Boltzmann's Theorem Revisited: Inaccurate Time-to-Action Clocks in Affective Disorders.

Timely goal-oriented behavior is essential for survival and is shaped by experience. In this paper, a multileveled approach was employed, ranging from the polymorphic level through thermodynamic molecular, cellular, intracellular, extracellular, non-neuronal organelles and electrophysiological waves, attesting for signal variability. By adopting Boltzmann's theorem as a thermodynamic conceptualization of brain work, we found deviations from excitation-inhibition balance and wave decoupling, leading to wider signal variability in affective disorders compared to healthy individuals. Recent evidence shows that the overriding on-off design of clock genes paces the accuracy of the multilevel parallel sequencing clocks and that the accuracy of the time-to-action is more crucial for healthy behavioral reactions than their rapidity or delays. In affective disorders, the multilevel clocks run free and lack accuracy of responsivity to environmentally triggered time-to-action as the clock genes are not able to rescue mitochondria organelles from oxidative stress to produce environmentally-triggered energy that is required for the accurate time-to-action and maintenance of the thermodynamic equilibrium. This maintenance, in turn, is dependent on clock gene transcription of electron transporters, leading to higher signal variability and less signal accuracy in affective disorders. From a Boltzmannian thermodynamic and energy-production perspective, the option of reversibility to a healthier time-to-action, reducing entropy is implied. We employed logic gates to show deviations from healthy levelwise communication and the reversed conditions through compensations implying the role of nonneural cells and the extracellular matrix in return to excitation-inhibition balance and accuracy in the time-to-action signaling.

Diverse Underlying Mechanisms and Sex Differences Found in Translational Models of Cannabinoids Use: Towards Validation in Human Studies.

This Special Issue represents a continuation of our previous Special Issue entitled "Endocannabinoids, Cannabinoids and Psychiatry: Biological Mechanisms" [...].

Control systems theory revisited: new insights on the brain clocks of time-to-action.

To outline the complex biological rhythms underlying the time-to-action of goal-oriented behavior in the adult brain, we employed a Boolean Algebra model based on Control Systems Theory. This suggested that "timers" of the brain reflect a metabolic excitation-inhibition balance and that healthy clocks underlying goal-oriented behavior (optimal range of signal variability) are maintained by XOR logic gates in parallel sequences between cerebral levels. Using truth tables, we found that XOR logic gates reflect healthy, regulated time-to-action events between levels. We argue that the brain clocks of time-to-action are active within multileveled, parallel-sequence complexes shaped by experience. We show the metabolic components of time-to-action in levels ranging from the atom level through molecular, cellular, network and inter-regional levels, operating as parallel sequences. We employ a thermodynamic perspective, suggest that clock genes calculate free energy versus entropy and derived time-to-action level-wise as a master controller, and show that they are receivers, as well as transmitters of information. We argue that regulated multileveled time-to-action processes correspond to Boltzmann's thermodynamic theorem of micro- and macro-states, and that the available metabolic free-energy-entropy matrix determines the brain's reversible states for its age-appropriate chrono-properties at given moments. Thus, healthy timescales are not a precise number of nano- or milliseconds of activity nor a simple phenotypic distinction between slow vs. quick time-to-action, but rather encompass a range of variability, which depends on the molecules' size and dynamics with the composition of receptors, protein and RNA isoforms.

When the Mind Comes to Live Inside the Body: The Ontogeny of the Perceptual Control Clock.

In this editorial, we discuss the neurobiological processes underlying the early emergence of awareness that we term the "when" and "how" the mind comes to live inside the body. We describe an accumulative developmental process starting during embryonic life and continuing to fetal and postnatal development, of coupling of heart rate, body movements, and sleep states on the behavioral level with underlying mechanisms on the structural, functional, cellular, and molecular levels. A developmental perspective is proposed based on Perceptual Control Theory (PCT). This includes a developing sequence of modules starting from early sensing of neural intensities to early manifestation of human mindful capacities. We also address pharmacological treatments administered to preterm infants, which may interfere with this development, and highlight the need to consider this potential "side effect" of current pharmaceuticals when developing novel pharmacogenomic treatments.

