Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

The World Health Organization declared the coronavirus outbreak a pandemic on March 11th 2020. Since then, the containment measures were leading to increasing mental health problems in the general population and worsening of some pre‑existing psychiatric conditions. To our knowledge, there are few studies characterizing the impact of the COVID‑19 pandemic on psychiatric hospitalizations across the world.

We aimed to compare the number and characteristics of the hospitalizations in the mental health department of a Portuguese psychiatric hospital from March 2nd 2019 to October 31st 2019 with those that occurred in the same period in 2020.

We conducted a retrospective observational study including all patients admitted to hospital during these periods (n=805). Sociodemographic data, clinical characteristics and information about the context of hospitalization were collected. Statistical analysis was performed using t Student Test, Mann‑Whitney and Chi‑square.

In the pandemic period there was a marked reduction in the number of psychiatric hospitalizations. There was a statistically significant difference in the median length of stay and in the percentage of involuntary hospitalizations between the two periods. In 2019, the most frequent International Classification of Diseases (10th Revision) diagnostic categories were F30‑F39 (mood disorders) and in 2020 were F20‑F29 (schizophrenia, schizotypal and delusional disorders).

The reorganization of services and the decrease in admissions through the emergency department may explain these results.

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Recurrent Depressive Disorder is a chronic condition that significantly impacts the quality of life. Despite various treatment options, some patients face severe and treatment-resistant relapses. This case is related to research on ketamine in Electroconvulsive Therapy (ECT) for RDD. One study highlighted the efficacy and safety of ketamine compared to other anaesthetic agents in ECT for major depression. Additionally, another study explored subanesthetic doses of ketamine before each ECT session to improve therapeutic outcomes and sleep quality in patients with major depressive disorder.

To present a clinical case of a patient with Recurrent Depressive Disorder (RDD) who improved following a change in the Electroconvulsive Therapy (ECT) protocol using ketamine as an anaesthetic inducer.

We examined the patient’s medical records, including her medical history, previous treatments, and therapeutic responses.

A 65-year-old childless woman with a history of stroke, bilateral carotid atheromatosis, and hypothyroidism suffered from RDD. Despite multiple prior treatments and ECT, she experienced a severe depressive relapse. Eight intensive ECT sessions were administered, with observed memory lapses. Due to the lack of response, the anaesthetic inducer etomidate was replaced with ketamine, resulting in a positive response. The patient continued pharmacological treatment with improved mood, but recent and evident memory alterations persisted, possibly related to anterograde amnesia.

This case highlights the complexity of RDD in patients with comorbidities and treatment-resistant relapses. The change in the ECT protocol using ketamine was effective, emphasizing the importance of alternative therapeutic approaches in refractory cases. The successful treatment of RDD in this patient using ketamine in ECT underscores the need for personalized therapeutic options in treatment-resistant patients. These scientific resources reinforce the relevance of exploring therapeutic alternatives in contemporary clinical practice. We need more research to understand the underlying mechanisms and how this approach could be enhanced in similar cases.

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Schizotypal personality is a condition suffered by 4% of the population. It is defined by presenting interpersonal, behavioral and perceptual features similar to the clinical features of psychotic disorders, such as schizophrenia, in less intensity and dysfunctionality, but at risk of reaching psychosis.

Presentation of a clinical case about a patient with premorbid schizotypal personality traits presenting with an acute psychotic episode.

Literature review on association between schizotypal personality and psychosis.

A 57-year-old woman with a history of adaptive disorder due to work problems 13 years ago, currently without psychopharmacological treatment, goes to the emergency room brought by the emergency services due to behavioral alteration. She reports that “her husband and son wanted to sexually abuse her”, so she had to run away from home and has been running through the streets of the town without clothes and barefoot.

Her husband relates attitude alterations and extravagant behaviors of years of evolution, such as going on diets of eating only bread for 40 days or talking about exoteric and religious subjects, as believing that the devil got inside her husband through a dental implant. He reports that these behaviors have been accentuated during the last month. She has also created a tarot website, and has even had discussions with several users. She is increasingly suspicious of him, has stopped talking to him and stays in his room all day long, with unmotivated laughter and soliloquies.

It was decided to admit him to Psychiatry and risperidone 4 mg was started. At the beginning, she was suspicious and reticent in the interview. As the days went by, communication improved, she showed a relaxed gesture and distanced herself from the delirious ideation, criticizing the episode.

In recent years, there has been increasing interest in understanding the association between schizotypy and serious mental disorder. Several theories understand schizotypy as a natural continuum of personality that reveals genetic vulnerability and that can lead to psychotic disorder when added to precipitating factors. Other theories define schizotypy as a “latent schizophrenia” where symptoms are contained and expressed in less intensity.

Around 20% evolves to paranoid schizophrenia or other serious mental disorders. It is complex to distinguish between those individuals in whom schizotypy is a prodrome and those in whom it is a stable personality trait. To date, studies applying early psychotherapeutic or pharmacological interventions have had insufficient and contradictory results, and the follow-up and treatment of these individuals could be a stress factor and a stigma. Some studies are looking for reliable markers of evolution to schizophrenia in order to establish adequate protocols for detention, follow-up and treatment.

