To send this article to your account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send this article to your Kindle, first ensure email@example.com is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
To give a review of the history of SCNP since the first meeting in 1960 with specific focus on UKU.
Consulting the appropriate minutes from the meetings.
One of the major goals of the SCNP was the standardization of clinical trials with psychotropic drugs. In 1969, the SCNP established a Committee for Clinical Investigations (UKU) with the representation of clinical investigators and the drug industry; moreover, during the 1970s and ’80s, the UKU initiated clinical trialsand contributed to the methodology of clinical investigations with psychotropic drugs. With the decrease in governmental funding and increasing influence of the US Food and Drug Administration on themethodology of clinical investigations around the world in the 1990s, the UKU was dissolved. The changes had a detrimental effect on the developments on the methodology of clinical investigations, and the lack of clinical feedback led to an impasse in psychotropic drug development with some pharmaceutical companies abandoning research in the central nervous system area.
It is suggested that a revival of UKU to provide a platform for dialogue among government, industry, and academia could help break the impasse.
Intrauterine growth restriction (IUGR) has been associated with metabolic disorders later in life such as obesity and diabetes as well as psychiatric disorders such as depression and schizophrenia. Therefore, we wanted to investigate whether behavioural, metabolic or neuroendocrine abnormalities could be provoked or exacerbated by a high-fat diet (HFD) in an experimental model of IUGR.
Pregnant dams were exposed to dexamethasone (DEX) in the third gestational week to induce IUGR. Late adolescent male offspring of DEX- and vehicle-treated dams were then fed a HFD or standard chow for 8 weeks and subjected to a variety of assessments.
Only diet affected the hypothalamus-pituitary-adrenal (HPA) axis stress response, as HFD doubled the observed corticosterone levels following acute restraint. HFD and prenatal DEX exposure concomitantly exacerbated depressive-like behaviour in the forced swim test, even though no interaction was seen. Prenatal DEX treatment tended to increase the basal acoustic startle response (ASR), while an interaction between HFD and DEX was present in the ASR pre-pulse inhibition suggestive of fundamental changes in neuronal gating mechanisms. Metabolic parameters were only affected by diet, as HFD increased fasting glucose and insulin levels.
We conclude that chronic HFD may be more important in programming of the HPA axis stress responsiveness than an adverse foetal environment and therefore potentially implies an increased risk for developing psychiatric and metabolic disease.
Monoamine oxidase A (MAOA) gene promoter region includes a variable number of tandem repeat (VNTR) associated with antisocial behaviour in adverse environment. We have examined the effect of the MAOA-uVNTR on mental health and academic success by using a population representative sample and a longitudinal design.
The data of the older cohort (n = 593, aged 15 years at the original sampling) of the longitudinal Estonian Children Personality, Behaviour and Health Study (ECPBHS) were used. Follow-ups were conducted at ages 18 and 25 years. Aggressiveness, inattention and hyperactivity were reported by class teachers or, at older age, self-reported. Stressful life events, psychological environment in the family and interactions between family members were self-reported. Data of general mental abilities and education were obtained at the age of 25, and lifetime psychiatric disorder assessment was carried out with the Mini-International Neuropsychiatric Interview (MINI) interview.
MAOA-uVNTR genotype had no independent effect on aggressiveness, hyperactive and inattentive symptoms, and neither was there a genotype interaction with adverse life events. Interestingly, the proportion of male subjects with higher education by the age of 25 was significantly larger among those with MAOA low-activity alleles (χ2 = 7.13; p = 0.008). Logistic regression revealed that MAOA low-activity alleles, higher mental abilities, occurrence of anxiety disorders and absence of substance-use disorder were significant independent predictors for higher education in male subjects.
In a population representative sample of young subjects, the MAOA-uVNTR ‘risk genotype’ predicted better life outcomes as expressed in higher level of education.
The underlying biology of bipolar disorder and the mechanisms by which effective medications induce their therapeutic effects are not clear. Appropriate use of animal models are essential to further understand biological mechanisms of disease and treatment, and further understanding the therapeutic mechanism of mood stabilisers requires that clinically relevant administration will be effective in animal models. The clinical regimens for mood-stabilising drugs include chronic oral administration; however, much of the work with animal models includes acute administration via injection. An effective chronic and oral administration of the prototypic mood stabiliser lithium was already established and the present study was designed to do the same for the mood stabiliser carbamazepine.
Mice were treated for 3 weeks with carbamazepine in food. ICR mice were treated with 0.25%, 0.5% and 0.75%, and C57bl/6 mice with 0.5% and 0.75%, carbamazepine in food (w/w, namely, 2.5, 5.0 or 7.5 g/kg food). Mice were then tested for spontaneous activity, forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperactivity.
Oral carbamazepine administration resulted in dose-dependent blood levels reaching 3.65 μg/ml at the highest dose. In ICR mice, carbamazepine at the 0.5% dose had no effect on spontaneous activity, but significantly reduced immobility in the TST by 27% and amphetamine-induced hyperactivity by 28%. In C57bl/6 mice, carbamazepine at the 0.75% dose reduced immobility time in the FST by 26%.
These results demonstrate a behaviourally effective oral and chronic regimen for carbamazepine with mood stabilising-like activity in a standard model for mania-like behaviour and two standard models for depression-like behaviour.
