Advocates of the therapeutic use of psychedelic drugs have argued that a promising approach to treatment was prematurely abandoned in the 1960s primarily because of Richard Nixon's ‘War on Drugs’.

This paper (1) briefly describes research in the 1950s and 1960s in North America on the use of LSD to treat alcohol dependence, anxiety in terminal illness, and anxiety and depression; and (2) discusses the factors that led to its abandonment.

An analysis of historical scholarship on psychedelic research in the 1950s, 1960s and 1970s in North America.

Research on psychedelic drugs in psychiatry was abandoned for a number of reasons that acted in concert. A major factor was that clinical research on psychedelic drugs was caught up in the tighter regulation of pharmaceutical research after the Thalidomide disaster in 1963. Psychedelic drugs also presented special challenges for randomised, placebo-controlled clinical trials in the 1970s that were not as positive as the claims made by their advocates in the 1950s and 1960s. Clinical research became more difficult after 1965 when Sandoz ceased providing psychedelic drugs for research and their nonmedical use was prohibited in 1970.

The demise of psychedelic drug research was not solely due to the ‘War on Drugs’. It was hastened by tighter regulation of pharmaceutical research, the failure of controlled clinical trials to live up to the claims of psychedelic advocates, and the pharmaceutical industry's lack of interest in funding clinical trials.

Both attention-deficit/hyperactivity disorder (ADHD) and insomnia have been independently related to poorer quality of life (QoL), productivity loss, and increased health care use, although most previous studies did not take the many possible comorbidities into account. Moreover, ADHD and insomnia often co-occur. Symptoms of ADHD and insomnia together may have even stronger negative effects than they do separately. We investigated the combined effects of symptoms of ADHD and insomnia, in addition to their independent effects, on QoL, productivity, and health care use, thereby controlling for a wide range of possible comorbidities and confounders.

Data from the third wave of the Netherlands Mental Health Survey and Incidence Study-2 were used, involving N = 4618 from the general population. Both the inattention and the hyperactivity ADHD symptom dimensions were studied, assessed by the ASRS Screener.

Mental functioning and productivity were negatively associated with the co-occurrence of ADHD and insomnia symptoms, even after adjusting for comorbidity and confounders. The results show no indication of differences between inattention and hyperactivity. Poorer physical functioning and health care use were not directly influenced by the interaction between ADHD and insomnia.

People with both ADHD and sleep problems have increased risk for poorer mental functioning and productivity loss. These results underscore the importance of screening for sleep problems when ADHD symptoms are present, and vice versa, and to target both disorders during treatment.

Major depressive disorder is characterized by a high risk of relapse. We aimed to compare the prophylactic effects of different antidepressant medicines (ADMs).

PubMed, Cochrane Central Register of Controlled Trials, Embase and the Web of Science were searched on 4 July 2019. A pooled analysis of parametric survival curves was performed using a Bayesian framework. The main outcomes were hazard ratios (HRs), relapse-free survival and mean relapse-free months.

Forty randomized controlled trials were included. The 1-year relapse-free survival for ADM (76%) was significantly better than that for placebo (56%). Most of the relapse difference (86.5%) occurred in the first 6 months. Most HRs were not constant over time. Proof of benefit after 6 months of follow-up was not established partially because of small differences between the drug and placebo after 6 months. Almost all studies used an ‘enriched’ randomized discontinuation design, which may explain the high relapse rates in the first 6 months after randomization.

The superiority of ADM v. placebo was mainly attributed to the difference in relapse rates that occurred in the first 6 months. Our analysis provided evidence that the prophylactic efficacy was not constant over time. A beneficial effect was observed, but the prevention of new episodes after 6 months was questionable. These findings may have implications for clinical practice.

Disease trajectories of patients with anxiety disorders are highly diverse and approximately 60% remain chronically ill. The ability to predict disease course in individual patients would enable personalized management of these patients. This study aimed to predict recovery from anxiety disorders within 2 years applying a machine learning approach.

In total, 887 patients with anxiety disorders (panic disorder, generalized anxiety disorder, agoraphobia, or social phobia) were selected from a naturalistic cohort study. A wide array of baseline predictors (N = 569) from five domains (clinical, psychological, sociodemographic, biological, lifestyle) were used to predict recovery from anxiety disorders and recovery from all common mental disorders (CMDs: anxiety disorders, major depressive disorder, dysthymia, or alcohol dependency) at 2-year follow-up using random forest classifiers (RFCs).

