Volume 36 - August 2016
Original article
Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers
- A. Modabbernia, E. Velthorst, C. Gennings, L. De Haan, C. Austin, A. Sutterland, J. Mollon, S. Frangou, R. Wright, M. Arora, A. Reichenberg
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- Published online by Cambridge University Press:
- 23 March 2020, pp. 1-6
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Background
Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia.
MethodsWe analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb2+), manganese (Mn2+), cadmium (Cd2+), copper (Cu2+), magnesium (Mg2+), and zinc (Zn2+), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry.
ResultsWe found higher early-life Pb2+ exposure among patients with schizophrenia than controls. The differences in log Mn2+ and log Cu2+ changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb2+ levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb2+ levels and adult IQ.
ConclusionsIn our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.
Long-term antipsychotic use and its association with outcomes in schizophrenia – the Northern Finland Birth Cohort 1966
- J.M. Moilanen, M. Haapea, E. Jääskeläinen, J.M. Veijola, M.K. Isohanni, H.J. Koponen, J. Miettunen
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- 23 March 2020, pp. 7-14
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Background
Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes.
MethodsThe sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers.
ResultsDuring the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319 mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score.
ConclusionsIn our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.
Mental health, migration stressors and suicidal ideation among Latino immigrants in Spain and the United States
- L.R. Fortuna, K. Álvarez, Z. Ramos Ortiz, Y. Wang, X. Mozo Alegría, B.L. Cook, M. Alegría
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- Published online by Cambridge University Press:
- 23 March 2020, pp. 15-22
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Background
Immigration stress appears to augment the risk for suicide behaviors for Latinos. Yet, specific risk factors that contribute to suicidal ideation (SI) among diverse Latino immigrant populations are not well established.
MethodsData were collected in Boston, Madrid and Barcelona using a screening battery assessing mental health, substance abuse risk, trauma exposure, demographics, and sociocultural factors. Prevalence rates of lifetime and 30-day SI were compared across sites. Logistic regression modeling was used to identify sociodemographic, clinical, and sociocultural-contextual factors associated with 30-day SI.
ResultsFive hundred and sixty-seven Latino patients from primary care, behavioral health and HIV clinics and community agencies participated. Rates of lifetime SI ranged from 29–35%; rates for 30-day SI were 21–23%. Rates of SI were not statistically different between sites. Factors associated with SI included exposure to discrimination, lower ethnic identity, elevated family conflict, and low sense of belonging (P < 0.01). In the adjusted model, higher scores on depression, posttraumatic stress disorder, and trauma exposure were significantly associated with 30-day SI (OR = 1.14, 1.04, and 7.76, respectively). Greater number of years living in the host country was significantly associated with increased odds of having SI (OR = 2.22) while having citizenship status was associated with lower odds (OR = 0.45).
ConclusionLatinos suffering depression, trauma exposure, and immigration stressors are more likely to experience SI. Despite differences in country of origin, education, and other demographic factors between countries, rates of SI did not differ. Recommendations for prevention and clinical practice for addressing suicidal ideation risk among Latino immigrants are discussed.
Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia
- J. Li, F. Ye, W. Xiao, X. Tang, W. Sha, X. Zhang, J. Wang
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- Published online by Cambridge University Press:
- 23 March 2020, pp. 23-28
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Background
Many schizophrenia patients experience residual symptoms even after treatment. Electroconvulsive therapy (ECT) is often used in medication-resistant schizophrenia patients when pharmacologic interventions have failed; however, the mechanism of action is unclear. Brain-derived neurotrophic factor (BDNF) levels are reduced in drug-naive, first-episode schizophrenia and are increased by antipsychotic treatment. We tested the hypothesis that ECT increases serum BDNF levels by measuring BDNF concentrations in schizophrenia patients before and after they received ECT.
MethodsA total of 160 patients with schizophrenia were examined. The ECT group (n = 80) was treated with antipsychotics and ECT (eight to 10 sessions administered every other day). The drug therapy group (n = 80) received only antipsychotic treatment. A control group (n = 77) was recruited that served as the baseline for comparison.
ResultsBaseline serum BDNF level in ECT group was lower than in controls (9.7 ± 2.1 vs. 12.4 ± 3.2 ng/ml; P < 0.001), but increased after ECT, such that there was no difference between the two groups (11.9 ± 3.3 vs. 12.4 ± 3.2 ng/ml; P = 0.362). There was no correlation between patients’ Positive and Negative Syndrome Scale (PANSS) score and serum BDNF level before ECT; however, a negative correlation was observed after ECT (total: r = −0.692; P < 0.01). From baseline to remission after ECT, serum BDNF level increased (P < 0.001) and their PANSS score decreased (P < 0.001). Changes in BDNF level (2.21 ± 4.10 ng/ml) and PANSS score (28.69 ± 14.96) were positively correlated in the ECT group (r = 0.630; P < 0.01).
