Coping Strategy Enhancement for Auditory Verbal Hallucinations Within Routine Clinical Practice.

ABSTRACT: Auditory verbal hallucinations (AVH) are often multiple distressing experiences. Emerging evidence suggests that interventions informed by the principles of cognitive behavioral therapy, such as brief Cognitive Strategy Enhancement (brief-CSE), can reduce the distress related to AVH. The benefits of brief-CSE have been demonstrated for English-speaking patients. This uncontrolled pilot study, conducted in routine clinical practice, evaluated the benefits of brief-CSE within a group of French-speaking AVH hearers. Thirty-two patients were offered the brief-CSE intervention. Self-administered questionnaires were completed pre-post intervention. A significant reduction was observed in AVH distress, with a large effect size, and for more than half of the patients, this reduction was clinically meaningful. AVH severity and anxiety also decreased significantly. This study demonstrates that brief-CSE can be implemented in non-English-speaking routine clinical practice and can reduce several aspects of AVH subjective experience. There is a need to confirm these findings in a larger sample.

[ICD-11: New revision and impact of this classification in psychiatry]. / CIM-11 (OMS) : nouvelle révision et impact de la classification onusienne en psychiatrie.

OBJECTIVES: After more than 20 years of work, the World Health Organization's efforts have culminated in the adoption of the 11th revision of the International Classification of Diseases (ICD-11). The process has been guided by the principles of global applicability, scientific validity, and clinical utility. The update of the chapter on mental, behavioral, and neurodevelopmental disorders (MBND) within the ICD-11 has generated widespread interest worldwide. This has raised various questions about the status of mental disorder nosology, changes to diagnostic guidelines, and the potential implications for clinical practice. METHODS: We conducted a narrative analysis of the literature in four different languages to track the various stages of the ICD-11 revision and to highlight the major changes. We searched databases such as PubMed, EMBASE, MEDLINE, and Google Scholar, and consulted the official websites of the WHO, APA, and UNICEF. A total of 79 articles from 40 different editorials and websites were analyzed and included in this study. RESULTS: The new chapters on mental disorders in the ICD-11 include 21 groups, as opposed to the 11 in the ICD-10. The changes aim to align the diagnoses with those of the DSM-5 and introduce a new chapter structure, new diagnostic categories, modifications to diagnostic criteria, and advancements in dimensionality. For the first time in the history of the ICD, sleep and wakefulness disorders, as well as disorders related to sexual health, have been addressed in separate chapters of the international classification. Four new diagnoses have been added: complex post-traumatic stress disorder (PTSD), gaming disorder, prolonged grief disorder, and compulsive sexual behavior which replaces "excessive sexual activity" in the ICD-10. Moreover, the ICD-11 revision has brought about a fundamental change in the clinical conceptualization of addictive behaviors, introducing a distinction between substance use disorders and addictive behaviors. The criteria for many existing conditions have been revised, particularly those related to bipolar disorders, eating disorders, and gender identity disorders. CONCLUSIONS: The revision process for mental, behavioral, and neurodevelopmental disorders in the ICD-11 has witnessed unprecedented participation in the history of mental disorder classification. These changes could have a significant impact on clinical practice in psychiatry. However, it is crucial to examine the advantages and limitations of this new classification compared to previous versions.

Validation and clinical usefulness of the Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) among French-speaking voice-hearers.

Auditory verbal hallucinations (AVH), also called voices, are often distressing to individuals experiencing them. Valid and reliable instruments are necessary to document the hearing voices experience across cultures. The Hamilton Program for Schizophrenia Voices Questionnaire (HPSVQ) is becoming a widely used self-administered instrument for assessing characteristics, content and subjective effect of AVH. This study investigates the psychometric characteristics of the HPSVQ French version (HPSVQ FV) in a clinical sample of voice-hearers. The results showed that the HPSVQ yields a global score (HPSVQ-Global) as well as a distress (HPSVQ-Distress) and a severity (HPSVQ-Severity) sub-score having good, acceptable and questionable internal consistency respectively. Significant correlations were found between hallucination severity (BPRS 4.0), distress (PSYRATS-AH), voices acceptance (VAAS-9), anxiety and depression (HADS). However, no significant associations were observed between Suspicion and Unusual Thoughts (BPRS 4.0). At a one-week interval, the temporal stability of the three indices was excellent. Moreover, after a brief cognitive intervention, a significant reduction was observed in all indices. Taken together, the HPSVQ FV demonstrated good construct validity, reliability and sensitivity to change. These findings support the use of the HPSVQ in francophone clinical and research settings. However, the bi-factorial solution of the HPSVQ FV should be further examined in larger samples.

