Drug classes are grouped based on their chemical and pharmacological properties, but prescription and illicit drugs differ in other important ways. Potential differences in genetic and environmental influences on the (mis)use of prescription and illicit drugs that are subsumed under the same class should be examined. Opioid and stimulant classes contain prescription and illicit forms differentially associated with salient risk factors (common route of administration, legality), making them useful comparators for addressing this etiological issue.

A total of 2410 individual Australian twins [Mage = 31.77 (s.d. = 2.48); 67% women] were interviewed about prescription misuse and illicit use of opioids and stimulants. Univariate and bivariate biometric models partitioned variances and covariances into additive genetic, shared environmental, and unique environmental influences across drug types.

Variation in the propensity to misuse prescription opioids was attributable to genes (41%) and unique environment (59%). Illicit opioid use was attributable to shared (71%) and unique (29%) environment. Prescription stimulant misuse was attributable to genes (79%) and unique environment (21%). Illicit stimulant use was attributable to genes (48%), shared environment (29%), and unique environment (23%). There was evidence for genetic influence common to both stimulant types, but limited evidence for genetic influence common to both opioid types. Bivariate correlations suggested that prescription opioid use may be more genetically similar to prescription stimulant use than to illicit opioid use.

Prescription opioid misuse may share little genetic influence with illicit opioid use. Future research may consider avoiding unitary drug classifications, particularly when examining genetic influences.

Negative symptoms of schizophrenia have recently been proposed to result from a decoupling of (intact) hedonic experience and (diminished) approach behavior. The current study challenged this view by exploring the hypothesis that negative symptoms are driven by a specific type of emotional experience abnormality, a reduction in the positivity offset (i.e. the tendency to experience greater levels of positive relative to negative emotion in low-arousal contexts), which limits the production of approach behaviors in neutral environments.

Participants included outpatients with SZ (n = 44) and healthy controls (CN: n = 48) who completed one week of active (ecological momentary assessment surveys of emotional experience and symptoms) and passive (geolocation, accelerometry) digital phenotyping. Mathematical modeling approaches from Cacioppo's Evaluative Space Model were used to quantify the positivity offset in daily life. Negative symptoms were assessed via standard clinical ratings, as well as active (EMA surveys) and passive (geolocation, accelerometry) digital phenotyping measures.

Results indicated that the positivity offset was reduced in SZ and associated with more severe anhedonia and avolition measured via clinical interviews and active and passive digital phenotyping.

These findings suggest that current conceptual models of negative symptoms, which assume hedonic normality, may need to be revised to account for reductions in the positivity offset and its connection to diminished motivated behavior. Findings identify key real-world contexts where negative symptoms could be targeted using psychosocial treatments.

Preschool psychiatric symptoms significantly increase the risk for long-term negative outcomes. Transdiagnostic hierarchical approaches that capture general (‘p’) and specific psychopathology dimensions are promising for understanding risk and predicting outcomes, but their predictive utility in young children is not well established. We delineated a hierarchical structure of preschool psychopathology dimensions and tested their ability to predict psychiatric disorders and functional impairment in preadolescence.

Data for 1253 preschool children (mean age = 4.17, s.d. = 0.81) were drawn from three longitudinal studies using a similar methodology (one community sample, two psychopathology-enriched samples) and followed up into preadolescence, yielding a large and diverse sample. Exploratory factor models derived a hierarchical structure of general and specific factors using symptoms from the Preschool Age Psychiatric Assessment interview. Longitudinal analyses examined the prospective associations of preschool p and specific factors with preadolescent psychiatric disorders and functional impairment.

A hierarchical dimensional structure with a p factor at the top and up to six specific factors (distress, fear, separation anxiety, social anxiety, inattention-hyperactivity, oppositionality) emerged at preschool age. The p factor predicted all preadolescent disorders (ΔR2 = 0.04–0.15) and functional impairment (ΔR2 = 0.01–0.07) to a significantly greater extent than preschool psychiatric diagnoses and functioning. Specific dimensions provided additional predictive power for the majority of preadolescent outcomes (disorders: ΔR2 = 0.06–0.15; functional impairment: ΔR2 = 0.05–0.12).

