Neuroses - characteristics and classification

Neurosis is a functional disorder of the central nervous system (CNS) generally characterized by excessive anxiety without evidence of neurologic disease, sometimes accompanied by defensive or immature behaviours. It is a general term describing a group of widespread mental illnesses also known as neurotic disorders, and thus, those suffering from them are said to be neurotics. It is also an emotional disorder that affects a part of the personality. Neuroses include a large variety of psychiatric disorders exhibiting a range of symptoms such as phobias, anxiety, tics and others. These disorders are quite a heterogeneous entity that is difficult to delimit. The myriad of factors that have been implicated makes the outline of a single psychopathological theory of neurosis difficult, and this has convinced some modern authors to remove the term. Although the American Diagnostic and Statistic Manual of Mental Disorders (DSM) has eliminated the category of neurosis, many authors still refer to them. Sometimes it is named anxiety neurosis or anxiety and phobic disorders. Anxiety, one of the most common symptoms of neurosis, is a physical symptom that frequently includes palpitations, nausea, chest pain, sweating, and trembling, amongst others.

Some authors consider that the main characteristics of neuroses are the existence of psychic, somatic and behavioural troubles without anatomical and psychological changes, with the patient being aware of the pathology of their symptoms but unable to control them (although social adaptation is satisfactory except in serious forms of the disorder). There is also an obvious but variable response to therapy (medicines, psychotherapy, relaxing techniques, hypnosis). Historically, the definition and classification of neuroses were frequently restructured according to different explicative theories. Therefore, the neuroses-related terminology is very variable. Essentially, neurotic symptoms are considered as a symbolic expression of an internal drama that the subject is unable to control because its essential elements drop out of their consciousness. Some authors include the social phobias, agoraphobias, hypochondria, panic disorder and even hysteria in neuroses. Generally, neurosis means poor ability to adapt to ones environment, an inability to change one’s life pattern, and the inability to develop a richer, more complex, more satisfying personality (Boeree, 2002). Some professionals use the term to describe anxious symptoms and associated behaviour, or to describe the range of mental illnesses outside of the psychiatric disorders. Others use the term neurosis to describe the internal process itself that triggers the anxiety characteristics.

The International Classification of Diseases (ICD)

10 (World Health Organisation, 1992) grouped the neurotic disorders together with stress and somatophorm disturbances because of their historical association with the term neurosis, and because of their association with psychological causes. The concept of neurosis was not the major organizing principle. The combination of symptoms is common (most frequent being the associated depression-anxiety), especially in the less serious variants of these disturbances that are met in the first instance. ICD-10 introduces this type of disorder in the chapter “Neurotic, stress-related and somatoform disorders”:

a.

phobic anxiety disorders: agoraphobia with panic attacks, agoraphobia without panic attacks, social phobia, specific phobia, other phobic anxiety disorders (specified and unspecified)

b.

other anxiety disorders: panic disorder, generalized anxiety disorder, mixed anxiety and depressive disorder, other anxiety disorders (specified and unspecified)

c.

obsessive-compulsive disorders

d.

reactions to severe stress, and adjustment disorders

e.

dissociative disorders

f.

somatoform disorders

g.

other neurotic disorders.

Excessive anxiety and fear are common symptoms of neurotic disorders. According to Boeree (2002), the signs and symptoms of neurosis refer to a variety of psychological problems involving persistent experience of negative affects including anxiety, sadness and depression, anger, irritability, mental confusion, low sense of self-worth, behavioural symptoms such as phobic avoidance, vigilance, impulsive and compulsive acts, lethargy, cognitive problems such as unpleasant and disturbing thoughts, repetition of thoughts and obsessions, habitual fantasizing, negativity and cynicism. Neurosis or neurotic disorder can vegetatively affect the person’s ability to function, thus affecting the activities of daily living. Some factors (education, culture) may serve to override any predisposing physiological conditions, or to exacerbate them. An essential point concerns the triggering stressors in a person’s life, which lead to the various emotional, behavioural, and cognitive symptoms of neurosis.

