Neurodevelopment and mood stabilizers

Mood disorders and schizophrenia share a number of common properties, including: genetic susceptibility; differences in brain structure and drug based therapy. Some genetic loci may even confer susceptibility for bipolar mood disorder and schizophrenia, and some atypical antipsychotic drugs are used as mood stabilizers. As schizophrenia is associated with aberrant neurodevelopment, could this also be true for mood disorders? Such changes could arise pre- or post-natal, however the recent interest in neurogenesis in the adult brain has suggested involvement of these later processes in the origins of mood disorders. Interestingly, the common mood stabilizing drugs, lithium, valproic acid (VPA) and carbamazepine, are teratogens, affecting a number of aspects of animal development. Recent work has shown that lithium and VPA interfere with normal cell development, and all three drugs affect neuronal morphology. The molecular basis for mood stabilizer action in the treatment of mood is unknown, however these studies have suggested both targets and potential mechanisms. Lithium directly inhibits two evolutionarily conserved signal transduction pathways: the protein kinase Glycogen Synthase Kinase-3 (GSK-3) and inositol signaling. VPA can up-regulate gene expression through inhibition of histone deacetylase (HDAC) and indirectly reduce GSK-3 activity. VPA effects are not conserved between cell types, and carbamazepine has no effect on the GSK-3 pathway. All three mood stabilizers suppress inositol signaling, results further supported by studies on the enzyme prolyl oligopeptidase (PO) and the sodium myo-inositol transporter (SMIT). Despite these intriguing observations, it remains unclear whether GSK-3, inositol signaling or both underlie the origins of bipolar disorder.     

Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder

Bipolar disorder is a psychiatric condition characterized by episodes of elevated mood interspersed with episodes of depression. While treatment developments and understanding the disruptive nature of this illness have focused on these episodes, it is also evident that some patients may have chronic week-to-week mood instability. This is also a major morbidity. The longitudinal pattern of this mood instability is poorly understood as it has, until recently, been difficult to quantify. We propose that understanding this mood variability is critical for the development of cognitive neuroscience-based treatments. In this study, we develop a time-series approach to capture mood variability in two groups of patients with bipolar disorder who appear on the basis of clinical judgement to show relatively stable or unstable illness courses. Using weekly mood scores based on a self-rated scale (quick inventory of depressive symptomatology-self-rated; QIDS-SR) from 23 patients over a 220-week period, we show that the observed mood variability is nonlinear and that the stable and unstable patient groups are described by different nonlinear time-series processes. We emphasize the necessity in combining both appropriate measures of the underlying deterministic processes (the QIDS-SR score) and noise (uncharacterized temporal variation) in understanding dynamical patterns of mood variability associated with bipolar disorder.     

Tricyclics modulate frequency of mood cycles

In 5 female manic-depressive patients studied longitudinally, mood cycle frequency was markedly accelerated from 1 cycle/2-8 months to 1 cycle/1-6 weeks by tricyclic antidepressant drugs. In a sixth patient a similar effect was observed with a monoamine oxidase inhibitor (another major type of antidepressant medication). Affective disorders are inherently cyclic. In the group of patients reported here the action of 'antidepressant' drugs can be more broadly conceived as accelerating the entire cyclic illness process rather than counter-acting only one of its phases. The effect of these drugs on the spontaneous frequencies of other rhythmic biological processes should be explored.     

Hypericum perforatum: nature's mood stabilizer

Hypericum perforatum (HP), better known as St. John's Wort, has been used clinically for centuries. Modern usage is still quite diverse and includes kidney and lung ailments, insomnia and depression. Standardised extracts of HP are widely used in the treatment of psychovegetative disorders and especially for mild forms of depression. Several bioactive constituents of this plant may play important role in its well-known antidepressant activity, which are discussed in the present article. Furthermore, emphasis is also given on its botany, chemistry, pharmacology and clinical efficacy.     

Premenstrual mood changes in affective disorders.

Mood changes during the premenstrual phase have been the focus of considerable research in recent years. Although there has been significant progress in the diagnosis and etiology of major affective disorders, the relation between these disorders and menstrual changes remains controversial. There have been contradictory reports and speculations on women''s susceptibility to psychiatric disorders during the premenstrual phase. We describe three patients with a history of mood swings associated with menstruation in whom major affective disorders developed, necessitating intensive psychiatric treatment or admission to hospital. Among women who manifest menstrual mood changes, manic-depressive illness may develop only in a subgroup with genetic predisposition. In such cases the possibility of postpartum mania or depression should be kept in mind in follow-up.     

Determinants of mood in general practitioners.

A pilot study was conducted in which 44 general practitioners completed cognitive behavioural self monitoring diaries. Hourly changes in emotional state were recorded together with associated circumstances. Lowering of mood was associated mainly with "hassle" at work, pressure of time, and domestic dissatisfaction. Improvement in mood was associated with domestic happiness and satisfaction at working efficiently and to time. Mood was significantly lower when the doctor was on call. Women doctors were more prone to mood changes associated with domestic matters. Responses to a questionnaire suggested that the doctors preferred traditional clinical medicine to problems of a social or psychological origin. Managerial skills would help alleviate several of the problems identified in this study and should be more prominent in the training that all doctors receive.     

