PREDICTORS OF POST-TRAUMATIC STRESS DISORDER IN MILITARY PERSONNEL DEPLOYED TO PEACEKEEPING MISSIONS.

As the empirical evidence suggests PTSD, depression and anxiety represent prevalent and severe problem in armed forces. High co morbidity of these disorders with each other further complicates clinical picture. Georgian military personnel regularly take part in different peacekeeping missions, however there is no existing data regarding associations of mental health problems in Georgian armed forces. Data was collected between 2014 and 2015, after 6 month deployment. Participants were 2810 Georgian military personnel who took part in peacekeeping missions. All participants were male, average age: M=31,2 (SD=6,3). All instruments used in the study were self-report scales. PTSD was measured by PCL-5; Depression and anxiety was measured by PHQ (Patient Health Questionnaire). Both variables - Severity of Anxiety symptoms and severity of depression symptoms independently predicted PTSD, but after being placed together in the same regression model, only depression symptom severity accounted for significant portion of variance. Due to the fact that the participants of our study (n=69) were young (M=29,68 ; SD=5,8) male personnel, our findings cannot be generalized. Also it should be considered, that for PTSD screening we used self-report questionnaires, which reduces liability of participants' answers and increases the tendency of self-biased responses. It is advisable for clinical practitioners and therapists to consider depression symptoms in patients with PTSD and screen for depression additionally, in order to exclude or include co morbidity factors in treatment course.

Effects of trihexyphenydil, the structural analog of phencyclidine, on neocortical and hippocampal electrical activity in sleep-waking cycle.

Finding about structural and functional relation between NMDA receptors specific binding and phencyclidine sites was very important for a possible modulation of NMDA receptors' function. We have therefore got interested what would happen with EEG and vegetative patterns of PS in the case when NMDA receptors function is modulated by blocking of phencyclidines' site. Consequently, we studied the effects of Trihexyphenydil, the structural analog of phencyclidine, on neocortical and hippocampal electrical activity in SWC. On cats (n=5) metallic electrodes were implanted under Nembutal anesthesia. EEG registration lasting 12 hr daily started after animals' recovery. Trihexyphenydil was administered intraperitoneally (0.5 mg/kg - 1 mg/kg). Statistical processing was made by Students' t-test. Trihexyphenydil resulted in dissociated triggering of PS. Rapid eye movements and PGO waves appeared on the face of active waking state. Therefore on the background of behavioral active waking according to electrical activity of the visual cortex and rapid eye movements, electrographic patterns of paradoxical sleep were recorded. Thus in our experiments it was shown firstly that the mechanism of hallucinogenic action of Trihexyphenydil is closely related to the disturbance of paradoxical sleep integrity. Blocking of NMDA receptors phencyclidines site and therefore functional modulation of these receptors produce the splitting of PS patterns and their intrusion in waking state. Such an effect never takes place in normal conditions since the waking system has the powerful inhibitory influence on the PS triggering system. Suggestion is make that NMDA glutamate receptors must be involved in mechanisms providing structural and functional integrity of PS and that fulfillment of such function is possible in the case when the NMDA receptors phencyclidine site isn't in blocked state. Normal functioning of NMDA receptors phencyclidine site represents the mechanism which inhibits and/or hampers appearance of hallucination. NMDA glutamate receptors, possessing phencyclidine site, are implicated in the mechanisms providing structural and functional integrity of PS.

Influence of diazepam on different behavioral states of sleep-waking cycle.