Relationship between magnesium and neuroses

There are studies that show the involvement of magnesium in the pathogeny of most symptoms that can appear in neuroses. The magnesium level in the brain is more stable and decreases more slowly than in other tissues, but small decreases have important influences on neuronalfunctioning. Taking into account the existence of some symptoms, both in magnesium deficiency and in neurosis (latent tetany, hyperventilation syndrome, anxiety, hyper emotionality, fatigue and sometimes migraine, dizziness, nervous fits such as panic attack, particularly, the sensation of a “lump in the throat”), one can speculate that a relationship between magnesium deficiency and neurosis exists.

The most frequent and characteristic form of magnesium deficit disorders in the central nervous system is nervous hyperexcitability (Durlach, 1998; Durlach et al., 1997), and hence nervous forms of magnesium deficiency represent the most commonly seen form in clinical practice whatever the age. Nervous hyperexcitability is, at the same time, one of the most frequent features of neuroses. Oral administration of magnesium leads to the correction of the symptomatology and the normalization of the electropolygraphic modifications, ECG and other static and dynamic parameters.

Panic is an essential symptom of neuroses. A few studies have determined the plasma concentration of magnesium and other bivalent cations of panic disorder patients. Nahar et al., (2010) did not find significant differences in the magnesium plasma concentration in panic disorder patients versus the control group, but the intracellular concentrations were not determined. ATPase activity was studied in the erythrocytes of the patients with phobic neurosis. Sechenov (1975) found an increased activity of the Mg²⁺ATPase in these patients but a decreased activity of the Na⁺/K⁺ATPase as compared with the control group. The significance of these changes is not clear.

In anxiety neurosis, there was not only a decrease in magnesium concentration, but also modified quantitative proportions between magnesium and other blood plasma or cytoplasmic components. It was shown that the blood fatty acids/magnesium ratio was increased and the magnesium level was decreased in anxiety neurotic patients (Iakushev et al., 1989).

Regarding the mechanism by which magnesium reduces panic and anxiety, we consider that the main elements are decreased glutamate action and increased action of the GABAergic systems. Magnesium reduces anxiety by a number of mechanisms (Figure 1). These include reducing actions at the level of the calcium channelcoupled with NMDA receptors, reducing the presynaptic cerebral release of epinephrine and nor-epinephrine, increasing GABA concentration in some brain areas, and acting as a modulator of glutamate release at the presynaptic level.

Figure 1.

Magnesium mechanisms of action in anxiety and panic. -, inhibition; +, stimulation (increase).

Glutamate is the most important excitatory neurotransmitter in mammalian brain. It acts at three major receptor types including the NMDA ionotropic receptor coupled to a Ca²⁺ channel, the AMPA (alpha-amino-3 hydroxy-5 methyl-4- isoxazole propionic acid) receptor, and the metabotropic glutamate receptor (mGluR) group (at least 8 subtypes). Glutamate metabotropic receptors are divided into three groups, group I including mGluR1 and mGluR5 subtypes, group II including mGluR2 and mGluR3 subtypes, and group III including mGluR4, mGluR6, mGluR7 and mGluR8 subtypes.

The most important postsynaptic receptor population for glutamate is the NMDA receptors. Dorsomedial hippocampal neurons express both NMDA and AMPA receptors for glutamate (Bailey et al., 2003; Goren et al., 2003). Magnesium doesn’t have a noticeable influence upon AMPA receptors and the existing data implicate the NMDA hypothalamic receptors in producing anxiety and panic disorders. Magnesium does reduce the effect of NMDA receptor stimulation and this is the main mechanism of its anxiolytic effect (Coan and Collingridge, 1985). Chronic stress involved in the pathogeny of some neuroses increases the hypothalamic NMDA receptor expression (Lee et al., 2003).

