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For decades clinicians and researchers have been thinking and writing about the spectrum of schizophrenia disorders. Indeed both Kraepelin and Bleuler believed in schizophrenia as a spectrum, both in a clinical (individual) and hereditary (family) continuum, from just some exquisite personality traits to unquestionable chronic and debilitating psychosis. Other authors would put the schizophrenia spectrum disorders on different levels of continuum: developmental, psychofunctional, existential, and genetic. Here, we would like to present an historical chronology for the schizophrenia–schizoaffective–bipolar spectra plus a tridimensional model for these spectra: the first axis for categories (affective versus nonaffective psychoses), the second axis for dimensions (personality versus full blown psychosis), and a third axis for biomarkers (remission versus relapse). We believe that without the schizophrenia–schizoaffective–bipolar spectra concept in our minds all our efforts will keep failing one the hardest quest: searching for biomarkers in schizophrenia and related disorders.
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient’s age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges to consider at each stage of life. A variety of Food and Drug Administration (FDA)-approved stimulant and nonstimulant formulations are available with different modes of delivery and durations of effect. This armamentarium of ADHD medications can be used to individualize ADHD treatment for each patient’s needs. This article combines current information from the literature and the first-hand experience of the authors to provide guidance on ADHD treatment options for patients of different ages and for some of the more common comorbidities.
Ethnic differences may significantly influence the outcome of psychopharmacological treatment, in terms of prescription, adherence, clinical response, emergence of side effects, as well as pharmacokinetics and pharmacodynamics. The purpose of this review was to explore the available literature in order to provide general suggestions to help clinicians in choosing the best therapeutic option for patients, taking into account ethnicity. Although findings are sometimes controversial, the overall published studies suggest that ethnicities other than Caucasians tend to show a lower response to antidepressants and a reduced compliance. Africans tend to be more prescribed with antipsychotics, probably due to cultural stereotypes, except with clozapine, probably for their chronic benign neutropenia. Asians usually require less antipsychotic dosages than Caucasians. The differential response and side effect profile of antidepressants and antipsychotics have been related to individual intrinsic factors, to genetic make-up, but also to cultural and contextual variables. Interestingly, albeit limited data suggest ethnic-related genetic heterogeneity at the level of the serotonin transporters, the cytochromes and some neuroreceptors. Taken together, no conclusive findings are available about the role and impact of ethnicity in psychopharmacology. One of the main problems is that the majority of the studies in psychopharmacology have been conducted on Caucasians, so that there is an urgent need to have data in other populations. Furthermore, in the era of precision medicine, the role of ethnicity may be also supported by genetic analysis.
Most antidepressants have a delayed onset of action and must be administered for several weeks to generate therapeutic effects. Trazodone is a serotonin antagonist and reuptake inhibitor approved for the treatment of major depressive disorder. The once-a-day (OAD) formulation of trazodone has an improved tolerability profile compared to its conventional formulations. In this study, we systematically reviewed the evidence available for the antidepressant efficacy and early improvement in depressive symptoms with trazodone OAD treatment.
We conducted a PubMed database search for randomized controlled trials published from 2005 to 2020.
Two studies, a placebo-controlled and an active-comparator (venlafaxine extended-release or XR) study were found. Both the studies demonstrated that trazodone exhibits antidepressant activity at a starting dose of 150 mg/day and results in statistically significant greater reduction in Hamilton Depression Rating Scale (HAM-D17) scores within 1 week of starting treatment compared to placebo or venlafaxine XR (P < .05). Trazodone also resulted in significant early improvement in the HAM-D17 sleep disturbance factor compared to placebo or venlafaxine XR at day 7 (P < .05). This clinical effect is supported by in vitro proprietary data for the affinity of trazodone for different target receptors. Activity at these receptors may underlie trazodone’s fast antidepressant action.
Trazodone, if properly dosed, can be an effective antidepressant with early onset of action and good tolerability. Future studies designed to specifically evaluate onset and timing of improvement of depressive symptoms remain necessary to confirm and extend these results.
