Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression.

Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery–Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD.

We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05).

Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

Serotonin norepinephrine reuptake inhibitors (SNRIs) have been postulated to afford benefits in alleviating anhedonia and amotivation. This post hoc pooled analysis evaluated the effect of venlafaxine XR, an SNRI, on these symptoms in patients with major depressive disorder (MDD).

Data was pooled from five short-term randomized, placebo-controlled studies of venlafaxine XR for the treatment of MDD, comprising 1087 (venlafaxine XR, n = 585; placebo, n = 502) adult subjects. The change from baseline score in the MADRS anhedonia factor (based on items 1 [apparent sadness], 2 [reported sadness], 6 [concentration difficulties], 7 [lassitude], and 8 [inability to feel]) for anhedonia, and in motivational deficits (based on 3 items of HAM-D17: involvement in work and activities, psychomotor retardation, and energy level [ie, general somatic symptoms]) for amotivation, were measured through 8 weeks. Mixed model repeated measures (MMRMs) were used to analyze changes over time and ANCOVA to analyze the change from baseline at week 8 with LOCF employed to handle missing data.

At the end of 8 weeks, the change from baseline was significantly greater in patients on venlafaxine XR in both anhedonia (mean, 95% CI: −2.73 [−3.63, −1.82], p < 0.0001) and amotivation scores (mean, 95% CI: −0.78 [−1.04, −0.52], p < 0.0001) than those on placebo. For both measures, the between-group separation from baseline was statistically significant starting from week 2 onwards, and it increased over time.

This analysis demonstrates that venlafaxine XR is effective in improving symptoms of anhedonia and motivational deficits in patients with MDD.

Post-COVID-19 condition (PCC) is associated with a host of psychopathological conditions including prominent anxiety symptoms. However, it is not known what effect anxious symptoms have on measures of well-being in individuals living with PCC. This study aims to evaluate anxiety’s association with measures of well-being in people with PCC.

This is a post hoc analysis utilizing data from a placebo-controlled, randomized, double-blind clinical trial assessing the effect of vortioxetine on cognitive impairment in individuals with PCC (NCT05047952). Baseline data with respect to anxiety and well-being were collected using the Generalized Anxiety Disorder Scale, 7-Item (GAD-7), and the World Health Organization (WHO) Well-Being Index, 5-Item (WHO-5), respectively. A generalized linear model (GLM) analysis on baseline GAD-7 and WHO-5 scores was conducted with age, sex, employment status, education level, previous major depressive disorder (MDD) diagnosis, and confirmed COVID-19 cases as covariates.

Data was analyzed in a sample of 144 participants (N = 144). After controlling for the aforementioned covariates, the results found that GAD-7 and WHO-5 scores had a significant negative correlation (β = −0.053, p = <0.001), signifying that increased anxiety had adverse effects on the overall well-being of individuals with PCC.

Herein, we observed a clinically meaningful level of anxiety in individuals with PCC. We also identified a robust correlation between anxiety in PCC and measures of general well-being. Our results require replication, providing the impetus for recommending screening and targeting anxious symptoms as a tactic to improve general well-being and outcomes in individuals with PCC.

Gambling disorder affects 0.5–2.4% of the population and shows strong associations with lifetime alcohol use disorder. Very little is known regarding whether lifetime alcohol use disorder can impact the clinical presentation or outcome trajectory of gambling disorder.

Data were pooled from previous clinical trials conducted on people with gambling disorder, none of whom had current alcohol use disorder. Demographic and clinical variables were compared between those who did versus did not have lifetime alcohol use disorder.

Of the 621 participants in the clinical trials, 103 (16.6%) had a lifetime history of alcohol use disorder. History of alcohol use disorder was significantly associated with male gender (relative risk [RR] = 1.42), greater body weight (Cohen’s D = 0.27), family history of alcohol use disorder in first-degree relative(s) (RR = 1.46), occurrence of previous hospitalization due to psychiatric illness (RR = 2.68), and higher gambling-related legal problems (RR = 1.50). History of alcohol use disorder was not significantly associated with other variables that were examined, such as severity of gambling disorder or extent of functional disability. Lifetime alcohol use disorder was not significantly associated with the extent of clinical improvement in gambling disorder symptoms during the subsequent clinical trials.

These data highlight that lifetime alcohol use disorder is an important clinical variable to be considered when assessing gambling disorder because it is associated with several untoward features (especially gambling-related legal problems and prior psychiatric hospitalization). The study design enabled these associations to be disambiguated from current or recent alcohol use disorder.

