Twitter psychosis: a rare variation or a distinct syndrome?

The authors report the development of psychosis in a young woman coinciding with excessive use of the online communication system Twitter and the results of an experimental account to argue that Twitter may have a high potential to induce psychosis in predisposed users.

How the cerebral serotonin homeostasis predicts environmental changes: a model to explain seasonal changes of brain 5-HTT as intermediate phenotype of the 5-HTTLPR.

Molecular imaging studies with positron emission tomography have revealed that the availability of serotonin transporter (5-HTT) in the human brain fluctuates over the course of the year. This effect is most pronounced in carriers of the short allele of the 5-HTT promoter region (5-HTTLPR), which has in several previous studies been linked to an increased risk to develop mood disorders. We argue that long-lasting fluctuations in the cerebral serotonin transmission, which is regulated via the 5-HTT, are responsible for mediating responses to environmental changes based on an assessment of the expected "safety" of the environment; this response is obtained in part through serotonergic modulation of the hypothalamic-pituitary-adrenal (HPA) axis. We posit that the intermediate phenotype of the s-allele may properly be understood as mediating a trade-off, wherein increased responsiveness of cerebral serotonin transmission to seasonal and other forms of environmental change imparts greater behavioral flexibility, at the expense of increased vulnerability to stress. This model may explain the somewhat higher prevalence of the s-allele in some human populations dwelling at geographic latitudes with pronounced seasonal climatic changes, while this hypothesis does not rule out that genetic drift plays an additional or even exclusive role. We argue that s-allele manifests as an intermediate phenotype in terms of an increased responsiveness of the 5-HTT expression to number of daylight hours, which may serve as a stable surrogate marker of other environmental factors, such as availability of food and safety of the environment in populations that live closer to the geographic poles.

Ventral striatal prediction error signaling is associated with dopamine synthesis capacity and fluid intelligence.

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subsample of 17 subjects also with positron emission tomography using 6-[(18) F]fluoro-L-DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA K inapp). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that individual differences in the capacity for flexible problem solving relate to ventral striatal activation during reward-related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity.

Decline in prefrontal catecholamine synthesis explains age-related changes in cognitive speed beyond regional grey matter atrophy.

PURPOSE: Age-related decline in cognitive speed has been associated with prefrontal dopamine D1 receptor availability, but the contribution of presynaptic dopamine and noradrenaline innervation to age-related changes in cognition is unknown. METHODS: In a group of 16 healthy participants aged 22-61 years, we used PET and the radioligand FDOPA to measure catecholamine synthesis capacity (K (in) (app); millilitres per gram per minute) and the digit symbol substitution test to measure cognitive speed, a component of fluid IQ. RESULTS: Cognitive speed was associated with the magnitude of K (in) (app) in the prefrontal cortex (p < 0.0005). Both cognitive speed (p = 0.003) and FDOPA K (in) (app) (p < 0.0005) declined with age, both in a standard voxel-wise analysis and in a volume-of-interest analysis with partial volume correction, and the correlation between cognitive speed and K (in) (app) remained significant beyond the effects of age (p = 0.047). MR-based segmentation revealed that these age-related declines were not attributable to age-related alterations in grey matter density. CONCLUSION: Our findings indicate that age-related changes in the capacity of the prefrontal cortex to synthesize catecholamines, irrespective of cortical atrophy, may underlie age-related decline in cognitive speed.

Loss of serotonin 2A receptors exceeds loss of serotonergic projections in early Alzheimer's disease: a combined [11C]DASB and [18F]altanserin-PET study.

In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT(2A)) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT(2A) receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State Examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [(18)F]altanserin and [(11)C]N,N-Dimethyl-2-(2-amino-4-cyanopheylthio)benzylamine ([(11)C]DASB). Overall [(18)F]altanserin binding was markedly reduced in AD by 28%-39% (p = 0.02), whereas the reductions in [(11)C]DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = .0005). No change in [(11)C]DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT(2A) receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.

Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine.

RATIONALE: We have previously reported decreased frontal cortical serotonin2A receptor binding in 30 antipsychotic naïve first-episode schizophrenic patients and a relationship between this binding and positive psychotic symptoms. Until now, no longitudinal studies of serotonin2A receptor in first-episode antipsychotic-naïve schizophrenia patients have reported on the relationship between serotonin2A receptor occupancy and treatment effect after sustained treatment with a specific atypical antipsychotic compound. OBJECTIVES: Here, we measured serotonin2A receptor occupancy with [(18)F]altanserin PET in 15 first-episode antipsychotic-naïve schizophrenia patients before and after 6 months of quetiapine treatment. Moreover, we investigated possible relationships between clinical efficacy, oral dose, and plasma levels of quetiapine RESULTS: Significant nonlinear relationships were found between serotonin2A receptor occupancy, quetiapine dose, and plasma concentration. There was a modest effect on positive symptoms up until a serotonin2A receptor occupancy level of approximately 60%. A receptor occupancy level between 60% and 70% appeared to exert the optimal serotonin2A receptor related treatment effect on positive symptoms whereas no additional serotonin2A receptor associated treatment effect was obtained above a receptor occupancy of 70%. CONCLUSIONS: Taken together, the data point to a therapeutic role of the serotonin2A receptor in the treatment of subgroups of patients with schizophrenia. Specifically, the study indicates a serotonin2A receptor associated therapeutic window on positive symptoms in responding patients in the range between 60% and 70% occupancy in antipsychotic-naïve first-episode schizophrenia. We speculate that non-responding patients need higher dopamine D(2) receptor blockade. Future studies with concurrent measurement of interactions with the dopamine system are, however, warranted to clarify this.

