Genes,environment and responsibility for violent behavior: “Whatever genes one has it is preferable that you are prevented from going around stabbing people”

For the legal system to function effectively people are generally viewed as autonomous actors able to exercise choice and responsible for their actions. It is conceivable that genetic traits associated with violent and antisocial behavior could call into question an affected individual's responsibility for acts of criminal violence. Evidence concerning genes associated with violent and antisocial behavior has been introduced in criminal courts in the USA and Italy, either alone or with associated environmental factors. One example of a “genetic defense” is based on low levels of monoamine oxidase A (MAOA) activity, with a prevalence of around 30% in Caucasian males. In countries with trial by jury it is particularly relevant to consider the views of publics on criminal liability and the significance they assign to evidence citing genetic influences on behavior. This article draws on largely qualitative research looking at participants' explanations of, and assigning of responsibility for, violent and antisocial behavior where environmental or genetic influences are claimed. Genetic factors were not viewed deterministically by participants but were considered by most to be irrelevant to personal responsibility. Notions of human agency, free will and choice were crucial to explanations of problem behaviors and ensured that offenders could be held responsible despite evidence on environmental and genetic factors.     

Impaired dopamine release and synaptic plasticity in the striatum of Parkin−/− mice

Parkin is the most common causative gene of juvenile and early-onset familial Parkinson's diseases and is thought to function as an E3 ubiquitin ligase in the ubiquitin-proteasome system. However, it remains unclear how loss of Parkin protein causes dopaminergic dysfunction and nigral neurodegeneration. To investigate the pathogenic mechanism underlying these mutations, we used parkin −/− mice to study its physiological function in the nigrostriatal circuit. Amperometric recordings showed decreases in evoked dopamine release in acute striatal slices of parkin −/− mice and reductions in the total catecholamine release and quantal size in dissociated chromaffin cells derived from parkin −/− mice. Intracellular recordings of striatal medium spiny neurons revealed impairments of long-term depression and long-term potentiation in parkin −/− mice, whereas long-term potentiation was normal in the Schaeffer collateral pathway of the hippocampus. Levels of dopamine receptors and dopamine transporters were normal in the parkin −/− striatum. These results indicate that Parkin is involved in the regulation of evoked dopamine release and striatal synaptic plasticity in the nigrostriatal pathway, and suggest that impairment in evoked dopamine release may represent a common pathophysiological change in recessive parkinsonism.     

Postnatal experiences and genetic effects on squirrel monkey social affinities and emotional distress

Most nonhuman primate research on risk factors underlying vulnerability to stress has focused on early psychosocial experiences in various species of macaques. To test for genetic and experiential effects on emotional vulnerability in randomly bred squirrel monkeys, here we combined a paternal half-sibling analysis with three postnatal rearing protocols that altered aspects of maternal availability. In one condition offspring were periodically removed from natal groups, whereas differences in maternal availability were produced in two other conditions by manipulating the effort required of lactating mothers to successfully locate food. After completion of these protocols at 21 weeks of age, social affinities, maternal separation induced peep-calls, and plasma levels of cortisol were assessed from 29 to 37 weeks of age. Significant postnatal rearing effects and the lowest heritabilities were detected in peak elevations of cortisol measured 1 day after the removal of mothers from otherwise undisturbed groups. Individual differences in cortisol 3-7 days later revealed negligible postnatal rearing effects and the highest heritabilities (h(2) approximately. 70), as offspring sired by certain fathers failed to return to the preseparation level found in undisturbed natal groups. Paternal half-siblings that responded with long lasting increases in cortisol spent more time near their mother in undisturbed groups and exhibited long-lasting increases in separation induced peep-calls. These findings concur with human twin studies that suggest genetic and experiential factors contribute to individual differences in vulnerability to emotional distress.     

Men's experience of their partners' postpartum psychiatric disorders: narratives from the internet

Objectives Postpartum psychiatric disorders (PPPD) can be serious and disabling, and may lead to long-term adverse consequences. Partners of women with PPPD are also affected by the illness, but their experiences are seldom described. The aim of this study was to explore men's experience of women with PPPD.Methods Eleven written narratives from the internet were used to analyse men's perceived experience of their partner's PPPDs. Data were analysed using content analysis.Results The men revealed a major disruption in their lives. They expressed fear, confusion and anger; they were also extremely concerned about their partners, and felt unable to help in overcoming the disorder. Most of the men described making sacrifices in order to hold the relationship and the family together. Although the disorder improved over time, they were left to face an uncertain future with a woman who seemed to be very different from the person they had known previously. Most of the men gained maturity and increased self-esteem, but for some the result was divorce, custody disputes and loneliness.Conclusions The men in this study experienced the woman's PPPD as a difficult time, when everything familiar was turned upside down. Health professionals should pay more attention to men's mental health in the postpartum period. Furthermore, information regarding the possibility of these disorders should be given to expectant couples in prenatal classes. Further research is needed to ascertain how and to what extent this should be included in the education.     