At follow-up, 484 patients (54.6%) had recovered from anxiety disorders. RFCs achieved a cross-validated area-under-the-receiving-operator-characteristic-curve (AUC) of 0.67 when using the combination of all predictor domains (sensitivity: 62.0%, specificity 62.8%) for predicting recovery from anxiety disorders. Classification of recovery from CMDs yielded an AUC of 0.70 (sensitivity: 64.6%, specificity: 62.3%) when using all domains. In both cases, the clinical domain alone provided comparable performances. Feature analysis showed that prediction of recovery from anxiety disorders was primarily driven by anxiety features, whereas recovery from CMDs was primarily driven by depression features.

The current study showed moderate performance in predicting recovery from anxiety disorders over a 2-year follow-up for individual patients and indicates that anxiety features are most indicative for anxiety improvement and depression features for improvement in general.

Seeking compensation has been shown to have an adverse effect on the psychological health and recovery of injured patients, however, this effect requires clarification.

A total of 2019 adults sustaining a traffic injury were recruited. Of these, 709 (35.1%) lodged a compensation claim. Interviews occurred at 1-, 6- and 12-month post-injury. Outcomes were psychological distress (posttraumatic stress (PTS) and depressive symptoms) and health-related functioning (HrF) (quality of life measured by EQ-5D-3L and disability by WHODAS) over 12-months post-injury. Covariates included individual stress vulnerability (preinjury, injury-related factors).

Compared with non-compensation participants, compensation groups had higher stress vulnerability (more severe injuries and negative reactions) and poorer baseline outcomes (psychological health and HrF). After adjustment, we found an effect of compensation on HrF [β-0.09 (−0.11 to −0.07), p < 0.001] and PTS [β = 0.36 (0.16 to 0.56), p = 0.0003], but not on depression [β = −0.07 (−0.42 to 0.28), p = 0.7]. Both groups improved over time. Vulnerable individuals (β = 1.23, p < 0.001) and those with poorer baseline outcomes (PTS: β = 0.06, p = 0.002; HrF: β = −1.07, p < 0.001) were more likely to lodge a claim. In turn, higher stress vulnerability, poor baseline outcomes and claiming compensation were associated with long-term psychological distress and HrF. Nevertheless, concurrent HrF in the model fully accounted for the compensation effect on psychological distress (β = −0.14, p = 0.27), but not vice versa.

This study provides convincing evidence that seeking compensation is not necessarily harmful to psychological health. The person's stress vulnerability and injury-related disability emerge as major risk factors of long-term psychological distress, requiring a whole-systems approach to address the problem.

Nitric oxide synthase (NOS) activity, an enzyme potentially involved in the major depressive episodes (MDE), could be indirectly measured by the L-Citrulline/L-Arginine ratio (L-Cit/L-Arg). The aim of this study was: (1) to compare the NOS activity of patients with a MDE to that of healthy controls (HC); (2) to assess its change after antidepressant treatment.

A total of 460 patients with a current MDE in a context of major depressive disorder (MDD) were compared to 895 HC for NOS activity (L-Cit/L-Arg plasma ratio). L-Arg and L-Cit plasma levels were measured using a MS-based liquid chromatography method. Depressed patients were assessed at baseline, and after 3 and 6 months of antidepressant treatment for depression severity and clinical response.

Depressed patients had a lower NOS activity than HC at baseline [0.31 ± 0.09 v. 0.38 ± 0.12; 95% confidence interval (CI) −0.084 to −0.062, p < 0.0001]. Lower NOS activity at baseline predicted a higher response rate [odds ratio (OR) = 29.20; 95% CI 1.58–536.37; p = 0.023]. NOS activity in depressed patients increased significantly up to 0.34 ± 0.08 after antidepressant treatment (Est = 0.0034; 95% CI 0.0002–0.0067; p = 0.03).

Depressed patients have a decreased NOS activity that improves after antidepressant treatment and predicts drug response. NOS activity may be a promising biomarker for MDE in a context of MDD.

Even though recent research indicates that sexual symptoms are highly prevalent in post-traumatic stress disorder following childhood sexual abuse and cause severe distress, current treatments neither address them nor are they effective in reducing them. This might be due to a lack of understanding of sexual symptoms' specific role in the often complex and comorbid psychopathology of post-traumatic stress disorder following childhood abuse.

