Family History Of Mood Disorders Research Articles

Pretreatment Thyroid Profile and its Relationship with Response to Treatment with Lithium in Bipolar Mood Disorder: A Longitudinal Study from Northeast India

Abstract Background: The thyroid hormone’s significant impact on the treatment of depressive and other mood disorders is well documented. Even minor hypothyroidism can modify the progression and treatment results of major depressive disorder. This research aims to explore the correlation between initial thyroid levels and the treatment outcome in bipolar mood disorder using lithium, a well-established treatment method. Methodology: The study involved 45 bipolar mood disorder patients diagnosed according to the Diagnostic and Statistical Manual 5 criteria and admitted to a tertiary care teaching institute in Northeast India. The patients received lithium treatment, with injectable lorazepam used for immediate agitation control when necessary. On the 1st day, a semi-structured questionnaire and Brief Psychiatric Rating Scale (BPRS) 24-item scale were used to evaluate symptoms, and samples were collected for a thyroid profile, including T3, T4, FT3, FT4, and thyroid-stimulating hormone (TSH). The BPRS scale was used again on the 30th day to assess treatment response. Results: The BPRS subscale showed the highest treatment response for grandiosity and the lowest for depression. Factors such as age, illness duration, substance use, and family history of mood disorder were inversely correlated with the BPRS score’s decrease. Initial thyroid levels were identified as a predictor of treatment response, with baseline T4 levels showing a significant positive correlation with treatment response, while baseline TSH levels showed a negative correlation. Conclusion: Lithium proved to be an effective treatment for bipolar mood disorder, particularly for the manic subtype. Initial T4 and TSH levels were found to significantly predict treatment response, with T4 showing a positive correlation and TSH showing a negative correlation.

Neurocognitive risk phenotyping to predict mood symptoms in adolescence.

Predicting mood disorders in adolescence is a challenge that motivates research to identify neurocognitive predictors of symptom expression and clinical profiles. This study used machine learning to test whether neurocognitive variables predicted future manic or anhedonic symptoms in two adolescent samples risk-enriched for lifetime mood disorders (Sample 1, n = 73, ages = 13-25, M [SD] = 19.22 [2.49] years, 68% lifetime mood disorder) or familial mood disorders (Sample 2, n = 154, ages = 13-21, M [SD] = 16.46 [1.95] years, 62% first-degree family history of mood disorder). Participants completed cognitive testing and functional magnetic resonance imaging at baseline, for behavioral and neural measures of reward processing and executive functioning. Next, participants completed a daily diary procedure for 8-16 weeks. Penalized mixed-effects models identified neurocognitive predictors of future mood symptoms and stress-reactive changes in mood symptoms. Results included the following. In both samples, adolescents showing ventral corticostriatal reward hyposensitivity and lower reward performance reported more severe stress-reactive anhedonia. Poorer executive functioning behavior was associated with heightened anhedonia overall in Sample 1, but lower stress-reactive anhedonia in both samples. In Sample 1, adolescents showing ventral corticostriatal reward hypersensitivity and poorer executive functioning reported more severe stress-reactive manic symptoms. Clustering analyses identified, and replicated, five neurocognitive subgroups. Adolescents characterized by neural or behavioral reward hyposensitivities together with average-to-poor executive functioning reported unipolar symptom profiles. Adolescents showing neural reward hypersensitivity together with poor behavioral executive functioning reported a bipolar symptom profile (Sample 1 only). Together, neurocognitive phenotypes may hold value for predicting symptom expression and profiles of mood pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Predictor of Postpartum Depression: Literature Review