Both general and specific dimensions of preschool psychopathology are useful for predicting clinical and functional outcomes almost a decade later. These findings highlight the value of transdiagnostic dimensions for predicting prognosis and as potential targets for early intervention and prevention.

Considerable heterogeneity exists in treatment response to first-line posttraumatic stress disorder (PTSD) treatments, such as Cognitive Processing Therapy (CPT). Relatively little is known about the timing of when during a course of care the treatment response becomes apparent. Novel machine learning methods, especially continuously updating prediction models, have the potential to address these gaps in our understanding of response and optimize PTSD treatment.

Using data from a 3-week (n = 362) CPT-based intensive PTSD treatment program (ITP), we explored three methods for generating continuously updating prediction models to predict endpoint PTSD severity. These included Mixed Effects Bayesian Additive Regression Trees (MixedBART), Mixed Effects Random Forest (MERF) machine learning models, and Linear Mixed Effects models (LMM). Models used baseline and self-reported PTSD symptom severity data collected every other day during treatment. We then validated our findings by examining model performances in a separate, equally established, 2-week CPT-based ITP (n = 108).

Results across approaches were very similar and indicated modest prediction accuracy at baseline (R2 ~ 0.18), with increasing accuracy of predictions of final PTSD severity across program timepoints (e.g. mid-program R2 ~ 0.62). Similar findings were obtained when the models were applied to the 2-week ITP. Neither the MERF nor the MixedBART machine learning approach outperformed LMM prediction, though benefits of each may differ based on the application.

Utilizing continuously updating models in PTSD treatments may be beneficial for clinicians in determining whether an individual is responding, and when this determination can be made.

Borderline personality disorder (BPD) is characterized by instability in affective regulation that can result in a loss of cognitive control. Triggers may be neuronal responses to emotionally valenced context and/or stimuli. ‘Neuronal priming’ indexes the familiarity of stimuli, and may capture the obligatory effects of affective valence on the brain's processing system, and how such valence mediates responses to the repeated presentation of stimuli. We investigated the effects of affective valence of stimuli on neuronal priming (i.e. changes in activation to repeated presentation of stimuli), and if these effects distinguished BPD patients from controls.

Forty BPD subjects and 25 control subjects (age range: 18–44) participated in an episodic memory task during fMRI. Stimuli were presented in alternating epochs of encoding (six images of positive, negative, and neutral valence) and recognition (six images for ‘old’ v. ‘new’ recognition). Analyses focused on inter-group differences in the change in activation to repeated stimuli (presented during Encoding and Recognition).

Relative to controls, BPD showed greater priming (generally greater decrease from encoding to recognition) for negatively valenced stimuli. Conversely, BPD showed less priming for positively valenced stimuli (generally greater increase from encoding to recognition).

Plausibly, the relative familiarity of negative valence to patients with BPD exerts an influence on obligatory responses to repeated stimuli leading to repetition priming of neuronal profiles. The specific effects of valence on memory and/or attention, and consequently on priming can inform the understanding of mechanisms of altered salience for affective stimuli in BPD.

The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global health crisis that may cause mental health problems and heighten suicide risk. We investigated the impact of the COVID-19 pandemic on trends in suicide attempts and suicide deaths in New Taipei City, Taiwan.

The current study used the official daily data on suicide attempts and deaths in New Taipei City, Taiwan (4 million inhabitants) between 2015 and 2020 from the Taiwan National Suicide Prevention Reporting System. Interrupted time-series (ITS) analyses with parameters corrected by the estimated autocorrelations were applied on weekly aggregated data to examine whether the suicide trends during the early COVID-19 pandemic (late January to July 2020) deviated from previous trends (January 2015 to late January 2020). The impact due to the suicide prevention policy change was also examined (since August 2020).