The mGluRs are a family of G-protein coupled receptors that have a widespread expression in the CNS (Niswender and Conn, 2010). They have a modulator role in synaptic transmission and in normal excitability in the brain, playing a key role in the modulation of glutamatergic activity, glutamate secretion and presynaptic release, GABAergic system activity and in regulation of neuroendocrine activity. The normal and pathological implications of the activation of these receptors are very different. Glutamate action on these brain receptors is important in normal and in pathologic situations such as fear, anxiety, addiction, panic, withdrawal syndrome, and posttraumatic stress disorders. Notably, divalent cations modulate the activity of mGluRs (Francesconi and Duvoisin, 2004). A mounting and important role in not only in anxiety, but also in other CNS disorders, is attributed to malfunction of the mGluRs. Regarding the symptoms in neurosis (anxiety, fear, cognitive impairment, working memory), the mGluR2 and the mGluR7 are the most important types of mGluRs and they are highly expressed in hippocampus (Desai, 1992). The mGluR7, in particular, has a wide distribution in the brain, and is preferentially localized to presynaptic axon terminals in the amygdala and hippocampus (Masugi et al., 1999). This receptor has a low affinity for glutamate, and Niswender and Conn (2010) consider that it only activates in the case of overstimulation by glutamate, and reduces glutamatergic activity. Selective stimulation of mGluR7 induced anxiolytic-like effects in mice by enhancement of GABAergic neurotransmission, and by reduction of glutamate synthesis and action (Stachowicz et al., 2008). The lack of mGluR7 caused a deficit in fear response and conditioned taste aversion (Masugi et al., 1999). Magnesium is important for mGluR7 receptor activity and may explain the enhancement of anxiety in hypomagnesemia (Niswender and Conn, 2010).

The agonists of some mGluRs are promising drugs in the future treatment of some psychiatric disorders. The agonists and positive allosteric modulators of group I mGluRs might treat anxiety disorders (Krystal et al., 2010). The mGluR group II agonists block fear learning when they are administrated into the amygdala prior to training (Walker and Davis, 2002). Mares et al., (2010) showed in immature rats that some mGluRs are involved in production of anxiolysis. Magnesium is also a positive allosteric modulator for some mGluRs.

The ratio between glutamate-induced excitatory activity and GABAergic inhibition in some brain areas (such as the amygdala, dorsomedial hypothalamus and cortex) plays an essential role in behaviour and imbalances are involved in the pathogenic mechanism of anxiety, panic disorder and phobia. Experimental chronic inhibition of GABA synthesis and enhancement of glutamatergic activity in the dorsomedial hypothalamus induced panic-like responses in rats (Johnson and Shekhar, 2006). Glutamate NMDA receptors are the most important receptor group involved in experimental lactate-inducedpanic-like responses in rats, but other receptors for glutamate are also involved.

Carbamazepine, an antiepileptic drug, is also used for the treatment of many nonepileptic disorders, including anxiety. The anxiolytic effects of carbamazepine seem to be mediated, at least in part, by interactions with the GABAergic system because muscimol (a GABA_A receptor agonist) enhanced the carbamazepine anxiolytic effect. The anxiogenic effect of NMDA administration was also reversed by carbamazepine (Rezvanfard et al., 2009). In our studies (Nechifor et al., 2005; 2007), carbamazepine administration in therapeutic doses in human subjects increased the intracellular magnesium level. We believe that the anxiolytic effect of carbamazepine is due, at least in part, to the increased intracellular magnesium concentration.

