Preschool anxiety disorders predict different patterns of amygdala-prefrontal connectivity at school-age.

OBJECTIVE: In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. METHODS: Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. RESULTS: A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. CONCLUSIONS: Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders.

How common are common mental disorders? Evidence that lifetime prevalence rates are doubled by prospective versus retrospective ascertainment.

BACKGROUND: Most information about the lifetime prevalence of mental disorders comes from retrospective surveys, but how much these surveys have undercounted due to recall failure is unknown. We compared results from a prospective study with those from retrospective studies. METHOD: The representative 1972-1973 Dunedin New Zealand birth cohort (n=1037) was followed to age 32 years with 96% retention, and compared to the national New Zealand Mental Health Survey (NZMHS) and two US National Comorbidity Surveys (NCS and NCS-R). Measures were research diagnoses of anxiety, depression, alcohol dependence and cannabis dependence from ages 18 to 32 years. RESULTS: The prevalence of lifetime disorder to age 32 was approximately doubled in prospective as compared to retrospective data for all four disorder types. Moreover, across disorders, prospective measurement yielded a mean past-year-to-lifetime ratio of 38% whereas retrospective measurement yielded higher mean past-year-to-lifetime ratios of 57% (NZMHS, NCS-R) and 65% (NCS). CONCLUSIONS: Prospective longitudinal studies complement retrospective surveys by providing unique information about lifetime prevalence. The experience of at least one episode of DSM-defined disorder during a lifetime may be far more common in the population than previously thought. Research should ask what this means for etiological theory, construct validity of the DSM approach, public perception of stigma, estimates of the burden of disease and public health policy.

The impact of anxiety-inducing distraction on cognitive performance: a combined brain imaging and personality investigation.

BACKGROUND: Previous investigations revealed that the impact of task-irrelevant emotional distraction on ongoing goal-oriented cognitive processing is linked to opposite patterns of activation in emotional and perceptual vs. cognitive control/executive brain regions. However, little is known about the role of individual variations in these responses. The present study investigated the effect of trait anxiety on the neural responses mediating the impact of transient anxiety-inducing task-irrelevant distraction on cognitive performance, and on the neural correlates of coping with such distraction. We investigated whether activity in the brain regions sensitive to emotional distraction would show dissociable patterns of co-variation with measures indexing individual variations in trait anxiety and cognitive performance. METHODOLOGY/PRINCIPAL FINDINGS: Event-related fMRI data, recorded while healthy female participants performed a delayed-response working memory (WM) task with distraction, were investigated in conjunction with behavioural measures that assessed individual variations in both trait anxiety and WM performance. Consistent with increased sensitivity to emotional cues in high anxiety, specific perceptual areas (fusiform gyrus--FG) exhibited increased activity that was positively correlated with trait anxiety and negatively correlated with WM performance, whereas specific executive regions (right lateral prefrontal cortex--PFC) exhibited decreased activity that was negatively correlated with trait anxiety. The study also identified a role of the medial and left lateral PFC in coping with distraction, as opposed to reflecting a detrimental impact of emotional distraction. CONCLUSIONS: These findings provide initial evidence concerning the neural mechanisms sensitive to individual variations in trait anxiety and WM performance, which dissociate the detrimental impact of emotion distraction and the engagement of mechanisms to cope with distracting emotions. Our study sheds light on the neural correlates of emotion-cognition interactions in normal behaviour, which has implications for understanding factors that may influence susceptibility to affective disorders, in general, and to anxiety disorders, in particular.

Autobiographical memories of anxiety-related experiences.

Ninety-nine undergraduate students retrieved three memories associated with each of the five emotional experiences: panic, trauma, worry, social anxiety, and feeling content. Subsequently, they answered 24 questions assessing properties of each memory, including the vividness and perceived accuracy of the memories and sensory, emotional, and anxiety-related experiences during retrieval. Memories were coded for affective tone and specificity. Results indicated that panic-related and trauma-related memories were rated similarly as content memories, but that they generally were associated with more imagery and emotional experiencing than worry-related or social anxiety-related memories. Participants experienced panic and worry symptoms to the greatest degree when they retrieved panic-related and trauma-related memories. All anxiety-related memories were characterized by more negative tone than content memories. Panic-related and trauma-related memories were more specific than worry-related, social anxiety-related, and content memories. These findings can explain partially why individuals with some, but not all, anxiety disorders experience enhanced memory for threatening material.

Changes in neuroticism following trauma exposure.

