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1.  The cross-national epidemiology of specific phobia in the World Mental Health Surveys 
Psychological medicine  2017;47(10):1744-1760.
Background
Although specific phobia is highly prevalent, associated with impairment, and an important risk factor for the development of other mental disorders, cross-national epidemiological data are scarce, especially from low and middle-income countries. This paper presents epidemiological data from 22 low, lower-middle, upper-middle and high-income countries.
Method
Data came from 25 representative population-based surveys conducted in 22 countries (2001–2011) as part of the World Health Organization World Mental Health Surveys initiative (N=124,902). The presence of specific phobia as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition was evaluated using the World Health Organization Composite International Diagnostic Interview.
Results
The cross-national lifetime and 12-month prevalence rates of specific phobia were, respectively, 7.4% and 5.5%, being higher in females (9.8% and 7.7%) than in males (4.9% and 3.3%) and higher in high and higher-middle income countries than in low/lower-middle income countries. The median age of onset was young (8 years). Of the 12-month patients, 18.7% reported severe role impairment (13.3%–21.9% across income groups) and 23.1% reported any treatment (9.6%–30.1% across income groups). Lifetime comorbidity was observed in 60.2% of those with lifetime specific phobia, with the onset of specific phobia preceding the other disorder in most cases (72.6%). Interestingly, rates of impairment, treatment-use and comorbidity increased with the number of fear subtypes.
Conclusion
Specific phobia is common and associated with impairment in a considerable percentage of cases. Importantly, specific phobia often precedes the onset of other mental disorders, making it a possible early-life indicator of psychopathology vulnerability.
doi:10.1017/S0033291717000174
PMCID: PMC5674525  PMID: 28222820
specific phobia; epidemiology; comorbidity; cross-national; impairment; treatment
2.  An investigation of emotion dynamics in major depressive disorder patients and healthy persons using sparse longitudinal networks 
PLoS ONE  2017;12(6):e0178586.
Background
Differences in within-person emotion dynamics may be an important source of heterogeneity in depression. To investigate these dynamics, researchers have previously combined multilevel regression analyses with network representations. However, sparse network methods, specifically developed for longitudinal network analyses, have not been applied. Therefore, this study used this approach to investigate population-level and individual-level emotion dynamics in healthy and depressed persons and compared this method with the multilevel approach.
Methods
Time-series data were collected in pair-matched healthy persons and major depressive disorder (MDD) patients (n = 54). Seven positive affect (PA) and seven negative affect (NA) items were administered electronically at 90 times (30 days; thrice per day). The population-level (healthy vs. MDD) and individual-level time series were analyzed using a sparse longitudinal network model based on vector autoregression. The population-level model was also estimated with a multilevel approach. Effects of different preprocessing steps were evaluated as well. The characteristics of the longitudinal networks were investigated to gain insight into the emotion dynamics.
Results
In the population-level networks, longitudinal network connectivity was strongest in the healthy group, with nodes showing more and stronger longitudinal associations with each other. Individually estimated networks varied strongly across individuals. Individual variations in network connectivity were unrelated to baseline characteristics (depression status, neuroticism, severity). A multilevel approach applied to the same data showed higher connectivity in the MDD group, which seemed partly related to the preprocessing approach.
Conclusions
The sparse network approach can be useful for the estimation of networks with multiple nodes, where overparameterization is an issue, and for individual-level networks. However, its current inability to model random effects makes it less useful as a population-level approach in case of large heterogeneity. Different preprocessing strategies appeared to strongly influence the results, complicating inferences about network density.
doi:10.1371/journal.pone.0178586
PMCID: PMC5453553  PMID: 28570696
3.  Major depressive disorder subtypes to predict long-term course 
Depression and anxiety  2014;31(9):765-777.
Background
Variation in course of major depressive disorder (MDD) is not strongly predicted by existing subtype distinctions. A new subtyping approach is considered here.
Methods
Two data mining techniques, ensemble recursive partitioning and Lasso generalized linear models (GLMs) followed by k-means cluster analysis, are used to search for subtypes based on index episode symptoms predicting subsequent MDD course in the World Mental Health (WMH) Surveys. The WMH surveys are community surveys in 16 countries. Lifetime DSM-IV MDD was reported by 8,261 respondents. Retrospectively reported outcomes included measures of persistence (number of years with an episode; number of with an episode lasting most of the year) and severity (hospitalization for MDD; disability due to MDD).