ITS analyses revealed no significant increases in both mean and trend on weekly suicide deaths during the COVID-19 pandemic and after the policy change. In contrast, there was a significant increasing trend in weekly suicide attempts since the COVID-19 outbreak at the rate of 1.54 attempts per week (95% confidence interval 0.49–2.60; p = 0.004). Sex difference analysis revealed that, however, this increasing trend was observed only in females not in males.

The COVID-19 pandemic has different impacts on suicides attempts and deaths during the early pandemic in New Taipei City, Taiwan. The COVID-19 outbreak drastically increased the trend of suicide attempts. In contrast, the number of suicide deaths had remained constant in the investigated periods.

The COVID-19 pandemic highlighted the need for mental health interventions that can be easily disseminated during a crisis. Behavioural activation (BA) is a cost-effective treatment that can be administered by non-specialists; however, it is unclear whether it is still effective during a time of lockdown and social distancing, when opportunities for positive activity are significantly constrained.

Between May and October 2020, we randomised 68 UK participants with mild to moderate low mood to either a 4-week online programme of non-specialist administered BA or to a passive control group. Before and after the intervention, we collected self-report data on mood and COVID-related disruption, as well as measuring emotional cognition as an objective marker of risk for depression.

In comparison to the control group, the BA group showed a significant decrease in depression, anxiety and anhedonia after the intervention, as well as an increase in self-reported activation and social support. Benefits persisted at 1-month follow-up. BA also decreased negative affective bias on several measures of the Facial Emotion Recognition Task and early change in bias was associated with later therapeutic gain. Participants rated the intervention as highly acceptable.

This study highlights the benefits of online BA that can be administered by non-specialists after brief training. These findings can help inform the policy response towards the rising incidence of mental health problems during a crisis situation such as a pandemic. They also highlight the use of objective cognitive markers of risk across different treatment modalities.

Whether smoking should be regarded as a risk factor for mental disorders remains unresolved. Prescribed psychotropic drugs can be used as indications for mental disorders. We investigated how smoking was prospectively related to prescription of antipsychotics, mood stabilizers, antidepressants, and anxiolytics.

Information about smoking, including the Fagerström Test for Nicotine Dependence, and relevant confounders, were obtained from the population-based Young in Norway Study (N = 2602), with four data collection waves between 1992 and 2006. These survey data were linked with information on prescriptions for psychotropic drugs from the comprehensive, nationwide Norwegian Prescription Database from 2007 to 2015.

Daily smoking with high dependence in 2006 at age 28.5 (s.d. = 2.0) was associated with filling prescriptions of antipsychotics (OR, 6.57, 95% CI 2.19–19.70, p = 0.001), mood stabilizers (OR, 7.11, 95% CI 2.51–20.15, p < 0.001) and antidepressants (OR, 1.91, 95% CI 1.13–3.23, p = 0.016) 1–9 years later. Associations remained significant after adjustment for a variety of potential confounders measured before the assessment of smoking, including sociodemographic background, conduct problems, cannabis use, mental distress, and previous prescriptions for psychotropic medications. The association between smoking and prescription of anxiolytics was weaker and more unstable.

In this study of young adults, daily smoking with high dependence was associated with later prescriptions of antipsychotics, mood stabilizers and antidepressants, indicating smoking as a risk factor for mental disorders treated with these drugs.

Magnetic resonance imaging (MRI) studies on major depressive disorder (MDD) have predominantly found short-term electroconvulsive therapy (ECT)-related gray matter volume (GMV) increases, but research on the long-term stability of such changes is missing. Our aim was to investigate long-term GMV changes over a 2-year period after ECT administration and their associations with clinical outcome.

In this nonrandomized longitudinal study, patients with MDD undergoing ECT (n = 17) are assessed three times by structural MRI: Before ECT (t0), after ECT (t1) and 2 years later (t2). A healthy (n = 21) and MDD non-ECT (n = 33) control group are also measured three times within an equivalent time interval. A 3(group) × 3(time) ANOVA on whole-brain level and correlation analyses with clinical outcome variables is performed.