Post-traumatic, dissociative, depressive, and sexual symptoms were assessed in 445 inpatients with post-traumatic stress disorder following childhood sexual abuse. Comorbidity structure was analyzed using a partial correlation network with regularization.

A total of 360 patients (81%) reported difficulties engaging in sexual activities and 102 patients (23%) reported to suffer from their sexual preferences. Difficulties engaging in sexual activities were linked to depressive and hyperarousal symptoms, whereas sexual preferences causing distress were linked to anger and dissociation. Dissociative amnesia, visual intrusions, and physical reactions to trauma reminders were of central importance for the network. Dissociative amnesia, depressed mood, lack of energy, and difficulties engaging in sexual activities were identified as bridge symptoms. Local clustering analysis indicated the non-redundancy of sexual symptoms.

Sexual symptoms are highly prevalent in survivors of childhood sexual abuse with post-traumatic stress disorder. Further research is needed regarding the link of difficulties engaging in sexual activities, depression, and post-traumatic stress disorder, as well as regarding the association of dissociation and sexual preferences causing distress. Sexual symptoms require consideration in the treatment of post-traumatic stress disorder following childhood sexual abuse.

Despite a sizable minority of persons with serious mental illness (SMI) acting aggressively toward family members, little is known about this topic. The objectives of the present analyses are to examine the association of offenders' SMI status with offender behaviors and victim outcomes and to compare the immediate contextual characteristics of incidents involving offenders with and without SMI.

Using a cross-sectional design, all incidents of domestic violence to which police were called between adult children and their parents in Philadelphia, PA, in 2013 (N = 6191) were analyzed. Additionally, incidents in which the offender was indicated to have SMI (n = 327) were matched with a sample of incidents in which the offender was not indicated to have SMI (n = 327).

Offenders having SMI was not associated with using a bodily weapon or gun, threatening victims, or damaging property. Offenders having SMI was associated with a decreased risk of offenders using a non-gun external weapon and victims being observed to have a complaint of pain or visible injuries. When offenders had SMI, conflict was less likely to focus on family issues and more likely to focus on offenders' behaviors and to involve contextual characteristics related to mental illness.

Efforts to prevent gun and other violence between non-intimate partner family members should target factors more strongly associated with violence than SMI (e.g. history of domestic violence, substance abuse). Intervening in family aggression by persons with SMI likely requires addressing unique circumstances these parties experience.

It has been claimed that functional somatic syndromes share a common etiology. This prospective population-based study assessed whether the same variables predict new onsets of irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS) and fibromyalgia (FM).

The study included 152 180 adults in the Dutch Lifelines study who reported the presence/absence of relevant syndromes at baseline and follow-up. They were screened at baseline for physical and psychological disorders, socio-demographic, psycho-social and behavioral variables. At follow-up (mean 2.4 years) new onsets of each syndrome were identified by self-report. We performed separate analyses for the three syndromes including participants free of the relevant syndrome or its key symptom at baseline. LASSO logistic regressions were applied to identify which of the 102 baseline variables predicted new onsets of each syndrome.

There were 1595 (1.2%), 296 (0.2%) and 692 (0.5%) new onsets of IBS, CFS, and FM, respectively. LASSO logistic regression selected 26, 7 and 19 predictors for IBS, CFS and FM, respectively. Four predictors were shared by all three syndromes, four predicted IBS and FM and two predicted IBS and CFS but 28 predictors were specific to a single syndrome. CFS was more distinct from IBS and FM, which predicted each other.

Syndrome-specific predictors were more common than shared ones and these predictors might form a better starting point to unravel the heterogeneous etiologies of these syndromes than the current approach based on symptom patterns. The close relationship between IBS and FM is striking and requires further research.

Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables.

Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level.

At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = −0.11, 95% CI (−0.18 to −0.04), p < 0.01] and depressive symptoms [B = −0.06, 95% CI (−0.10 to −0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = −0.03, 95% CI (−0.06 to −0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = −0.91, 90% CI (−1.70 to −0.11), p = 0.06], depressive symptoms [B = −0.83, 90% CI (−1.24 to −0.41), p < 0.01], and suicidal ideation [B = −0.32, 90% CI (−0.62 to −0.01), p = 0.08].

Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.

It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.

Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.

The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.

Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

While negative affect reliably predicts binge eating, it is unknown how this association may decrease or ‘de-couple’ during treatment for binge eating disorder (BED), whether such change is greater in treatments targeting emotion regulation, or how such change predicts outcome. This study utilized multi-wave ecological momentary assessment (EMA) to assess changes in the momentary association between negative affect and subsequent binge-eating symptoms during Integrative Cognitive Affective Therapy (ICAT-BED) and Cognitive Behavior Therapy Guided Self-Help (CBTgsh). It was predicted that there would be stronger de-coupling effects in ICAT-BED compared to CBTgsh given the focus on emotion regulation skills in ICAT-BED and that greater de-coupling would predict outcomes.

Adults with BED were randomized to ICAT-BED or CBTgsh and completed 1-week EMA protocols and the Eating Disorder Examination (EDE) at pre-treatment, end-of-treatment, and 6-month follow-up (final N = 78). De-coupling was operationalized as a change in momentary associations between negative affect and binge-eating symptoms from pre-treatment to end-of-treatment.

There was a significant de-coupling effect at follow-up but not end-of-treatment, and de-coupling did not differ between ICAT-BED and CBTgsh. Less de-coupling was associated with higher end-of-treatment EDE global scores at end-of-treatment and higher binge frequency at follow-up.

Both ICAT-BED and CBTgsh were associated with de-coupling of momentary negative affect and binge-eating symptoms, which in turn relate to cognitive and behavioral treatment outcomes. Future research is warranted to identify differential mechanisms of change across ICAT-BED and CBTgsh. Results also highlight the importance of developing momentary interventions to more effectively de-couple negative affect and binge eating.

Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.

Factor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692).

Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised β range: 0.057–0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10−3–3.94 × 10−7).

An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.

Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC.

Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors.

A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863–0.981), male gender (OR 5.661, 95% CI 1.473–21.762), and longer illness duration (OR 1.085, 95% CI 1.006–1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance.

Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.

Little is known about the determinants of community integration (i.e. recovery) for individuals with a history of homelessness, yet such information is essential to develop targeted interventions.

We recruited homeless Veterans with a history of psychotic disorders and evaluated four domains of correlates of community integration: perception, non-social cognition, social cognition, and motivation. Baseline assessments occurred after participants were engaged in supported housing services but before they received housing, and again after 12 months. Ninety-five homeless Veterans with a history of psychosis were assessed at baseline and 53 returned after 12 months. We examined both cross-sectional and longitudinal relationships with 12-month community integration.

The strongest longitudinal association was between a baseline motivational measure and social integration at 12 months. We also observed cross-sectional associations at baseline between motivational measures and community integration, including social, work, and independent living. Cross-lagged panel analyses did not suggest causal associations for the motivational measures. Correlations with perception and non-social cognition were weak. One social cognition measure showed a significant longitudinal correlation with independent living at 12 months that was significant for cross-lagged analysis, consistent with a causal relationship and potential treatment target.

The relatively selective associations for motivational measures differ from what is typically seen in psychosis, in which all domains are associated with community integration. These findings are presented along with a partner paper (Study 2) to compare findings from this study to an independent sample without a history of psychotic disorders to evaluate the consistency in findings regarding community integration across projects.

Self-efficacy is a pivotal factor in the etiology and prognosis of major depression. However, longitudinal studies on the relationship between self-efficacy and major depressive disorder (MDD) are scarce. The objectives were to investigate: (1) the associations between self-efficacy and the 1-year and 2-year risks of first onset of MDD and (2) the associations between self-efficacy and the 1-year and 2-year risks of the persistence/recurrence of MDD, in a sample of first-year university students.

We followed 8079 first-year university students for 2 years from April 2018 to October 2020. MDD was ascertained by the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0) based on self-report. Self-efficacy was measured by the 10-item General Self-efficacy (GSE) scale. Random effect logistic regression modeling was used to estimate the associations.

Among participants without a lifetime MDD, the data showed that participants with high baseline GSE scores were associated with a higher risk of first onset of MDD over 2 years [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.08]. Among those with a lifetime MDD, participants with high baseline GSE scores were less likely to have had a MDD over 2 years (OR 0.93, 95% CI 0.88–0.99) compared to others.

A high level of GSE may be protective of the risk of persistent or recurrent MDD. More longitudinal studies in university students are needed to further investigate the impact of GSE on the first onset of MDD.