Offspring exposed to prenatal maternal depression (PMD) are vulnerable to depression across their lifespan. The underlying cause(s) for this elevated intergenerational risk is most likely complex. However, depression is underpinned by a dysfunctional frontal-limbic network, associated with core information processing biases (e.g. attending more to sad stimuli). Aberrations in this network might mediate transmission of this vulnerability in infants exposed to PMD. In this study, we aimed to explore the association between foetal exposure to PMD and frontal-limbic network function in infancy, hypothesising that, in response to emotional sounds, infants exposed to PMD would exhibit atypical activity in these regions, relative to those not exposed to PMD.

We employed a novel functional magnetic resonance imaging sequence to compare brain function, whilst listening to emotional sounds, in 78 full-term infants (3–6 months of age) born to mothers with and without a diagnosis of PMD.

After exclusion of 19 datasets due to infants waking up, or moving excessively, we report between-group brain activity differences, between 29 infants exposed to PMD and 29 infants not exposed to PMD, occurring in temporal, striatal, amygdala/parahippocampal and frontal regions (p < 0.005). The offspring exposed to PMD exhibited a relative increase in activation to sad sounds and reduced (or unchanged) activation to happy sounds in frontal-limbic clusters.

Findings of a differential response to positive and negative valanced sounds by 3–6 months of age may have significant implications for our understanding of neural mechanisms that underpin the increased risk for later-life depression in this population.

The coronavirus disease 2019 (COVID-19) pandemic and associated lockdown could be considered a ‘perfect storm’ for increases in emotional distress. Such increases can only be identified by studies that use data collected before and during the pandemic. Longitudinal data are also needed to examine (1) the roles of previous distress and stressors in emotional distress during the pandemic and (2) how COVID-19-related stressors and coping strategies are associated with emotional distress when pre-pandemic distress is accounted for.

Data came from a cohort study (N = 768). Emotional distress (perceived stress, internalizing symptoms, and anger), COVID-19-related stressors, and coping strategies were measured during the pandemic/lockdown when participants were aged 22. Previous distress and stressors were measured before COVID-19 (at age 20).

On average, participants showed increased levels of perceived stress and anger (but not internalizing symptoms) during the pandemic compared to before. Pre-COVID-19 emotional distress was the strongest predictor of during-pandemic emotional distress, followed by during-pandemic economic and psychosocial stressors (e.g. lifestyle and economic disruptions) and hopelessness, and pre-pandemic social stressors (e.g. bullying victimization and stressful life events). Most health risks to self or loved ones due to COVID-19 were not uniquely associated with emotional distress in final models. Coping strategies associated with reduced distress included keeping a daily routine, physical activity, and positive reappraisal/reframing.

In our community sample, pre-pandemic distress, secondary consequences of the pandemic (e.g. lifestyle and economic disruptions), and pre-pandemic social stressors were more consistently associated with young adults' emotional distress than COVID-19-related health risk exposures.

T long-term effects of cognitive therapy and behavior therapy (CTBT) for menopausal symptoms are unknown, and whether the effects are different between natural menopause and treatment-induced menopause are currently unclear. Therefore, we sought to conduct an accurate estimate of the efficacy of CTBT for menopausal symptoms.

We conducted searches of Cochrane Library, EMBASE, PsycINFO, PubMed, and Web of Science databases for studies from 1 January 1977 to 1 November 2021. Randomized controlled trials (RCTs) comparing intervention groups to control groups for menopausal symptoms were included. Hedge's g was used as the standardized between-group effect size with a random-effects model.

We included 14 RCTs comprising 1618 patients with a mean sample size of 116. CTBT significantly outperformed control groups in terms of reducing hot flushes [g = 0.39, 95% confidence interval (CI) 0.23–0.55, I2 = 45], night sweats, depression (g = 0.50, 95% CI 0.34–0.66, I2 = 51), anxiety (g = 0.38, 95% CI 0.23–0.54, I2 = 49), fatigue, and quality of life. Egger's test indicated no publication bias.

CTBT is an effective psychological treatment for menopausal symptoms, with predominantly small to moderate effects. The efficacy is sustained long-term, although it declines somewhat over time. The efficacy was stronger for natural menopause symptoms, such as vasomotor symptoms, than for treatment-induced menopause symptoms. These findings provide support for treatment guidelines recommending CTBT as a treatment option for menopausal symptoms.

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.

Schizophrenia (SZ) is a complex brain disorder linked to cognitive and neurostructural abnormalities that involves genetic and environmental factors with obstetric complications (OCs) at birth conferring a high risk for the disease. Indeed, current research in the general population describes the deleterious effect of OCs on cognitive performance in adulthood. With this rationale, we aim to review the relationship between OCs and cognition in SZ and related psychotic disorders.