Difficulties with emotion regulation have been associated with multiple psychiatric conditions. In this study, we aimed to investigate emotional regulation difficulties in young adults who gamble at least occasionally (ie, an enriched sample), and diagnosed with a range of psychiatric disorders using the validated Difficulties in Emotion Regulation Scale (DERS).

A total of 543 non-treatment-seeking individuals who had engaged in gambling activities on at least 5 occasions within the previous year, aged 18–29 were recruited from general community settings. Diagnostic assessments included the Mini International Neuropsychiatric Inventory, Minnesota Impulsive Disorders Interview, attention-deficit/hyperactivity disorder World Health Organization Screening Tool Part A, and the Structured Clinical Interview for Gambling Disorder. Emotional dysregulation was evaluated using DERS. The profile of emotional dysregulation across disorders was characterized using Z-scores (those with the index disorder vs. those without the index disorder).

Individuals with probable ADHD displayed the highest level of difficulties in emotional regulation, followed by intermittent explosive disorder, social phobia, and generalized anxiety disorder. In contrast, participants diagnosed with obsessive-compulsive disorder showed relatively lower levels of difficulties with emotional regulation.

This study highlights the importance of recognizing emotional dysregulation as a trans-diagnostic phenomenon across psychiatric disorders. The results also reveal differing levels of emotional dysregulation across diagnoses, with potential implications for tailored treatment approaches. Despite limitations such as small sample sizes for certain disorders and limited age range, this study contributes to a broader understanding of emotional regulation’s role in psychiatric conditions.

Gambling disorder is common, affects 0.5–2% of the population, and is under-treated. Duration of untreated illness (DUI) has emerged as a clinically important concept in the context of other mental disorders, but DUI in gambling disorder, has received little research scrutiny.

Data were aggregated from previous clinical trials in gambling disorder with people who had never previously received any treatment. DUI was quantified, and clinical characteristics were compared as a function of DUI status.

A total of 298 individuals were included, and the mean DUI (standard deviation) was 8.9 (8.4) years, and the median DUI was 6 years. Longer DUI was significantly associated with male gender, older age, earlier age when the person first started to gamble, and family history of alcohol use disorder. Longer DUI was not significantly associated with racial-ethnic status, gambling symptom severity, current depressive or anxiety severity, comorbidities, or disability/functioning. The two groups did not differ in their propensity to drop out of the clinical trials, nor in overall symptom improvement associated with participation in those trials.

These data suggest that gambling disorder has a relatively long DUI and highlight the need to raise awareness and foster early intervention for affected and at-risk individuals. Because earlier age at first gambling in any form was strongly linked to longer DUI, this highlights the need for more rigorous legislation and education to reduce exposure of younger people to gambling.

Inadequate response to first- and second-line pharmacological treatments for psychiatric disorders is commonly observed. Ketamine has demonstrated efficacy in treating adults with treatment-resistant depression (TRD), with additional off-label benefits reported for various psychiatric disorders. Herein, we performed a systematic review and meta-analysis to examine the therapeutic applications of ketamine across multiple mental disorders, excluding mood disorders.

We conducted a multidatabase literature search of randomized controlled trials and open-label trials investigating the therapeutic use of ketamine in treating mental disorders. Studies utilizing the same psychological assessments for a given disorder were pooled using the generic inverse variance method to generate a pooled estimated mean difference.

The search in OVID (MedLine, Embase, AMED, PsychINFO, JBI EBP Database), EBSCO CINAHL Plus, Scopus, and Web of Science yielded 44 studies. Ketamine had a statistically significant effect on PTSD Checklist for DSM-5 (PCL-5) scores (pooled estimate = ‒28.07, 95% CI = [‒40.05, ‒16.11], p < 0.001), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) scores (pooled estimate = ‒14.07, 95% CI = [‒26.24, ‒1.90], p = 0.023), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (pooled estimate = ‒8.08, 95% CI = [‒13.64, ‒2.52], p = 0.004) in individuals with PTSD, treatment-resistant PTSD (TR-PTSD), and obsessive compulsive disorder (OCD), respectively. For alcohol use disorders and at-risk drinking, there was disproportionate reporting of decreased urge to drink, increased rate of abstinence, and longer time to relapse following ketamine treatment.

Extant literature supports the potential use of ketamine for the treatment of PTSD, OCD, and alcohol use disorders with significant improvement of patient symptoms. However, the limited number of randomized controlled trials underscores the need to further investigate the short- and long-term benefits and risks of ketamine for the treatment of psychiatric disorders.

Treatment and management for difficult-to-treat depression are challenging, especially in a subset of patients who are at high risk for relapse and recurrence. The conditions that represent this subset are recurrent depressive disorder (RDD) and bipolar disorder (BD). In this context, we aimed to examine the effectiveness of maintenance transcranial magnetic stimulation (TMS) on a real-world clinical basis by retrospectively extracting data from the TMS registry data in Tokyo, Japan.