The incidence of postpartum depression is quite high. The largest percentage occurs when they have their first child, and have a family history of mood disorders. The incidence of postpartum depression is 50 - 60% in mothers when they have their first child, and around 20% in mothers who give birth to subsequent children. This study aims at reviewing and synthesizing the determinants factor of depression among adolescent in rural area. This study design was a systematic review using the PICO framework. This data was carried out from various journal databases 2012-2022, including Scopus, ScienceDirect, PubMed. 16 articles meet the inclusion criteria and meet the qualifications for review. A systematic procedure is used to collect articles, as well as a critical appraisal and data synthesis with qualitative synthesis. The analysis of the literature review found that aspects of findings related to predictors of postpartum depression are as follows: socio-demographic factors (age, socio-economic status, education, risk age group), maternal factors (pregnancy spacing, parity, pregnancy condition, birth experience, postpartum complications), biological factors (hypothalamus function, prolactin, CRH, inflammatory process), psychosocial factors (negative mood, anxiety, unpreparedness, history of depression), cultural factors (children care stress, wisdom), support system (support husband, family support, decision-making patterns). Healthcare professionals should be aware of this phenomenon and strategies such as primary, secondary, and tertiary prevention interventions may be applied. Women should be screened for potential risk factors and depressive symptoms during pregnancy and postpartum periods so that appropriate interventions if needed, can be initiated in a timely fashion.

Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders

Mood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts. To examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls. This community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools. The youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder. Body mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight. Of 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (β = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (β = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age. In this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.

Family History of Mood Disorders as a Risk Factor for Recurrent Depressive Disorder and Bipolar Disorder: Results of Cross-Sectional Study

Background: affective disorders (AD) are often aggregated in families among relatives of several generations. It suggests the presence of genetic risk factors for recurrent depressive disorder (RDD) or bipolar affective (BD) disorders.The objective: to assess the risks of affective disorders in individuals with a positive family history, as well as to analyze the clinical characteristics of RDD and BD in family cases.Participants and method: this family cross-sectional study included 36 families with affective disorders (36 probands with AD and 68 relatives), as well as 23 families for the comparison group (23 probands without affective disorders and 53 relatives). The final sample size was 180 people. The study used a case report form developed by the authors, as well as a semi-structured MINI interview (Mini International Neuropsychiatric Interview).Results: it was revealed that a family history of AD is a significant risk factor for RDD or BD in probands. The risks of AD based on the assessment of familial recurrence risk in probands with a burdened family history were also higher than in the general population. When comparing probands with AD with their relatives who had RDD or BD diagnoses, it was found that the age at onset of the underlying disease was significantly less in patients with BD, and probands with BD had significantly longer hypo-/manic episodes. This fact may indicate an aggravation of the course of these pathologies in persons with a positive family history.Conclusion: a burdened family history is an important clinical predictor of the development of AD and their subsequent course. Further multicenter family studies on the Russian population are needed to increase the sample size and analyze the features of aggregation in families of RDD and BD separately using modern molecular genetic methods.

Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder

BackgroundSunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.MethodsData for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001.ResultsThe 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.ConclusionUVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

First-episode mania after COVID-19: A case series in Iran.

Increasing reports of manic episodes in patients during acute infection with COVID-19 have been documented since the pandemic began, including individuals without a previous personal or family history of bipolar disorder. As infections and autoimmunity have putative roles in bipolar disorder, we aimed to document the clinical presentations, associated stressors, family aggregation patterns, and brain imaging and electroencephalographic correlates with a series of patients with episodes of mania that emerged shortly after COVID-19 infections. We obtained all relevant clinical information from 12 patients whose first manic episode started within a month of COVID-19 infection and were treated at Rasool-e-Akram hospital and Iran psychiatric hospital, two tertiary medical centers in Tehran, Iran, in 2021. Patients had a mean age of 44. The interval between the onset of symptoms of COVID and mania ranged between 0 and 28 days (mean: 16.25, median: 14 days); it was observed to be shorter in patients with a family history of mood disorders but not in those receiving corticosteroids. Alongside a descriptive overview of our sample, we provide detailed narrative descriptions of two of the cases for illustrative purposes and discuss our observations in the context of other cases reported elsewhere and the state-of-the-art regarding infectious diseases, COVID-19, and bipolar disorder as reported in previous literature. Our case series documents observational and naturalistic evidence from a dozen of cases of mania in the context of acute COVID-19, which, while limited, calls for analytical research of the phenomenon, and points at a family history of bipolar disorder and the use of corticosteroids as factors for particular focus.

