Psychobiological correlates of distress in pregnancy

Thesis (PhD (Psychiatry))--University of Stellenbosch, 2011.ENGLISH ABSTRACT: Pregnancy is often accompanied by distressing psychological symptoms such as anxiety. These symptoms may result from changes in cognitive-affective processing, which in turn reflect hormonal changes during this time. However, findings on associations between psychological distress, cognitive-affective changes and hormones have been inconsistent. Furthermore, few studies have investigated the neural circuitry underlying distress and cognitive-affective processing in pregnancy. The prefrontal cortex (PFC) plays a specific role in regulating emotion. Determining the relationship between these changes in cognitive-affective processing and in prefrontal circuitry is important, given the high prevalence of depressive and anxiety disorders in pregnancy. The overall objective of this study was to investigate distressing psychological symptoms and their association with cognitive-affective processes and neurobiological changes over the course of pregnancy. Pregnant women with low risk singleton pregnancies were recruited from Midwife Obstetric Units in the Western Cape. Non-pregnant healthy controls were also recruited from the same demographic area. Distress levels were assessed using the K-10, Spielberger State -Trait Inventory, and Perceived Stress Scale. Subjectively experienced cognitive ability was asked about. Objective cognitive ability was assessed using standardized neuropsychological tests. Selective attention to threat such as fear and anger was assessed using a Facial Stroop Task. Neural circuitry was assessed using Near-Infrared Spectroscopy while viewing dynamic emotional facial expressions of threat (Emotion Recognition Task). Glucocorticoid (cortisol) and gonadal hormonal levels (estrogen, progesterone, and testosterone) were also determined at each trimester of pregnancy. Associations between distressing psychological symptoms, cognitive-affective processes and neurobiology were assessed using standard statistical methods. The main findings to emerge from this research were that, 1. pregnant women had significantly higher trait anxiety at trimester 2, compared to trimester 1 of pregnancy; 2. compared to non-pregnant women, pregnant women paid significantly more attention to fearful faces across trimesters, suggesting altered cognitive-affective processing in pregnancy compared to non-pregnancy; 3. pregnant women demonstrated significantly increased PFC activation in response to fearful and angry faces (all trimesters) that was particularly evident at trimester 2; 4. the PFC activation was, across trimesters, significantly correlated with distress and selective attention to threat; and 5. the PFC activation was, across trimesters, also significantly associated with increased glucocorticoid and gonadal hormone levels. The main findings of this study are consistent with previous literature insofar as distress has previously been associated with altered cognitive-affective processing and prefrontal cortex activation, but extend it by showing that emotional regulation is altered in pregnancy compared to the non-pregnant state. These data provide an important insight into distressing psychological symptoms and their associations with cognitive-affective processes, and changes in neural circuitry and in hormone levels in pregnancy. These findings are also the first to show that structures involved in emotional processing (e.g. the PFC) also play a role in the regulation of affect in pregnancy. Future research should explore the causal mechanisms underlying altered emotional regulation in pregnancy, and include pregnant women that are clinically depressed or anxious as comparison subjects.AFRIKAANSE OPSOMMING: Swangerskap word dikwels