Data on patients diagnosed with treatment-resistant RDD and BD who received maintenance intermittent theta burst stimulation (iTBS) weekly after successful treatment with acute iTBS between March 2020 and October 2023 were extracted from the registry.

All patients (21 cases: 10 cases with RDD and 11 cases with BD) could sustain response, and 19 of them further maintained remission. In this study, maintenance iTBS did not exacerbate depressive symptoms in any of the cases, but may rather have the effect of stabilizing the mental condition and preventing recurrence.

This case series is of great clinical significance because it is the first study to report on the effectiveness of maintenance iTBS for RDD and BD, with a follow-up of more than 2 years. Further validation with a randomized controlled trial design with a larger sample size is warranted.

Visual release hallucinations are perceptual disturbances that occur in individuals who have experienced vision loss. Almost 50 million people worldwide are believed to experience visual release hallucinations, yet they are profoundly underdiagnosed. Although first described within the Charles Bonnet syndrome, the paradigm underlying this syndrome precludes their consideration in many populations, such as those with underlying psychiatric illness or dementia. Consequently, visual release hallucinations have rarely been studied in patients presenting with psychosis. We conducted a scoping review to determine whether visual-release hallucinations occur in psychotic patients.

The PubMed research database was searched from inception through April 2023. Cases were collected reporting on psychotic patients experiencing suspected visual release hallucinations. Individual treatment courses and responses were extracted.

Thirteen cases compiled from 11 different studies were summarized to provide baseline characteristics and overall trends in treatment response. Most patients did not remit from pharmacological management alone. All patients who received reafferentation therapy remitted, though many were not candidates. Almost half of the patients did not achieve remission.

Visual release hallucinations can manifest in psychosis and may contribute to treatment-resistant psychosis among psychiatric populations. A shift in our understanding of visual release hallucinations may aid their recognition in psychotic patients by shifting the focus toward visual release features. Recognizing release features among patients with hallucinatory conditions may open new treatment avenues for managing patients with psychosis. A preliminary screening index for visual release features is provided to support this shift.

Recent guidance from UK health authorities strongly cautions against the use of valproic acid (VPA) in persons under 55 because of reevaluated risk of teratogenicity.

To summarize the extant literature documenting VPA-associated anatomical, behavioral, and cognitive teratogenicity.

Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web of Science, and Google Scholar were searched in accordance with PRISMA guidelines. Collected data covered study design, participant characteristics, anatomical, behavioral, or cognitive effects, and folic acid outcomes.

122 studies were identified meeting inclusion comprised of studies evaluating anatomical (n = 67), behavioral (n = 28), and cognitive (n = 47) teratogenicity. Twenty studies were identified reporting on the risk mitigation effects of folic acid supplementation. Prenatal VPA exposure is associated with anatomical teratogenicity including major congenital malformations (odds ratio [OR] 2.47–9.30; p < 0.005). Behavioral teratogenicity including autism (OR 1.70–4.38), impaired motor development (OR 7.0), and ADHD (OR 1.39) are also significantly associated with VPA exposure. VPA was associated with intellectual disability and low IQ (hazard ratio [HR] 2.4–4.48, verbal intelligence: Spearman’s ρ = −0.436, respectively). Teratogenic effects were dose-dependent across all domains and were significant when compared with controls and other antiepileptic drugs (eg, carbamazepine, lamotrigine, and levetiracetam). Folic acid supplementation does not significantly reduce the hazard associated with VPA.

VPA is significantly associated with anatomical, behavioral, and cognitive teratogenicity. Folic acid supplementation does not abrogate the risk of teratogenicity associated with VPA exposure. Available evidence supports recommendations to reduce VPA exposure in women of reproductive age.

The COVID-19 pandemic impacted mental health across different groups, including healthcare workers (HWs). To date, few studies focused on potential positive aspects that may follow the exposure to the pandemic. We investigated the prevalence of posttraumatic stress disorder (PTSD) in Italian HWs and whether posttraumatic growth (PTG) dimensions affected the risk of suicidal ideation (SI) during the first COVID-19 wave.

An online self-report survey was conducted between April and May 2020. Sociodemographic data, information about COVID-19-related stressful events, Impact of the Event Scale-revised, and Post-Traumatic Growth Inventory-Short Form (PTGI-SF) scores were collected and compared between participants. Patient Health Questionnaire-9 scores were also collected to assess SI through item 9. Multivariate logistic regression was used to assess the relationship between PTGI and SI.