Human impulsivity is a complex multidimensional construct encompassing cognitive, emotional, and behavioural aspects. Previous animal studies have suggested that striatal dopamine receptors play a critical role in impulsivity. In this study, we investigated the relationship between self-reported impulsiveness and dopamine D2/3 receptor availability in striatal subdivisions in healthy subjects using high-resolution positron emission tomography (PET) with [11C]raclopride.
Twenty-one participants completed 3-T magnetic resonance imaging and high-resolution PET scans with [11C]raclopride. The trait of impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11). Partial correlation analysis was performed between BIS-11 scores and D2/3 receptor availability in striatal subregions, controlling for the confounding effects of temperament characteristics that are conceptually or empirically related to dopamine, which were measured by the Temperament and Character Inventory.
The analysis revealed that the non-planning (p = 0.004) and attentional (p = 0.007) impulsiveness subscale scores on the BIS-11 had significant positive correlations with D2/3 receptor availability in the pre-commissural dorsal caudate. There was a tendency towards positive correlation between non-planning impulsiveness score and D2/3 receptor availability in the post-commissural caudate.
These results suggest that cognitive subtrait of impulsivity is associated with D2/3 receptor availability in the associative striatum that plays a critical role in cognitive processes involving attention to detail, judgement of alternative outcomes, and inhibitory control.
Cognitive deficits in schizophrenia play a crucial role in its clinical manifestation and seem to be related to changes in the cholinergic system, specifically the action of acetylcholinesterase (AChE). Considering this context, the aim of this study was to evaluate the chronic effects of ketamine in the activity of AChE, as well as in behavioural parameters involving learning and memory.
The ketamine was administered for 7 days. A duration of 24 h after the last injection, the animals were submitted to behavioural tests. The activity of AChE in prefrontal cortex, hippocampus and striatum was measured at different times after the last injection (1, 3, 6 and 24 h).
The results indicate that ketamine did not affect locomotor activity and stereotypical movements. However, a cognitive deficit was observed in these animals by examining their behaviour in inhibitory avoidance. In addition, an increase in AChE activity was observed in all structures analysed 1, 3 and 6 h after the last injection. Differently, serum activity of AChE was similar between groups.
Chronic administration of ketamine in an animal model of schizophrenia generates increased AChE levels in different brain tissues of rats that lead to cognitive deficits. Therefore, further studies are needed to elucidate the complex mechanisms associated with schizophrenia.
Stress can stimulate increased production of oxygen radicals. We investigated the correlations between serum levels of lipid peroxidation markers and those in brain samples in different stress models.
Animals (n = 96) were divided equally into eight groups: a control group and groups treated with vitamin E (Vit E); exposed to immobilisation stress; exposed to immobilisation stress and treated with Vit E; exposed to cold stress; exposed to cold stress and treated with Vit E; exposed to both immobilisation and cold stress; and a final group exposed to both immobilisation and cold stress and treated with Vit E. Thiobarbituric acid-reactive substance (TBARS) in brain samples and levels of TBARS, corticosterone, conjugated dienes (CD), lipids, and paraoxonase-1 (PON1) activity in serum were analysed.
Serum corticosterone (p < 0.001), CD (p < 0.05), lipid (p < 0.05) levels, and brain TBARS (p < 0.05) levels were significantly higher in all stress groups than in controls, and the elevated levels were reversed in the Vit E-treated stress groups (p < 0.05). Serum PON1 activity was not different among the groups (p > 0.05). Serum TBARS levels increased significantly in all stress groups (p < 0.05), but this elevation was only reversed in the group exposed to both immobilisation and cold stress and treated with Vit E (p < 0.001).
These results suggest that serum levels of lipid peroxidation markers can be determined readily and may be useful as indicators to evaluate the effects of oxidative stress in the brain.
Catatonic features are observed in several psychiatric illnesses but can also be found following substance misuse. Loperamide is an anti-diarrhoeal medication that acts on opioid receptors in the intestine, reducing peristalsis. It is normally unable to pass through the intestinal wall or the blood–brain barrier; however, high dosages can in fact induce the effects on the central nervous system.
We describe the case of a 20-year-old man who presented with severe catatonia following excessive intake of loperamide, fully remitted with lorazepam.
We speculate on a possible increase of loperamide's bioavailability after overdose owing to reduced expression and functioning of P-glycoprotein.
Aripiprazole has a low risk for causing extrapyramidal syndrome and can remit neuroleptic-induced tardive dyskinesia (TD). Here, we presented a case in which TD was suppressed, but not cured, by long-term aripiprazole treatment.
This 74-year-old male patient had bipolar I disorder and had developed TD many times after several antipsychotic treatments. The lowest chlorpromazine dose equivalent among the previous antipsychotic treatments was 25 mg/day of quetiapine. His TD always improved immediately after the dosage was shifted to aripiprazole. However, his insomnia or other psychiatric symptoms worsened the first three times when the treatment was shifted to aripiprazole, making the transition a failure. Before the fourth attempt of aripiprazole transition, the patient was in a euthymic state but again developed TD under olanzapine 10 mg/day treatment. During the fourth attempt of aripiprazole transition, his TD had remained in complete remission for more than 1 year after the dosage shifted to 10 mg/day of aripiprazole. He developed TD again when we tapered the aripiprazole dose to 5 mg/day, but his TD remitted when we restored his aripiprazole dose to 10 mg/day.
Aripiprazole could be an effective drug in elderly bipolar patients with antipsychotic-induced TD while the patients are in a euthymic state. However, aripiprazole may only suppress TD rather than cure it.