The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.

Apolipoproteins and Suicide: A Potential Psychiatric Biomarker.

Every year around 800,000 people commit suicide, this represents one death every 40 s. In the search for possible biological biomarkers associated with suicide and/or psychiatric disorders, serum cholesterol levels have been extensively explored. Several studies indicate that cholesterol and associated proteins, especially apolipoproteins (Apos), may play an important role in the diagnosis, prognosis, and susceptibility of suicidal behavior. Here, we describe the current knowledge and findings in the relationship between apolipoproteins and suicide.HIGHLIGHTSThis is the first systematic review of Apos in relation to suicidal behavior.Dysregulations of Apos expression has been observed in patients with suicidal behavior.Apos seem to be associated with cognitive dysfunction in suicide attempters.ApoE is a potential biomarker regarding suicidal behavior.

Hippocampal volume as treatment predictor in antidepressant naïve patients with major depressive disorder.

Major depression disorder (MDD) limits psychosocial functioning and quality of life. One of the biological alterations is a hippocampal volume (HV) reduction. Previous prospective neuroimaging studies present inconsistencies regarding HV reductions and clinical features and response of antidepressant treatment of the participants. To clarify the relationship between antidepressant response and the HV reported, we prospectively evaluated antidepressant-naïve subjects diagnosed with MDD for the first time. We recruited twenty-one subjects and applied the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and the Clinical Global Impression (CGI) scale. The participants underwent brain Magnetic Resonance Imaging (MRI) scanning to measure the HV, and subsequently were treated naturalistically with first-line antidepressant medication for eight weeks. Thirteen subjects met the criteria for remission at eight weeks of treatment. The baseline right and left hippocampal volumes were larger in subjects who achieved remission (p = 0.012) and (p = 0.001), respectively. The main finding of this study is that the antidepressant naïve subjects who met the criteria for clinical remission according to the HAM-D, MADRS, and the CGI scale scores, had larger pretreatment hippocampal volumes. Our results assess the HV as a treatment outcome predictor.

[Response to serotonergic and noradrenergic antidepressants: a crossover study of fluoxetine and desipramine in patients with first major depression episode]. / Respuesta a antidepresivos serotoninérgicos y noradrenérgicos: estudio cruzado con fluoxetina y desipramina en pacientes con un primer episodio depresivo mayor.

BACKGROUND: Response rate data from studies with different kinds of antidepressant drugs help in the development of guidelines for the rational prescription of pharmacotherapy. However, there are still few comparative studies with selective reuptake inhibition on serotonin or norepinephrine in the same sample of major depression patients. METHODS: First episode major depression (DSM-III-R) outpatients who completed 6 weeks in two double-blind randomized trials with fluoxetine and desipramine were crossed over to treatment with the other drug under open conditions for 6 weeks. Response was considered if patient's final Hamilton depression scale score decreased 50% or more from baseline. RESULTS: No significant differences were found by drug treatment or sequence of treatment. Ten of the 18 patients (55.5%) were responders to both fluoxetine and desipramine, 3 (16.6%) were resistant to fluoxetine, 3 (16.6%) to desipramine and 2 (11.1%) to both drugs. DISCUSSION: These data suggest that among first major depressive episode outpatients fluoxetine and desipramine are equally effective. In patients who have been non-responders to one of the studied drugs, the other one is strikingly effective; this kind of treatment maneuver should be considered in such patients.

Estudio controlado doble-ciego con clonazepam y placebo en pacientes con trastorno de ansiedad social / Double-blind controlled study with clonazapam and placebo in social anxiety disorder

Introduction Social anxiety disorder or social phobia affects approximately 4.7% of the general population as shown in Mexican epidemiological studies and studies done in other countries. The symptoms of this disorder are more frequent in women (5.4%) than in men (3.8%) and younger people (18 to 29 years), with an average onset age of 13 years. The main clinical characteristic of social phobia is an intense and irrational fear to be exposed to social situations. Social phobia emerges to anticipate or be submitted into situations where the subject could be evaluated or be observed by others. Treatment of social phobia is important because this disorder has been associated with an increase rate of suicidal intents, financial dependency and psychiatric comorbidity. Pharmacological treatment of social phobia includes SSRI and MAOI antidepressants and benzodiacepines. For the treatment of social phobia, potent benzodiacepines, such as alprazolam and clonazepam, have showed efficacy in several studies. In 1993 Davidson et al. published the first double-blind controlled study with clonazepam in patients with social phobia. They found that patients using clonazepam showed an improvement from the first week of treatment and that improvement persisted during the study and was superior to placebo. The objective of the present study was to improve our knowledge about the efficacy and tolerability of clonazepam in patients with social phobia. We studied a group of social phobic patients during 24 weeks in a double-blind treatment study with clonazepam and placebo. Patients took one week single-blind of placebo, followed by 16 weeks of double-blind treatment with clonazepam or placebo. During the first six weeks of the double-blind treatment, dosage was adjusted looking for maximal improvement and tolerability. After this phase we selected only those patients who improved and they were treated double-blind for 10 more weeks with clonazepam or placebo. Discontinuation of treatment was done in a period of two weeks during which clonazepam was changed to placebo and then patients followed with a four weeks of single-blind treatment with placebo. Methods All patients signed consent forms for the study which was approved by our hospital Ethical Committee. Patients were selected from those who looked for help in our Anxiety and Depression Research Clinic or by newspaper advertising. All candidate patients were interviewed with the SCID-I Anxiety Disorders section for DSM-III-R diagnosis of social phobia. Also, patients had to rank in the PARS scale a higher score in the Social phobia section than in the Separation phobia section. Also, patients included had to have at least a moderate severity of social anxiety disorder. Exclusion criteria required that patients had not had any other psychiatric disorders, including psychotic disorders, bipolar disorder, major depression, history of abuse or addiction to alcohol or drugs, eating disorders and anxiety disorders as panic disorder, generalized anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Also, patients needed to be free of any psychotropic medication. A two week of discontinuation phase was conducted with patients receiving benzodiacepines or antidepressants (six weeks for fluoxetine). From a total of 85 patients (78% males and 22% females), 62 were admitted in the fist single-blind week of placebo. Mean age of patients included (± DS) was 28.17 (8.95) years (79 % male and 79% single). Of them, nine patients (14.5%) showed a placebo response and were not admitted to the double-blind treatment phase. A clinical evaluation of the patients was carried out on each visit with the Clinical Global Impression of severity and improvement of eight points for the Global severity of social phobia, Anticipatory anxiety and Phobic avoidance, the Hamilton anxiety and COVI scales, the Liebowitz Social Phobic Disorder Rating Form (LSPD) and the Hamilton depression and Raskin scales. Also, patients completed on each visit the Global impression of severity and improvement of 8 points, the Liebowitz social anxiety scale (LSAS), the Marks' fear questionnaire and an Incapacity score. Patients were evaluated each week for the first four weeks of double-blind treatment and later each two weeks.