Psychotic symptoms prior or concomitant to diagnosis of multiple sclerosis: a systematic review of case reports and case series.

OBJECTIVE: We aimed to examine the clinical features of psychotic symptoms preceding or concomitant to multiple sclerosis (MS) diagnosis. METHOD: From the 1st to 10th of January 2020 a systematic review was conducted through an electronic search of different databases. Results were limited to English, French, German, Italian and Spanish language articles. RESULTS: We identified 599 titles, and included 32 cases from case-report and case series. One case report from our department was added. The mean age of first psychiatric symptoms was 25.8 ± 10.2 years, the mean age of MS diagnosis was 31.2 ± 10.7 years and the mean delay until MS diagnosis was 2.7 ± 3 years. Most reported symptoms were delusions (81%), auditory hallucinations (59%) and visual hallucinations (50%). Upon the MS diagnosis, immunosuppressive therapy was significantly more effective for psychotic symptoms than antipsychotics (OR = 9.0; 95%CI: 2.15-37; p = 0.002). Diffuse periventricular lesions were found in 95.6% of cases, with mostly temporal or frontal predominant lesions. In cases affected by predominant temporal lesions, 83% of cases presented visual hallucinations (p < 0.05). CONCLUSION: Poor response or resistance to antipsychotics treatment should alert clinicians on the need to consider a differential diagnosis. Considering the impact of delay in MS diagnosis further research regarding this subject is warranted.KEY POINTSInsight into the occurrence of psychotic symptoms in multiple sclerosis (MS) is mainly limited to case reports and case series.Delay in MS management between initial psychotic symptoms and the MS diagnosis is 2.73 ± 3 years and 0.8 ± 1.2 years for patients presenting a first episode of psychosis.The resistance and poor response to antipsychotics found in most cases (75%) were associated with an excellent improvement (95%) of both psychiatric and neurologic symptoms with corticosteroids.Prospective studies are needed to investigate the spectrum of psychosis in MS.

Prevalence and risk factors for seclusion and restraint in old-age psychiatry inpatient units.

BACKGROUND AND OBJECTIVES: Coercion in psychiatry is legally tolerated as a last resort. The reduction of the use of coercion is a shared goal of hospital administrators, medical and nursing staff and representatives of patients and families but requires the identification of risk factors for coercion. These risk factors in geriatric psychiatric inpatient settings are not well known, especially regarding seclusion. Through examining the prevalence of coercion and patients' characteristics, this study aims to identify risk factors for coercion in elderly people. METHODS: The use of coercion in the geriatric psychiatry division of Geneva University Hospital in 2017 was retrospectively analyzed. The incidence rate ratios were estimated with multivariable Poisson regressions to assess risk factors for coercion. RESULTS: Eighty-one of 494 patients (16.4%) experienced at least one coercive measure during their stay (mainly seclusion). The risk factors for coercion were younger age, male gender, being divorced or married, cognitive disorders, high item 1 of the Health of the Nation Outcome Scales (HoNOS) score (overactive, aggressive, disruptive or agitated behavior) at admission, previous psychiatric hospitalizations and involuntary referrals from the emergency department. Other disorders and global HoNOS scores were not associated with the use of coercion. CONCLUSION: Higher risks of coercion were outlined in men with cognitive disorders, agitated behaviors, and previous psychiatric hospitalizations. They differed from those observed in younger adults in terms of age, civil status, disorders, global HoNOS scores and referrals. Therefore, geriatric psychiatric populations should be specifically investigated for the development of interventions aiming coercion reduction.

Effect of Quetiapine, from Low to High Dose, on Weight and Metabolic Traits: Results from a Prospective Cohort Study.