Multi-level hypothalamic neuromodulation of self-regulation and cognition in preterm infants: Towards a control systems model.

Preterm infants, age-corrected for prematurity, score on average, 10 points lower on IQ tests than full-term infants tested at comparable ages. This review focuses on the potential contribution of the hypothalamus to cognitive neuro-regulatory development in preterm infants through its bidirectional neural connections with the prefrontal cortex and its neuroendocrine activity. It aims to clarify the central role of the hypothalamus in preterm high stress situations and in influencing cognitive development via its connectivity to the cerebral cortex. The review further evaluates epigenomic sensitivity to environmental inputs. Recent results suggest that an optimal range of DNA methylations (via a continuous process of decreasing levels of receptor methylations that are too high, and increasing levels that are too low) appears necessary in order to reach an adaptive level of receptor availability. Several studies have demonstrated amelioration of preterm infants' stress while in the Newborn Intensive Care Unit (NICUs) and following discharge. The authors postulate that feedback mechanisms and correction signals are the basis for a hypothalamic homeostatic modulating function, a "hypothalamic resistance response", which may account for the stress reduction brought about by in- and post-NICU early interventions and their results of promoting self-regulation and cognition.

The Inanimate Third: Going Beyond Psychodynamic Approaches for Remote Psychotherapy during the COVID-19 Pandemic.

The COVID-19 pandemic exposed the field of psychotherapy to the need to provide treatment remotely. We discuss the question of whether remote therapy can be curative and if the electronic device used to manage these sessions unites or separates the therapist and the patient. We term the electronic device as 'the inanimate third' in the therapeutic process and discuss the objectivity of the device as opposed to the subjective emotional processes involved. We deal with emotional themes relevant to the COVID-19 pandemic and associated social distancing practices, such as longing, loneliness, the perception of the future and the lost past, and the efficacy of the therapeutic stimulation of fantasy and hope. We also evaluate the possibility of existing transference and countertransference processes while working remotely. We suggest the term 'social paradox' to describe the situation in which an objective entity such as the digital media symbolizes both distance and intimacy as well as separation and unity. We conclude by stating that containment of the social paradox by the therapeutic dialogue is possible as the existence of the dialogue eliminates elements of the paradox.

Perceived social support in the social distancing era: the association between circles of potential support and COVID-19 reactive psychopathology.

BACKGROUND AND OBJECTIVES: Stressors related to the COVID-19 pandemic are risk factors for psychopathology, but psychosocial protective factors might play a crucial role in buffering the pathogenic effects of the outbreak. DESIGN: In the current study, we examined the association of inner resources and potential external sources of support for coping with the pandemic and related lockdowns to mental health during the pandemic, while controlling for sociodemographic variables as covariates. METHODS: We tested the model in a probability-based internet survey of a representative sample of the Israeli adult population (N = 812) conducted during the COVID-19 pandemic. RESULTS: Perceived support in close relationships was negatively associated with the intensity of depression, anxiety, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). Larger rings of potential support such as perceived belongingness to a community and trust in government were also negatively related to anxiety and depression but were positively associated with the intensity of OCD and PTSD. CONCLUSIONS: Findings support the "tend and befriend" theory in the social distancing era and highlight the importance of keeping personal relationships alive when facing a mass trauma.

The roots of paternal depression: Experienced and nonexperienced trauma or Folie a Deux?

The transition to fatherhood may be challenged with anxiety and trepidation. A high prevalence has been found for paternal depression and it is reactive to maternal depression. This review aims to address potential sources of paternal depression, which may have adverse consequences on child development. We describe through three hypotheses how fathers may be at risk of depression during the transition to fatherhood: (1) psychological (interacting with ecological systems); (2) brain functional∖structural changes; and (3) (epi)genomic. We propose that paternal stressful experiences during the transition to fatherhood may be the source for paternal depression through direct stressful paternal experiences or via (potential, currently debated) nonexperienced (by the father) epigenomic transgenerational transmission. On the other hand, we suggest that resilient fathers may undergo a transient dysphoric period affected by identifying with the newborn's vulnerability as well as with the mother's postpartum vulnerability resulting in "paternity blues." In accordance with recent views on paternal "heightened sensitivity" toward the infant, we propose that the identification of both parents with the vulnerability of the newborn creates a sensitive period of Folie a Deux (shared madness) which may be a healthy transient, albeit a quasi-pathological period, recruited by the orienting response of the newborn for survival.