Understanding left-handedness.

BACKGROUND: The human cerebrum is asymmetrical, consisting of two hemispheres with differing functions. Recent epidemiological and neurobiological research has shed new light on the development of the cerebral lateralization of motor processes, including handedness. In this article, we present these findings from a medical perspective. METHOD: We selectively searched the PubMed online database for articles including the terms "handedness," "left handedness," "right handedness," and "cerebral lateralization." Highly ranked and commonly cited articles were included in our analysis. RESULTS: The emergence of handedness has been explained by physiological and pathological models. Handedness arose early in evolution and has probably been constitutive for the development of higher cognitive functions. For instance, handedness may have provided the basis for the development of speech and fine motor skills, both of which have played a critical role in the evolution of mankind. The disadvantages of certain types of handedness are discussed, as some cases seem to be associated with disease. CONCLUSION: The consideration of handedness from the epidemiological, neurobiological, and medical points of view provides insight into cerebral lateralization.

A nonlinear relationship between cerebral serotonin transporter and 5-HT(2A) receptor binding: an in vivo molecular imaging study in humans.

Serotonergic neurotransmission is involved in the regulation of physiological functions such as mood, sleep, memory, and appetite. Within the serotonin transmitter system, both the postsynaptically located serotonin 2A (5-HT(2A)) receptor and the presynaptic serotonin transporter (SERT) are sensitive to chronic changes in cerebral 5-HT levels. Additionally, experimental studies suggest that alterations in either the 5-HT(2A) receptor or SERT level can affect the protein level of the counterpart. The aim of this study was to explore the covariation between cerebral 5-HT(2A) receptor and SERT in vivo in the same healthy human subjects. Fifty-six healthy human subjects with a mean age of 36 +/- 19 years were investigated. The SERT binding was imaged with [(11)C]3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) and 5-HT(2A) receptor binding with [(18)F]altanserin using positron emission tomography. Within each individual, a regional intercorrelation for the various brain regions was seen with both markers, most notably for 5-HT(2A) receptor binding. An inverted U-shaped relationship between the 5-HT(2A) receptor and the SERT binding was identified. The observed regional intercorrelation for both the 5-HT(2A) receptor and the SERT cerebral binding suggests that, within the single individual, each marker has a set point adjusted through a common regulator. A quadratic relationship between the two markers is consistent with data from experimental studies of the effect on SERT and 5-HT(2A) receptor binding of chronic changes in 5-HT levels. That is, the observed association between the 5-HT(2A) receptor and SERT binding could be driven by the projection output from the raphe nuclei, but other explanations are also at hand.

[Pharmacotherapy of neuropsychiatric symptoms in dementia in nursing homes: a comparison of service provision by psychiatric outpatient clinics and primary care psychiatrists]. / Pharmakotherapie von neuropsychiatrischen Symptomen bei Demenz in Altenpflegeheimen: Ein Vergleich der Versorgung durch psychiatrische Institutsambulanzen und niedergelassene Fachärzte.

BACKGROUND: Neuropsychiatric symptoms of dementia like agitation, depression and apathy often result in increased prescriptions of psychotropics. In Germany, outpatient clinics at psychiatric hospitals play an important role in the treatment of neuropsychiatric symptoms in nursing homes. The aim of this study was to test whether the severity and pharmacotherapy differed in patients treated by outpatient clinics at psychiatric hospitals, as compared to primary care specialists. METHODS: A cross-sectional study of the prevalence of agitation, apathy, and depression, and the amount of psychotropics prescribed in defined daily dosages (DDD) in 304 residents with dementia in 18 Berlin nursing homes. RESULTS: Patients treated by outpatient clinics at psychiatric hospitals suffered from more severe neuropsychiatric symptoms (p < 0.05), were prescribed more antidepressants and antidementia agents (p < 0.05) and, when adjusting for the severity of agitation, less neuroleptics (p < 0.05) as compared to primary care specialists. CONCLUSION: Psychiatric outpatient clinics at hospitals treat more severely demented patients who suffer from severe neuropsychiatric symptoms. The pharmacotherapy provided by these clinics displays a favourable profile according to established treatment guidelines.

Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia.