INTRODUCTION: The atypical antipsychotic quetiapine is known to induce weight gain and other metabolic complications. The underlying mechanisms are multifactorial and poorly understood with almost no information on the effect of dosage. Concerns were thus raised with the rise in low-dose quetiapine off-label prescription (i. e.,<150 mg/day). METHODS: In this study, we evaluated the influence of quetiapine dose for 474 patients included in PsyMetab and PsyClin studies on weight and metabolic parameter evolution. Weight, blood pressure, lipid, and glucose profiles were evaluated during a follow-up period of 3 months after treatment initiation. RESULTS: Significant dose-dependent metabolic alterations were observed. The daily dose was found to influence weight gain and increase the risk of undergoing clinically relevant weight gain (≥7% from baseline). It was also associated with a change in plasma levels of cholesterol (total cholesterol, LDL cholesterol, and HDL cholesterol) as well as with increased odds of developing hypertriglyceridemia, as well as total and LDL hypercholesterolemia. No impact of a dose increase on blood pressure and plasma glucose level was observed. DISCUSSION: The dose-dependent effect highlighted for weight gain and lipid alterations emphasizes the importance of prescribing the minimal effective dose. However, as the effect size of a dose increase on metabolic worsening is low, the potential harm of low-dose quetiapine should not be dismissed. Prescriptions must be carefully evaluated and regularly questioned in light of side effect onset.

Major depression impairs incentive processing: evidence from the heart and the face.

BACKGROUND: The present study tested the hypothesis of a differential pattern of reward and punishment responsiveness in depression measuring effort mobilization during anticipation and facial expressions during consumption. METHODS: Twenty patients with major depressive disorder (MDD) and 20 control participants worked on a memory task under neutral, reward, and punishment instructions. Effort mobilization was operationalized as cardiovascular reactivity, while facial expressions were measured by facial electromyographic reactivity. Self-report measures for each phase complemented this multi-method approach. RESULTS: During anticipation, MDD patients showed weaker cardiac pre-ejection period (PEP) reactivity to reward and blunted self-reported wanting, but weaker PEP reactivity to punishment and unchanged self-reported avoidance motivation. During consumption, MDD patients showed reduced zygomaticus major muscle reactivity to reward and blunted self-reported liking, but unchanged corrugator supercilii muscle reactivity to punishment and unchanged self-reported disliking. CONCLUSIONS: These findings demonstrate reduced effort mobilization during reward and punishment anticipation in depression. Moreover, they show reduced facial expressions during reward consumption and unchanged facial expressions during punishment consumption in depression.

Validation of the Recovery Style Questionnaire in Outpatients With Affective Disorders.

Considering how patients recover from mental illness is crucial to offer appropriate therapeutic interventions. This study was designed to determine the psychometric characteristics of the Recovery Style Questionnaire (RSQ) in a sample of outpatients recruited among the referrals to a crisis intervention center presenting with mood or anxiety disorders. Assessments completed at intake and at discharge examined the recovery styles with the RSQ, psychiatric symptoms with the Brief Psychiatric Rating Scale version 4.0, and the Symptom Checklist-Revised; defense mechanisms with the Defense Style Questionnaire 40 items; and global functioning with the Global Assessment Functioning. The RSQ has acceptable reliability, divergent validity, and sensitivity to change after treatment. These findings suggest that the RSQ is a valid and reliable instrument to assess recovery style. They also offer evidence of the usefulness of the RSQ in various clinical settings, such as in crisis intervention centers.

Sexual Identity Disorder and Psychosis in Klinefelter Syndrome: A Synthesis of Literature and a Case Report.

Klinefelter syndrome (KS) 47, XXY is the most frequent chromosomal abnormality causing hypogonadism in humans. This chromosomal abnormality of number in its classical form called homogeneous (supernumerary X) is generally the result of a meiosis accident. Several studies have suggested that individuals with KS are at greater risk of developing various psychiatric disorders, including depression and schizophrenia. The diagnosis is made based on subnormal testosterone with high pituitary gonadotropins and confirmed by determining the karyotype on a blood simple. We did a literature review using an electronic search in three databases: Pubmed/MEDLINE, Google Scholar, and PsychInfo. We found that since 1989, seven case reports with KS and mental disorders with similar and different characteristics of our case illustration of a patient with KS and psychosis were published.

[Programm 4F: tailored physical activity and nutrition for young patients with mental diseases]. / Programme 4F à Genève:activité physique et nutrition adaptées lors de troubles psychiatriques.