ConclusionsBDNF level was lower in schizophrenia patients relative to healthy controls before ECT and medication. BDNF level increased after ECT and medication, and its longitudinal change was associated with changes in patients’ psychotic symptoms. These results indicate that BDNF mediates the antipsychotic effects of ECT.
Review
Videoconferencing in psychiatry, a meta-analysis of assessment and treatment
- A. Drago, T.N. Winding, N. Antypa
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- Published online by Cambridge University Press:
- 23 March 2020, pp. 29-37
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Context
Videoconferencing in psychiatry allows psychiatric counseling to be dealt remotely. A number of human randomised clinical trials (RCTs) on this topic were conducted but not systematically analysed since 2005.
ObjectsA meta-analysis was undertaken to test the hypothesis of non-inferiority of remote psychiatric counseling, including both assessment and treatment, compared to face-to-face setting. Focus of research was the general psychiatric approach, which includes pharmacotherapy, counseling and some not specific psychotherapeutic techniques such as listening, reformulation and clarification among others. Specific forms of psychotherapies were not included in this analysis.
DesignRCTs including ≥ 10 subjects per arm were identified in Medline, the Cochrane Library, Embase and the reference list of single papers. A random-effect and a mixed-effect model served for test the hypothesis under analysis.
ResultsTwenty-six RCTs were included in the analysis, involving 765 (assessment) and 1585 patients (efficacy). The non-inferiority of remote psychiatric counseling was reported both for assessment and treatment. Heterogeneity could not be excluded for assessment, but was excluded for treatment while taking into account clinical and study related variables (P-values = 0.003 and 0.06, respectively).
ConclusionHigh levels of consistency between remote and in vivo psychiatric assessment is reported. Efficacy of remote psychiatric counseling was shown to be not inferior compared to in vivo settings. Heterogeneity could not be excluded for assessment, and further analyses are mandatory. The presence of multiple diagnoses included in the analysis was a limit of the present investigation.
Original article
Genome-wide association study of pathological gambling
- M. Lang, T. Leménager, F. Streit, M. Fauth-Bühler, J. Frank, D. Juraeva, S.H. Witt, F. Degenhardt, A. Hofmann, S. Heilmann-Heimbach, F. Kiefer, B. Brors, H.-J. Grabe, U. John, A. Bischof, G. Bischof, U. Völker, G. Homuth, M. Beutel, P.A. Lind, S.E. Medland, W.S. Slutske, N.G. Martin, H. Völzke, M.M. Nöthen, C. Meyer, H.-J. Rumpf, F.M. Wurst, M. Rietschel, K.F. Mann
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- Published online by Cambridge University Press:
- 23 March 2020, pp. 38-46
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Background
Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.
MethodsFour hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.
ResultsNo genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.
ConclusionsThe present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.
Genome-wide significant loci for addiction and anxiety
- K. Hodgson, L. Almasy, E.E.M. Knowles, J.W. Kent, J.E. Curran, T.D. Dyer, H.H.H. Göring, R.L. Olvera, P.T. Fox, G.D. Pearlson, J.H. Krystal, R. Duggirala, J. Blangero, D.C. Glahn
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- 23 March 2020, pp. 47-54
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Background
Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology.
MethodsHere we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing these traits.
ResultsAddiction phenotypes and anxiety were shown to be heritable and univariate genome-wide linkage scans revealed significant quantitative trait loci for drug dependence (14q13.2-q21.2, LOD = 3.322) and a broad anxiety phenotype (12q24.32-q24.33, LOD = 2.918). Significant positive genetic correlations were observed between anxiety and each of the addiction subtypes (ρg = 0.550–0.655) and further investigation with bivariate linkage analyses identified significant pleiotropic signals for alcohol dependence-anxiety (9q33.1-q33.2, LOD = 3.054) and drug dependence-anxiety (18p11.23-p11.22, LOD = 3.425).
ConclusionsThis study confirms the shared genetic underpinnings of addiction and anxiety and identifies genomic loci involved in the etiology of these comorbid disorders. The linkage signal for anxiety on 12q24 spans the location of TMEM132D, an emerging gene of interest from previous GWAS of anxiety traits, whilst the bivariate linkage signal identified for anxiety-alcohol on 9q33 peak coincides with a region where rare CNVs have been associated with psychiatric disorders. Other signals identified implicate novel regions of the genome in addiction genetics.
Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model
- W.H. Lee, S.H. Lisanby, A.F. Laine, A.V. Peterchev
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- 23 March 2020, pp. 55-64
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Background
This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST).
MethodsThe electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes.
ResultsThe standard ECT configurations and current amplitude of 800–900 mA produced the strongest overall stimulation with median of 1.8–2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST.
ConclusionsThe relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio.
Front matter
EAP volume 36 Cover and Front matter
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- Published online by Cambridge University Press:
- 23 March 2020, p. f1
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