The "Entourage Effect": Terpenes Coupled with Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders.

Mood disorders are the most prevalent mental conditions encountered in psychiatric practice. Numerous patients suffering from mood disorders present with treatment-resistant forms of depression, co-morbid anxiety, other psychiatric disorders and bipolar disorders. Standardized essential oils (such as that of Lavender officinalis) have been shown to exert clinical efficacy in treating anxiety disorders. As endocannabinoids are suggested to play an important role in major depression, generalized anxiety and bipolar disorders, Cannabis sativa was suggested for their treatment. The endocannabinoid system is widely distributed throughout the body including the brain, modulating many functions. It is involved in mood and related disorders, and its activity may be modified by exogenous cannabinoids. CB1 and CB2 receptors primarily serve as the binding sites for endocannabinoids as well as for phytocannabinoids, produced by cannabis inflorescences. However, 'cannabis' is not a single compound product but is known for its complicated molecular profile, producing a plethora of phytocannabinoids alongside a vast array of terpenes. Thus, the "entourage effect" is the suggested positive contribution derived from the addition of terpenes to cannabinoids. Here, we review the literature on the effects of cannabinoids and discuss the possibility of enhancing cannabinoid activity on psychiatric symptoms by the addition of terpenes and terpenoids. Possible underlying mechanisms for the anti-depressant and anxiolytic effects are reviewed. These natural products may be an important potential source for new medications for the treatment of mood and anxiety disorders.

Melatonin and mental capacities in newborn infants.

OBJECTIVES: To investigate the role of melatonin in the emergence of mental capacities in the newborn infant. STUDY DESIGN: Assessment of Preterm Infant Behavior examination was performed at 2 weeks post-term age for 39 (21 preterm and 18 term) infants. 6-Suphatoxymelatonin from nocturnal urine samples was analyzed by enzyme-linked immunosorbent assays, and the Mental Developmental Index, assessed by Bayley scales, was correlated at 4, 6, and 9 months' corrected age. RESULTS: Multivariate analysis of variance with repeated measures showed that improved autonomic function at 2 weeks of age was associated with higher Mental Developmental Index scores at 9 months when related to the amount of melatonin at 4, 6, and 9 months of age. CONCLUSIONS: Early compromised autonomic system function in preterm infants is associated with lower mental capacities and is related to lower melatonin levels at later ages.

The father-infant co-regulation and infant social proficiency with a stranger.

A growing body of knowledge is available on the father's instrumental role in the development of the child, but there is less data on the role he fulfills in preparing the child for challenging social encounters. The present study was designed to investigate the predictive value of the toddler's co-regulation with the father and the capacities the infant shows during a later encounter with a stranger, beyond the effect of the co-regulation of the toddler with the mother. Thirty-one toddlers were engaged in three interactions: with the mother, father, and a stranger. The order of the first two interactions was randomized, while the session with the stranger, which involved a game of peek-a-boo with an object, was always last. The sessions were videotaped and coded according the Early Interaction Scale (EIS) off-line by trained coders. The results indicate that the extent of the infant's proficiency in interacting with the stranger was predicted by his or her social proficiency and his or her co-regulation with the father, beyond the contribution of his or her proficiency and co-regulation with the mother.

Neurobehavioural assessment of skin-to-skin effects on reaction to pain in preterm infants: a randomized, controlled within-subject trial.