Nowadays, new psychotropic treatments might result on rapid onset of weight gain also related to other factors such as individual vulnerability, poor diet and lack of exercise. Many studies have reported that weight gain is only the premise of a series of metabolic disturbances and cardiovascular complications. In this context, we have established since June 2017 in an ambulatory centre in Geneva, a 4F program (Fit, Fun, Feel and Food), to optimize the measures and strategies needed to prevent and reduce weight gain in these patients. This transversal program is naturalistically and systematically centered on physical activity, healthy diet and improved body perception. We will show some preliminary results of 4F program.

Nous avons mis en place en juin 2017 un programme de soins centré sur la reprise de l'activité physique, intitulé 4F (Fit, Fun, Feel et Food) qui a comme objectif de limiter la prise de poids et la sédentarité chez des patients souffrants de troubles psychiques modérés à sévères. En effet, la littérature récente dans ce domaine rapporte que certains traitements psychotropes peuvent être obésogènes ainsi que d'autres facteurs tels qu'une vulnérabilité individuelle, un mauvais équilibre nutritionnel et un manque d'exercice physique. Devant ce constat, ce programme de prévention multidisciplinaire de 8 semaines, composé de 4 groupes hebdomadaires, est proposé afin que les patients puissent modifier leur hygiène de vie, leur équilibre nutritionnel et mieux se réapproprier leur corps grâce à une prise en charge adaptée et personnalisée. Cette perturbation pondérale a été notée comme n'étant que la prémisse d'une cascade de perturbations métaboliques et de complications cardiovasculaires.

Schizophrenia and Criminal Responsibility: A Systematic Review.

The significant progress of psychiatry in the 20th century provided a sophisticated theoretical framework to analyze the complex relationships between crime and mental illness. Schizophrenia has been traditionally associated with severe cognitive and affective deficits that heavily influence empathy, judgment capacities, but also control of impulsiveness. Although there is an association between psychotic disorders and absence or decrease of legal responsibility, their relationship is also determined by sociodemographic, developmental, and clinical factors. These disorders are associated not only with abolished criminal responsibility but also with diminished responsibility. We conduct a systematic literature review to examine the relation between schizophrenia and criminal responsibility. We have found that this clinical entity is often associated with diminished or abolished criminal liability. We discuss these findings, focusing on the specific deficits found in patients with schizophrenia and examining how this problem affects their behavior and eventually their accountability for their crimes.

Determinants of dropout in a community-based mental health crisis centre.

BACKGROUND: Dropping out during the course of medical follow up is defined as an early therapy withdrawal without the agreement of the therapist. In a psychiatric crisis unit in Geneva, we empirically observed that almost 50% of the patients were not showing up to their first appointments, which were scheduled for 3 to 7 days post discharge. METHODS: The aim of this naturalistic descriptive cohort study is to identify the demographic, patient and care-related predictive factors of dropout in a community-based psychiatric crisis centre. We included 245 consecutive outpatients followed-up for 4 to 6 weeks of intensive outpatient psychiatric treatment. Logistic regression models were built to examine the association between dropout and demographic, care and patient-related variables. RESULTS: Among the 245 outpatients, dropout occurred in 37.5% of cases, and it most frequently occurred (81.8%) in the first 2 days of follow-up. Among care-related variables, referral by hospital units or private psychiatrists led to significantly lower levels of dropout compared to patients referred by the psychiatric emergency unit (respectively: OR = .32; p = .04; 95% CI [.10, .93]; OR = .36; p = .04; 95% CI [.13, .96]; OR = .22; p = .002; 95% CI [.08, .58]). Among patient-related variables, younger age increased the risk of dropout (OR = .96; 95%; p = .002; 95% CI [.94, .99]). Anxiety and personality but not mood disorders were also related to higher rates of dropout (respectively: OR = 2.40; p = .02; 95% CI [1.14, 4.99]; and OR = 1.98; p = .02; 95% CI [1.09, 3.59]). Unipolar depression (72.2%; OR = 1.47; p = .48; 95% CI [.34, 1.21]) was the most frequent primary diagnosis in this sample. CONCLUSIONS: This study makes clear the need for increased efforts to improve care adherence in young patients with anxious or personality disorders seen in emergency rooms because they are prone to early discontinuation of treatments. Future studies in this field are warranted to gain a better understanding into the complex reasons that surround discontinuation of care in outpatient settings.

Genetics of psychotropic medication induced side effects in two independent samples of bipolar patients.