Among 948 HWs, 257 (27.0%) reported a provisional PTSD diagnosis. The median PTGI-SF score was 24. Participants reporting PTSD symptoms had higher scores in the Spiritual change, Appreciation of life, and New possibilities domains, and in the total PTG scale. A total of 100 HWs (10.8%) screened positive for SI. Improvements in Relating to others domain of PTGI-SF (odds ratioOR: .46; 95% confidence interval: .25–.85) were associated with lower odds of SI.

COVID-19 pandemic has been indicated as a risk factor for SI, also among HWs. PTG may have a protective role on suicide risk. Improvements in Relating to others domain reduced odds of SI, consistently with the role of loneliness and lack of connectedness with others in enhancing suicidal risk.

Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD.

Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections.

Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5).

These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Tending to patients with a diagnosis of borderline personality disorder (BPD) is a challenging task for clinicians due to stigma and differences in opinion within the psychiatric community. Various symptoms of BPD including affective instability, mood reactivity, and extremes of idealization are associated with challenging emotions toward patients with BPD. This observational research study utilized an adaptation of the 37-question Attitude to Personality Disorder Questionnaire (APDQ) to assess the attitudes of clinicians toward patients with BPD.

This questionnaire was distributed to 139 clinicians including psychiatry attendings, psychiatry residents, registered nurses, nurse practitioners, social workers, recreation and art therapists, and psychologists who worked with patients diagnosed with BPD on an inpatient unit. Responses of participants were compared based on occupation, gender, and duration of years worked on an inpatient psychiatric unit.

Results show that individuals employed in occupations under the “other health professionals” category had more positive transference (which included feelings of respect toward BPD patients along with feelings of closeness and warmth) toward patients with BPD, and nurses had an increased total score for lack of valid difficulties compared with other health professionals. When grouping by gender and duration of year spent working on an inpatient unit, there were no significant differences in the response toward patients with BPD in affective situations.

Clinical implications are discussed, as well as the need for training to help improve staff attitudes toward this patient population.

Scientific literature has highlighted the link between autism spectrum disorder (ASD) and anxiety disorders, but few studies have delved into the relationship between ASD and panic-agoraphobic disorders. The aim of this study is to investigate the relationship between autism spectrum and panic-agoraphobic symptoms, examining whether and which autistic domains are predictive of the presence of specific panic-agoraphobic symptoms.

Forty-five adult subjects with ASD and 50 healthy controls (HCs) were evaluated through the Structured Clinical Interview for DSM-5, Research Version and assessed with the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Panic-Agoraphobic – Short Version (PAS-SV) questionnaires. Statistical analyses included Mann–Whitney U test, chi-square test, and a set of linear and logistic regression analyses.

The PAS-SV total and domain scores were significantly higher in the ASD group than in the HC group. A higher AdAS total score appeared to be predictive of a higher PAS-SV total score. The AdAS domain Restricted Interests and Rumination would increase the risk of obtaining higher PAS-SV total and domain scores. Conversely, the AdAS Spectrum domain Inflexibility and Adherence to Routine would predict lower total PAS-SV score.

This study revealed a greater representation of panic-agoraphobic symptoms in adults with ASD, as well as an increased risk of showing such symptoms in the presence of significant autistic traits. Restricted interests and ruminative thinking emerged as predominant risk factors for panic-agoraphobic manifestations.

Conventional treatment methods have limited effectiveness in addressing late-life depression (LLD) that does not respond well. While a new approach called priming repetitive transcranial magnetic stimulation (rTMS) has shown promise in treating depression in adults, its effectiveness in LLD has not been explored. This study aimed to investigate the impact of priming rTMS on LLD.

This study investigated the effectiveness of priming rTMS in 31 patients with LLD who did not improve after an adequate trial of antidepressants. Patients were randomly assigned to receive either active priming rTMS or sham priming rTMS. Active priming rTMS was delivered over the right dorsolateral prefrontal cortex for 10 sessions, lasting 31 minutes each, over a period of 2 weeks.

The group receiving active priming rTMS demonstrated greater improvements in scores on the Hamilton Rating Scale for Depression (p < 0.037; partial η2 0.141) and the Geriatric Depression Rating Scale (p < 0.045; partial η2 0.131) compared to the sham priming group, with a mild effect size. At the end of the second and fourth weeks, the priming rTMS group achieved a response rate of 50%, while the sham priming group had response rates of 26.7% and 6.7%, respectively. No adverse effects requiring intervention were observed.

Priming rTMS is well-tolerated for the treatment of LLD and not only reduces the severity of depression but also maintains the achieved response over time.

Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients.

Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed.

During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm (p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported.

Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.