Exaggerated effect of fluvoxamine in heterozygote serotonin transporter knockout mice

Clearance rates for serotonin (5-HT) in heterozygote (+/-) and homozygote (-/-) serotonin transporter (5-HTT) knockout (KO) mice have not been determined in vivo. Moreover, the effect of selective serotonin reuptake inhibitors (SSRIs) on 5-HT clearance in these mice has not been examined. In this study, the rate of clearance of exogenously applied 5-HT was measured in the CA3 region of the hippocampus of anesthetized mice using high-speed chronoamperometry. Compared with wild-type mice, the maximal rate of 5-HT clearance from extracellular fluid (ECF) was decreased in heterozygotes and more markedly so in KO mice. Heterozygote mice were more sensitive to the 5-HT uptake inhibitor, fluvoxamine, resulting in longer clearance times for 5-HT than in wild-type mice; as expected, the KO mice were completely unresponsive to fluvoxamine. There were no associated changes in norepinephrine transporter density, nor was there an effect of the norepinephrine uptake inhibitor, desipramine, on 5-HT clearance in any genotype. Thus, adaptive changes in the norepinephrine transport system do not occur in the CA3 region of hippocampus as a consequence of 5-HTT KO. These data highlight the potential of the heterozygote 5-HTT mutant mice to model the dynamic in vivo consequences of the human 5-HTT polymorphism.     

Arabidopsis SOI33／AtENT8 Gene Encodes a Putative Equilibrative Nucleoside Transporter That Is Involved in Cytokinin Transport In Planta

The plant phytohormone cytokinin plays an important role in many facets of plant growth and development by regulating cell division and differentiation. Recent studies have shed significant light into the mechanisms of cytokinin metabolism and signaling. However, little is known about how the hormone is transported in planta, although it has been proposed that the hormone is presumably transported in nucleoside-conjugated forms. Here, we report the identification and characterization of cytokinin transporters in Arabidopsis. We previously reported that a gain-of-function mutation in the PGA22/AtlPT8 gene caused overproduction of cytokinins in planta. In an effort to screen for suppressor of pga22/atipt8 (soi) mutants, we identified a mutant soi33-1. Molecular and genetic analyses indicated that S0133 encodes a putative equilibrative nucleoside transporter (ENT), previously designated as AtENT8. Members of this small gene family are presumed to be involved in the transport of nucleosides in eukaryodc cells. Under conditions of nitrogen starvation, loss-of-function mutations in SOI33/AtENT8 or in a related gene AtENT3 cause a reduced sensitivity to the nucleoside-type cytokinins isopentenyladenine riboside (iPR) and transzeatin riboside (tZR), but display a normal response to the free base-type cytokinins isopentenyladenine (iP) and trans-zeatin (tZ). Conversely, overexpression of SOI33/AtENT8 renders transgenic plants hypersensitive to iPR but not to iP. An in planta measurement experiment indicated that uptake efficiency of^3Hlabeled iPR was reduced more than 40% in soi33 and atent3 mutants. However, a mutation in AtENT1 had no substantial effect on the cytokinin response and iPR uptake efficiency. Our results suggest that SOI33/AtENT8 and AtENT3 are involved in the transport of nucleoside-type cytokinins in Arabidopsis.     

Disruption of Nucleotide Homeostasis by the Antiproliferative Drug 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Monophosphate (AICAR)

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside monophosphate (AICAR) is a natural metabolite with potent anti-proliferative and low energy mimetic properties. At high concentration, AICAR is toxic for yeast and mammalian cells, but the molecular basis of this toxicity is poorly understood. Here, we report the identification of yeast purine salvage pathway mutants that are synthetically lethal with AICAR accumulation. Genetic suppression revealed that this synthetic lethality is in part due to low expression of adenine phosphoribosyl transferase under high AICAR conditions. In addition, metabolite profiling points to the AICAR/NTP balance as crucial for optimal utilization of glucose as a carbon source. Indeed, we found that AICAR toxicity in yeast and human cells is alleviated when glucose is replaced by an alternative carbon source. Together, our metabolic analyses unveil the AICAR/NTP balance as a major factor of AICAR antiproliferative effects.     