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Dual pathology, characterized by the simultaneous presence of substance use disorders and psychiatric disorders, is a topic of growing interest in the scientific community. In particular, obsessive-compulsive disorder (OCD) is a common comorbid psychiatric condition in patients with substance use disorders.

To evaluate the efficacy of rTMS on comorbid disorder symptoms by applying specific protocols for OCD and substance use disorder in a clinical case of dual pathology.

Case Description: A 36-year-old male diagnosed with OCD and habitual cocaine use (an average of 6 times per month). Previous unsuccessful attempts to quit substance use. Undergoing psychotherapy and psychopharmacological treatment for OCD since the age of 22 with no significant clinical improvement.

Methodology: The severity of OCD was quantified before and after the intervention using the Yale-Brown Obsessive Compulsive Scale (YBOCS). To assess addictive behavior, the Maudsley Addiction Profile (MAP) was used. During the intervention period, the occurrence of substance use was recorded based on the patient’s and family members’ reports. The intervention involved the administration of an rTMS protocol tailored to the specific case, consisting of the simultaneous application, using a double-cone coil, of rTMS at 20Hz over the right dorsomedial prefrontal cortex (DMPFC) at an intensity of 100% of the resting motor threshold (RMT) to treat OCD symptoms, followed by intermittent theta burst stimulation (TBS) over the left DMPFC at an intensity of 120% of the RMT to address substance addiction. The patient received a total of 30 sessions at a rate of one session per day, five days a week, for six weeks.

Results: The results showed an improvement in the total score on the YBOCS scale, decreasing from a value of 26 in the pre-intervention assessment to 16 in the post-intervention assessment, representing a reduction of more than 35% from pre- to post-intervention, meeting response criteria. Thus, there was a decrease in both obsessive and compulsive symptoms, with reduced associated distress and increased control. Additionally, throughout the intervention, there was a gradual decrease in substance use, decreasing from an average of 6 monthly instances before treatment initiation to a total of 1 in the month the treatment ended.

Conclusions: This unique case study represents a therapeutic window for the treatment of patients with comorbid disorders, demonstrating promising preliminary benefits of the combined rTMS intervention for both conditions, especially in the field of addictions.

Keywords: rTMS, neuromodulation, obsessive-compulsive disorder, addictions

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Mood disorders in patients with ASD (Autism Spectrum Disorder) have a significant impact on their well-being. Major depression and bipolar disorder are among the most common co-occurring psychiatric diagnoses in autism. Prevalence estimates range from 10-50% for depression and approximately 5% for bipolar disorder. These figures are markedly higher than those reported in the general population.

The diagnosis of these disorders in patients with autism poses several challenges: mood problems may be “overshadowed” by the diagnosis itself, symptoms vary between individuals and may present “atypically” (psychomotor agitation, regression, reduced self-care, and severe irritability). The use of assessment tools based largely on criteria developed and validated in the general population is common.

A case of a patient diagnosed with ASD and co-occurring mood disorder is presented followed by a theoretical review on the topic.

A case is presented with a bibliographic review.

A 20-year-old patient with a diagnosis of severe autism spectrum disorder was referred to the emergency department for behavioral disturbances based on episodes of heteroaggressiveness and self-aggressiveness, with a daily frequency, in the last 2 months. His parents attribute this decompensation to the introduction of Sertraline and changes in his routine, which has implied less stimulation. Having ruled out underlying organic pathology, given that her father refers to frequent episodes of crying and abandonment of leisure activities of his liking, we suspect a mood disorder.

In hospitalization, Sertraline was withdrawn and Valproic Acid was introduced. Likewise, Risperidone dose was increased, already prescribed in outpatient care. Progressively, a notable improvement was observed.

Current clinical recommendations on the use of selective serotonin reuptake inhibitors (SSRIs) for mood problems are largely based on evidence from typically developing groups. However, it has been shown that some individuals with autism show different neural responses to pharmacological challenge compared to neurotypical individuals. In addition, the use of SSRIs in ASD may result in increased adverse side effects, such as agitation, impulsivity, hyperactivity, stereotypy, and insomnia, and it has been suggested that they should therefore only be considered on a “case-by-case” basis. A systematic review reported that mood stabilizers (Lithium, Valproic Acid) are preferable to atypical antipsychotics, which are associated with a large number of side effects.

Because of the lack of strong evidence on the efficacy of pharmacologic interventions and issues regarding safety and side effects, risperidone and aripiprazole are among the few medications approved by the FDA for the treatment of irritability in people with autism. More research aimed at effective medications to treat mood problems in ASD needs to be advocated.

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Obsessive-compulsive disorder (OCD) has a high prevalence and causes a significative reduction in functionality and quality of life.

First and second line treatment is ineffective in a variable percentage of patients. In such cases transcranial magnetic stimulation (TMS) may be considered.