Assessing suicide risk in patients with obsessive-compulsive disorder: a dimensional approach.

Although an association has been found recently between obsessive-compulsive disorder and an increased risk of suicide, the prevalence of both suicidal ideation and attempts vary considerably and are generally assessed categorically. Our aims were to evaluate the prevalence of suicidal ideation and behaviors using a dimensional approach. The sample included 129 patients with obsessive-compulsive disorder. Suicidality was assessed by administering the Columbia-Suicide Severity Rating Scale. Logistic and linear regressions were used to examine predictors of suicidal ideation, severe suicidal ideation, and suicidal behavior. The lifetime prevalence of suicidal ideation and behaviors were 64.3% and 16.3%, respectively. Lifetime suicidal ideation was associated with the number of stressful life events, duration of illness, Hamilton Rating Scale for Depression scores, and family history of mood disorders. A family history of obsessive-compulsive disorder was associated with a lower probability of lifetime suicidal ideation. Severe suicidal ideation was related to greater severity of the most stressful life event, Hamilton Rating Scale for Depression scores, and longer duration of untreated illness. The probability of lifetime suicidal behavior was related to Hamilton Rating Scale for Anxiety scores, symmetry obsessions, and washing and checking compulsions. The probability of lifetime non-suicidal self-injurious behaviors was related to Hamilton Rating Scale for Anxiety scores. Recognizing predictors of suicidal ideation/behavior is crucial to identifying patients at greater risk.

Utility of portable functional near-infrared spectroscopy (fNIRS) in patients with bipolar and unipolar disorders: A comparison with healthy controls

BackgroundThis study aimed to evaluate portable functional near-infrared spectroscopy (fNIRS) device as an adjunct diagnostic tool for bipolar and unipolar disorders while performing cognitive tasks. Methods150 participants were divided into three groups including bipolar, unipolar disorder, and healthy controls (50:50:50), matched by age, gender, and family history of mood disorder. Hemodynamics in the frontal cortex were monitored by fNIRS during the Stroop Color-Word Test and Verbal Fluency Test. The GLM compared the differences in oxy-hemoglobin levels between the two groups. The Receiver Operating Characteristic (ROC) graph was generated for each neuroanatomical area. ResultsFor people with BD group, the area under the ROC curve (AUC) for the left orbitofrontal cortex was maximal during the VFT [AUC = 0.727, 95%CI = 0.617–0.824]. The Youden's index reached a peak (0.40) at the optimal cut-point value (HbO2 cutoff <0.180 μmol/ml for BD) in which the sensitivity was 82 %; specificity was 58 %; PPV was 0.66; NPV was 0.76 and correct classification rate was 70 %. Regarding the UD group, during VFT, the highest value AUC [AUC = 0.822, 95%CI = 0.740–0.903] was recorded in the left dorsolateral prefrontal cortex with the optimal cut-off value (HbO2cutoff ≥0.163 μmol/ml for healthy controls; <0.163 for unipolar disorder), the sensitivity was 72 %; specificity was 82 %; PPV was 0.80; NPV was 0.75, correct classification rate was 77 %, and the Youden's index was 0.54. ConclusionAssessing hemodynamics during VFT using portable fNIRS offers the potential as an adjunct diagnostic tool for mood disorders in low-resource environments.

Research and Diagnostic Algorithmic Rules (RADAR) for mood disorders, recurrence of illness, suicidal behaviours, and the patient's lifetime trajectory.