Arabidopsis SOI33/AtENT8 Gene Encodes a Putative Equilibrative Nucleoside Transporter That Is Involved in Cytokinin Transport In Planta

The plant phytohormone cytokinin plays an important role in many facets of plant growth and development by regulating cell division and differentiation. Recent studies have shed significant light into the mechanisms of cytokinin metabolism and signaling. However, little is known about how the hormone is transported in planta, although it has been proposed that the hormone is presumably transported in nucleoside-conjugated forms. Here, we report the identification and characterization of cytokinin transport ers in Arabidopsis. We previously reported that a gain-of-function mutation in the PGA22/AtIPT8 gene caused overproduction of cytokinins in planta. In an effort to screen for suppressor of pga22/atipt8 (soi) mutants, we identified a mutant soi33-1. Molecular and genetic analyses indicated that SOI33 encodes a putative equilibrative nucleoside transporter (ENT), previously designated as AtENT8. Members of this small gene family are presumed to be involved in the transport of nucleosides in eukaryotic cells. Under conditions of nitrogen starvation, loss-of-function mutations in SOI33/AtENT8 or in a related gene AtENT3 cause a reduced sensitivity to the nucleoside-type cytokinins isopentenyladenine riboside (iPR) and trans zeatin riboside (tZR), but display a normal response to the free base-type cytokinins isopentenyladenine (iP) and trans-zeatin (tZ). Conversely, overexpression of SOI33/AtENT8 renders transgenic plants hyper sensitive to iPR but not to iP. An in planta measurement experiment indicated that uptake efficiency of 3H labeled iPR was reduced more than 40% in soi33 and atent3 mutants. However, a mutation inAtENT1 had no substantial effect on the cytokinin response and iPR uptake efficiency. Our results suggest that SOI33/ AtENT8 and AtENT3 are involved in the transport of nucleoside-type cytokinins in Arabidopsis.     

Towards a second-person neuropsychiatry

Psychiatric disorders can affect our ability to successfully and enjoyably interact with others. Conversely, having difficulties in social relations is known to increase the risk of developing a psychiatric disorder. In this article, the assumption that psychiatric disorders can be construed as disorders of social interaction is reviewed from a clinical point of view. Furthermore, it is argued that a psychiatrically motivated focus on the dynamics of social interaction may help to provide new perspectives for the field of social neuroscience. Such progress may be crucial to realize social neuroscience''s translational potential and to advance the transdiagnostic investigation of the neurobiology of psychiatric disorders.     

“It could just be an additional test couldn't it?” 1 Genetic testing for susceptibility to aggression and violence

Much of the current genetic research into aggressive and violent behavior focuses on young people and might appear to offer the hope of targeted prediction and intervention. In the UK data are collected on children from various agencies and collated to produce “at risk of offending” identities used to justify intervention. Information from behavioral genetic tests could conceivably be included. Regulatory frameworks for collecting, storing and using information from DNA samples differ between the health service and the police particularly in the need for consent and the treatment of children. This paper draws on discussions with professionals involved with “problem” young people to consider their views on the utility of genetic research for tackling violent/aggressive behavior and the impact an identification of genetic susceptibility might have on their clients.     

Exocytotic release of dopamine in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice

The present study used voltammetry to ascertain whether electrically stimulated somatodendritic dopamine release in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice was due to exocytosis or dopamine transporter reversal, as has been debated. The maximal concentration of electrically evoked dopamine release was similar between ventral tegmental area slices from dopamine transporter knockout and C57BL/6 mice. Dopamine transporter blockade (10 μM nomifensine) in slices from C57BL/6 mice inhibited dopamine uptake but did not alter peak evoked dopamine release. In addition, dopamine release and uptake kinetics in ventral tegmental area slices from dopamine transporter knockout mice were unaltered by the norepinephrine transporter inhibitor, desipramine (10 μM), or the serotonin transporter inhibitor, fluoxetine (10 μM). Furthermore, maximal dopamine release in ventral tegmental area slices from both C57BL/6 and dopamine transporter knockout mice was significantly decreased in response to Na⁺ channel blockade by 1 μM tetrototoxin, removal of Ca²⁺ from the perfusion media and neuronal vesicular monoamine transporter inhibition by RO-04-1284 (10 μM) or tetrabenazine (10 and 100 μM). Finally, the glutamate receptor antagonists AP-5 (50 and 100 μM) and CNQX (20 and 50 μM) had no effect on peak somatodendritic dopamine release in C57BL/6 mice. Overall, these data suggest that similar mechanisms, consistent with exocytosis, govern electrically evoked dopamine release in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice.