD-I patients are related to smaller brain volumes and to what extent smaller brain volumes can explain differences between premorbid IQ estimates and IQ after a diagnosis of BD-I. METHODS Magnetic resonance imaging brain scans, IQ and premorbid IQ scores were obtained from 195 BDI patients and 160 controls. We studied the relationship of (global, cortical and subcortical) brain volumes with IQ and IQ change. Additionally, we investigated the relationship between childhood trauma, lithium- and antipsychotic use and IQ. RESULTS Total brain volume and IQ were positively correlated in the entire sample. This correlation did not differ between patients and controls. Although brain volumes mediated the relationship between BD-I and IQ in part, the direct relationship between the diagnosis and IQ remained significant. Childhood trauma and use of lithium and antipsychotic medication did not affect the relationship between brain volumes and IQ. However, current lithium use was related to lower IQ in patients. CONCLUSIONS Our data suggest a similar relationship between brain volume and IQ in BD-I patients and controls. Smaller brain volumes only partially explain IQ deficits in patients. Therefore, our findings indicate that in addition to brain volumes and lithium use other disease factors play a role in IQ deficits in BD-I patients.

Characterizing users of new psychoactive substances using psychometric scales for risk-related behavior

INTRODUCTION Studies investigating risk-related behavior in relation to new psychoactive substance (NPS) use are sparse. The current study investigated characteristics of NPS users by comparing risk-related behavior of NPS users to that of illicit drugs (ID) users and licit substances users and non-users (NLC) users. METHODS In this cross-sectional study we included 528 individuals across an age range of 18-72years. Using a web-based questionnaire we collected self-report data on substance use, sensation seeking, impulsivity, peer substance use and risk perception of substance use. RESULTS NPS and ID users had a higher level of sensation seeking compared to NLC users (NPS users: p<0.001; ID users: p<0.001). NPS users (p<0.001), but not ID users (p=0.16), had increased levels of impulsivity compared to NLC users. NPS users had significantly higher scores for sensation seeking (F1,423=51.52, p<0.001) and impulsivity (F1,423=6.15, p=0.01) compared to ID users. Additionally, NPS users had significantly more peers who use substances compared to ID and NLC users. Also, NPS and ID users had lower risk perception for most substances than NLC users. NPS users had lower risk perception for most substances than ID users. CONCLUSIONS The findings highlight that NPS users show substantial more risk-related behavior than both ID and NLC users. Therefore, NPS users might be considered as a distinctive group of substance users that need another approach in terms of prevention.