Gerben Meynen

Increased arginine vasopressin mRNA expression in the human hypothalamus in depression : A preliminary report

BACKGROUND Elevated arginine vasopressin (AVP) plasma levels have been observed in major depression, particularly in relation to the melancholic subtype. Two hypothalamic structures produce plasma vasopressin: the supraoptic nucleus (SON) and the paraventricular nucleus (PVN). The aim of this study was to establish which structure is responsible for the increased vasopressin plasma levels in depression. METHODS Using in situ hybridization, we determined the amount of vasopressin messenger ribonucleic acid (mRNA) in the PVN and SON in postmortem brain tissue of nine depressed subjects (six with the melancholic subtype) and eight control subjects. RESULTS In the SON, a 60% increase of vasopressin mRNA expression was found in depressed compared with control subjects. In the melancholic subgroup, AVP mRNA expression was significantly increased in both the SON and the PVN compared with control subjects. CONCLUSIONS We found increased AVP gene expression in the SON in depressed subjects. This might partly explain the observed increased vasopressin levels in depression.

Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results

PurposeMajor depressive disorder (MDD) has been related to both a dysfunctional γ-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GABAA-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment.MethodsEleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls. The subjects were scanned using the positron emission tomography (PET) tracer [11C]flumazenil ([11C]FMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (VT) and binding potential (BPND) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed.ResultsIn MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced [11C]FMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus (p uncorrected ≤0.001). In the temporal area, [11C]FMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with [11C]FMZ binding in the right insula. Following treatment with citalopram, voxel-based analysis revealed reduced binding in the right lateral temporal gyrus and dorsolateral prefrontal cortex.ConclusionThe bilateral reduction in limbic parahippocampal and right temporal [11C]FMZ binding found in MDD indicates decreased GABAA-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABAA binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition.

Increased cerebrospinal fluid cortisol level in Alzheimer's disease is not related to depression

Hypothalamo-pituitary-adrenal (HPA)-axis hyperactivity is well established in a large proportion of both Alzheimers disease (AD) patients and idiopathic depression patients, resulting in, e.g. increased cerebrospinal fluid (CSF) cortisol levels. We hypothesized that HPA-axis activity in depressed AD patients is even more increased than in non-depressed AD patients, resulting in higher CSF cortisol levels. Cortisol levels were measured in post mortem CSF of depressed and non-depressed AD patients and in controls. Cortisol levels in AD patients were more than double those of controls, while no significant differences were found between depressed and non-depressed AD patients. These results suggest a different pathogenetic mechanism in depression in AD than in idiopathic depression.

Prison brain? Executive dysfunction in prisoners

A better understanding of the functioning of the brain, particularly executive functions, of the prison population could aid in reducing crime rates through the reduction of recidivism rates. Indeed, reoffending appears to be related to executive dysfunction and it is known that executive functions are crucial for self-regulation. In the current paper, studies to executive functions in regular adult prisoners compared to non-offender controls were reviewed. Seven studies were found. Specific executive functions were found to be impaired in the general prison population, i.e., attention and set-shifting, as well as in separate subgroups of violent (i.e., set-shifting and working memory) and non-violent offenders (i.e., inhibition, working memory and problem solving). We conclude that the limited number of studies is remarkable, considering the high impact of this population on society and elaborate on the implications of these specific impairments that were found. Further empirical research is suggested, measuring executive functioning within subjects over time for a group of detainees as well as a control group.