The treatment of bipolar disorder (BD) usually requires combination therapies, with the critical issue of the emergence of adverse drug reactions (ADRs) and the possibility of low treatment adherence. Genetic polymorphisms are hypothesized to modulate the pharmacodynamics of psychotropic drugs, representing potential biological markers of ADRs. This study investigated genes involved in the regulation of neuroplasticity (BDNF, ST8SIA2), second messenger cascades (GSK3B, MAPK1, and CREB1), circadian rhythms (RORA), transcription (SP4, ZNF804A), and monoaminergic system (HTR2A and COMT) in the risk of neurological, psychic, autonomic, and other ADRs. Two independent samples of BD patients naturalistically treated were included (COPE-BD n = 147; STEP-BD n = 659). In the COPE-BD 34 SNPs were genotyped, while in the STEP-BD polymorphisms in the selected genes were extracted from the genome-wide dataset. Each ADRs group was categorized as absent-mild or moderate-severe and logistic regression with appropriate covariates was applied to identify possible risk genotypes/alleles. 58.5 and 93.5 % of patients were treated with mood stabilizers, 44.2 and 50.7 % were treated with antipsychotics, and 69.4 and 46.1 % were treated with antidepressants in the COPE-BD and STEP-BD, respectively. Our findings suggested that ST8SIA2 may be associated with psychic ADRs, as shown in the COPE-BD (rs4777989 p = 0.0017) and STEP-BD (rs56027313, rs13379489 and rs10852173). A cluster of RORA SNPs around rs2083074 showed an effect on psychic ADRs in the STEP-BD. Trends supporting the association between HTR2A and autonomic ADRs were found in both samples. Confirmations are needed particularly for ST8SIA2 and RORA since the few available data regarding their role in relation to psychotropic ADRs.

Family history of major depression and residual symptoms in responder and non-responder depressed patients.

BACKGROUND: Little is known about the extent to which a family history of major depression (MD) affects residual depressive symptoms in responder and non-responder patients suffering from MD. METHODS: Nine hundred eighty-six patients with MD were recruited within the context of a large multicenter project. Information about the family history of MD, as well as about total depressive symptoms and specific depressive clusters, was collected and analyzed. RESULTS: No significant difference was observed in overall depressive symptoms between patients with and those without a family history of MD. However, non-responder patients with a family history of MD showed significantly higher scores in core symptoms as compared with responder patients without a family history of MD. CONCLUSIONS: Non-responder MD patients with a positive family history of MD could represent a slightly different sub-group of MD patients with more consistent core depressive symptoms as compared with responder patients without a family history of MD. However, taking into account the retrospective assessment of data, the use of positive or negative family history as a dichotomous indicator of familial loading and the cross-sectional design of the present study, further research is needed to draw more definitive conclusions.

Shared and unique characteristics of metabolic syndrome in psychotic disorders: a review.

Introduction: People with psychosis spectrum disorders (PSD) face an elevated risk of metabolic syndrome (MetS), which may reduce their life expectancy by nearly 20%. Pinpointing the shared and specific characteristics and clinical implications of MetS in PSD is crucial for designing interventions to reduce this risk, but an up-to-date review on MetS across the psychosis spectrum is lacking. Methods: This narrative review fills this gap by examining the clinical literature on characteristics and implications of MetS in both distinct PSD and transdiagnostically, i.e., across traditional categorical diagnoses, with a focus on psychiatric and cardio-metabolic management. Results: We discuss common and specific characteristics of MetS in PSD, as well as factors contributing to MetS development in PSD patients, including unhealthy lifestyle factors, genetic predisposition, pro-inflammatory state, drugs consumption, antipsychotic medication, and psychotic symptoms. We highlight the importance of early identification and management of cardio-metabolic risk in PSD patients, as well as the existing gaps in the literature, for instance in the screening for MetS in younger PSD patients. We compare hypotheses-generating clinical associations and characteristics of MetS in different PSD, concluding by reviewing the existing recommendations and challenges in screening, monitoring, and managing MetS in PSD. Conclusion: Early identification and management of MetS are crucial to mitigate the long-term cardio-metabolic toll in PSD patients. Interventions should focus on healthy lifestyle and appropriate pharmacological and behavioral interventions. Further translational and clinical research is needed to develop targeted interventions and personalized treatment approaches for this vulnerable population, aiming at improving physical health and overall well-being.

Mindfulness-based interventions for patients with schizophrenia spectrum disorders: A systematic review of the literature.