The top-down Diagnostic and Statistical Manual/International Statistical Classification of Diseases categories of mood disorders are inaccurate, and their dogmatic nature precludes both deductive (as indisputable) and inductive (as top-down) remodelling of case definitions. In trials, psychiatric rating scale scores employed as outcome variables are invalid and rely on folk psychology-like narratives. Using machine learning techniques, we developed a new precision nomothetic model of mood disorders with a recurrence of illness (ROI) index, a new endophenotype class, namely Major Dysmood Disorder (MDMD), characterised by increased ROI, a more severe phenome, and more disabilities. Nonetheless, our previous studies did not compute Research and Diagnostic Algorithmic Rules (RADAR) to diagnose MDMD and score ROI, lifetime (LT), and current suicidal behaviours, as well as the phenome of mood disorders. Here, we provide rules to compute bottom-up RADAR scores for MDMD, ROI, LT and current suicidal ideation and attempts, the phenome of mood disorders, and the lifetime trajectory of mood disorder patients from a family history of mood disorders and substance abuse to adverse childhood experiences, ROI, and the phenome. We also demonstrate how to plot the 12 major scores in a single RADAR graph, which displays all features in a two-dimensional plot. These graphs allow the characteristics of a patient to be displayed as an idiomatic fingerprint, allowing one to estimate the key traits and severity of the illness at a glance. Consequently, biomarker research into mood disorders should use our RADAR scores to examine pan-omics data, which should be used to enlarge our precision models and RADAR graph.

Ventral prefrontal serotonin 1A receptor binding: a neural marker of vulnerability for mood disorder and suicidal behavior?

Mood disorders and suicidal behavior have moderate heritability and are associated with altered corticolimbic serotonin 1A receptor (5-HT1A) brain binding. However, it is unclear whether this reflects genetic effects or epigenetic effects of childhood adversity, compensatory mechanisms, or illness stress-related changes. We sought to separate such effects on 5-HT1A binding by examining high familial risk individuals (HR) who have passed through the age of greatest risk for psychopathology onset with and without developing mood disorder or suicidal behavior. PET imaging quantified 5-HT1A binding potential BPND using [11C]CUMI-101 in healthy volunteers (HV, N = 23) and three groups with one or more relatives manifesting early-onset mood disorder and suicide attempt: 1. unaffected HR (N = 23); 2. HR with lifetime mood disorder and no suicide attempt (HR-MOOD, N = 26); and 3. HR-MOOD with previous suicide attempt (HR-MOOD + SA, N = 20). Findings were tested in an independent cohort not selected for family history (HV, MOOD, and MOOD + SA, total N = 185). We tested for regional BPND differences and whether brain-wide patterns distinguished between groups. Low ventral prefrontal 5-HT1A BPND was associated with lifetime mood disorder diagnosis and suicide attempt, but only in subjects with a family history of mood disorder and suicide attempt. Brain-wide 5-HT1A BPND patterns including low ventral prefrontal and mesiotemporal cortical binding distinguished HR-MOOD + SA from HV. A biological endophenotype associated with resilience was not observed. Low ventral prefrontal 5-HT1A BPND may reflect familial mood disorder and suicide-related pathology. Further studies are needed to determine if higher ventral prefrontal 5-HT1A BPND confers resilience, reducing risk of suicidal behavior in the context of familial risk, and thereby offer a potential prevention target.

Family history of mood disorder weakens the association between personality traits and suicidality in depressed patients