OBJECTIVE: To assess the immediate and sustained effects of Kangaroo Care on reaction to pain of premature infants. PATIENTS AND METHODS: A controlled, within-subject randomized study, performed in a large neonatal intensive care unit. Thirty premature infants were observed with blood test stick (BT) or without the blood test stick (W) procedure, either during Kangaroo care (K) or during standard within-crib care (C). Each of the four conditions (BTK, WK, BTC, WC) was observed in four separate sessions: baseline session - 10 min; intervention (BT or W) - 2 min; posttest - 10 min and follow-up - 20 min, in crib (starting 1 h after treatment). For neurobehavioural assessment, the naturalistic observation method was adopted from the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). RESULTS: During the BTK session (blood test stick with K-care), we observed a decrease in motor disorganization and extension movements and an increase in attention signs, both negative and positive. Significant neurobehavioural changes were sustained in the follow-up period after K-care in comparison to the within-crib-care intervention sessions. CONCLUSIONS: K-care, as compared to within-crib condition, led to a decrease in stressful neurobehavioural signs after BT procedures in premature infants. Painful procedures such as the BT procedure in premature infants should be performed while the infants are being held in K-care position.

The development of maternal touch across the first year of life.

The developmental trajectories of specific forms of maternal touch during natural caregiving were examined across the first year in relation to the development of mother-infant reciprocal communication. One hundred and thirty-one mothers and infants in four groups aged 3, 6, 9, and 12 months were observed in a cross-sectional design at home during natural caregiving and mother-child play sessions. Microanalytic coding of the caregiving sessions considered nine forms of maternal touch, which were aggregated into three global touch categories: affectionate, stimulating, and instrumental. Play sessions were coded for maternal sensitivity and dyadic reciprocity. Maternal affectionate and stimulating touch decreased significantly during the second 6 months of life. In parallel, dyadic reciprocity increased in the second half year. Dyadic reciprocity was predicted by the frequency of affectionate touch but not by any other form of touch. Results contribute to specifying the role of touch as it evolves across the first year of life within the global mother-infant communication system.

Does sympathetic activity contribute to growth of preterm infants?

BACKGROUND: Emerging evidence on faster growth in preterm infants with higher heart rate as opposed to the classical approach calls for further research. AIMS: to test whether (1) high or low heart rate and (2) heart rate during the first days of life predict greater weight gain in preterm infants. METHODS: A retrospective study analyzing two daily measures of heart rate obtained during restful sleep, total daily calorie intake and daily weight gain measured always in the morning before meal were collected from the medical files. RESULTS: Analysis of 90 healthy preterm infants born at 32-36 weeks of gestation revealed that increased mean heart rate during hospitalization predicted greater weight gain even when controlling for calorie intake, birth weight, gestational age, appropriateness of birth weight for gestational age, and length of hospitalization. Mean heart rate during the first three days of life yielded the same pattern of results. Post-hoc analysis of variance between infants with mean daily heart rate /=140 bpm showed that infants with higher heart rate achieved a significantly higher weight gain. CONCLUSIONS: It is suggested that, contrary to adults, in neonates an anabolic activity is represented by increased sympathetic functioning within the normal range. The implications of a slower growth rate for additional developmental care and individual considerations of appropriate stimulation in preterm infants are discussed.

The roles of pain catastrophizing and anxiety in the prediction of postoperative pain intensity: a prospective study.

OBJECTIVES: This study was a prospective investigation of the extent to which psychologic variables could be predictive of postoperative pain. Study aims were: 1) to evaluate whether an assessment of pre-operative distress factors could predict the intensity of postoperative pain; and 2) to characterize the unique pattern in which anxiety and pain catastrophizing scores relate to postoperative pain. METHODS: The Pain Catastrophizing Scale and the State-Trait Anxiety Inventory were administered to 38 patients scheduled for elective abdominal surgery. The questionnaires were completed on the day of admission, a day before the operation. On day 1 and day 2 following the operation, perception of pain intensity at the surgical wound was assessed by visual analog scale. RESULTS: The Pain Catastrophizing Scale and State-Trait Anxiety Inventory scores were significantly correlated with the postoperative pain scores. A linear regression analysis showed that Pain Catastrophizing Scale predicted the level of postoperative pain intensity even after controlling for state anxiety and that trait anxiety was not a significant predictor. In addition, analysis of the unique pattern of each predictor related to postoperative pain intensity indicated a linear curve for the Pain Catastrophizing Scale and curvilinear curve for the state anxiety. DISCUSSION: The results are discussed in light of appraisal and coping theories. It is suggested that a simple assessment of preoperative catastrophizing tendency and anxiety scores may assist medical teams in postoperative pain management.