CONTEXT: Postmortem investigations and the receptor affinity profile of atypical antipsychotics have implicated the participation of serotonin(2A) receptors in the pathophysiology of schizophrenia. Most postmortem studies point toward lower cortical serotonin(2A) binding in schizophrenic patients. However, in vivo studies of serotonin(2A) binding report conflicting results, presumably because sample sizes have been small or because schizophrenic patients who were not antipsychotic-naive were included. Furthermore, the relationships between serotonin(2A) binding, psychopathology, and central neurocognitive deficits in schizophrenia are unclear. OBJECTIVES: To assess in vivo brain serotonin(2A) binding potentials in a large sample of antipsychotic-naive schizophrenic patients and matched healthy controls, and to examine possible associations with psychopathology, memory, attention, and executive functions. DESIGN: Case-control study. SETTING: University hospital, Denmark. PARTICIPANTS: A sample of 30 first-episode, antipsychotic-naive schizophrenic patients, 23 males and 7 females, and 30 matched healthy control subjects. INTERVENTIONS: Positron emission tomography with the serotonin(2A)-specific radioligand fluorine 18-labeled altanserin and administration of a neuropsychological test battery. MAIN OUTCOME MEASURES: Binding potential of specific tracer binding, scores on the Positive and Negative Syndrome Scale, and results of neuropsychological testing. RESULTS: Schizophrenic patients had significantly lower serotonin(2A) binding in the frontal cortex than did control subjects. A significant negative correlation was observed between frontal cortical serotonin(2A) binding and positive psychotic symptoms in the male patients. No correlations were found between cognitive functions and serotonin(2A) binding. CONCLUSION: The results suggest that frontal cortical serotonin(2A) receptors are involved in the pathophysiology of schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00207064.

Seasonal changes in brain serotonin transporter binding in short serotonin transporter linked polymorphic region-allele carriers but not in long-allele homozygotes.

BACKGROUND: A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with seasonality both in patients with seasonal affective disorder and in the general population. METHOD: We used in vivo molecular imaging to measure cerebral serotonin transporter (5-HTT) binding in 57 healthy Scandinavians and related the outcome to season of the year and to the 5-HTTLPR carrier status. RESULTS: We found that the number of daylight minutes at the time of scanning correlated negatively with 5-HTT binding in the putamen and the caudate, with a similar tendency in the thalamus, whereas this association was not observed for the midbrain. Furthermore, in the putamen, an anatomic region with relatively dense serotonin innervation, we found a significant gene x daylight effect, such that there was a negative correlation between 5-HTT binding and daylight minutes in carriers of the short 5-HTTLPR allele but not in homozygote carriers of the long allele. CONCLUSIONS: Our findings are in line with S-carriers having an increased response in neural circuits involved in emotional processing to stressful environmental stimuli but here demonstrated as a endophenotype with dynamic changes in serotonin reuptake.

A probabilistic approach to delineating functional brain regions.

UNLABELLED: The purpose of this study was to develop a reliable observer-independent approach to delineating volumes of interest (VOIs) for functional brain regions that are not identifiable on structural MR images. The case is made for the raphé nuclei, a collection of nuclei situated in the brain stem known to be densely packed with serotonin transporters (5-hydroxytryptaminic [5-HTT] system). METHODS: A template set for the raphé nuclei, based on their high content of 5-HTT as visualized in parametric (11)C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile PET images, was created for 10 healthy subjects. The templates were subsequently included in the region sets used in a previously published automatic MRI-based approach to create an observer- and activity-independent probabilistic VOI map. The probabilistic map approach was tested in a different group of 10 subjects and compared with a manual delineation approach. RESULTS: In addition to providing an observer-independent solution, the probabilistic map approach returned a higher specific binding determined in a larger region, ultimately providing better data fitting in kinetic modeling. CONCLUSION: We developed a fast, observer-independent, reliable approach to delineating regions that can be identified only by functional imaging, here exemplified by the raphé nuclei. This approach can be used in future studies to create functional VOI maps based on neuroreceptor fingerprints retrieved through in vivo brain imaging.

The personality trait openness is related to cerebral 5-HTT levels.

Potentiation of serotonergic transmission increases cognitive flexibility, but can in other circumstances increase sensitivity to stressful environmental cues. The personality trait Openness to Experience reflects and is also associated with an increased risk for mood disorders. We hypothesized that the personality trait has an association with a biomarker of serotonergic transmission, the plasma membrane serotonin transporter (5-HTT). In 50 healthy volunteers, we tested for correlations between scores on the NEO-PI-R scale Openness to Experience and its subscales, and cerebral binding of the 5-HTT selective PET radioligand [11C]DASB. Subjects were genotyped for the 5-HTT long/short polymorphism, and for a single nucleotide polymorphism in the long allele, designated LA/LG. Midbrain [11C]DASB binding correlated negatively with scores for Openness to Experience and its two subscales, Openness to Actions and Openness to Values. The latter subscore was negatively correlated with [11C]DASB binding in all brain regions in which [11C]DASB binding was quantified. Genetic analysis showed that homozygote LA carriers had significantly higher [11C]DASB binding in the caudate nucleus, but no significant differences in openness scores. Thus, high scores in personality facets indicative of cognitive flexibility and openness to change are associated with lower [11C]DASB binding. Lower abundance of 5-HTT sites may result in potentiation of serotonergic signaling, which occurs during treatment with SSRIs. We speculate that the set-point of serotonergic signaling in an individual represents a trade-off between flexibility and vulnerability when exposed to environmental stress.