geassosieër met stres-veroorsakende sielkundige simptome soos angstigheid. Hierdie simptome mag die gevolg wees van veranderinge in kognitief-affektiewe prosessering, wat op sy beurt mag dui op hormonale veranderinge. Bevindinge oor assosiasies tussen sielkundige stres, kognitief-affektiewe prosessering en hormone is tot dusver onbeslis. Voorts was min studies gerig op die neurologiese meganika onderliggend aan stres en kognitief-affektiewe prosessering tydens swangerskap. Die prefrontale korteks (PFK) het 'n spesifieke rol in die regulering van emosie. Die bepaling van spesifieke assosiasies tussen veranderinge in kognitief-affektiewe prosessering en in prefrontale regulering is belangrik, gegewe die hoë voorkoms van toestande soos depressie en angssteurings tydens swangerskap. Die doel met hierdie studie was 'n ondersoek na assosiasies tussen stres-veroorsakende sielkundige simptome, kognitief-affektiewe prosesse en neurobiologie tydens swangerskap. Swanger vroue met lae risiko enkel-swangerskappe is gewerf by klinieke in Wes-Kaapland. Gesonde nie-swanger vroue is uit dieselfde omgewing gewerf as kontroles. Angs-vlakke is geevalueer met behulp van die K-10; die Spielberger State-Trait Inventory en die Perceived Stress Scale. Vrae is tydens ondersoeke gevra oor subjektief-ervaarde kognitiewe vermoë. Voorts is kognitiewe vermoë geëvalueer met behulp van gestandardiseerde neurosielkundige toetse. Hierbenewens is selektiewe aandag aan bedreigende gesigte wat vrees en woede toon, geëvalueer met behulp van 'n Facial Stroop Task. Neurologiese funksie is geëvalueer met gebruik van Na-Infrarooi Spektroskopie terwyl dinamiese bedreigende emosionele gesigsuitdrukkings vertoon is (Emotion Recognition Task). Gluko-kortikoïed (kortisol) en geslagshormoonvlakke (estrogeen, progesteroon, en testosteroon) is gemeet tydens elke trimester. Verwantskappe tussen stresvolle simptome, kognitief-affektiewe prosessering en neurobiologie is geëvalueer met standaard statistiese metodes. Die hoofbevindinge het op die volgende gedui: 1. swanger vroue het betekenisvolle hoër trait angs-vlakke getoon in trimester 2, vergeleke met trimester 1; 2. vergeleke met nie-swanger vroue, het swanger vroue beduidend meer aandag geskenk aan angstige gesigsuitdrukkings tydens elke trimester wat mag dui op veranderde kognitief-affektiewe prosessering tydens swangerskap vergeleke met nie-swangerskap; 3. swanger vroue het beduidend hoër PFK aktivering getoon teenoor angstige en kwaai gesigte in alle trimesters, maar veral in trimester 2; 4. swanger vroue se PFK aktivering het, in alle trimesters, beduidend gekorreleer het met stres-vlakke en selektiewe aandag teenoor bedreigende stimuli; en 5. swanger vroue se PFK aktivering het, in alle trimesters, ook 'n beduidende verwantskap getoon met verhoogde gluko-kortikoïed en geslagshormoonvlakke. Die hoofbevindinge in hierdie studie stem ooreen met vorige literatuur wat aangedui het dat daar 'n verband is tussen stres en veranderinge in kognitief-affektiewe prosessering en in prefrontale korteks aktivering, maar dui verder op veranderinge in emosionele regulering tydens swangerskap vergeleke met nie-swangerskap. Die data bied 'n belangrike insig in stres-veroorsakende sielkundige simptome; hul verwantskap met kognitief-affektiewe prosesse; veranderinge in neurologiese netwerke; en veranderinge in hormoonvlakke tydens swangerskap. Sover bekend is dit ook die eerste keer bevind dat strukture wat betrokke is by emosionele prosessering (bv. die PFK), ook betrokke is in die regulering van emosie tydens swangerskap. Dit is belangrik dat toekomstige navorsing die onderliggende meganismes wat veranderinge in emosionele regulering teweeg bring, ondersoek. Verdere ondersoek om hierdie veranderinge in swanger depressie-lyers of diegene met angssteurings te vergelyk is ook van belang