Free will and mental disorder: Exploring the relationship

A link between mental disorder and freedom is clearly present in the introduction of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). It mentions “an important loss of freedom” as one of the possible defining features of mental disorder. Meanwhile, it remains unclear how “an important loss of freedom” should be understood. In order to get a clearer view on the relationship between mental disorder and (a loss of) freedom, in this article, I will explore the link between mental disorder and free will. I examine two domains in which a connection between mental disorder and free will is present: the philosophy of free will and forensic psychiatry. As it turns out, philosophers of free will frequently refer to mental disorders as conditions that compromise free will and reduce moral responsibility. In addition, in forensic psychiatry, the rationale for the assessment of criminal responsibility is often explained by referring to the fact that mental disorders can compromise free will. Yet, in both domains, it remains unclear in what way free will is compromised by mental disorders. Based on the philosophical debate, I discuss three senses of free will and explore their relevance to mental disorders. I conclude that in order to further clarify the relationship between free will and mental disorder, the accounts of people who have actually experienced the impact of a mental disorder should be included in future research.

Depression, possibilities, and competence: A phenomenological perspective

Competent decision-making is required for informed consent. In this paper, I aim, from a phenomenological perspective, to identify the specific facets of competent decision-making that may form a challenge to depressed patients. On a phenomenological account, mood and emotions are crucial to the way in which human beings encounter the world. More precisely, mood is intimately related to the options and future possibilities we perceive in the world around us. I examine how possibilities should be understood in this context, and how, in depression, decision-making might be compromised. I suggest that, based on this analysis, a specific emphasis and alertness in assessments of competence in depressed patients is called for. In fact, close attention should be paid to the range of future possibilities depressed patients are able to perceive. In addition, providing environmental cues to these patients might be one way of enhancing their decision-making capacity. The practical suggestions arrived at are open to empirical research.

A neurolaw perspective on psychiatric assessments of criminal responsibility: Decision-making, mental disorder, and the brain

In some criminal law cases, the defendant is assessed by a forensic psychiatrist or psychologist within the context of an insanity defense. In this article I argue that specific neuroscientific research can be helpful in improving the quality of such a forensic psychiatric evaluation. This will be clarified in two ways. Firstly, we shall adopt the approach of understanding these forensic assessments as evaluations of the influence of a mental disorder on a defendants decision-making process. Secondly, I shall point to the fact that researchers in neuroscience have performed various studies over recent years on the influence of specific mental disorders on a patients decision-making. I argue that such research, especially if modified to decision-making in criminal scenarios, could be very helpful to forensic psychiatric assessments. This kind of research aims to provide insights not merely into the presence of a mental disorder, but also into the actual impact of mental disorders on the decisions defendants have made in regard to their actions.

Does the brain "initiate" freely willed processes? A philosophy of science critique of Libet-type experiments and their interpretation

In the extensive, recent debates on free will, the pioneering experiments by Benjamin Libet continue to play a significant role. It is often claimed that these experiments demonstrate the illusory nature of freely willed actions. In this article, we provide a detailed analysis and evaluation of Libet’s experiments from a philosophy of science perspective. Our analysis focuses on Libet’s central notion of the “initiation” of freely willed processes by the brain. We examine four interpretations of the notion of initiation: in terms of a cause, a necessary condition, a correlation, and a regular succession. We argue that none of these four interpretations can be supported by the design and results of Libet’s experiments. In addition, we analyze two recent Libet-type experiments. Our general conclusion is that neither Libet’s original experiments nor later Libet-type experiments can justify the claim that allegedly freely willed processes are in fact initiated by the brain.

A systematic review of the literature about competence and poor insight

Ruissen AM, Widdershoven GAM, Meynen G, Abma TA, van Balkom AJLM. A systematic review of the literature about competence and poor insight.

Why medication in involuntary treatment may be less effective: the placebo/nocebo effect

Involuntary medication is one of the coercive measures used in psychiatry. We argue that direct extrapolation of placebo and nocebo effects of psychiatric medication in the voluntary setting to the situation of coercive treatment is probably not justified. Both placebo and nocebo effects are based upon patient expectations about the medication, but, in general, patient expectations in settings of involuntary medication tend to be less positive than in voluntary settings. As a consequence, placebo effects are likely to be diminished in coercive treatment, while nocebo effects are probably increased. This may result in an overall decreased effectiveness of medication in coercive settings.