Prenatal growth markers in schizophrenia: a monozygotic co-twin control study.

OBJECTIVE: This co-twin study investigated monozygotic twins who were discordant for schizophrenia for evidence of prenatal growth differences between the affected and well co-twins. METHOD: Four dermatoglyphic markers of prenatal growth were obtained by established procedures from 26 monozygotic twin pairs discordant for schizophrenia, 13 monozygotic twin pairs concordant for schizophrenia, and several normal monozygotic twin samples. RESULTS: The a-b ridge count differences between the affected and well co-twins were greater than those found for concordant and normal monozygotic pairs. In comparison with their well co-twins, the affected twins, in discordant pairs, had developed fewer epidermal ridges in the a-b interdigital area of their right palms. In contrast, no significant differences were found between the affected twins and their well co-twins on markers associated with fetal development before 13 or after 15 weeks estimated gestational age. CONCLUSIONS: Because the a-b ridges are known to complete development between 13 and 15 weeks estimated gestational age, the results provide physical evidence suggesting that the schizophrenia-affected monozygotic twins alone experienced a time-specific and time-limited dysgenesis during this time. Commonalities in the ontogeny of epidermal and neurological structures are discussed

Etiology of structural brain asymmetry in schizophrenia, an alternative hypothesis

During normal development of the fetal brain, the left hemisphere lags behind the right hemisphere in intrauterine growth, causing the left hemisphere to be smaller than the right hemisphere throughout the early and mid-prenatal period. By the end of the second trimester, the right hemisphere has achieved almost full-term size; thus second-trimester injuries affecting neurons, that is, anoxic, ischemic, toxic, or infectious insults that are systemic and bilateral, will affect the left hemisphere more than the right hemisphere. While other explanations for brain asymmetries in schizophrenia have been proposed, the embryological literature is consistent with the hypothesis that a prenatal injury may be one etiological factor in producing the structural brain asymmetries seen in psychotic adult patients

Assymetric rotational (circling) behavior, a dopamine-related asymmetry, preliminary findings in unmedicated and never-medicated schizophrenic patients

Circling behavior is one of the best understood behaviors in animals. It is, for the most part, dopaminergically mediated and related to asymmetry in dopaminergic activity between the left and right basal ganglia or left and right frontal cortex. As a rule, animals rotate toward the hemisphere with lower striatal dopaminergic activity. A direct technique to find human analogs of circling behavior was not available. We have developed an automated rotometer with which we can apply the circling rodent model to humans. Left-prone circling behavior (neglect of right-sided turning) was found in 10 unmedicated schizophrenic patients, whereas 85 normal controls demonstrated almost equal right and left turning. These preliminary results may suggest the presence of a dopaminergic asymmetry in some unmedicated schizophrenic patients; that is, right anterior subcortical or cortical structures of the brain may manifest a relative dopaminergic overactivity compared to left anterior structures in at least some unmedicated patients with schizophrenia

Phencyclidine and (+)-MK-801-induced circling preference: correlation with monoamine levels in striatum of the rat brain

Phencyclidine (PCP; angel dust) is a drug of abuse known to produce a behavioral state in humans resembling schizophrenia/psychosis. PCP is a noncompetitive NMDA receptor antagonist and produces a variety of behaviors in rats including circling. The behavioral effects of other noncompetitive NMDA receptor antagonists such as (+)-MK-801 are still being elucidated. Here, adult female rats were dosed with PCP (10 mg/kg, IP), or (+)-MK-801 (0.1 mg/kg, IP) and circling preference was recorded for 2 h before sacrifice to determine monoamine levels by HPLC/EC. Animals injected with PCP or (+)-MK-801 showed a preference to turn to the left (65% and 72%, respectively). PCP and (+)-MK-801 also produced a significant increase of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in whole striatum on both sides of the brain. Further dissection of the striatum into medioventral and dorsolateral regions revealed that HVA was increased bilaterally except in globus pallidus where we found significant increases in dopamine (DA), DOPAC, and HVA only on the left side after PCP and (+)-MK-801 administration. These data suggest that PCP and (+)-MK-801 produce a greater preference to turn left than right, a finding similar to that found in human psychosis. Furthermore, it is possible that this preference to turn toward the left hemispace is due to an asymmetry in dopamine function found in the globus pallidus after administration of PCP and similar drugs

Second-trimester markers of fetal size in schizophrenia: a study of monozygotic twins

OBJECTIVE: Since the second prenatal trimester is the critical period of massive neural cell migration to the cortex, and fingertip dermal cells migrate to form ridges during this same period, the authors sought to determine whether there are differences in fingertip ridge count in pairs of monozygotic twins discordant for schizophrenia, possibly indicating that a prenatal anatomical insult affected the twins differently. METHOD: The fingertip dermal ridges of 30 pairs of monozygotic twins (23 pairs in which the twins were discordant for schizophrenia and seven pairs in which both twins were normal) were counted by two persons trained in anthropometric research. Intrapair differences in the counts were then measured, and the differences among the pairs of normal twins were compared with the differences among the pairs discordant for schizophrenia. RESULTS: The twins discordant for schizophrenia had significantly greater absolute intrapair differences in total finger ridge count and significantly greater percent intrapair differences than the normal twins; i.e., their fingerprints were significantly less "twin-like." CONCLUSIONS: The study suggests that various second-trimester prenatal disturbances in the epigenesis of one twin in a pair discordant for schizophrenia may be related to the fact that only one of the twins expresses his or her genetic predisposition toward schizophrenia. This is consistent with a "two-strike" etiology of schizophrenia: a genetic diathesis plus a second-trimester environmental stressor

Subclinical microcrania, subclinical macrocrarnia, and fifth-month fetal markers (of growth retardation or edema) in schizophrenia: a co-twin control study of discordant monozygotic twins.