GABA antagonizes glutamate hyperexcitation in some brain regions such as the dorsomedial hypothalamus and protects against anxiety and panic disorders (Millan, 2003). Favouring the idea that the GABAergic system plays an important role in preventing and reducing panic and anxiety, a low GABA concentration in brain has been associated with anxiety behaviours in rats and mice. In rats, chronic administration of 1- allylglicine (a GABA synthesis inhibitor) in the dorsomedial hypothalamus induced panic disorder and enhanced panic-like behaviour produced by sodium lactate infusion (Schekhar et al., 1996; 2003). A reduction of GABAergic system activity has also been shown in non-medicated panic disorder patients. The subjects without major depression had a 22% reduction of the total occipital cortex GABA concentration compared with the normal control group (Goddard et al., 2001). Crestani et al., (1999) and Goddard et al., (2001) also showed that impaired brain GABA and benzodiazepine receptor activity is involved in phobic behaviours in mice. Glutamatergic system hyperactivity is also involved in other symptoms of neurosis, for example the dysregulation of the fear memory, the extinction of the fear memory and post-stress neuroses. An NMDA receptor agonist, D- cycloserine (5 mg/kg), blocked fear extinction in rats (Yang et al., 2007).

The catecholamines are also involved in fear and panic disorders. The injection of an α1-blocker in the dorsomedial hypothalamus blocks panic-like responses of animals (Johnson and Shekhar, 2006). The systemic administration of yohimbine induced panic-like responses, by blocking presynaptic α2-receptors and increasing epi- nephrine and norepinephrine release (Lowry et al., 2003). Yohimbine administration in healthy subjects increases the plasma level of norepinephrine, increases adrenergic activity, and results in increased anxiety and nervousness in the patients. Charney et al., (1984) found a significant positive correlation between the plasma level of the norepinephrine metabolite, 3- methoxy-4-hydroxyphenylglicol (MHPG), and patient anxiety and panic attacks. Notably, magnesium reduces epinephrine and nor- epinephrine synthesis and release, decreases anxiety and could prevent the panic attacks.

Magnesium deficiency, even when mild, increases susceptibility to various types of neurologic and psychological stressors in healthy human subjects and diverse groups of patients. Repletion of deficiency reverses this increased stress sensitivity, and pharmacologic loading of magnesium salts induces resistance to neuropsychological stressors. Mild magnesium deficiency appears to be common among patients with disorders considered functional or neurotic and appears to contribute to a symptom complex that includes asthenia, sleep disorders, irritability, hyperarousal, spasm of striated and smooth muscle, and hyperventilation (Galland, 1991-1992). Stress, being a frequent cause of neurosis, influences magnesium concentration in the organism. Adrenergic stress induces a shift of magnesium from the intracellular to the extracellular space and increases urinary magnesium loss. In contrast, magnesium deficiency increases the vulnerability of human body to stress and the damage induced by stress (Galland, 1991). Magnesium deficiency also increases neuronal excitability, not only by increasing the excitatory effect of glutamate mediated by NMDA receptors, but possibly by increasing the calcium current in pre- and post- synaptic membranes and by alteration of the Na⁺/K⁺ ATPases (Morris, 1992).

Glutamate induces a powerful stimulation of norepinephrine release in the amygdala and in hippocampal slices (Fink et al., 1992). Mg²⁺ ions and MK-801 (dizocilpine, an NMDA receptorantagonist) reduced the NMDA-evoked overflow of norepinephrine. Norepinephrine release related to the stimulation of AMPA receptors by glutamate does not seem to be influenced by Mg²⁺. Since the activation of mGluR4 and mGluR7 induces a decrease in glutamate release from presynaptic areas (Schrader and Tasker, 1997), it is possible that presynaptic mGluRs can thereby influence norepinephrine release.

Another important problem is the frequency of sleep disturbances in patients with neurosis. There are data that support the possible involvement of magnesium in sleep regulation. In rats, magnesium deficiency is associated with a decrease in sleep time. Magnesium content in four brain areas was also highly and positively correlated with the length of sleep periods (Chollet et al., 2000). Erythrocyte magnesium concentrations are low in adult human subjects with chronic sleep deprivation (1.1 ± 0.4 mg/dl) versus a control group (1.8 ± 0.4 mg/dl) (Tanabe et al., 1997). The reduction of sleep time is frequently associated with chronic fatigue. Chronic sleep deprivation is associated with an increase of plasma catecholamine release and with a decrease of intracellular magnesium level. These changes occur relatively quickly. In healthy male students (20-24 years aged), 4 weeks of partial sleep deprivation was sufficient for the appearance of these changes in the intracellular concentration of magnesium, and in the plasma epinephrine and norepinephrine concentrations. The students with chronic sleep deprivation over the 4-week period (sleep was < 80% compared to ordinary days) had significantly decreased intracellular magnesium levels (Takase et al., 2004a; 2004b).