IntroductionDepression is associated with a high risk of suicidal thoughts (ST) and behaviour (SB). Suicidality and depression have partially shared genetic underpinnings and family history of mood disorders (FH) can reflect genetic impact on specific features of depression. Thus, in depressed patients, FH may affect suicidality and its associations with other risk factors, such as personality traits.ObjectivesWe conducted a cross-sectional study to test the impact of FH on the association between suicidality and personality traits in depressed patients.Methods200 depression in- and outpatients (64% (n=128) women, mean age (M(SD):36,21(15,09)) were enrolled. 28% (n=56) reported FH (“FH+” cohort), other patients comprised the “FH-” cohort. Columbia-Suicide Severity Rating Scale (C-SSRS) was used to assess ST and SB during the most suicidal period of life. Personality traits were assessed by Cloninger Temperament and Character Inventory (TCI-125). Information about FH and history of suicide attempts (SA) was obtained during the clinical interview.ResultsPersonality traits and suicidality characteristics (ST, SB, SA) did not differ between FH+ and FH- patients. In FH+, no differences in TCI-125 scores between suicide attempters and non-attempters were found, while in FH-, attempters had higher scores of TCI-125 “Novelty seeking” (p=0.002) and “Self-transcendence” (p=0.031) subscales. Multiple correlations between ST, SB and TCI-125 subscales were found only in FH-, In FH+, only one correlation (between ST and TCI-125 “Persistence” subscale (r=-0.288, p=0.038) was found.ConclusionsOur results showed a weakened association between personality traits and suicidality in depressed patients with FH of mood disorders, although more data on larger samples are needed.DisclosureThe study was supported by RSF grant # 20-15-00132

Early-Onset Depression Is Associated With Specific Neurovegetative Symptoms

IntroductionThe age at onset of depression is not only an important clinical predictor of the further disease course, but also a robust marker, reflecting the genetic impact on depression risk.ObjectivesThis study aimed to find whether early-onset depression had an association with specific clinical symptoms, comorbid psychiatric disorders and family history of mood disorders.MethodsThis pilot cross-sectional, multicenter study was performed under the supervision of the Russian National Consortium for Psychiatric Genetics. Early-onset depression was defined as the first depressive episode before the median age of onset in the sample (Me=29 years). Logistic regression models were used to determine the independent association of early-onset depression, after adjusting for the effects of sex and age, with binary characteristics.ResultsA total of 172 patients with depression were enrolled in the study (64.5% women; age - 40.9 (15.9) years). Early-onset depression was associated with psychomotor retardation (p=0,025; OR=2,3; 95%CI [1,1 - 4,9]), decreased libido (p=0,014; OR=2,8; 95%CI [1,2 - 6,2]), and lower prevalence of weight loss/decreased appetite (p=0,011; OR=0,4; 95%CI [0,2 - 0,8]). No associations were found with the history of comorbid psychiatric disorders and the family history of mood disorders.ConclusionsEarly-onset depression is associated with specific neurovegetative symptoms. Further clinical and genetic studies are needed to evaluate the specific effects of age at onset of depression on its clinical course.DisclosureResearch is supported by an RSF grant №20-15-00132.

Prevalence and determinants of postpartum depression among adolescent mothers

This study aims to determine the factor affecting the incidence of postpartum depression in adolescent mothers. The incidence of postpartum depression is quite high in Asia. The highest percentage occurred when having a first child and family history of mood disorders. The cause of this issue is varied. This study used a cross-sectional approach. The study was conducted from May 2021 to March 2022. It involved a total of 886 adolescent mothers as respondents. The instrument used the Edinburg Postnatal Depression Scale (EDPS) questionnaire. Multiple logistic regression was used to estimate the factors associated with postpartum depression. the prevalence of Postpartum depression is 50.68%. Family monthly income (95%CI: 4.09-6.75, p-value: 0.001), planned pregnancy (95%CI: 1.26-4.9, p-value: 0.000), wanted pregnancy (95%CI: 2.37-5.67, p- value: 0.001), type of delivery (95%CI: 4.39 – 5.21, p-value: 0.002), satisfied with baby's sex (95%CI: 4.39 – 5.21, p-value: &lt;0.000), husband support (95% CI: 2.89-5.88, p-value: 0.000) were statistically significant with postpartum depression. Mothers with postpartum depression have a negative impact on themselves, their babies, and their families.