Analyses yield a significant group × time interaction (pFWE < 0.001) resulting from significant volume increases from t0 to t1 and decreases from t1 to t2 in the ECT group, e.g., in limbic areas. There are no effects of time in both control groups. Volume increases from t0 to t1 correlate with immediate and delayed symptom increase, while volume decreases from t1 to t2 correlate with long-term depressive outcome (all p ⩽ 0.049).

Volume increases induced by ECT appear to be a transient phenomenon as volume strongly decreased 2 years after ECT. Short-term volume increases are associated with less symptom improvement suggesting that the antidepressant effect of ECT is not due to volume changes. Larger volume decreases are associated with poorer long-term outcome highlighting the interplay between disease progression and structural changes.

Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia.

The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected.

Patients with schizophrenia showed higher CTQ-SF scores (t = 12.549, p < 0.001), lower SFS scores (t = −46.951, p < 0.001), and lower plasma oxytocin levels (t = −5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia (t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033–0.044]).

The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.

To offer support for patients who decide to discontinue antipsychotic and antidepressant medication, identifying which potentially modifiable factors correlate with discontinuation success is crucial. Here, we analyzed the predictive value of the professional support received, circumstances prior to discontinuation, a strategy of discontinuation, and use of functional and non-functional coping strategies during discontinuation on self-reported discontinuation success and on objective discontinuation.

Patients who had attempted discontinuing antipsychotics (AP) and/or antidepressants (AD) during the past 5 years (n = 316) completed an online survey including questions on subjective and objective discontinuation success, sociodemographic, clinical and medication-related factors, and scales to assess the putative predictors.

A regression model with all significant predictors explained 20–30% of the variance in discontinuation success for AD and 30–40% for AP. After controlling for baseline sociodemographic, clinical and medication-related factors, the most consistent predictor of subjective discontinuation success was self-care behavior, in particular mindfulness, relaxation and making use of supportive relationships. Other predictors depended on the type of medication: For AD, good alliance with the prescribing physician predicted higher subjective success whereas gradual tapering per se was associated with lower subjective success and a lower chance of full discontinuation. In those tapering off AP, leaving time to adjust between dose reductions was associated with higher subjective success and fewer negative effects.

The findings can inform evidence-based clinical guidelines and interventions aiming to support patients during discontinuation. Further studies powered to take interactions between variables into account are needed to improve the prediction of successful discontinuation.

Deficiency in contextual and enhanced responding in cued fear learning may contribute to the development of posttraumatic stress disorder (PTSD). We examined the responses to aversive Pavlovian conditioning with an unpredictable spatial context as conditioned stimulus compared to a predictable context. We hypothesized that the PTSD group would demonstrate less hippocampal and ventromedial prefrontal cortex (vmPFC) activation during acquisition and extinction of unpredictable contexts and an over-reactive amygdala response in the predictable contexts compared to controls.

A novel combined differential cue-context conditioning paradigm was applied using virtual reality with spatial contexts that required configural and cue processing. We assessed 20 patients with PTSD, 21 healthy trauma-exposed (TC) and 22 non-trauma-exposed (HC) participants using functional magnetic resonance imaging, skin conductance responses, and self-report measures.

During fear acquisition, patients with PTSD compared to TC showed lower activity in the hippocampi in the unpredictable and higher activity in the amygdalae in the predictable context. During fear extinction, TC compared to patients and HC showed higher brain activity in the vmPFC in the predictable context. There were no significant differences in self-report or skin conductance responses.

Our results suggest that patients with PTSD differ in brain activation from controls in regions such as the hippocampus, the amygdala, and the vmPFC in the processing of unpredictable and predictable contexts. Deficient encoding of more complex configurations might lead to a preponderance of cue-based predictions in PTSD. Exposure-based treatments need to focus on improving predictability of contextual processing and reducing enhanced cue reactivity.