Results
Recursive partitioning found significant clusters defined by the conjunctions of early onset, suicidality, and anxiety (irritability, panic, nervousness-worry-anxiety) during the index episode. GLMs found additional associations involving a number of individual symptoms. Predicted values of the four outcomes were strongly correlated. Cluster analysis of these predicted values found three clusters having consistently high, intermediate, or low predicted scores across all outcomes. The high-risk cluster (30.0% of respondents) accounted for 52.9-69.7% of high persistence and severity and was most strongly predicted by index episode severe dysphoria, suicidality, anxiety, and early onset. A total symptom count, in comparison, was not a significant predictor.
Conclusions
Despite being based on retrospective reports, results suggest that useful MDD subtyping distinctions can be made using data mining methods. Further studies are needed to test and expand these results with prospective data.
doi:10.1002/da.22233
PMCID: PMC5125445  PMID: 24425049
Epidemiology; Depression; Anxiety/Anxiety Disorders; Suicide/Self Harm; Panic Attacks
4.  Testing a machine-learning algorithm to predict the persistence and severity of major depressive disorder from baseline self-reports 
Molecular psychiatry  2016;21(10):1366-1371.
Heterogeneity of major depressive disorder (MDD) illness course complicates clinical decision-making. While efforts to use symptom profiles or biomarkers to develop clinically useful prognostic subtypes have had limited success, a recent report showed that machine learning (ML) models developed from self-reports about incident episode characteristics and comorbidities among respondents with lifetime MDD in the World Health Organization World Mental Health (WMH) Surveys predicted MDD persistence, chronicity, and severity with good accuracy. We report results of model validation in an independent prospective national household sample of 1,056 respondents with lifetime MDD at baseline. The WMH ML models were applied to these baseline data to generate predicted outcome scores that were compared to observed scores assessed 10–12 years after baseline. ML model prediction accuracy was also compared to that of conventional logistic regression models. Area under the receiver operating characteristic curve (AUC) based on ML (.63 for high chronicity and .71–.76 for the other prospective outcomes) was consistently higher than for the logistic models (.62–.70) despite the latter models including more predictors. 34.6–38.1% of respondents with subsequent high persistence-chronicity and 40.8–55.8% with the severity indicators were in the top 20% of the baseline ML predicted risk distribution, while only 0.9% of respondents with subsequent hospitalizations and 1.5% with suicide attempts were in the lowest 20% of the ML predicted risk distribution. These results confirm that clinically useful MDD risk stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models.
doi:10.1038/mp.2015.198
PMCID: PMC4935654  PMID: 26728563
5.  Decomposing the heterogeneity of depression at the person-, symptom-, and time-level: latent variable models versus multimode principal component analysis 
Background
Heterogeneity of psychopathological concepts such as depression hampers progress in research and clinical practice. Latent Variable Models (LVMs) have been widely used to reduce this problem by identification of more homogeneous factors or subgroups. However, heterogeneity exists at multiple levels (persons, symptoms, time) and LVMs cannot capture all these levels and their interactions simultaneously, which leads to incomplete models. Our objective is to briefly review the most widely used LVMs in depression research, illustrating their use and incompatibility in real data, and to consider an alternative, statistical approach, namely multimode principal component analysis (MPCA).
Methods
We applied LVMs to data from 147 patients, who filled out the Quick Inventory of Depressive Symptomatology (QIDS) at 9 time points. Compatibility of the results and suitability of the LVMs to capture the heterogeneity of the data were evaluated. Alternatively, MPCA was used to simultaneously decompose depression on the person-, symptom- and time-level and to investigate the interactions between these levels.
Results
QIDS-data could be decomposed on the person-level (2 classes), symptom-level (2 factors) and time-level (2 trajectory-classes). However, these results could not be integrated into a single model. Instead, MPCA allowed for decomposition of the data at the person- (3 components), symptom- (2 components) and time-level (2 components) and for the investigation of these components’ interactions.
Conclusions
Traditional LVMs have limited use when trying to define an integrated model of depression heterogeneity at the person, symptom and time level. More integrative statistical techniques such as MPCA can be used to address these relatively complex data patterns and could be used in future attempts to identify empirically-based subtypes/phenotypes of depression.
Electronic supplementary material
The online version of this article (doi:10.1186/s12874-015-0080-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12874-015-0080-4
PMCID: PMC4608190  PMID: 26471992
Data cube; Latent variable models; 3PCA; MPCA; Heterogeneity; Multimodal data; Depression
6.  Major depressive disorder as a nonlinear dynamic system: bimodality in the frequency distribution of depressive symptoms over time 
BMC Psychiatry  2015;15:222.