Validation of a rating scale for bedside cognitive assessment

Thesis (MMed)--University of Stellenbosch, 2004.ENGLISH ABSTRACT: Numerous tests exist for the assessment of general cognitive functioning. Most of these tests were developed within the discipline of psychology. Neuropsychological tests are very useful, but have some limitations. Administration of the tests is limited to a psychologist, is very timeconsuming in that it can take 3-8 hours to administer and often need specialized equipment. At the other end of the continuum are very brief screening tests. General practitioners, psychiatrists and occupational therapists, in addition to psychologists, also use these tests. Although useful, the short tests only provide limited information. An intermediate level test streamlining the assessment process between the very short and longer neuropsychological tests is therefore introduced by this study. The Bedside Cognitive Assessment Battery (BCAB) was developed in 1995 and are since used, at Tygerberg Hospital's Memory Clinic, to assess patients and teach students. The test comprehensively assesses the six main classes of cognitive functioning, namely attention and concentration, speech, memory, motor functioning, perceptual functioning and executive functioning. Approximately 35-45 minutes is required for administration and training is needed to administer the BCAB. No specialized equipment is needed for administration. The battery can therefore be used at the bedside, in the office or at old age homes. The aims of this study were to validate the BCAB for use with people aged eighteen years and older, and provide normative values for use in clinical settings. The test was revised in 1997 and 2001, and extensively so in 2002, but was never formally evaluated for validity. Well-known single tests were used to compile the BCAB. Most of these tests have proven validity and reliability, but only for foreign populations. In addition, some items were reformulated and others created by the researchers. The introduction of normative values would also be useful to assist in the delineation of cognitively intact and impaired individuals. This study succeeded in providing a table of normative values. One-hundred-and-sixty Afrikaans and English participants, and fourteen Xhosa participants were assessed in their mother tongue language. This project thus also introduced a Xhosa version of the BCAB. The purpose of the Xhosa version was to address the lack of culturally relevant cognitive assessment instruments. Results were evaluated for the effects of the variables' language, gender, age and education. The effect of language was most noticeable in the Xhosa group. Gender did not affect results as dramatically as age and especially, education. These significant effects on the aforementioned variables have been described in previous reports. The BCAB is thus relevant and useful as a detector of mild to moderate impairment. It can also be used to identify specific impairment. This can narrow down the investigation of psychologists, thus saving time and money. In addition, medical and nonmedical staff can use the BCAB. Some limitations were also identified. The sample used may limit the generalization of results. Some test items also need revision, along with further validation studies. Clinicians are therefore advised to use the BCAB only in addition to complete clinical examinations when making decisions regarding a patient's cognitive status. The BCAB appears to be a valid tool for bedside assessment. However, this study could only set the stage for further research, especially studies concerned with establishing normative values.AFRIKAANSE OPSOMMING: Verskeie toetse bestaan vir die evaluering van algemene kognitiewe funksionering, waarvan die meeste ontwikkel is binne die sielkunde. Neuro-sielkundige toetse is baie bruikbaar, maar het sekere beperkings. Administrasie van die toetse is beperk tot sielkundiges, maar tydrowend weens 'n tydsduur van drie tot agt uur, en verg dikwels gespesialiseerde toerusting. Aan die ander kant is heelwat kart siftings-toetse beskikbaar. Aigemene praktisyns, sielkundiges en arbeidsterapeute, asook sielkundiges, gebruik dit. Hoewel bruikbaar, bied die kart toetse beperkte inligting. 'n lntermediere vlak toets om die evaluerings-proses tussen kart en langer neuro-sielkundige toetse te integreer word met hierdie studie beoog. Die Bedkant Kognitiewe Evaluasie Battery (BKEB) is in 1995 ontwikkel en gebruik in die Geheue-kliniek van die Tygerberg Hospitaal om pasiente te evalueer en studente op te lei. Die toets is gerig op die omvattende evaluering van die ses hoof-klasse van kognitiewe funksionering. Hierdie klasse omvat aandag en konsentrasie, spraak, geheue, motoriese funksionering, perseptuele funksionering en uitvoerende funksionering. Sowat 35 tot 45 minute word benodig vir administrasie terwyl opleiding vereis word vir die neem van die toets. Geen gespesialiseerde toerusting is nodig nie. Die battery kan dus by die bedkant, in die kantoor of in ouetehuise gebruik word. Die doelwitte van hierdie studie is om die BKEB te evalueer in gebruik by 18-jariges en ouer, en normatiewe waardes te bepaal vir gebruik in kliniese omgewings. Die toets is in 1997 en 2001 hersien. In 2002 is dit uitvoerig hersien, maar nooit ge-evalueer vir geldigheid nie. Bekende enkel-toetse is gebruik am die BKEB saam te stel. Dit is as geldig en betroubaar bewys, hoewel slegs onder buitelandse bevolkingsgroepe. Hierbenewens is sekere items herformuleer en ander bygewerk deur die navorsers. Normatiewe waardes sal oak handig wees in die afbakening van kognitief normaal-funksionerende en kognitief-ingekorte individue. Hierdie studie het daarin geslaag am 'n tabel van normatiewe waardes daar te stel. Een-honderd-en-sestig Afrikaans- en Engels-sprekendes, en 14 Xhosa-sprekendes is tydens hierdie studie in hulle moedertaal ge-evalueer. Hierdie projek het dus oak 'n Xhosaweergawe van die BKEB geskep. Die doel van die Xhosa-weergawe was am die gebrek aan 'n kultureel toepaslike kognitiewe instrument te beklemtoon. Resultate is ge-evalueer gedagtig aan veranderlikes soos taal, geslag, ouderdom en opleidingsvlak. Taal het die grootste invloed gehad op uitslae van Xhosa-deelnemers. Geslag het nie die uitslae so dramaties bernvloed soos ouderdom, en veral opleidingsvlak nie. Literatuur het meestal die groot uitwerking van hierdie veranderlikes bevestig. Die BKEB is dus relevant en handig in die naspeuring van ligte tot matige kognitiewe ingekortheid. Dit kan ook gebruik word om spesifieke kognitiewe ingekortheid te identifiseer. Die kan die omvang van ondersoek deur sielkundiges vernou, wat kan lei tot In groot besparing in tyd en geld. Hierbenewens kan mediese en nie-mediese personeel aangewend word in die gebruik van die BKEB. Sekere tekortkominge is ge·,dentifiseer. Die steekproef mag egter die veralgemening van die uitslae beperk. Sekere toets-items mag ook hersiening vereis, tesame met verdere geldigheid-studies. Kliniese praktisyns word daarom aangeraai om die BKEB slegs in aanvulling tot omvattende kliniese ondersoeke te gebruik vir besluite m.b.t. In pasient se kognitiewe status. Die BKEB kom voor as In geldige instrument vir bedkant evaluering. Hierdie studie kon egter slegs die tafel dek vir verdere ondersoek, veral t.o.v. studies wat poog om normatiewe waardes daar te stel