Experimental magnesium restricted diets in rats also increases the cerebral dopamine and norepinephrine concentration. This rise is associated with a decrease of sleep time and an increase in electroencephalographic wakefulness (Poenaru et al., 1984). Magnesium deficiency is accompanied by a decrease of sleep duration and by an increase of brain dopamine level (Chollet et al., 2000). These data strongly support the reduction of cerebral catecholamine release by magnesium. The effect of MgSO₄ (0.5 mg MgSO₄/h between 20.30 hours till 7.00 hours) on sleep electroencephalogram (EEG, recorded between 23.00 and 7.00 hours) in healthy adult men showed an increase of the third sleep cycle with unchanged delta power throughout the night (Murch and Steiger, 1998). The activation of GABA receptors is very important for the initiation and maintenance of nor-rapid-eye movement (NREM) sleep. Magnesium stimulates the activity of cerebral GABAergic systems by behaving as a modulator of GABA receptors, increasing their activity.

Magnesium has a favourable effect with respect to sleep onset and maintenance and also tiredness, which appears as a consequence of sleep deprivation. In their studies of chronic sleep deprivation, Tanabe et al., (1998) reported a reduction of intracellular magnesium level. This reduction was associated with a decreased exercise tolerance. Specifically, when subjects were submitted to a bicycle ergometer cardiopulmonary exercise test, the sleep- deprived subjects had a decreased exercise tolerance. The administration of 100 mg magnesium orally per day for 1 month improved the exercise tolerance. There was no difference between the sleep-deprived patients and the normal sleep patients regarding the peak oxygen uptake and anaerobic threshold. The mechanism through which chronic sleep deprivation can reduce intracellular magnesium concentration is unknown, but we consider that the excess catecholamines that appear in sleep deprivation could accelerate magnesium disposal. Hornyak et al., (1998) showed that magnesium therapy can be useful in periodic leg movements related to insomnia. Magnesium was administered orally, 12.4 mmol in the evening during 4-6 weeks. After magnesium administration, periodic limb movements during sleep decreased significantly and the total sleep duration increased.

Attention deficit and hyperactivity disorders (ADHD) are only found in school children and in many patients with neurosis. In these patients, the plasma and erythrocyte magnesium level is low. In an animal experimental model of attention deficit, the hippocampal glutamate- stimulated release of norepinephrine was significantly higher. The stimulatory effect of glutamate on norepinephrine release was reduced by 1µM CNQX (an AMPA receptor antagonist) suggesting that in this case the AMPA receptor stimulation by glutamate plays an important role. The NMDA receptor antagonist MK-801 (10µM) did not reduce the glutamate- stimulated release of norepinephrine (Howells and Russell, 2008). An involvement of dopamine in attention deficit disorder from the neurotic patient is also possible, because in patients with ADHD there is dysfunction of the dopaminergic system. In an experimental rat model for ADHD, glutamate-stimulated dopamine release in the substantia nigra is higher. Warton et al., (2009) consider that abnormal dopaminergic system function in ADHD could be the result of a change in dopamine central neurons (dopamine synthesis, dopamine transporters or dopamine receptors), or an indirect effect of imbalanced glutamate regulation of dopaminergic neurons. We think that a similar process also occurs in the case of attention deficit in the neurotic patients. Magnesium can directly reduce dopamine release at the presynaptic level and can also reduce the stimulatory effect of glutamate on dopamine release. Treatment with Mag-B6 was useful in attention deficit syndrome and in hyperactivity treatment (Nogovitsina and Levitina, 2006; 2007). Mag-B6 improved behaviour, decreased the level of anxiety and aggression, increased attention and corrected the magnesium homeostasis in children with ADHD.