The goal of this study is to evaluate the impact of TMS treatment on obsessive-compulsive, anxious and depressive symptomatology in patients with OCD.

A prospective observational study was conducted, including all patients diagnosed with OCD who underwent TMS in the Psychiatry department of Centro Hospitalar Universitário de São João since March 2023.

Symptomatology was assessed using the Yale Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D) before and after treatment.

Statistical analysis was performed using the SPSS-Statistics program. A significance level of 0.05 was considered.

As of October 31, 2023, nine individuals with OCD completed treatment with TMS, 33% male and with a median age of 40 years (range 33-57).

The median Y-BOCS score pre-TMS was 30 (range 20-33) and post-TMS 28 (range 16-34). The median difference was 2.5 (range -5-14) and was not statistically significant (p=0.128).

The median score on the HAM-A pre-TMS was 21 (range 9-41) and post-TMS 18 (range 11-24). The median difference was 0 points (range -4-21) and was not statistically significant (p=0.345).

The median HAM-D score pre-TMS was 26 (range 14-40) and post-TMS 19 (range 10-32). The median difference was 2.5 (range -3-20) and was not statistically significant (p=0.225).

Preliminary findings suggest that the impact of TMS on obsessive-compulsive, anxious, and depressive symptomatology in patients with OCD does not appear to be clinically or statistically significant.

Further results are necessary to confirm this trend.

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Liver cirrhosis, a chronic liver disease, can be closely linked to chronic alcohol abuse, posing a significant medical challenge. Hepatic encephalopathy (HE), a neuropsychiatric condition resulting from liver dysfunction, commonly occurs in cirrhotic patients due to the accumulation of neurotoxic substances like ammonia and manganese in the body. Managing cirrhosis and alcohol addiction is crucial to enhancing the quality of life for these patients, as HE can manifest in various ways and with varying degrees of severity.

To emphasize the importance of recognizing and treating hepatic encephalopathy as a potential complication of liver cirrhosis and sedatives during alcohol withdrawal.

We compiled clinical data, medical history, neuroimaging tests, and therapeutic interventions applied.

A 55-year-old man with a complex medical history, including Child-Pugh B liver cirrhosis, portal hypertension, hypertension, diabetes mellitus, and chronic alcohol abuse with numerous prior hospitalizations for acute pancreatitis and severe head trauma related to alcohol consumption, presented to the emergency department with symptoms of alcohol withdrawal and suicidal thoughts, leading to lorazepam administration and a recommendation for admission to a specialized Therapeutic Community. After 72 hours, he developed hepatic encephalopathy with symptoms such as confusion, sleep disturbance, sweet-smelling breath, abnormal hand movements, conjunctival icterus, and urinary difficulties.

An EEG revealed a globally attenuated and disorganized bioelectrical activity with triphasic waves. The magnetic resonance imaging showed signs of hepato-cerebral degeneration, including T1-weighted hyperintensity in the lentiform and mesencephalic nuclei due to manganese deposition. Treatment was adjusted to reduce sedative use, and therapy with Rifaximin and Lactulose was initiated to control blood ammonia levels. After a week, the patient exhibited significant neurological improvement, underscoring the importance of appropriate management in patients with hepatic encephalopathy related to liver cirrhosis and chronic alcohol abuse.

This case underscores the complexity of HE in patients with liver cirrhosis and alcohol dependence. HE can present in various ways, from subtle symptoms to severe episodes of confusion and coma. Findings on EEG, such as triphasic waves, are characteristic of HE and reflect brain dysfunction. Furthermore, manganese accumulation in the brain, as evidenced by magnetic resonance imaging, may contribute to neurological symptoms in cirrhotic patients. In this context, the early recognition and multidisciplinary treatment are emphasized to improve the quality of life and prevent the progression of this neuropsychiatric complication. EEG and magnetic resonance imaging findings play an essential role in the evaluation of these patients.

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tardive dysphoria is a relatively new term used to describe the phenomenon of clinical worsening of depression after long-term antidepressant use. Most of the theories proposed to explain this talk about antidepressants tachyphylaxis that implies the loss of efficacy with its prolonged use, or even a pro-depressant effect of antidepressants when used for long periods of time.

to explore the concept of tardive dysphoria, potential causes and clinical implications, by making a literature review on the topic. Moreover we pretend to understand the challenges in its diagnosis and treatment.

bibliographical search in PubMed database, using the key-words “long-term antidepressant”, “tardive dysphoria” and “antidepressant tachyphylaxis”, limited to works published in the last twenty years.

from our search resulted 53 articles, 26 were chosen for further analysis.

the concept of tardive dysphoria is controversial, namely doubt persists if it constitutes a clinical entity by itself caused by long-term antidepressant use or if it simply relates to cases of treatment-resistant depression. We conclude that it is necessary further investigation in this area given the significant implications on clinical practice specifically in the psychopharmacological treatment with antidepressants, which is very common in psychiatric and general practices, with antidepressants being used to treat many mental health conditions.

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