Risk factors for substance use in pregnant women in South Africa

Objectives. To study the prevalence of alcohol and substance use in a South African antenatal population and its correlates with socio-demographic factors, depression and perceived stress. Methods. A prospective self-report study on all women presenting for their first antenatal visit who consented to the study at a midwife obstetric unit (MOU) in the East Metropole district, Cape Town, using the Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), Edinburgh Depression Scale (EDS) and Perceived Stress Scale (PSS). Statistical analyses using the chi-square test, separate one-way analyses of variance (ANOVA) and logistic regression analyses were performed as appropriate. Outcome measures were depression, alcohol use and substance use. Results. The questionnaire was completed by 323 women. During pregnancy 36.8% of women smoked, 20.2% used alcohol and 4% used substances. Using EDS cut-off scores of 12 and 15, respectively, 48.9% and 33.6% of the sample had scores consistent with major depression. An EDS cut-off score of 12 was significantly associated with both alcohol use (25.9% v. 15.2%, p=0.019) and risky drinking (76.9% v. 36.8%, p=0.04), while an EDS cut-off score of 15 was significantly associated with substance use (8.2% v. 1.4%, p=0.004) as well as alcohol dependence (23.1% v. 3.1%). Conclusions. We found high rates of both alcohol abuse and antenatal depression, and a significant association between depression, substance use and alcohol abuse; EDS scores greater than 12 could be used to identify women at risk of alcohol dependence and/or substance abuse

Assessing cognition in children with prenatal methamphetamine exposure in South Africa

CITATION: Roos, A., Stein, D. J. & Donald, K. A. 2019. Assessing cognition in children with prenatal methamphetamine exposure in South Africa. Comprehensive Psychiatry, 95:152111, doi:10.1016/j.comppsych.2019.07.005.The original publication is available at https://www.sciencedirect.comNo abstract available.https://www.sciencedirect.com/science/article/pii/S0010440X19300355Publisher's versio

Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study.

Magnetic resonance imaging (MRI) is an indispensable tool for investigating brain development in young children and the neurobiological mechanisms underlying developmental risk and resilience. Sub-Saharan Africa has the highest proportion of children at risk of developmental delay worldwide, yet in this region there is very limited neuroimaging research focusing on the neurobiology of such impairment. Furthermore, paediatric MRI imaging is challenging in any setting due to motion sensitivity. Although sedation and anesthesia are routinely used in clinical practice to minimise movement in young children, this may not be ethical in the context of research. Our study aimed to investigate the feasibility of paediatric multimodal MRI at age 2-3 years without sedation, and to explore the relationship between cortical structure and neurocognitive development at this understudied age in a sub-Saharan African setting. A total of 239 children from the Drakenstein Child Health Study, a large observational South African birth cohort, were recruited for neuroimaging at 2-3 years of age. Scans were conducted during natural sleep utilising locally developed techniques. T1-MEMPRAGE and T2-weighted structural imaging, resting state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy sequences were included. Child neurodevelopment was assessed using the Bayley-III Scales of Infant and Toddler Development. Following 23 pilot scans, 216 children underwent scanning and T1-weighted images were obtained from 167/216 (77%) of children (median age 34.8 months). Furthermore, we found cortical surface area and thickness within frontal regions were associated with cognitive development, and in temporal and frontal regions with language development (beta coefficient ?0.20). Overall, we demonstrate the feasibility of carrying out a neuroimaging study of young children during natural sleep in sub-Saharan Africa. Our findings indicate that dynamic morphological changes in heteromodal association regions are associated with cognitive and language development at this young age. These proof-of-concept analyses suggest similar links between the brain and cognition as prior literature from high income countries, enhancing understanding of the interplay between cortical structure and function during brain maturation

Central white matter integrity alterations in 2-3-year-old children following prenatal alcohol exposure.