Risk factors for Deliberate Self Harm in Bipolar Affective Disorder patients presenting to Tertiary care center- A cross-sectional study

Abstract:-&#x0D; Background: Deliberate Self Harm (DSH) is a complex event, associated with psychosomatic, biological, social factors and psychiatric disorders. Current literature shows that, there is rise in DSH in psychiatric disorders and it has been recognised as major public health problem in India. So, objective of this study was to assess the underlying risk factors for DSH in patients with Bipolar Affective Disorder (BPAD).&#x0D; Methods:&#x0D; This cross-sectional study was conducted on 150 patients diagnosed with BPAD as per International Classification of Diseases; tenth revision (ICD-10). Semi-structured socio-demographic proforma was used to record basic profile. Deliberate self harm inventory (DSHI) was administered to assess the type of DSH. Young Mania Rating scale and Beck Depression Inventory were used to assess severity of symptoms.&#x0D; Results:&#x0D; Prevalence of DSH in present study was 33%. In socio-demographic profile, younger age group, lower education levels and being single were significant risk factors for DSH (p- value &lt;.001, .016 and &lt;.001 respectively) and among clinical variables, early years of disorder, severe mania, moderate and severe depressive episode in presence of medium to high suicidal intent, family history of mood disorders and co-morbid substance use and medical disorder were significant risk factors for DSH in BPAD with statistical significance (p&lt;.0001).&#x0D; Conclusion:&#x0D; DSH is considered to be the significant predictor of suicide. BPAD is associated with high risk of DSH, which can be present in either depressive or manic episode. Patients with BPAD in early years of illness, should be evaluated thoroughly for risk factors, so that DSH risk can be minimised

Borderline Personality Disorder: Clinical Guidelines for Treatment.

Borderline personality disorder (BPD) is fundamentally a syndrome composed of symptoms (primarily of emotional dysregulation) and a number of true personality traits (such as inordinate anger, impulsivity, and a tendency to stress-related paranoid ideation). Whereas schizotypal personality disorder, with its cognitive peculiarities (ideas of reference, odd beliefs, eccentric speech), is closely linked as a genetic condition-"borderline" to the major condition schizophrenia-BPD is less closely linked to bipolar disorder. Some cases of BPD are linked genetically to and are in the "border" of bipolar disorder. But the condition can also arise from adverse post-natal factors: parental cruelty or neglect, or incest. In some BPD patients, both are present: risk genes for bipolar disorder and adverse conditions within the family. The genetic risk is often overlooked. To avoid this, initial evaluations should always include a careful and extensive family history for mood disorders, and should extend out to grandparents, aunts, uncles, and cousins. Where the history suggests a genetic link to bipolar disorder, a mood stabilizer such as lithium or lamotrigine, even in modest doses, may be particularly beneficial, more so than conventional antidepressants. In some patients, ADHD was present in childhood, BPD was diagnosed during or after puberty, and a form of bipolar disorder becomes apparent during their 20s. As for the psychotherapeutic component, the patient's cognitive style and capacity for introspection will help determine whether a primarily expressive (psychoanalytically oriented) technique is preferable or a primarily cognitive-behavioral technique. Flexibility is necessary, since during emotional crises, supportive and limit-setting interventions will be needed, along with psychotropic medications, and where necessary, programs to help combat substance abuse (which is common among patients with BPD).

Resting-state functional connectivity graph-properties correlate with bipolar disorder-risk in young medication-free depressed subjects: Bipolar-risk Resting State Functional Connectivity in Major Depression