Using longitudinal data, the present study examined change in midlife neuroticism following trauma exposure. Our primary analyses included 670 participants (M(age) = 60.55; 65.22% male, 99.70% Caucasian) who completed the NEO Personality Inventory at ages 42 and 50 and reported their lifetime exposure to traumatic events approximately 10 years later. No differences in pre- and post-trauma neuroticism scores were found among individuals who experienced all of their lifetime traumas in the interval between the personality assessments. Results were instead consistent with normative age-related declines in neuroticism throughout adulthood. Furthermore, longitudinal changes in neuroticism scores did not differ between individuals with and without histories of midlife trauma exposure. Examination of change in neuroticism following life-threatening traumas yielded a comparable pattern of results. Analysis of facet-level scores largely replicated findings from the domain scores. Overall, our findings suggest that neuroticism does not reliably change following exposure to traumatic events in middle adulthood. Supplemental analyses indicated that individuals exposed to life-threatening traumas in childhood or adolescence reported higher midlife neuroticism than individuals who experienced severe traumas in adulthood. Life-threatening traumatic events encountered early in life may have a more pronounced impact on adulthood personality than recent traumatic events.

Practices and outcomes of self-treatment with helminths based on physicians' observations.

The successful use of helminths as therapeutic agents to resolve inflammatory disease was first recorded 40 years ago. Subsequent work in animal models and in humans has demonstrated that the organisms might effectively treat a wide range of inflammatory diseases, including allergies, autoimmune disorders and inflammation-associated neuropsychiatric disorders. However, available information regarding the therapeutic uses and effects of helminths in humans is limited. This study probes the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians. Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.

Serotonin synthesis, release and reuptake in terminals: a mathematical model.

BACKGROUND: Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system. METHODS: We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data. RESULTS: We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct in silico experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine. CONCLUSIONS: Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.

Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3.

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

People who expect to enter psychotherapy are prone to believing that they have forgotten memories of childhood trauma and abuse.

We asked 1004 undergraduates to estimate both the probability that they would enter therapy and the probability that they experienced but could not remember incidents of potentially life-threatening childhood traumas or physical and sexual abuse. We found a linear relation between the expectation of entering therapy and the belief that one had, but cannot now remember, childhood trauma and abuse. Thus individuals who are prone to seek psychotherapy are also prone to accept a suggested memory of childhood trauma or abuse as fitting their expectations. In multiple regressions predicting the probability of forgotten memories of childhood traumas and abuse, the expectation of entering therapy remained as a substantial predictor when self-report measures of mood, anxiety, post-traumatic stress disorder symptom severity, and trauma exposure were included.

Monitoring maternal Beta carotene and retinol consumption may decrease the incidence of neurodevelopmental disorders in offspring.

Retinoic acids (13-cis and 13-trans) are known teratogens, and their precursor is retinol, a form of vitamin A. In 1995, Rothman et al demonstrated an association between excessive vitamin A, >10,000 IU/day, during the first trimester of pregnancy and teratogenic effects, particularly in the central nervous system. However, vitamin A deficiency has long been known to be deleterious to the mother and fetus. Therefore, there may be a narrow therapeutic ratio for vitamin A during pregnancy that has not previously been fully appreciated. Neurodevelopmental disorders may not be apparent by macroscopic brain examination or imaging, and proving the existence of a behavioral teratogen is not straightforward. However, an excess of retinoic acid and some neurodevelopmental disorders are both associated with abnormalities in cerebellar morphology. Physical and chemical evidence strongly supports the notion that beta carotene crosses the placenta and is metabolized to retinol. Only very limited amounts of beta carotene are stored in fetal fat cells as evidenced by the fact that maternal fat is yellow from beta carotene, whereas non-brown neonatal fat is white. Furthermore, newborns of carotenemic mothers do not share the yellow complexion of their mothers. The excess 13-trans retinoic acid derived from metabolized beta carotene in the fetus increases the concentration of the more teratogenic 13-cis retinoic acid since the isomerization equilibrium is shifted to the left. Therefore, this paper proposes that consideration be given to monitoring all potential sources of fetal 13-cis and 13-trans retinoic acid, including nutritional supplements, dietary retinol, and beta carotene, particularly in the first trimester of pregnancy.

Substance use disorders and co-morbidities among Asian Americans and Native Hawaiians/Pacific Islanders

© Cambridge University Press 2014.Background Asian Americans (AAs) and Native Hawaiians/Pacific Islanders (NHs/PIs) are the fastest growing segments of the US population. However, their population sizes are small, and thus AAs and NHs/PIs are often aggregated into a single racial/ethnic group or omitted from research and health statistics. The groups' substance use disorders (SUDs) and treatment needs have been under-recognized. Method We examined recent epidemiological data on the extent of alcohol and drug use disorders and the use of treatment services by AAs and NHs/PIs. Results NHs/PIs on average were less educated and had lower levels of household income than AAs. Considered as a single group, AAs and NHs/PIs showed a low prevalence of substance use and disorders. Analyses of survey data that compared AAs and NHs/PIs revealed higher prevalences of substance use (alcohol, drugs), depression and delinquency among NHs than among AAs. Among treatment-seeking patients in mental healthcare settings, NHs/PIs had higher prevalences of DSM-IV diagnoses than AAs (alcohol/drug, mood, adjustment, childhood-onset disruptive or impulse-control disorders), although co-morbidity was common in both groups. AAs and NHs/PIs with an SUD were unlikely to use treatment, especially treatment for alcohol problems, and treatment use tended to be related to involvement with the criminal justice system. Conclusions Although available data are limited by small sample sizes of AAs and NHs/PIs, they demonstrate the need to separate AAs and NHs/PIs in health statistics and increase research into substance use and treatment needs for these fast-growing but understudied population groups.