Diazepam is a widely used benzodiazepine. Their prolonged usage leads to deterioration of cognitive functions and to the reduction of the level of vigilance what is explained by hypnotic effect but not by anxiolytic action of this drug. The novelty of our investigation is the elucidation of whether diazepam produces slow wave sleep reduction likely to the other benzodiazepines and if so what is the bases of positive therapeutic effect of diazepam in insomniac patients. For this aim we decided the study of diazepam effects on the ultradian structure of sleep-waking cycle. On cats (n=5) metallic electrodes were implanted under Nembutal anesthesia. EEG registration lasting 12 hr daily started after animals' recovery. Diazepam was administered intraperitoneally (0.37; 0.75; 1.5; 2 mg/kg). Statistical processing was made by Students' t-test. Diazepam prolonged sleep onset latency and waking overall time. Incidence and overall percentage of deep slow wave sleep decreased significantly but doze dependently. Paradoxical sleep latency was also significantly increased after diazepam action. All dozes of drug used by us significantly decrease the duration of each episode of paradoxical sleep. Diazepam significantly increase incidence of paradoxical sleep episodes with maximal duration till to 5 min. Under the influence of diazepam paradoxical sleep coursed without emotional coloring, without any patterns reflecting the level of emotional tension during this phase. The first episode of paradoxical sleep with partial restoration of patterns of emotional tension developed after 9+/-2 postinjectional hours at the 2 mg/kg doze of diazepam. All parameters reflecting the level of emotional tension during paradoxical sleep wholly recovered after 27+/-2 hour of diazepam administration. Diazepam administration worsens the quality of slow wave sleep. It is suggested that positive therapeutic effect of this drug may be related with the reduction of emotional tension during paradoxical sleep and modulation of behavioral and EEG patterns of this behavioral state.

Septo-hippocampal cholinergic/gabaergic relationship and sleep-waking cycle.

There is controversy in the literature in the results of various septal lesions on the sleep-waking cycle (SWC) ultradian structure. Current investigation was aimed to study the effects of interruption of septo-hippocampal cholinergic/GABAergic afferentation on the ultradian structure of SWC and on PS major indices. Experiments were carried out on 12 adult cats, operated under overall anesthesia (Nembutal, 35-40 mg/kg). Three groups of animals were used: I. Implanted sham lesioned control; II. With isolated lesion of medial septal part; III. With combined lesion of medial and lateral septal parts. Lesion was made by passing of direct current. Continuous EEG registration of SWC was lasted 12 hour. Results were evaluated statistically with Student's t test. Isolated lesion of medial septum doesn't produce significant changes of motivational-emotional behavior, but combined lesion of medial and lateral septal parts lead to enhancement of food and water motivation, development of hyper emotionality and hyperactivity. Interruption of septo-hippocampal cholinergic/GABAergic input, increased sleep onset latency, incidence and percentage of active waking (AW) and passive waking (PW) and PS latency but the last effect was dependent from sleep latency change. In the period from appearance of first PS episode to the end of EEG registration PS incidence and percentage wasn't changed significantly. This surgery completely abolished theta rhythm in waking and PS. Combined lesion of medial and lateral septal parts increased sleep latency still more. Total time of AW and PW increased twice. DSWS was significantly decreased. In this case PS latency was also increased still more. PS incidence and total percentage in whole 12 h registration period were reduced substantially, but for the period calculated after appearance of first PS episode until to the end of EEG registration PS mean value was the same as in sham lesioned animals. It is concluded that: 1.Septo-hippocampal cholinergic/GABAergic relationship doesn't play significant role in the triggering mechanisms of SWC ultradian structure; 2. GABAergic part of this input as well as hippocampo-mesodiecephalic descending pathways through the lateral septum have powerful modulatory influence on basic triggering mechanisms of SWS; 3. Development of hippocampal theta rhythm is the only event of PS affected after medial septal lesion; 4. Septo-hippocampal cholinergic input is not essential in triggering mechanisms of PS.

Effects of electric stimulation and destruction of caudate nucleus on short-term memory.

The effects of stimulation and destruction of the caudate nucleus on the cat short-term memory were studied by the method of classical delayed reactions. Short-term memory improved, if electrical stimulation of the caudate nucleus before presentation of the conditioned signal caused desynchronization of the electrocorticogram in the prefrontal and temporal cortex. Unilateral destruction of the caudate nucleus leading to the development of hyperactivity and attention disorders deteriorated short-term memory.

