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Evidence from the evolution of human cultural behavior and learning, embryology and genetics of the brain, and the behavior of human infants indicates that the critical and uniquely human motives for cooperative imagination and joint interest in objects and tasks are determined by expression of genes and epigenetic neural systems elaboration long before birth, along with essential peripheral organs of perception and motor expression that will serve in communication by rhythmic facial, vocal, gestural, and body movement signals. These cerebral motives continue to exercise their influence on neural development and behavior throughout life, transforming the behaviors of the developing individual through a succession of phases to which other individuals and cultural institutions are constrained to adapt. We discuss the theory of innate intersubjectivity and relate it to the hypothesis of an Innate Motive Formation that emerges in brain development as regulator of morphogenesis in neural systems, and that continues to function, postnatally, as generator of motives and emotions by which human contacts and relationships are regulated. We suggest that differentiates of the primary motive formation in the embryo brain later serve to generate intelligent exploration of the objective environment and the emergence of an additional dialogic mechanism that represents the self-subject as a partner for an other-subject, intersubjectively. Intersubjective communication in infancy leads, through systematic age-related transformations of the brain and behavior, to preverbal mimetic negotiation of cooperative awareness and joint task performance. Finally we discuss, in relation to this theory, interpretations of faulty communication and development at different stages of the life cycle that result from maternal postnatal depression, autism, premature birth and schizophrenia.
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PMID:Self/other organization in human psychological development. 944

This case report describes a set of monozygotic twins with severe intellectual disability, autism and affective disorder with a balanced translocation between chromosomes 4 and 12. Their mother, who carries the same balanced translocation, had severe postnatal depression. The association between autism affective disorder and these chromosome break points has not been reported previously. The implications are discussed.
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PMID:Association of a balanced chromosomal translocation (4; 12)(q21.3; q15), affective disorder and autism. 1089 81

We review research evidence on the emergence and development of active "self-and-other" awareness in infancy, and examine the importance of its motives and emotions to mental health practice with children. This relates to how communication begins and develops in infancy, how it influences the individual subject's movement, perception, and learning, and how the infant's biologically grounded self-regulation of internal state and self-conscious purposefulness is sustained through active engagement with sympathetic others. Mutual self-other-consciousness is found to play the lead role in developing a child's cooperative intelligence for cultural learning and language. A variety of preconceptions have animated rival research traditions investigating infant communication and cognition. We distinguish the concept of "intersubjectivity", and outline the history of its use in developmental research. The transforming body and brain of a human individual grows in active engagement with an environment of human factors--organic at first, then psychological or inter-mental. Adaptive, human-responsive processes are generated first by interneuronal activity within the developing brain as formation of the human embryo is regulated in a support-system of maternal tissues. Neural structures are further elaborated with the benefit of intra-uterine stimuli in the foetus, then supported in the rapidly growing forebrain and cerebellum of the young child by experience of the intuitive responses of parents and other human companions. We focus particularly on intrinsic patterns and processes in pre-natal and post-natal brain maturation that anticipate psychosocial support in infancy. The operation of an intrinsic motive formation (IMF) that developed in the core of the brain before birth is evident in the tightly integrated intermodal sensory-motor coordination of a newborn infant's orienting to stimuli and preferential learning of human signals, by the temporal coherence and intrinsic rhythms of infant behaviour, especially in communication, and neonates' extraordinary capacities for reactive and evocative imitation. The correct functioning of this integrated neural motivating system is found to be essential to the development of both the infant's purposeful consciousness and his or her ability to cooperate with other persons' actions and interests, and to learn from them. The relevance of infants' inherent intersubjectivity to major child mental health issues is highlighted by examining selected areas of clinical concern. We review recent findings on postnatal depression, prematurity, autism, ADHD, specific language impairments, and central auditory processing deficits, and comment on the efficacy of interventions that aim to support intrinsic motives for intersubjective communication when these are not developing normally.
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PMID:Infant intersubjectivity: research, theory, and clinical applications. 1120 23

Although a growing body of evidence supports the hypothesis that exposure to obstetric complications (OCs) increases the vulnerability for schizophrenia, some questions remain unanswered regarding the diagnostic specificity and the etiological significance of this association. Associations with a history of OCs have been reported for other severe psychiatric disorders, such as autism, anorexia nervosa, or psychotic affective disorder. Thus, OCs may increase in a relatively non-specific way the vulnerability for a range of severe mental disorders, the expression of this vulnerability depending on the interaction between OCs and other risk factors, such as the genetic liability for specific psychiatric disorder, or exposure to later environmental risk factors. The causal pathway between OCs, maternal psychopathology, and psychotic outcome in the offspring is not fully elucidated. The directions of the associations are often bi-directional, and the mediating variables, if any, are not clearly identified. OCs may have a direct negative impact on fetal brain development, may be on the causal pathway between prepartum maternal depression/exposure to stress and increased risk of schizophrenia, or may indirectly increase the risk of child's later psychiatric disorder by acting as risk factors for maternal postpartum depression. The links and possible interactions between somatic perinatal risk factors and maternal psychopathology in the association with offspring's increased vulnerability for psychosis have to be further explored.
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PMID:Perinatal risk factors for schizophrenia: diagnostic specificity and relationships with maternal psychopathology. 1245 83

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.
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PMID:Stimuli and consequences of dendritic release of oxytocin within the brain. 1795 24