BACKGROUND: Prenatal alcohol exposure (PAE) remains a potentially preventable, but pervasive risk factor to neurodevelopment. Yet, evidence is lacking on the impact of alcohol on brain development in toddlers. This study aimed to investigate the impact of PAE on brain white matter integrity in 2-3-year-old children. METHODS: Children (n = 83, 30-37 months old) of the Drakenstein Child Health Study birth cohort, underwent diffusion MRI on a 3 T Siemens scanner during natural sleep. Parameters were extracted in children with PAE (n = 25, 56 % boys) and unexposed controls (n = 58, 62 % boys) using Tract-based Spatial Statistics, and compared by group. The contribution of maternal tobacco smoking to white matter differences was also explored. RESULTS: Children with PAE had altered fractional anisotropy, radial diffusivity and axial diffusivity in brain stem, limbic and association tracts compared to unexposed controls. Notably lower fractional anisotropy was found in the uncinate fasciculus, and lower mean and radial diffusivity were found in the fornix stria terminalis and corticospinal tract (FDR corrected p < 0.05). There was a significant interaction effect of PAE and prenatal tobacco exposure which lowered mean, radial and axial diffusivity in the corticospinal tract significantly in the PAE group but not controls. CONCLUSION: Widespread altered white matter microstructural integrity at 2-3 years of age is consistent with findings in neonates in the same and other cohorts, indicating persistence of effects of PAE through early life. Findings also highlight that prenatal tobacco exposure impacts the association of PAE on white matter alterations, amplifying effects in tracts underlying motor function

Subcortical brain volumes in young infants exposed to antenatal maternal depression: Findings from a South African birth cohort.

BACKGROUND: Several studies have reported enlarged amygdala and smaller hippocampus volumes in children and adolescents exposed to maternal depression. It is unclear whether similar volumetric differences are detectable in the infants' first weeks of life, following exposure in utero. We investigated subcortical volumes in 2-to-6 week old infants exposed to antenatal maternal depression (AMD) from a South African birth cohort. METHODS: AMD was measured with the Beck Depression Inventory 2nd edition (BDI-II) at 28-32 weeks gestation. T2-weighted structural images were acquired during natural sleep on a 3T Siemens Allegra scanner. Subcortical regions were segmented based on the University of North Carolina neonatal brain atlas. Volumetric estimates were compared between AMD-exposed (BDI-II ⩾ 20) and unexposed (BDI-II < 14) infants, adjusted for age, sex and total intracranial volume using analysis of covariance. RESULTS: Larger volumes were observed in AMD-exposed (N = 49) compared to unexposed infants (N = 75) for the right amygdala (1.93% difference, p = 0.039) and bilateral caudate nucleus (left: 5.79% difference, p = 0.001; right: 6.09% difference, p < 0.001). A significant AMD-by-sex interaction was found for the hippocampus (left: F(1,118) = 4.80, p = 0.030; right: F(1,118) = 5.16, p = 0.025), reflecting greater volume in AMD-exposed females (left: 5.09% difference, p = 0.001, right: 3.54% difference, p = 0.010), but not males. CONCLUSIONS: Volumetric differences in subcortical regions can be detected in AMD-exposed infants soon after birth, suggesting structural changes may occur in utero. Female infants might exhibit volumetric changes that are not observed in male infants. The potential mechanisms underlying these early volumetric differences, and their significance for long-term child mental health, require further investigation

Early structural brain development in infants exposed to HIV and antiretroviral therapy in utero in a South African birth cohort.

INTRODUCTION: There is a growing population of children who are HIV-exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV-unexposed (HU). METHODS: Magnetic resonance imaging using a T2-weighted sequence was undertaken in a subgroup of infants aged 2-6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Mother-child pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio-economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure. RESULTS: One hundred forty-six infants (40 HEU; 106 HU) with high-resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (<350 cells/mm3 ) was associated with decreased infant grey matter volumes. There was no relationship between timing of ART exposure and grey matter volumes. CONCLUSIONS: Lower caudate and total grey matter volumes were found in infants who were HEU compared to HU in the first weeks of life, and maternal immunosuppression was associated with reduced volumes. These findings suggest that antenatal HIV exposure may impact early structural brain development and improved antenatal HIV management may have the potential to optimize neurodevelopmental outcomes of children who are HEU