[The organization of the neuronal activity of the cortical cingulate gyrus in the waking-sleep cycle]. / Organizatsiia neironnoi aktivnosti poiasnoi izviliny kory golovnogo mozga v tsikle bodrstvovanie--son.

Dynamics of the neuronal activity of the cingulate gyrus (CG) in the sleep-wakefulness cycle (SWC) was studied in free-moving cats. Most of neurons (65.4) discharged with high frequency during active wakefulness (AW) and emotional stage of paradoxical sleep (PS); the frequency of discharges decreased during the passive wakefulness (PW) and slow-wave sleep (SWS). 15% of neurons showed opposite dynamics of the activity. They fired more intensively during the SWS. 19.6% of neurons showed no statistically significant difference in the discharge frequency of different phases of the SWC. Most of neurons (75.2%) regularly changed the pattern of discharges at a chang of the phases of the SWC. In particular, those neurons discharged by single spikes, more or less uniformly distributed in time, against the background of AW and PS. With the development of the SWS neurons began to discharge according to the cluster-pause principle. During the development of the short fragments of the EEG arousal, most of neurons either decrease (42.6%) or did not change (50.4%) the activity. The involvement of the CG in the regulation of the SWC is discussed.

The influence of electrocoagulation of the septum and section of the entorhinal cortex on general behaviour and memory in cats.

In chronic experiments on cats it was shown that the lesion of the medial part of the septum does not result in the "septal syndrome"; the ratio of the different sleep-wakefulness cycle phases remains within the baseline values; the acquisition, retrieval and extinction of instrumental alimentary conditioned reflexes proceed normally; the delayed conditioned reflexes are impaired. Massive septal lesion, including its lateral part, leads to the development of the "septal syndrome"; there are changes in the structure and percentage of the different sleep-wakefulness cycle phases; the acquisition and extinction of instrumental alimentary reflexes with the sound discrimination are markedly retarded; the performance of delayed conditioned reflexes is completely destroyed. The section of the entorhinal cortex produces an increase in the number of repeated errors and perseverative movements during performance of instrumental alimentary reflexes, the deceleration of the acquisition and extinction of instrumental alimentary reflexes, complete disturbance of the delayed conditioned reflexes and does not affect the sleep-wakefulness cycle. The problems of the role of the hippocampus and its main inputs in the regulation of the short-term operative memory in the "pure form" as well as the significance of the descending influence of the hippocampus on the regulation of general animal behavior were also discussed.

Influence of some monoamine oxidase inhibitors on the sleep-wakefulness cycle of the cat.

The influence of some monoamine oxidase inhibitors (phenelzine, transamin [tranylcypromine], nialamide) on the structure of the sleep-wakefulness cycle of the cat was studied. It was shown that these monoamine oxidase inhibitors elicit and increase in slow-wave sleep in the sleep-wakefulness cycle due to complete suppression of paradoxical sleep and significant decrease in wakefulness. After the cessation of the action of the monoamine oxidase inhibitors, a selective rebound of wakefulness is observed against the background of complete or partial absence of paradoxical sleep. The gives grounds for the hypothesis that during partial deprivation of wakefulness under the influence of monoamine oxidase inhibitors an intensification occurs on the accumulation of specific need for this physiological state, the satisfaction of which is accomplished as the result of its rebound in the post-deprivational cycle, i.e., after the termination of the EEG of the synchronizing effect of the monoamine oxidase inhibitors.

[Self-deprivation of paradoxical sleep in cats]. / Samodeprivatsiia paradoksal'nogo sna u koshek.