Catastrophizing labor pain compromises later maternity adjustments.

OBJECTIVE: The purpose of this study was to evaluate the impact of labor pain intensity and labor pain catastrophizing on maternity blues and postpartum social functioning. STUDY DESIGN: Pain intensity and pain catastrophizing were assessed in 89 women in active labor before the administration of analgesia. Both these measures were assessed again retrospectively 2 days after delivery in 82 women who had a spontaneous vaginal delivery. Women also filled out the Edinburgh Postnatal Depression Scale. Six weeks later women completed the social functioning domain of the short form SF36 health survey. RESULTS: Pain catastrophizing during labor significantly predicted both maternity blues (P = .001) and postpartum social functioning (P = .001) when being controlled for maternal age and education, parity, type of analgesia, and labor pain intensity. Low level of education and younger age also contributed to the prediction of maternity blues and social functioning. CONCLUSION: Labor pain catastrophizing rather than labor pain intensity predicts postpartum maternal adjustments.

Delivery Pain and the Development of Mother-Infant Interaction.

This study examined delivery pain as a possible risk factor for the development of mother-infant interaction. Eighty-one mothers completed the Pain Catastrophizing Scale, the State-Trait Anxiety Inventory, and the Edinburgh Postnatal Depression Scale. A retrospective evaluation of labor pain was performed using the Visual Analog Scale at 2 days postpartum. Six weeks after birth the mothers were visited at home, completed measures of anxiety and depression, and were observed during a free play session with the infant. The mother's tendency to catastrophize pain predicted lower levels of mother-infant reciprocity at 6 weeks, controlling for maternal age, education, parity, epidural analgesia, pain perception, anxiety, and depression. Trait anxiety was related to lower maternal sensitivity. The mother's tendency to catastrophize pain was discussed in relation to the personality trait of exaggerated emotional perception of pain and its potential interference with the formation of the mother-infant relationship.

The nature of touch in mothers experiencing maternity blues: the contribution of parity.

BACKGROUND: Maternal touch (MT) is an essential part of the initial contact between the mother and her newborn and has developmental effects on the child. MT is known to be reduced in postpartum depression (PPD). The nature of MT in mothers experiencing maternity blues and the effect of parity are still unknown. STUDY DESIGN: Seventy-five mothers were recruited from the ongoing series of deliveries. SUBJECTS: The participating mothers were observed during interaction with their newborns on the second-day postpartum. Touching behavior was scored on-line according to the Touch Scoring Instrument, which includes nine types of MT. Mothers were categorized as exhibiting maternal blues according to Stein's depression scale. OUTCOME MEASURE: Touch Scoring Instrument. RESULTS: Primiparous mothers with blues avoided all types of touch whereas multiparous mothers with blues provided firm touch and holding. All mothers with blues avoided proprioceptive touch. Multiparous mothers without maternal blues provided various types of touch including affectionate holding and matter-of-fact touch whereas primiparous mothers without blues mostly provided holding. CONCLUSIONS: Mothers with maternity blues on day 2 exhibited a pattern of MT similar to that known to characterize postpartum depression. Mothers without blues are able to provide developmental touch in a manner known to facilitate CNS stability and newborn adjustment to the extra-uterine world. Parity modulates the effect of maternity blues on MT and buffers the withdrawal effect of depression. Maternal touch could be used as a diagnostic tool for detection of mothers at risk in a timely manner. Touch interventions, which were previously demonstrated in PPD mothers, may be utilized in an earlier stage postpartum.