Resumen Introducción El trastorno de ansiedad social o fobia social afecta a 4.7% de la población, de acuerdo con reportes epidemiológicos de México y otros países. Los síntomas de este trastorno son más frecuentes en la mujer (5.4%) que en el hombre (3.8%) y en personas jóvenes (18 a 29 años) con una edad de inicio de 13 años. El tratamiento de la fobia social es importante ya que este padecimiento se asocia con comorbilidad psiquiátrica, abuso y dependencia de sustancias, mayor incidencia de intentos suicidas y dependencia financiera. Entre los tratamientos farmacológicos para este trastorno contamos con antidepresivos del tipo ISRS e IMAO y benzodiacepinas. En 1993 Davidson et al. publicaron el primer estudio doble-ciego controlado con placebo y clonazepam en el tratamiento de la fobia social. Los autores encontraron que el clonazepam mejoraba a los pacientes desde la primera semana de tratamiento. Nosotros estudiamos la efectividad y tolerabilidad del clonazepam en pacientes con fobia social en un estudio de 24 semanas, doble-ciego con asignación al azar, controlado contra placebo. Este estudio incluyó una fase simple-ciego de tratamiento con placebo de una semana, 16 semanas de tratamiento doble-ciego con clonazepam o placebo y una fase final de discontinuación con placebo simple-ciego. Material y métodos El diagnóstico de fobia social se estableció de acuerdo con la sección de trastornos de ansiedad del SCID-I para establecer el diagnóstico de acuerdo a los criterios del DSM-III-R. Se incluyeron 62 pacientes en la fase simple-ciego, 53 de los cuales ingresaron a la fase doble-ciego del estudio por no haber mejorado. Las evaluaciones clínicas se realizaron con las escalas ICG de severidad y de mejoría de 8 puntos para la Enfermedad global, Ansiedad anticipatoria y Evitación fóbica, las escalas HamA y Covi, Liebowitz Social Phobic Disorder Rating Form (LSPD), HamD y de Raskin. Los pacientes completaron la ICG-S y la ICG-M de 8 puntos, la escala de Liebowitz para ansiedad social (LSAS), la escala de miedos de Marks y la escala de incapacidad. Resultados En la fase doble-ciego del estudio 27 pacientes recibieron placebo y 26, clonazepam. A la fase de seguimiento doble-ciego de 10 semanas entraron sólo los pacientes que mejoraron, 20 en clonazepam (73%) y siete en placebo (25.9%). Las evaluaciones clínicas fueron realizadas cada semana durante las primeras cuatro semanas y cada dos semanas posteriormente. El análisis de las evaluaciones clínicas al punto final del tratamiento mostró un mayor beneficio en los pacientes que recibieron clonazepam que aquellos que estuvieron con placebo (ANOVA p=.001). En la escala ICG de mejoría las respuestas «muy mejorado¼ y «mucho muy mejorado¼ al final del tratamiento se observaron en 65.3% (N=17) de los pacientes con clonazepam y en 29.6% (N=8) de pacientes con placebo. Con clonazepam se observó mejoría desde la segunda semana del tratamiento (ANOVA p=.001). La razón más frecuente para no completar el estudio fue la respuesta clínica insuficiente (19% en clonazepam n=5 y 66.6% en placebo n=18; P=.001), abandono del tratamiento (NS) y experiencias adversas (NS). La dosis final de clonazepam fue de 3.4±DS 2.27 mg/día. Se presentaron más eventos adversos con clonazepam (3.85 ± 3.13) que con placebo (0.81 ± 1.08) (p<.0001). Cuatro pacientes de 16 (25%) en clonazepam que iniciaron la fase de supresión abandonaron el estudio por síndromes de supresión del medicamento. Discusión Nuestro estudio corrobora los hallazgos del primer estudio controlado de Davidson et al., de 1993, y datos de numerosos estudios abiertos en el sentido de que el clonazepam es un tratamiento rápido y eficaz para el trastorno de ansiedad social. Nuestro estudio aporta también datos sobre la prevalencia de sucesos adversos y síntomas de supresión y recaídas tempranas al retirar el clonazepam hasta en 25% de pacientes. Las benzodiacepinas pueden estar contraindicadas en grupos de pacientes con patología comórbida y aquellos que abusan o son adictos al alcohol y las drogas. En tales casos la terapia cognoscitivo-conductual acompañada de medicamentos antidepresivos del tipo ISRS o IMAO puede ser una mejor opción de tratamiento primario para la fobia social.