Serotonin, inhibition, and negative mood

Pavlovian predictions of future aversive outcomes lead to behavioral inhibition, suppression, and withdrawal. There is considerable evidence for the involvement of serotonin in both the learning of these predictions and the inhibitory consequences that ensue, although less for a causal relationship between the two. In the context of a highly simplified model of chains of affectively charged thoughts, we interpret the combined effects of serotonin in terms of pruning a tree of possible decisions, (i.e., eliminating those choices that have low or negative expected outcomes). We show how a drop in behavioral inhibition, putatively resulting from an experimentally or psychiatrically influenced drop in serotonin, could result in unexpectedly large negative prediction errors and a significant aversive shift in reinforcement statistics. We suggest an interpretation of this finding that helps dissolve the apparent contradiction between the fact that inhibition of serotonin reuptake is the first-line treatment of depression, although serotonin itself is most strongly linked with aversive rather than appetitive outcomes and predictions.     

Pharmacological effects of berberine on mood disorders

Berberine, a natural isoquinoline alkaloid, is used in herbal medicine and has recently been shown to have efficacy in the treatment of mood disorders. Furthermore, berberine modulates neurotransmitters and their receptor systems within the central nervous system. However, the detailed mechanisms of its action remain unclear. This review summarizes the pharmacological effects of berberine on mood disorders. Therefore, it may be helpful for potential application in the treatment of mood disorders.     

Effects of nutritional lithium supplementation on mood

A total of 24 subjects, 16 males and 8 females, average age 29.4±6.5 y, were randomly divided into two groups. Group A received 400 μg/d of lithium orally, in tablets composed of a naturally lithium-rich brewer's yeast, for 4 wk. Group B was given normal, lithium-free brewer's yeast as a placebo. All the subjects of the study were former drug users (mostly heroin and crystal methamphetamine). Some of the subjects were violent offenders or had a history of domestic violence. The subjects completed weekly self-administered mood test questionnaires, which contained 29 items covering parameters measuring mental and physical activity, ability to think and work, mood, and emotionality. In the lithium group, the total mood test scores increased steadily and significantly during the period of supplementation. The 29 items were furthermore placed into three subcategories reflecting happiness, friendliness, and energy, as well as their negative counterparts. In Group A, the scores increased consistently for all subcategories until wk 4 and remained essentially the same in wk 5. In Group B, the combined mood test scores showed no consistent changes during the same period. The only positive change in some members of Group B occurred during wk 1 and was attributed to a placebo effect. In Group B, the placebo effect was noticeable for the subcategories of energy and friendliness; the happiness scores declined during the entire period of observation. Based on these results and the analysis of voluntary written comments of study participants, it is concluded that lithium at the dosages chosen had a mood-improving and stabilizing effect.     

An evolutionary model of low mood states

It has been suggested that low mood in humans is an adaptive response to unfavourable circumstances, and that the anhedonia, pessimism and fatigue that often accompany it function to minimise risk until circumstances improve. While this is plausible, it would be possible to make the opposite prediction equally plausibly: individuals in bad circumstances should take greater risks in order to improve their situations. Here, I present a simple analytical model adapted from the risk-sensitive foraging literature. It shows that in dire states, individuals should be risk-prone, in poor states, risk-averse, and in good states, risk-prone again. I discuss how the various kinds of mood state observed in humans might be understood as mechanisms for adaptively adjusting behavioural risk-taking to the current situation.     

Disturbances of affective cognition in mood disorders

正Mood disorders, also known as affective disorders, result in a consistent disturbance in mood. There are two major subtypes of mood disorders, i.e., major depressive disorder(MDD) and bipolar disorder (BD). Mood disorders affect hundreds of millions of people and are the most common mental disorders. According to China’s national survey in2009 (Phillips et al., 2009), the weighted 12-month prevalence of mental disorders was 17.5%and 9.3%, respectively. Mood disorders were among the highest prevalence rate disorders related to disease’s increased burdens.     

Time perception,emotions and mood disorders

In this review, we describe recent internal clock models accounting for time perception and look at how they try to explain the time distortions produced by emotion. We then discuss the results of studies of patients suffering from affective disorders (depression) who experience the feeling of time slowing down. A distinction is thus made between time perception and explicit awareness of the passage of time. We conclude that the feeling that time is passing slowly is not systematically associated with a disruption in the basic mechanisms underlying time perception.     

The evolutionary origins of mood and its disorders

The term 'mood' in its scientific usage refers to relatively enduring affective states that arise when negative or positive experience in one context or time period alters the individual's threshold for responding to potentially negative or positive events in subsequent contexts or time periods. The capacity for mood appears to be phylogenetically widespread and the mechanisms underlying it are highly conserved in diverse animals, suggesting it has an important adaptive function. In this review, we discuss how moods can be classified across species, and what the selective advantages of the capacity for mood are. Core moods can be localised within a two-dimensional continuous space, where one axis represents sensitivity to punishment or threat, and the other, sensitivity to reward. Depressed mood and anxious mood represent two different quadrants of this space. The adaptive function of mood is to integrate information about the recent state of the environment and current physical condition of the organism to fine-tune its decisions about the allocation of behavioural effort. Many empirical observations from both humans and non-human animals are consistent with this model. We discuss the implications of this adaptive approach to mood systems for mood disorders in humans.