Background
A defining characteristic of Major Depressive Disorder (MDD) is its episodic course, which might indicate that MDD is a nonlinear dynamic phenomenon with two discrete states. We investigated this hypothesis using the symptom time series of individual patients.
Methods
In 178 primary care patients with MDD, the presence of the nine DSM-IV symptoms of depression was recorded weekly for two years. For each patient, the time-series plots as well as the frequency distributions of the symptoms over 104 weeks were inspected. Furthermore, two indicators of bimodality were obtained: the bimodality coefficient (BC) and the fit of a 1- and a 2-state Hidden Markov Model (HMM).
Results
In 66 % of the sample, high bimodality coefficients (BC > .55) were found. These corresponded to relatively sudden jumps in the symptom curves and to highly skewed or bimodal frequency distributions. The results of the HMM analyses classified 90 % of the symptom distributions as bimodal.
Conclusions
A two-state pattern can be used to describe the course of depression symptoms in many patients. The BC seems useful in differentiating between subgroups of MDD patients based on their life course data.
doi:10.1186/s12888-015-0596-5
PMCID: PMC4574448  PMID: 26385384
7.  Simultaneous Decomposition of Depression Heterogeneity on the Person-, Symptom- and Time-Level: The Use of Three-Mode Principal Component Analysis 
PLoS ONE  2015;10(7):e0132765.
Although heterogeneity of depression hinders research and clinical practice, attempts to reduce it with latent variable models have yielded inconsistent results, probably because these techniques cannot account for all interacting sources of heterogeneity at the same time. Therefore, to simultaneously decompose depression heterogeneity on the person-, symptom and time-level, three-mode Principal Component Analysis (3MPCA) was applied to data of 219 Major Depression patients, who provided Beck Depression Inventory assessments every three months for two years. The resulting person-level components were correlated with external baseline clinical and demographic variables. The 3MPCA extracted two symptom-level components (‘cognitive’, ‘somatic-affective’), two time-level components (‘improving’, ‘persisting’) and three person-level components, characterized by different interaction-patterns between the symptom- and time-components (‘severe non-persisting’, ‘somatic depression’ and ‘cognitive depression’). This model explained 28% of the total variance and 65% when also incorporating the general trend in the data). Correlations with external variables illustrated the content differentiation between the person-components. Severe non-persisting depression was positively correlated with psychopathology (r=0.60) and negatively with quality of life (r=-0.50). Somatic depression was negatively correlated with physical functioning (r=-0.45). Cognitive depression was positively correlated with neuroticism (r=0.38) and negatively with self-esteem (r=-0.47). In conclusion, 3MPCA decomposes depression into homogeneous entities, while accounting for the interactions between different sources of heterogeneity, which shows the utility of the technique to investigate the underlying structure of complex psychopathology data and could help future development of better empirical depression subtypes.
doi:10.1371/journal.pone.0132765
PMCID: PMC4503625  PMID: 26177365
8.  Diagnostic heterogeneity in psychiatry: towards an empirical solution 
BMC Medicine  2013;11:201.
The launch of the 5th version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has sparked a debate about the current approach to psychiatric classification. The most basic and enduring problem of the DSM is that its classifications are heterogeneous clinical descriptions rather than valid diagnoses, which hampers scientific progress. Therefore, more homogeneous evidence-based diagnostic entities should be developed. To this end, data-driven techniques, such as latent class- and factor analyses, have already been widely applied. However, these techniques are insufficient to account for all relevant levels of heterogeneity, among real-life individuals. There is heterogeneity across persons (p:for example, subgroups), across symptoms (s:for example, symptom dimensions) and over time (t:for example, course-trajectories) and these cannot be regarded separately. Psychiatry should upgrade to techniques that can analyze multi-mode (p-by-s-by-t) data and can incorporate all of these levels at the same time to identify optimal homogeneous subgroups (for example, groups with similar profiles/connectivity of symptomatology and similar course). For these purposes, Multimode Principal Component Analysis and (Mixture)-Graphical Modeling may be promising techniques.
doi:10.1186/1741-7015-11-201
PMCID: PMC3846412  PMID: 24228940
DSM-5; Heterogeneity; Data-driven techniques; Cattell’s cube

Results 1-8 (8)