Neural mechanisms regulating different forms of risk-related decision-making: Insights from animal models

Over the past 20 years there has been a growing interest in the neural underpinnings of cost/benefit decision-making. Recent studies with animal models have made considerable advances in our understanding of how different prefrontal, striatal, limbic and monoaminergic circuits interact to promote efficient risk/reward decision-making, and how dysfunction in these circuits underlies aberrant decision-making observed in numerous psychiatric disorders. This review will highlight recent findings from studies exploring these questions using a variety of behavioral assays, as well as molecular, pharmacological, neurophysiological, and translational approaches. We begin with a discussion of how neural systems related to decision subcomponents may interact to generate more complex decisions involving risk and uncertainty. This is followed by an overview of interactions between prefrontal-amygdala-dopamine and habenular circuits in regulating choice between certain and uncertain rewards and how different modes of dopamine transmission may contribute to these processes. These data will be compared with results from other studies investigating the contribution of some of these systems to guiding decision-making related to rewards vs. punishment. Lastly, we provide a brief summary of impairments in risk-related decision-making associated with psychiatric disorders, highlighting recent translational studies in laboratory animals.     

Mania caused by a diencephalic lesion.

We describe the case of a young male patient, SN, who suffered a MR-documented ischaemic lesion of both dorsomedial thalami and presented with a transient maniform syndrome. SN's neuropsychological, structural and functional imaging findings are compared with similar reported cases and are discussed in the framework of fronto-subcortical circuits and their proposed behavioural disorders. SN's mania was characterized by restlessness, mood elevation, a tendency for pleasurable activities, inflated self-esteem and loss of disease awareness. Other symptoms were sexual disinhibition, tactlessness, abnormal discourse, and reduced need for food and sleep. His neuropsychological assessment revealed an anterograde amnesia, and an impairment of frontal-executive functions. A SPECT-study showed diaschisis-related areas of hypoperfusion in both prefrontal regions which were interpreted as equivalents of SN's frontal-dysexecutive syndrome. In addition, there was a perfusion deficit in the right orbitofrontal cortex, which was taken as the imaging correlate of SN's secondary mania and personality disorder. These findings suggest that SN's mania and his other symptoms result from the twofold disruption of fronto-subcortical connections, namely of the right orbitofrontal loop which is concerned with mood regulation and socially appropriate behaviour, and of the dorsolateral prefrontal loop which mediates executive cognitive functions.     

躁狂症患者血清一氧化氮水平研究

目的：了解躁狂症患者的血清一氧化氮(NO)水平。方法：对20例躁狂症患者的血清NO水平进行检测，采用Bech-Rafaelsen躁狂量表(BRMS)进行评定。以18例正常体检者为对照。结果：躁狂症组的血清NO水平明显高于正常对照组，血清NO水平与BRMS分之间未发现有相关性。结论：躁狂症患者存在相对较高的血清NO水平，可能是躁狂发作的病理生理基础。     

Tritiated imipramine binding to platelets in manic subjects

We studied 21 patients with bipolar affective disorder and 25 healthy controls in order to determine if tritiated imipramine binding to platelets distinguished the manic from the depressed phase of bipolar disorder. Depressed patients had a significantly lower mean Bmax value (754 +/- 149 fmole/mg protein) than the manic and control groups (1112 +/- 248 and 1237 +/- 201 fmole/mg protein, respectively), which did not differ from each other. These differences could not be attributed to differences in age, sex, menopausal status, the presence of psychotic features or medication history among the subject groups. These findings confirm that decreased imipramine binding to platelets is a state marker for bipolar depression and not a trait marker of bipolar disorder.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

自我角色认同护理在躁狂症护理中的应用效果分析

目的探讨自我角色认同护理在躁狂症中的应用效果。方法选取2017-2019年沈阳市铁西区精神卫生中心收治的成人躁狂症发作期患者50例,随机分为对照组和干预组各25例。对照组给予常规护理,干预组给予自我角色认同护理。分别采用激越行为量表和社交技能量表对两组的干预效果进行评价。结果干预后两组激越行为量表和社交技能评定目录量表各维度评分及总分差异均有统计学意义(P<0.05)。结论自我角色认同护理能进一步改善躁狂症患者的激越行为和社交技能,值得临床推广应用。     

Kraepelin-oriented research-diagnosable schizophrenia,mania, and depression in schneider-negative schizophrenics

Summary The rigorous neo-Kraepelinean research criteria of the St. Louis/ Iowa and Taylor groups were applied to case record data of 116 first admissions of Schneider-negative schizophrenics—that is, those without first-rank symptoms (FRSs)—hospitalized in a strongly Schneider-oriented German University Psychiatric Clinic from 1962 to 1971. This sample had a total of 45.7% (53 cases) of psychiatric illness diagnosable by research methods. Indeed, only 31% (36 cases) of Schneider-negative schizophrenics turned out to have research-positive Kraepelin-oriented schizophrenia; and of these, 21 fulfilled both sets of research criteria for schizophrenia. It is important that 14.6% (17 cases) of Schneider-negative schizophrenia consisted of research-diagnosable affective disorder, with mania making up 5.2% and depression 9.4% of this figure. The findings suggest that a sample of Schneider-oriented schizophrenia without FRSs as routinely diagnosed in Germany does not seem to represent a clear-cut homogeneous and uncontaminated group of schizophrenics.     

The effect of haloperidol on epinephrine-stimulated adenylate cyclase in humans

Administration of epinephrine in man has been shown previously to lead to a rise in plasma cyclic AMP levels by activation of the -adrenergic-stimulated adenylate cyclase. Therapeutic doses of lithium in humans block the epinephrine-induced rise in plasma cyclic AMP levels, suggesting that lithium inhibits -adrenergic adenylate cyclase. In contrast, ten subjects receiving haloperidol, a drug also effective in the treatment of mania, show a mean rise in plasma cyclic AMP levels after epinephrine administration and the magnitude of the response is the same as for non-drug treated individuals. These findings are discussed in relation to the possible pharmacological mechanisms of action of lithium and haloperidol in the control of mania.