A systematic review and meta-analysis describing cognitive function and OCs in patients with SZ and related disorders were conducted. PubMed, EmBase, SCOPUS, and the Cochrane Library were systematically searched to identify eligible studies up to January 2022. We calculated the effect sizes (Hedges' g) of cognitive domains within each study and quantified the proportion of between-study variability using the I2 statistic. Homogeneity was assessed using the Q-statistic (X2). The study was registered on PROSPERO (CRD42018094238).

A total of 4124 studies were retrieved, with 10 studies meeting inclusion criteria for the systematic review and eight for meta-analysis. SZ subjects with OCs showed poor verbal memory [Hedges' g = −0.89 (95% CI −1.41 to −0.37), p < 0.001] and working memory performance [Hedges' g = −1.47 (95% CI −2.89 to −0.06), p = 0.01] in a random-effect model compared to those without OCs.

OCs appear to have a moderate impact on specific cognitive such as working memory and verbal memory. Our findings suggest that OCs are associated with brain development and might underlie the cognitive abnormalities described at onset of psychosis.

Emotional disorders are highly prevalent in primary care. We aimed to determine whether a transdiagnostic psychological therapy plus treatment-as-usual (TAU) is more efficacious than TAU alone in primary care adult patients.

A randomized, two-arm, single-blind clinical trial was conducted in 22 primary care centres in Spain. A total of 1061 adult patients with emotional disorders were enrolled. The transdiagnostic protocol (n = 527) consisted of seven 90-min sessions (8–10 patients) delivered over a 12–14-week period. TAU (n = 534) consisted of regular consultations with a general practitioner. Primary outcome measures were self-reported symptoms of anxiety, depression, and somatizations. Secondary outcome measures were functioning and quality of life. Patients were assessed at baseline, post-treatment, and at 3, 6, and 12 months. Intention-to-treat and per-protocol analyses were performed.

Post-treatment primary outcomes were significantly better in the transdiagnostic group compared to TAU (anxiety: p < 0.001; Morris's d = −0.65; depression: p < 0.001; d = −0.58, and somatic symptoms: p < 0.001; d = −0.40). These effects were sustained at the 12-month follow-up (anxiety: p < 0.001; d = −0.44; depression: p < 0.001; d = −0.36 and somatic symptoms: p < 0.001; d = −0.32). The transdiagnostic group also had significantly better outcomes on functioning (d = 0.16–0.33) and quality of life domains (d = 0.24–0.42), with sustained improvement at the 12-month follow-up in functioning (d = 0.25–0.39) and quality of life (d = 0.58–0.72). Reliable recovery rates showed large between-group effect sizes (d > 0.80) in favour of the transdiagnostic group after treatment and at the 12-month follow-up.

Adding a brief transdiagnostic psychological intervention to TAU may significantly improve outcomes in emotional disorders treated in primary care.

isrctn.org identifier: ISRCTN58437086

Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes.

We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications.

The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50–0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28–0.44), olanzapine (aRRs: 0.46–0.72), and risperidone (aRRs: 0.53–0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68–0.84) and haloperidol (aRRs: 0.67–0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33–0.69).

There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes.

Patients with post-traumatic stress disorder (PTSD) show a different stress-related cognitive style compared with healthy controls (HC). The FK506 binding protein 5 gene (FKBP5), one of the PTSD known risk factors, is involved in the stress response through the hypothalamic-pituitary-adrenal axis and brain volumetric alterations. The present study aimed to uncover the neural correlates of stress-related cognitive styles through the analysis of the regional brain volumes and FKBP5 genotype in patients with PTSD compared with HC.

In this study, 51 patients with PTSD and 94 HC were assessed for stress-related cognitive styles, PTSD symptoms severity, and genotype of FKBP5 single nucleotide polymorphisms, and underwent T1-weighted structural magnetic resonance imaging. Diagnosis-by-genotype interaction for regional brain volumes was examined in 16 brain regions of interest.

Patients with PTSD showed significantly higher levels of catastrophizing, ruminative response, and repression, and reduced distress aversion and positive reappraisal compared with HC (p < 0.001). Significant diagnosis-by-genotype interactions for regional brain volumes were observed for bilateral hippocampi and left frontal operculum. A significant positive correlation between the severity of the repression and left hippocampal volume was found in a subgroup of patients with PTSD with FKBP5 rs3800373 (AA genotype) or rs1360780 (CC genotype).