To (1) confirm whether the Habit, Reward, and Fear Scale is able to generate a 3-factor solution in a population of obsessive-compulsive disorder and alcohol use disorder (AUD) patients; (2) compare these clinical groups in their habit, reward, and fear motivations; and (3) investigate whether homogenous subgroups can be identified to resolve heterogeneity within and across disorders based on the motivations driving ritualistic and drinking behaviors.
One hundred and thirty-four obsessive-compulsive disorder (n = 76) or AUD (n = 58) patients were assessed with a battery of scales including the Habit, Reward, and Fear Scale, the Yale-Brown Obsessive-Compulsive Scale, the Alcohol Dependence Scale, the Behavioral Inhibition/Activation System Scale, and the Urgency, (lack of
) Premeditation, (lack of
) Perseverance, Sensation Seeking, and Positive Urgency Impulsive Behavior Scale.
A 3-factor solution reflecting habit, reward, and fear subscores explained 56.6% of the total variance of the Habit, Reward, and Fear Scale. Although the habit and fear subscores were significantly higher in obsessive-compulsive disorder (OCD) and the reward subscores were significantly greater in AUD patients, a cluster analysis identified that the 3 clusters were each characterized by differing proportions of OCD and AUD patients.
While affective (reward- and fear-driven) and nonaffective (habitual) motivations for repetitive behaviors seem dissociable from each other, it is possible to identify subgroups in a transdiagnostic manner based on motivations that do not match perfectly motivations that usually described in OCD and AUD patients.
Epidemiological, clinical, and treatment response characteristics of major depression with anxious distress (ADS) are quite similar to those of mixed depression, but no study investigated the symptom interplay of these conditions.
To analyze the correlations among symptom criteria for major depression with ADS and for mixed depression using a network analysis.
Two hundred and forty-one outpatients with major depression were consecutively recruited. DSM-5 criteria for major depression with ADS or with mixed features (MF) and Koukopoulos’ criteria for mixed depression (MXD) were assessed using a structured clinical interview.
A total of 58.9% of patients met DSM-5 criteria for major depression with ADS, 48.5% for MXD, and 2.5% for major depression with MF, so that the symptoms of this specifier were excluded from the network analysis. The most frequent symptoms were difficulty concentrating due to worries (57.7%), feeling keyed up or on edge (51%) (major depression with ADS), and psychic agitation or inner tension (51%) (MXD). Psychic agitation or inner tension had a central position in the network and bridged MXD to major depression with ADS through feeling keyed up or on edge.
Criteria for major depression with ADS and for MXD are partially overlapping, with psychic agitation or inner tension and feeling keyed up or on edge that feature in both conditions and are difficult to distinguish in clinical practice. The clarification of the relationship between these two psychopathological conditions could bring important implications for diagnosis, prognosis, and treatment of depressive episodes.
Advanced neuroimaging techniques may offer the potential to monitor disease progression in amyotrophic lateral sclerosis (ALS), a neurodegenerative, multisystem disease that still lacks therapeutic outcome measures. We aim to investigate longitudinal functional and structural magnetic resonance imaging (MRI) changes in a cohort of patients with ALS monitored for one year after diagnosis.
Resting state functional MRI, diffusion tensor imaging (DTI), and voxel-based morphometry analyses were performed in 22 patients with ALS examined by six-monthly MRI scans over one year.
During the follow-up period, patients with ALS showed reduced functional connectivity only in some extramotor areas, such as the middle temporal gyrus in the left frontoparietal network after six months and in the left middle frontal gyrus in the default mode network after one year without showing longitudinal changes of cognitive functions. Moreover, after six months, we reported in the ALS group a decreased fractional anisotropy (P = .003, Bonferroni corrected) in the right uncinate fasciculus. Conversely, we did not reveal significant longitudinal changes of functional connectivity in the sensorimotor network, as well as of gray matter (GM) atrophy or of DTI metrics in motor areas, although clinical measures of motor disability showed significant decline throughout the three time points.
Our findings highlighted that progressive impairment of extramotor frontotemporal networks may precede the appearance of executive and language dysfunctions and GM changes in ALS. Functional connectivity changes in cognitive resting state networks might represent candidate radiological markers of disease progression.