A conceptual model detailing the process of bio-behavioral synchrony between the online physiological and behavioral responses of attachment partners during social contact is presented as a theoretical and empirical framework for the study of affiliative bonds. Guided by an ethological behavior-based approach, we suggest that micro-level social behaviors in the gaze, vocal, affective, and touch modalities are dynamically integrated with online physiological processes and hormonal response to create dyad-specific affiliations. Studies across multiple attachments throughout life are presented and demonstrate that the extended oxytocin (OT) system provides the neurohormonal substrate for parental, romantic, and filial attachment in humans; that the three prototypes of affiliation are expressed in similar constellations of social behavior; and that OT is stable over time within individuals, is mutually-influencing among partners, and that mechanisms of cross-generation and inter-couple transmission relate to coordinated social behavior. Research showing links between peripheral and genetic markers of OT with concurrent parenting and memories of parental care; between administration of OT to parent and infant's physiological readiness for social engagement; and between neuropeptides and the online synchrony of maternal and paternal brain response in social-cognitive and empathy networks support the hypothesis that human attachment develops within the matrix of biological attunement and close behavioral synchrony. The findings have conceptual implications for the study of inter-subjectivity as well as translational implications for the treatment of social disorders originating in early childhood, such as autism spectrum disorders, or those associated with disruptions to early bonding, such as postpartum depression or child abuse and neglect. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.
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PMID:Oxytocin and social affiliation in humans. 2228 34

The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the 'out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.
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PMID:Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy. 2369 33

Psychiatric disorders are equally common among pregnant and non-pregnant women, and many of these conditions are treated with psychotropic medications. The use of psychotropic medicines during pregnancy, especially antidepressants, became increasingly prevalent in the early 2000's, although many physicians prefer not to prescribe drugs for pregnant women due to concerns about teratogenicity. Current data on the risks of in utero exposure to psychotropic medications are limited, leaving women and physicians to make difficult decisions regarding the initiation or maintenance of treatment during pregnancy without a complete knowledge of the risks. Of all the psychotropics, antidepressant use in pregnancy has been relatively well studied. However, available studies have not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health-related behaviors such as smoking and alcohol use during pregnancy. This review focuses on the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, the antidepressants most commonly used to treat depression. In the evaluation of medication during pregnancy, teratogenicity and fetotoxicity must be considered. Most studies on the use of SSRIs during the first trimester of pregnancy have not shown an increase in the overall risk of major malformations, although several studies have suggested that SSRIs may be associated with a small increased risk of cardiovascular malformations, mainly involving ventricular and atrial septal defects. In addition to structural malformations, drugs were also observed to induce other adverse effects. Since SSRIs readily cross the placenta, concern has been raised about the short- or long-term effects of prenatal exposure to SSRIs on the developing offspring. Epidemiological studies have documented that 10-30% of neonates exposed to SSRIs near term had poor neonatal adaptation syndrome (PNAS). Some studies reported that persistent pulmonary hypertension of the newborn (PPHN) is weakly associated with in utero antidepressant exposure, while no association has been reported in other studies. Recent studies have raised questions about possible associations with antidepressant use during pregnancy and long-term effects on neurobehavioral development. Some individual studies have suggested associations between prenatal exposure to antidepressants and autism spectrum disorder; however, other studies identified no associations. On the other hand, depressive symptoms during pregnancy are also associated with increased risks of preterm delivery, fetal growth retardation, and postpartum depression. Therefore, the effects of untreated maternal depression on both maternal and child outcomes must be taken into consideration when making treatment decisions. Future research needs to focus on large prospective studies with adequate adjustments for key potential confounding factors, including maternal mental illness, other exposures, and an adequate length of follow-up, in order to obtain accurate child developmental outcomes.
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PMID:[Current evaluation of teratogenic and fetotoxic effects of psychotropic drugs]. 2582 51

Dopamine and prolactin exhibit opposite effects on lactation. However, a possible role for increased prolactin/dopamine ratio in postpartum mood and thought disorders and as a prognostic indicator of the mother's future mental health has not been well investigated. Postpartum depression is a serious condition with potentially devastating outcomes for both the mother and the infant. Early detection and treatment of this condition can have impressive results. Treatment options include antidepressant medications for mood disorders and use of antipsychotics and electroconvulsive therapy to address postpartum psychosis. Although there are obvious benefits of such treatments on the welfare of the mother and her child, broader implications of these treatments on lactation and child growth and development are not known. This review article explores a possible link between in-utero exposure to a high maternal prolactin/dopamine ratio and subsequent development of autism spectrum disorders. We hypothesize that a comprehensive, biologically oriented approach to the use of psychotropics in the regulation of neurotransmission during pre- and postpartum periods may result in better outcomes in this population.
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PMID:Placental Barrier and Autism Spectrum Disorders: The Role of Prolactin and Dopamine on the Developing Fetal Brain. 2663 76

Oxytocin (OXT) is a neuropeptide that plays a pivotal role among species peripherally and centrally. It recently has attracted much attention for its involvement in anxiety-related behavior, stress regulation, social behavior and various neuropsychiatric disorders. OXT is one of the important mediators of emotional and social behaviors such as maternal behavior, fear extinction, social support, happiness, and trust. It is also involved in learning and memory process. The recent progresses in OXT system have put this neuropeptide as an important psychotherapeutic intervention for various psychiatric disorders such as stress, anxiety disorders, social phobia, postpartum depression, bipolar disorder, autism, and schizophrenia. In this review, we highlight OXT's contributions to various physiological functions and psychological disorders and discuss its potential use as a therapeutic agent.
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PMID:Oxytocin system in neuropsychiatric disorders: Old concept, new insights. 2843 79


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