Both bulimia and anorexia are also symptoms found in patients with neurosis. In patients with anorexia nervosa (DSM-IV criteria), a decreased magnesium level was found compared to the control group. About 60% of the patients had low serum magnesium (Birmingham et al., 2004).

In neurotic and stressed patients, sexual dysfunction (reduced libido and sexual potency) is frequently present. This dysfunction is largely caused by increased prolactin (PRL) synthesis. It was experimentally shown that immobilization and other forms of stress (also implicated in the pathogeny of some cases of neuroses) increased PRL secretion. Pretreatment of the animals with magnesium aspartate in doses of 100 mg, 200 mg and 400 mg significantly decreased the stress- induced PRL secretion in a dose-dependent manner (Ali et al., 1987). D-aspartate increased PRL secretion by stimulation of NMDA receptors. In the fish S. Mossambicus, magnesium also lowered PRL secretion (Bonga et al., 1983).

There are a number of mechanisms by which magnesium may reduce PRL levels in neurosis, thereby lowering or preventing the effects of this anterior pituitary hormone. It can directly reduce secretion of PRL at the level of secretory cells, it can inhibit stimulation by prolactin releasing hormone at the pituitary level to decrease PRL secretion (Kasahara et al., 1993), it can reduce the stimulatory effect of glutamate on pituitary PRL release, and finally, magnesium can reduce the stimulatory effect of calcium ions on PRL secretion. In cultures of adult female rats, pituitary cell glutamate significantly increased the rate of PRL release. This release was augmented 4-fold after elimination of magnesium from the perfusate (Login, 1990). Both NMDA (100 µM) and kainate (100 µM) increased PRL secretion by NMDA receptor stimulation, whereas AMPA receptor agonists did not modify PRL secretion and release. The antagonism between magnesium and the calcium channels coupled to the NMDA receptors is the essential factor in reduction of PRL secretion by this bivalent cation.

Magnesium treatment of neuroses

There are a limited number of studies that show a beneficial effect of magnesium in treatment of the different symptoms of the diseases known as neurotic disorders. Using mice, Poleszak et al., (2004) demonstrated that doses of 20 and 30 mg magnesium/kg (doses which did not affect locomotor activity) produced anxiolytic-like effects measured using the plus-maze test. These doses were acutely or chronically administered and resulted in at least a 58% increase in serum magnesium concentration. Magnesium induced the anxiolytic-like effects without tolerance to these activities, suggesting a potential anxiolytic activity in these disorders in human.

Singewald et al., (2004) showed in an animal experiment (mice) that magnesium depletion leads to enhanced depression- and anxiety- related behaviour, which was further validated by the reversibility of the behavioural changes by known antidepressant and anxiolytic substances. Using a rat model, Fromm et al., (2004) demonstrated a reduced incidence of anxiety after traumatic brain injury using magnesium sulphate as an interventional treatment. The study of Bockova et al., (1992) demonstrated that the combination of an anxiolytic with a magnesium salt (lactate) resulted in a more rapid reduction of the symptoms of anxious depressive neurosis.

Taborska (1995) showed the curative effect of magnesium salts in patients suffering panic disorders and latent tetany. The symptoms of panic disorder are, with few exceptions, virtually identical with those of latent tetany. The author examined 20 patients treated in a psychiatric outpatient unit for panic disorder, examining for latent tetany plus serum and red blood cell magnesium. He found a concomitant incidence of latent tetany with a decreased level of intracellular magnesium. Remission of problems common to both nosological entities occurred in 90% of cases, in response to therapy with magnesium salts.

A double-blind, randomized, placebo-controlled study evaluated the efficacy and safety of a fixed combination containing two plant extracts and magnesium in the treatment of 264 patients presenting generalized anxiety of mild-to- moderate intensity. It was demonstrated that the preparation was safe and more effective than placebo (Hanus et al., 2004).