The phenomenon of paradoxical sleep (PS) self-deprivation has been detected and described. The self-deprivation is acquired just as a classical conditioned reflex during enforced PS deprivation both by water tank procedure and by the animal's awakenings in response to sensory stimuli or direct electric stimulation of activating structures of the midbrain and diencephalon, following the transition of slow-wave sleep to PS. In this situation the transition of the brain from one physiological state to another is a conditioned signal, and sensory stimulation or brain stimulation, resulting in arousal reaction, serves as an unconditioned stimulus. It is suggested that the detection and analysis of PS self-deprivation are of a great importance, on the one hand, for correct understanding of the functional significance of this physiological brain state, and, on the other hand, for accurate analysis and assessment of the dissociative processes, observed during PS deprivation and postdeprivation period.

[Effect of monoamine oxidase inhibitors with a broad range of action on the structure and phase ratio of the wakefulness-sleep cycle in the cat]. / Vliianie ingibitorov monoaminoksidazy shirokogo diapazona deistviia na strukturu i sootnosheniia faz tsikla bodrstvovanie--son u koshki.

The monoamine oxidase (MAO) inhibitors disturb the structure of the sleep-wakefulness cycle and its ultradian rhythms by prolongation of the slow-wave sleep, complete suppression of the paradoxical sleep (PS) and considerable shortage of the wakefulness phase. When synchronizing action of MAO inhibitors has stopped prolongation of wakefulness is observed both before and during partial recovery of the PS. This fact is considered as an indication of the accumulation of a need of wakefulness in the course of its partial deprivation by MAO inhibitors. MAO inhibitors exert a particularly strong effect on the PS producing long-term suppression of its tonic and phasic components. Complete inhibition of the PS is apparently due to selective deterioration of the functional state of its trigger mechanisms.

[Dynamics of the neuronal activity of the posterior hypothalamus during a phase shift of the wakefulness-sleep cycle]. / Dinamika aktivnosti neironov zadnego gipotalamusa pri smene faz tsikla bodrstvovanie--son.

Dynamics of neuronal activity of the posterior hypothalamus in the sleep-wakefulness cycle was studied in free moving cats using mobile metal microelectrodes. Computer analysis and statistical treatment of the data have shown that the majority of neurons (89.3%) in the above-mentioned area discharge with high frequency during active wakefulness and emotional stage of paradoxical sleep; the frequency of discharges decreases during passive wakefulness and nonemotional stage of paradoxical sleep and is the lowest in the slow wave sleep though it has been higher than at the other states. Comparatively small number of neurons (3.6%) show opposite dynamics of the activity. They fire more intensely during slow wave sleep and the frequency of discharges decreases during active wakefulness and paradoxical sleep. In posterior hypothalamus some neurons (7.1%) are found which fire intensely during active wakefulness as compared with slow wave sleep and paradoxical sleep. The neurophysiological mechanisms for regulation of the sleep-wakefulness cycle and the involvement of posterior hypothalamus in this process are discussed.

[Neurophysiological analysis of the effects of selective deprivation of paradoxical sleep]. / Neirofiziologicheskii analiz éffektov selektivnoi deprivatsii paradoksal'nogo sna.

Neurophysiological analysis of the effects of selective and total paradoxical sleep deprivation (PSD) involving the replacement of paradoxical sleep (PS) phases by equivalent (as to duration) episodes of wakefulness is carried out. In contrast to the "classical" method of momentary awakening of the animal, a new method does not lead to: (1) the accumulation of PS need associated with more frequent PS onsets during deprivation; (2) PS rebound in a postdeprivation period; (3) dissociation of PS components, i.e. their occasional occurrence in other phases of the sleep-wakefulness cycle due to the phenomenon of self-deprivation; (4) increase in the rate of pontogeniculo-occipital (PGO) spikes, eye movements and heart rate during PS phases in the postdeprivation period. The application of selective and total PSD techniques caused no noticeable changes in the functional state and integrative activity of the brain, the latter warranting its successful use for treatment of some psychoneurological disturbances in clinics. The assumption has been advanced about the similarity of the neurochemical changes forming the need both for wakefulness and PS.

