Reduced cooperativeness and reward-dependence in depression with above-normal plasma vasopressin concentration

The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of depression and correlating plasma AVP and cortisol concentrations. The data support the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression. The aim of the present study was to test whether above-normal plasma AVP concentration in depression is related to personality characteristics reflecting a specific social behaviour style. The data of 78 patients from a previously investigated sample were reanalysed. Fifty-eight patients were available after 2 years, 15 of whom with initially above-normal plasma AVP. The dimensions of the Temperament and Character Inventory (TCI) were scored, with particular focus on the dimensions of Cooperativeness (CO) and Reward-dependence (RD). Normative subjects and other depressed subjects were used as controls. After full remission, patients with initially above-normal AVP had low CO compared with normal and patient controls. During depression, these patients had both low CO and low RD compared with normal controls and low RD compared with patient controls. Low CO is a presumably premorbid trait and reduced RD a state-dependent characteristic in depression with above-normal plasma AVP. The low CO further supports the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression.     

The hypothalamus in episodic brain disorders

Episodic brain disorders (EBD) form an intriguing group of neurological diseases in which at least some of the symptoms occur in attacks. The hypothalamus integrates many brain functions, including endocrine and autonomic control, and governs various body rhythms. It seems a likely site in which the initiation of attacks of EBD can be modulated. Indeed, the hypothalamus has a crucial role in EBD such as narcolepsy and cluster headache. The same may be true for migraine and depression. Here we summarise the evidence supporting an important role for the hypothalamus in the initiation of disease episodes in various EBD. Study of the various pathophysiological concepts of EBD within the context of the hypothalamus may prove a fruitful example of cross-fertilisation between various research areas.     

Elevated alpha-amylase but not cortisol in generalized social anxiety disorder

Stress-system dysregulation is thought to increase the risk for anxiety disorders. Here we describe both hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS) activity in basal non-challenging conditions and after 0.5 mg dexamethasone in generalized social anxiety disorder (gSAD) patients. To ensure stress-free sampling we collected saliva and determined cortisol and alpha-amylase (sAA), the latter a relative new marker of autonomic activity.Forty-three untreated gSAD patients without comorbidity were compared with 43 age and gender matched controls in non-stressed conditions on sAA and cortisol after awakening, during the day (including late evening), and after a low dose (0.5 mg) of dexamethasone. Cortisol and sAA were analyzed with mixed models. Additional analyses were done with paired t-tests. Apart from the assessments in the morning, gSAD patients had significantly higher diurnal and post-dexamethasone 1600 h sAA levels. No differences between gSAD and controls in any cortisol measurements were found.In conclusion, in gSAD in basal, non-stimulated conditions and after dexamethasone, we found hyperactivity of the ANS, as measured with sAA, but not of the HPA-axis. This suggests a relative increased activity of the ANS as compared to the HPA-axis, in line with the observed hyperarousal in gSAD.     

Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene—involved in monoaminergic neurotransmission—as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD.     

Total ganglioside ablation at mouse motor nerve terminals alters neurotransmitter release level

Neuronal membrane gangliosides, forming a large family of sialylated glycosphingolipids, have been hypothesized to play important roles in synaptic transmission. We studied the ex vivo electrophysiological function of neuromuscular junctions of GM2/GD2‐synthase*GD3‐synthase compound null‐mutant mice after acute removal of GM3, the only remaining ganglioside in this mouse, by in vitro treatment with neuraminidase. We found 16% enhancement of the acetylcholine release per nerve impulse at low‐rate (0.3 Hz) nerve stimulation. Conversely, the treatment reduced the acetylcholine release evoked by high‐rate (40 Hz) nerve stimulation. Also, 25 ms paired‐pulse facilitation of endplate potentials was reduced by the neuraminidase‐treatment. These effects may indicate a modest modulatory influence of the negative electrical charges carried by the sialic acid molecules of gangliosides on the function of presynaptic Ca_v2.1 channels, affecting the magnitude and kinetics of the Ca²⁺ influx that induces neurotransmitter release from the motor nerve terminal. Our results show that gangliosides are to some extent involved in neurotransmission at the neuromuscular junction, but that their presence is not an absolute requirement in this process. Synapse 64:335–338, 2010. © 2009 Wiley‐Liss, Inc.     

Social and psychological characteristics of elderly visually handicapped patients with the Charles Bonnet Syndrome.

The Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically normal people. The syndrome occurs predominantly in the visually handicapped elderly. Little is known about its etiology and pathogenesis. The aim of this study was to examine the associations of CBS with psychological and social determinants. All subjects were patients older than 64 years from a low-vision unit. Using a case-control approach, 50 patients with CBS and 80 patients without visual hallucinations were interviewed about their educational level, social circumstances, number of social contacts, and ability to cope with visual handicap. Loneliness was measured with the De Jong-Gierveld-Kamphuis loneliness scale, and personality traits were examined with the Dutch-language short version of the Minnesota Multiphasic Personality Inventory ([MMPI] Nederlandse Verkorte MMPI [NVM]). Compared with the control group, significantly more CBS patients were lonely. Mean scores on the NVM shyness scale and extraversion scale were significantly higher and lower, respectively, in CBS patients. In multiple logistic regression analysis for the three determinants simultaneously, loneliness and low extraversion were significant predictors for CBS, but shyness was not. It is concluded that loneliness, low extraversion, and shyness are risk indicators for CBS in elderly visually handicapped people. The findings suggest that CBS is associated with a low quality of social contacts.     

Retardation in depression: assessment by means of simple motor tasks.

BACKGROUND: Psychomotor retardation in depression has mostly been assessed with tasks requiring both cognitive and motor processes. This study tested whether retardation could be measured if the cognitive demands of the task were minimal. METHODS: 30 inpatients with a major depressive episode were compared one week after the start of antidepressant treatment, to 30 healthy control persons, matched for age, sex and educational level. Tests consisted of ten simple drawing tasks. The kinematics of drawing movements were recorded using a specially designed pen, a graphics tablet and a personal computer. RESULTS: Patients showed marked motor slowing on all the tasks: longer movement durations, longer pauses and lower velocities. CONCLUSIONS: Psychomotor retardation in depressed patients treated with antidepressants occurs during drawing tasks, in which the cognitive demands are minimal and less than those required in the figure copying tasks used in our previous studies. LIMITATIONS: The use of co-medication can have influenced the results, although no correlations were found between the use of medication and the kinematic variables. CLINICAL RELEVANCE: Detailed registration and analysis of drawing movements enable a more precise diagnosis of psychomotor disturbances in depressed patients.