BACKGROUND: Mindfulness-based interventions (MBIs) have emerged as secular practices, including elements of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT). While MBIs have been widely adopted for physical and mental illness, only a few available programs are explicitly adapted for psychosis. However, previous reviews have reported the vital heterogeneity regarding treatment program structure. Therefore, this review aims to compare the structure of different mindfulness protocols applied to patients with schizophrenia spectrum disorder (SSD). METHODS: A systematic search was conducted up to March 2023 in PubMed, Embase and PsycInfo. Following our protocol (CRD 42023253356), we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. RESULTS: We included 22 randomized controlled trials (RCTs) involving 1500 patients SSD. All programs varied in structure, session components, duration, and instructor experience. While MBSR-like programs focused on stress reactivity, MBCT-like programs addressed primary symptoms of psychosis and relapse prevention. Despite the heterogeneity of programs, some common mechanisms emerged, including attention training, emotion and stress regulation, decentering, self-compassion, and cognitive restructuring. CONCLUSIONS: The critical heterogeneity found limits the interpretation of results. However, most recent trials present fewer risks of bias and more homogenous programs. Findings suggested potential benefits, such as reduced negative symptoms, increased well-being, and decreased hospitalization rates. For future studies, authors should align on more congruent MBIs programs for patients with SSD. Further research is needed to identify optimal mindfulness teaching approaches for patients with psychosis and investigate specific mechanisms of action, relevant processes, and optimal doses in varying settings.

Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Across Mental Disorders: A Systematic Review and Dose-Response Meta-Analysis.

Importance: Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown. Objective: To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders. Data Sources: Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge. Study Selection: Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older. Data Extraction and Synthesis: Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS. Results: A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings. Conclusions and Relevance: The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

Treatment resistance in severe unipolar depression: no association with psychotic or melancholic features.

BACKGROUND: Depressive subtypes generally have been neglected in research on treatment efficacy. We studied a sample of 699 severe unipolar depressed patients to detect any association between depressive features and treatment resistance. METHODS: Participants were divided into psychotic (PSY, n = 90), melancholic (MEL, n = 430) and non-melancholic (n = 179) subjects according to clinical features. Formal diagnostic criteria (Mini International Neuropsychiatric Interview items), and items from 17-item Hamilton Rating Scale for Depression (HRSD17) were compared across groups. Non-responders were defined by a HRSD17 cut-off score of ≥17 after the last adequate antidepressant treatment. Treatment-resistant depression (TRD) was defined as the failure to respond to ≥2 adequate antidepressant trials. Non-linear regression models were designed to detect associations between depressive subtypes and TRD. RESULTS: PSY and MEL patients appeared to be more severely affected and to share some "core" melancholic symptoms. Both PSY and MEL patients reported a higher rate of seasonality. However, we found no clinical or illness course variable associated with TRD. CONCLUSIONS: Our results indicate that psychotic and melancholic depression share some "core" melancholia symptoms, while no distinguishing psychopathological feature appears to be associated with TRD in severely depressed patients.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

The impact of adverse life events on clinical features and interaction with gene variants in mood disorder patients.

BACKGROUND: Adverse life events are precipitating and maintenance factors for mood and anxiety disorders. However, the impact of such events on clinical features and treatment response is still unclear. SAMPLING AND METHODS: The aim of this study was to investigate whether specific adverse events (early parental loss and physical abuse) influence clinical features in a sample of 1,336 mood disorder patients, and whether genetic parameters interact with adverse events to influence treatment outcomes in a subsample of 252 subjects. Participants were collected in the context of a European multicenter study and treated with antidepressants at adequate doses for at least 4 weeks. We focused on two genes (BDNF and CREB1) due to prior evidence of association with treatment outcomes in the same sample. RESULTS: Patients with a history of physical abuse had higher suicidal risk (including history of attempts), comorbid panic disorder, posttraumatic stress disorder and alcohol dependence compared to non-abused patients. Experience of early parental loss was a less detrimental type of life stressor. Treatment response was not affected by adverse events. No gene-environment interaction was found with genetic variations, using a corrected significance level. CONCLUSIONS: A limitation of the present study is that the subsample is too small for detecting gene-environment interactions. The clinical message of our findings is that mood disorder patients with a history of physical abuse showed a worse clinical profile, characterized by higher comorbid Axis I psychopathology and increased suicidal behavior.