Increasing evidence confirms a strict relationship between mental disorders and physical health. Particularly, stressful life events and post-traumatic stress disorder (PTSD) have been closely correlated with various physical disorders and somatic symptoms, such as chronic pain, gastrointestinal disorders, and headaches. The aim of this study was to investigate the emergence of somatic symptoms in a sample of young adult survivors 21 months after exposure to the L’Aquila 2009 earthquake, with particular attention to PTSD and gender impact.
Four hundred and fifty high-school senior students (253 male and 197 female) exposed to the 2009 L’Aquila earthquake, 21 months earlier, were enrolled and evaluated by the Trauma and Loss Spectrum Self-Report (TALS-SR), for symptomatological PTSD, and the Mood Spectrum Self-Report-Lifetime Version (MOODS-SR) “rhythmicity and vegetative functions” domain, for somatic symptoms.
Significantly higher rates of endorsement of the MOODS-SR somatic symptoms emerged in survivors with PTSD compared to those without. Females reported higher rates of endorsement of at least one MOODS-SR somatic symptom compared to males; however, a Decision Tree model and a two-way analysis of variance model confirmed a significant effect of PTSD only. A multivariate logistical regression showed a significant association between the presence of at least one MOOD-SR somatic symptom and re-experiencing and maladaptive coping TALS-SR domains.
This study corroborates a relevant impact of symptomatological PTSD, across both the genders, on somatic symptoms occurring in young adults after months from exposure to a massive earthquake.
The current study sought to examine the relationship between documented social media use and suicidality and self-injurious behaviors in adolescents at the time of psychiatric hospitalization.
We retrospectively identified adolescents (aged 12-17 years) hospitalized on an inpatient psychiatric unit during 1 year. Abstracted information included documented social media use, demographic variables, documented self-injurious behaviors, the Patient Health Questionnaire-9, and the Suicide Status Form-II. Logistic regression was implemented to examine the effect of social media use on the risk of self-injurious behaviors and suicidality.
Fifty-six adolescents who used social media were identified and matched with 56 non-social media users. Those with reported social media use had significantly greater odds of self-injurious behaviors at admission (odds ratio, 2.55; 95% confidence intervals, 1.17-5.71; P = .02) vs youth without reported social media use. Adolescents with reported social media use also had greater odds of increased suicidal ideation and suicide risk than those with no reported use, but these relationships were not statistically significant.
Social media use in adolescents with a psychiatric admission may be associated with the risk of self-injurious behaviors and could be a marker of impulsivity. Further work should guide the assessment of social media use as part of a routine adolescent psychiatric history.
Relatively few studies have assessed the prevalence, correlates, and independent impact on quality of life (QoL) of trichotillomania (TTM) in large samples.
Consecutive participants (N = 7639) were recruited from a cross-sectional web-based study. Sociodemographic data were collected and several validated self-reported mental health measures were completed (Minnesota Impulsive Disorders Interview, Hypomania checklist, Fagerström Test for Nicotine Dependence, Alcohol Use Disorders Identification Test, Early Trauma Inventory Self Report–Short Form, and the Symptom Checklist-90–Revised Inventory). Health-related QoL was assessed with the World Health Organization QoL abbreviated scale (WHOQOL-Bref). Multivariable models adjusted associations to potential confounders.
The sample was predominantly composed of young females (71.3%; mean age: 27.2 ± 7.9 years). The prevalence of probable TTM was 1.4% (95% confidence intervals [CI]: 1.2-1.7), and was more common among females. Participants with probable TTM had a greater likelihood of having co-occurring probable depression (adjusted odds ratio [ORadj] = 1.744; 95% CI: 1.187-2.560), tobacco (ORadj = 2.250; 95% CI: 1.191-4.250), and alcohol (ORadj = 1.751; 95% CI: 1.169-2.621) use disorders. Probable TTM was also independently associated with suicidal ideation (ORadj = 1.917; 95% CI: 1.224-3.003) and exposure to childhood sexual abuse (ORadj = 1.221; 95% CI: 1.098-1.358). In addition, a positive screen for TTM had more impaired physical and mental QoL.
TTM was associated with a positive screen for several psychiatric comorbidities as well as impaired physical and psychological QoL. Efforts towards the recognition and treatment of TTM across psycho-dermatology services are warranted.
The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.
Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.
The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.
The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear.
Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test.
DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls.
The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.