The present study showed the influences of FKBP5 genotype on the distorted cognitive styles in PTSD by measuring the volumetric alteration of hippocampal regions, providing a possible role of the hippocampus and left frontal operculum as significant neurobiological correlates of PTSD.

Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as ‘long COVID’. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID.

Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted.

Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes.

While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations.

Posttraumatic stress disorder (PTSD) is the most highly co-occurring psychiatric disorder among veterans with cannabis use disorder (CUD). Despite some evidence that cannabis use prospectively exacerbates the course of PTSD, which in turn increases the risk for CUD, the causal nature of the relationship between cannabis and psychiatric comorbidity is debated. The longitudinal relationship between PTSD diagnosis and traumatic intrusion symptoms with cannabis use and CUD was examined using cross-lagged panel model (CLPM) analysis.

Prospective data from a longitudinal observational study of 361 veterans deployed post-9/11/2001 included PTSD and CUD diagnoses, cannabis use, and PTSD-related traumatic intrusion symptoms from the Inventory of Depression and Anxiety Symptoms.

A random intercept CLPM analysis that leveraged three waves (baseline, 6 months and 12 months) of cannabis use and PTSD-related intrusion symptoms to account for between-person differences found that baseline cannabis use was significantly positively associated with 6-month intrusion symptoms; the converse association was significant but reduced in magnitude (baseline use to 6-month intrusions: β = 0.46, 95% CI 0.155–0.765; baseline intrusions to 6-month use: β = 0.22, 95% CI −0.003 to 0.444). Results from the two-wave CLPM reveal a significant effect from baseline PTSD to 12-month CUD (β = 0.15, 95% CI 0.028–0.272) but not from baseline CUD to 12-month PTSD (β = 0.12, 95% CI −0.022 to 0.262).

Strong prospective associations capturing within-person changes suggest that cannabis use is linked with greater severity of trauma-related intrusion symptoms over time. A strong person-level directional association between PTSD and CUD was evident. Findings have significant clinical implications for the long-term effects of cannabis use among individuals with PTSD.

The age-adjusted rate of suicide death in the USA has increased significantly since 2000 and little is known about national trends in non-fatal suicidal behaviors (ideation, plan, and attempt) among adults and their associated sociodemographic and clinical characteristics. This study examined trends in non-fatal suicidal behaviors among adults in the USA.

Data were obtained from adults 18–65 years of age who participated in the National Survey on Drug Use and Health (NSDUH), including mental health assessment, from 2009 to 2017 (n = 335 359). Examinations of data involved trend analysis methods with the use of logistic regressions and interaction terms.

Suicidal ideation showed fluctuation from 2009 to 2017, whereas suicide plan and attempt showed significantly positive linear trends with the odds increasing by an average of 3% and 4%, respectively. Suicide plan increased the most for females and adults ages 18–34, and attempt increased the most for adults with drug dependence. Both plan and attempt increased the most among adults who either had mental illness but were not in treatment or had no mental illness.

Given attempted suicide is the strongest known risk factor for suicide death, reducing non-fatal suicidal behaviors including attempt are important public health and clinical goals. The interactional findings of age, sex, mental health status, and drug dependence point toward the importance of tailoring prevention efforts to various sociodemographic and clinical factors.

Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested.

A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure.

The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; M = −0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; M = −275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms.

The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.

An aberrant neural connectivity has been known to be associated with bipolar disorder (BD). Local gyrification may reflect the early neural development of cortical connectivity and has been studied as a possible endophenotype of psychiatric disorders. This study aimed to investigate differences in the local gyrification index (LGI) in each cortical region between patients with BD and healthy controls (HCs).

LGI values, as measured using FreeSurfer software, were compared between 61 patients with BD and 183 HCs. The values were also compared between patients with BD type I and type II as a sub-group analysis. Furthermore, we evaluated whether there was a correlation between LGI values and illness duration or depressive symptom severity in patients with BD.

Patients with BD showed significant hypogyria in various cortical regions, including the left inferior frontal gyrus (pars opercularis), precentral gyrus, postcentral gyrus, superior temporal cortex, insula, right entorhinal cortex, and both transverse temporal cortices, compared to HCs after the Bonferroni correction (p < 0.05/66, 0.000758). LGI was not associated with clinical factors such as illness duration, depressive symptom severity, and lithium treatment. No significant differences in cortical gyrification according to the BD subtype were found.

BD appears to be characterized by a significant regionally localized hypogyria, in various cortical areas. This abnormality may be a structural and developmental endophenotype marking the risk for BD, and it might help to clarify the etiology of BD.

Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’.

In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated.

We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network.

These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.