Psychiatric correlates of snuff and chewing tobacco use.

Compared to the association between cigarette smoking and psychiatric disorders, relatively little is known about the relationship between smokeless tobacco use and psychiatric disorders. To identify the psychiatric correlates of smokeless tobacco use, the analysis used a national representative sample from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) wave 1. Smokeless tobacco use was classified as exclusive snuff use, exclusive chewing tobacco, and dual use of both snuff and chewing tobacco at some time in the smokeless tobacco user's life. Lifetime psychiatric disorders were obtained via structured diagnostic interviews. The results show that the prevalence of lifetime exclusive snuff use, exclusive chewing tobacco, and dual use of both snuff and chewing tobacco was 2.16%, 2.52%, and 2.79%, respectively. After controlling for sociodemographic variables and cigarette smoking, the odds of exclusive chewing tobacco in persons with panic disorder and specific phobia were 1.53 and 1.41 times the odds in persons without those disorders, respectively. The odds of exclusive snuff use, exclusive chewing tobacco, and dual use of both products for individuals with alcohol use disorder were 1.97, 2.01, and 2.99 times the odds for those without alcohol use disorder, respectively. Respondents with cannabis use disorder were 1.44 times more likely to use snuff exclusively than those without cannabis use disorder. Respondents with inhalant/solvent use disorder were associated with 3.33 times the odds of exclusive chewing tobacco. In conclusion, this study highlights the specific links of anxiety disorder, alcohol, cannabis, and inhalant/solvent use disorders with different types of smokeless tobacco use.

Challenges in the diagnosis and treatment of depression in autism spectrum disorders across the lifespan.

Diagnosis and treatment of comorbid neuropsychiatric illness is often a secondary focus of treatment in individuals with autism spectrum disorder (ASD), given that substantial impairment may be caused by core symptoms of ASD itself. However, psychiatric comorbidities, including depressive disorders, are common and frequently result in additional functional impairment, treatment costs, and burden on caregivers. Clinicians may struggle to appropriately diagnose depression in ASD due to communication deficits, atypical presentation of depression in ASD, and lack of standardized diagnostic tools. Specific risk and resilience factors for depression in ASD across the lifespan, including level of functioning, age, family history, and coping style, have been suggested, but require further study. Treatment with medications or psychotherapy may be beneficial, though more research is required to establish guidelines for management of symptoms. This review will describe typical presentations of depression in individuals with ASD, review current information on the prevalence, assessment, and treatment of comorbid depression in individuals with ASD, and identify important research gaps.

New World Gold Cultural Anxiety and Monetary Disorder in Early Modern Spain

Elvira Vilches examines economic treatises, stories of travel and conquest, moralist writings, fiction, poetry, and drama to reveal that New World gold ultimately became a problematic source of power that destabilized Spain’s sense of ...

Improving mental health among people living with HIV: a review of intervention trials in low- and middle-income countries.

People living with HIV (PLWH) experience greater psychological distress than the general population. Evidence from high-incomes countries suggests that psychological interventions for PLWH can improve mental health symptoms, quality of life, and HIV care engagement. However, little is known about the effectiveness of mental health interventions for PLWH in low and middle-income countries (LMICs), where the large majority of PLWH reside. This systematized review aims to synthesize findings from mental health intervention trials with PLWH in LMICs to inform the delivery of mental health services in these settings. A systematic search strategy was undertaken to identify peer-reviewed published papers of intervention trials addressing negative psychological states or disorders (e.g., depression, anxiety) among PLWH in LMIC settings. Search results were assessed against pre-established inclusion and exclusion criteria. Data from papers meeting criteria were extracted for synthesis. Twenty-six papers, published between 2000 and 2014, describing 22 unique interventions were identified. Trials were implemented in sub-Saharan Africa (n=13), Asia (n=7), and the Middle East (n=2), and addressed mental health using a variety of approaches, including cognitive-behavioral (n=18), family-level (n=2), and pharmacological (n=2) treatments. Four randomized controlled trials reported significant intervention effects in mental health outcomes, and eleven preliminary studies demonstrated promising findings. Among the limited mental health intervention trials with PLWH in LMICs, few demonstrated efficacy. Mental health interventions for PLWH in LMICs must be further developed and adapted for resource-limited settings to improve effectiveness.