[Dynamics of unit activity of the gigantocellular tegmental field in the sleep-wakefulness cycle of rats]. / Dinamika neuronnoi aktivnosti gigantokletochnogo polia pokryshki v tsikle bodrstvovanie--son u krys.

Computer analysis and statistical processing of the unit activity showed that the majority of neurons (65.2%) in the gigantocellular tegmental field were discharging with high frequency during active wakefulness and paradoxical sleep as compared to slow-wave sleep in unrestrained rats. 11.6% of the neurons revealed an inverse pattern of activity: they discharged more intensively during slow-wave sleep, their firing rate decreasing during active wakefulness and paradoxical sleep. Some neurons (23.2%) were found which fired intensively during active wakefulness, their firing rate decreasing both in slow-wave and paradoxical sleep. Involvement of the gigantocellular tegmental field in the neurophysiological mechanisms of phases and stages of the sleep-wakefulness cycle is discussed.

[Effect of various monoamine oxidase inhibitors on the structure of the sleep-wakefulness cycle of the cat]. / Vliianiie nekotorykh ingibitorov monoaminoksidazy na strukturu tsikla bodrstvovanie--son koshki.

The effect of some monoamine oxidase inhibitors (phenelzine, transamine, nialamide) on the structure of the cat sleep--wakefulness cycle involved an increase of slow-wave sleep at the expense of totally inhibited REM sleep and substantial reduction of wakefulness. Following this effect, selective rebound of wakefulness occurred against the background of total or partial absence of REM sleep. The partial deprivation of wakefulness induced with monoamine oxidase inhibitors seem to entail an accumulation of a specific need in the given physiological state, the gratification of which is effected through its rebound in the post-deprivation cycle.

[Interdependence of learning and paradoxical sleep in the cat]. / Vzaimovliianie obucheniia i paradoksal'nogo sna u koshek.

The effect of learning sessions on the structure of the sleep-wakefulness cycle, as well as the effect of paradoxical sleep (PS) deprivation (PSD) following learning sessions, on the acquisition and extinction of instrumental alimentary reflexes to two feeders with sound discrimination, were studied on cats. The analysis of the data obtained led to following conclusions: The above learning sessions have no marked effect on the structure of the sleep-wakefulness cycle in the post-learning period, i.e. the percentage ratio of its phases is not altered by the increase of one of them. When PSD by non-emotional awakening is used, the number of PS onsets is not affected by learning sessions. This indicates that learning does not produce any considerable effect on the formation of PS need. PSD by non-emotional awakening following learning sessions does not retard the acquisition and extinction of the instrumental alimentary reflexes. The above data are interpreted as indicating that PS has no specific significance in memory trace consolidation during formation of long-term memory.

[Effect of electrocoagulation of the septum on the behavior and memory of the cat]. / Vliianie élektrokoaguliatsii septum na povedenie i pamiat' u koshki.

Lesion effects of various areas of the septum on general behaviour, learning and memory were studied in cats. It appeared that electrocoagulation of the medial septum alone leading to the disappearance of the hippocampal theta rhythm does not result in the development of the septal syndrome signs; does not disturb the normal structure of the sleep-wakefulness cycle; does not delay the elaboration of instrumental alimentary reflexes (to approach two feeders) or their extinction, but does entirely disturb the delayed responses to conditioned stimuli. In cases when lesion involves also the lateral septum, it produces the development of all signs of the septal syndrome (hyperemotionality, hyperactivity, rage, hyperphagia, etc.), disturbance of the normal structure of the sleep-wakefulness cycle, delay of both the elaboration and extinction of instrumental alimentary reflexes, disturbance of pre-elaborated conditioned reactions with sound discrimination, entire disturbance of conditioned delayed responses. On the basis of these data, the specific significance of hippocampal theta-rhythm in the organization of learning and memory is rejected, and a more important role is attributed to the descending regulatory influence exerted by the hippocampus and other archipaleocortical structures on the activating and motivatiogenic structures of mesodiencephalon.