Summary: We tested the hypothesis that gestational injuries in some patients with schozophrenia would leave their mark as a subtle reduction in head circumference (subclinical microcrania). Conclusions: The head circumferences of all subjects were in the normal range. Decreased head circumference in affected MZ co-twins (relative to unaffected MZ co-twin) characteriazes discordant MZ pairs with larger finger-ridge-count differences (i.e., second-trimester fetal-size differences). This study using ideal genetic controls suggests that, while present only in some patients with schizophrenia, the decrease in head circumference is most likely a consequence of in-utero nonshared environmental deleterious events manifesting as groth retardation or as fetal edema and occurring around the fifth prenatal month

Correlation of severity of psychiatric patients' delusions with right hemispatial inattention (left-turning behavior)

Studies associate psychotic disorders with various forms of subtle inattention to the right hemispace (left-turning behavior). The authors examined the correlation between this dopamine-related sign and severity of delusions (presumably dopaminergic symptoms) in 20 psychotic patients. Delusions were significantly correlated with severity of left-turning bias, and this neurological sign accounted for 33% of the variance in severity of delusions

Tomophobia, the phobic fear caused by an invasive medical procedure - an emerging anxiety disorder: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tomophobia refers to fear or anxiety caused by forthcoming surgical procedures and/or medical interventions.</p> <p>Case presentation</p> <p>We present the case of a 69-year-old Caucasian man who refused urgently indicated medical intervention because of severe tomophobia.</p> <p>Conclusion</p> <p>Due to the rising number of surgical interventions in modern medicine, as well as the high number of unrecognised cases of tomophobia, this common but underdiagnosed anxiety disorder should be highlighted.</p

Neurodevelopmental risk factors in schizophrenia

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness

Evolutionism and genetics of posttraumatic stress disorder

The authors discuss, from the evolutionary concept, how flight and fight responses and tonic immobility can lead to a new understanding of posttraumatic stress disorder. Through the analysis of symptom clusters (revivals, avoidance and hyperexcitation), neurobiological and evolutionary findings are correlated. The current discoveries on posttraumatic stress disorder genetics are summarized and analyzed in this evolutionary perspective, using concepts to understand the gene-environment interaction, such as epigenetic. The proposal is that the research of susceptibility factors in posttraumatic stress disorder must be investigated from the factorial point of view, where their interactions increase the risk of developing the disorder, preventing a unique search of the cause of this disorder. The research of candidate genes in posttraumatic stress disorder must take into consideration all the systems associated with processes of stress response, such as the hypothalamus-pituitary-adrenal and sympathetic axes, mechanisms of learning, formation and extinguishing of declarative memories, neurogenesis and apoptosis, which involve many systems of neurotransmitters, neuropeptides and neurohormones.Os autores discutem, a partir do conceito evolutivo, como a resposta de estresse, nas suas possibilidades de fuga e luta e de imobilidade tônica, pode levar a uma nova compreensão etiológica do transtorno de estresse pós-traumático. Através da análise dos agrupamentos de sintomas desse diagnóstico - revivência, evitação e hiperexcitação -, procuram correlacionar os achados neurobiológicos e evolutivos. As descobertas atuais sobre a genética do transtorno de estresse pós-traumático são resumidas e colocadas nessa perspectiva evolutiva, dentro de conceitos que possibilitam o entendimento da interação gene/ambiente, como a epigenética. Propõem que a pesquisa dos fatores de risco do transtorno de estresse pós-traumático deva ser investigada do ponto de vista fatorial, onde a somatória destes aumenta o risco de desenvolvimento do quadro, não sendo possível a procura da causa do transtorno de forma única. A pesquisa de genes candidatos no transtorno de estresse pós-traumático deve levar em consideração todos os sistemas associados aos processos de respostas ao estresse, sistemas dos eixos hipotálamo-hipofisário-adrenal e simpático, mecanismos de aprendizado, formação de memórias declarativas, de extinção e esquecimento, da neurogênese e da apoptose, que envolvem vários sistemas de neurotransmissores, neuropeptídeos e neuro-hormônios.Universidade Federal de São Paulo (UNIFESP)(UNIFESP)UNIFESP Departamento de PsiquiatriaUniversidade de São Paulo Faculdade de Medicin Hospital de ClínicasUNIFESP, Depto. de PsiquiatriaSciEL