The studies of Durlach et al., (1997) concluded that the primary or secondary, acute or chronic nervous forms of magnesium deficiency induced by insufficient magnesium intake remain reversible over a long period by simply normalizing the magnesium intake. Untreated chronic forms may however bring irreversible organic disorders.

Physiological oral magnesium supplementation (5mg/kg/day) is simple and can be carried out via the diet or with magnesium salts. This treatment is able to cure all the functional symptoms of magnesium deficiency, including signs of neuromuscular hyperexcitability and psychiatric symptoms, which frequently mimic a neurotic pattern. It is necessary to highlight the curative and preventive importance of oral physiological maternal magnesium supplementation, not only during pregnancy, but also in the child throughout life from infancy to older age, to possibly prevent the so-called constitutional factor of neurolability.

We should emphasize that the nervous consequences of magnesium deficiency remain functional with an atomical integrity for a long time. They are, however, completely reversible since they can be restored to normal with simple oral physiological magnesium supplementation (Durlach et al., 1987; 1997).

Relationship between magnesium and neuroticism

As has already been shown, magnesium deficiency manifests at the central nervous system level as hyperemotivity, hyperexcitability, anxiety, and impulsivity, amongst others, and these are also observed in neuroticism. A relationship between magnesium deficiency and neuroticism is therefore suggested. Some studies (Tuchendria et al., 1998) suggest that magnesium deficiency can be a causal factor of neurotic tendencies in elderly persons. In a group of 80 aged persons, all cases with erythrocyte magnesium deficit presented two or more neurotic tendencies, most frequent being the depressive ones.

There are also a few studies on magnesium deficiency in children and its relationship with personality traits. Specifically, this relationship in children and teenagers was examined in two groups of pupils from different socioeconomic backgrounds, namely an orphanage (group I) and a regular state school (group II) (Papadopol at al, 2001). Magnesium level and personality features were compared, including psychoticism, neuro- ticism and extraversion. With regard to the magnesium level (Table 1), one can see a discord between serum magnesium levels and erythrocyte levels. It is known that serum values of magnesium are less stable than erythrocyte values, being quite easily influenced by factors such as stress or physical activity that increases magnesium requirements. Serum magnesium may be normal in spite of a significant magnesium deficiency. The children from the orphanage had a more uniform lifestyle, with a more regular program of eating, sleeping and physical activities. Nutrition is also very important for the tissue magnesium levels. The nutrition of the children from the orphanage is characterized by a satisfactory, uniform level for all the children, while the nutrition of the children who live with their families is very variable but generally better because of socioeconomic differences.

Table 1.

Mean magnesium values (mmol/L) in children from an orphanage (Group I) and a state school (Group II). Adapted from Papadopol et al., 2001.

The distribution of the subjects with respect to personality features in the two groups differed significantly in terms of psychoticism and neuroticism (Table 2). The more numerous pathological tendencies of group I were probably a consequence of the unfavourable emotional climate from the institutionalized milieu. An investigation of the relationship between magnesium levels and personality features pointed out only one significant difference between the two groups, namely neuroticism (Table 3). The positive correlation in magnesium deficit-neuroticism suggests that magnesium deficit may be a causal factor in this negative aspect of personality.

Table 2.

Comparison of outcomes of personality traits. Adapted from Papadopol et al., 2001.

Table 3.

Relationship between magnesium deficit and neuroticism in children from an orphanage (Group I) and a state school (Group II). Adapted from Papadopol et al., 2001.

In a study by Nizankovska-Blaz et al., (1993) on 249 girls and boys aged 5-15 years, serum magnesium level was decreased in 24 children and neurotic reactions or concentration disturbances were observed in 21 of them.

In conclusion, all the available clinical and experimental data prove the involvement and importance of magnesium in neuroses and neuroticism.