BackgroundMajor Depressive Disorder (MDD) is frequently associated with risk factors for the development of Bipolar Disorder (BD). Using graph theory, we investigated brain network properties associated with BD risk factors in young MDD subjects. MethodsResting-state fMRI was acquired from a large cohort (N= 104) of medication-free currently depressed participants (25 BD depression (BDD), 79 MDD). Lifetime mania symptom count (LMSC), current Young Mania Rating Scale (YMRS) score, and family history of mood disorders (FHMD) were examined as BD risk factors. Functional connectivity matrices from 280 regions of interests (ROIs) were first entered into the Network Based Statistic (NBS) toolbox to identify connections that varied with each risk factor. Next, within the correlated network for each risk factor, global and nodal graph properties for the top five linked nodes were calculated. Last, using identified graph properties, machine learning classification (MLC) between BDD, MDD with BD risk factors (MDD+), and without BD risk factors (MDD-) was conducted. ResultsLMSC positively correlated with left lateral orbitofrontal cortex (LOFC) Communication Efficiency and with left middle temporal Eigenvector Centrality. Current YMRS score positively correlated with right amygdala Communication Efficiency and Closeness Centrality. FHMD positively correlated with right insula Eigenvector Centrality. Acceptable MLC accuracy was seen between BDD and MDD- using middle temporal Eigenvector Centrality, whereas moderate accuracy was seen between MDD+ and MDD- using OFC Communication Efficiency. LimitationAlthough participants were medication-free, they were not medication-naïve. ConclusionFunctional connectome graph properties may serve as BD vulnerability biomarkers in young individuals with MDD.

Family history of mood disorders may weaken the link between adverse childhood experience and suicidality in patients with depression

To study the impact of family history of mood disorders (FHMD), comprising genetic factors associated with depression, on the association between adverse childhood experience (ACE) and suicidality in depression. This multicenter cross-sectional study included 200 in- and outpatients (64% (n=128) women, mean age - (M (SD)) 36.21 (15.09) yrs.) with depression. Self-reports about FHMD and lifetime suicide attempts were obtained in clinical interview. The lifetime intensity of suicidal ideas and behavior was assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), ACE - by the Adverse Childhood Experience International Questionnaire (ACE-IQ). FHMD did not affect the prevalence of ACE, suicide attempts and C-SSRS scores. We found that FHMD weakens the link between ACE and the risk of suicide attempt. The emotional neglect itself increased the risk of suicide attempt (p=0.001, OR=4.428, CI 95% [1.797-10.911]), but reduced it in patients with FHMD (p=0.03, OR=0.128, CI 95% [0.018-0.893]). GLM analysis revealed that FHMD significantly affected the association between suicidal ideas and domestic violence (p=0.045) and between suicidal behavior and emotional neglect (p=0.015) and abuse (p=0.044). FHMD may weaken the link between ACE and suicidality in patients with depression. Suicidality in these patients may be underlined by mechanisms not involved in the response to ACE although more studies are needed.

FURTHER VALIDATING PROFILES OF IMPULSIVE AGGRESSION IN YOUTH

Prior work identified distinct latent profiles of youth with common principal components between all data sets being aggression with impulsivity and reactivity (AIR), rule-breaking, mania, and depression. Our objective is to characterize youths with AIR by exploring associations between AIR and behavior inhibition and approach system (BIS/BAS), callous-unemotional traits and family history (FH), as well as caregiver’s mood symptoms. We also discuss neuropsychological differences between youth with AIR and those with other profiles. Univariate ANOVAs established correlations between parent/youth reports on the BIS/BAS scale and the established profiles with the principal components. Bivariate correlations and ANOVA explored associations and differences in severity between AIR component scores and Antisocial Process Screening Device (APSD) scores. Univariate ANOVAs, correlations, χ2 tests, and t tests examined correlations between the caregiver’s mood symptoms and FH with youth’s symptoms, including AIR. Univariate ANOVAs identified patterns across psychopathology profiles, and bivariate correlations evaluated relationships between psychopathology and 13 neuropsychological measures. Profiles that included AIR and/or ADHD and manic symptoms showed greater positive associations with BAS and negative associations with BIS, when compared to a profile characterized by depression. The AIR profile was most associated with impulsivity and narcissism, but not with callous-unemotional traits. Caregiver’s mood symptoms were highest in youths with mixed bipolar symptoms and/or AIR, and showed correlations with AIR, mood problems, and self-harm. FH of mood disorders was correlated with mania, depression, and AIR even though the AIR profile was distinct from mania or depression. Profiles with high hyperactivity/impulsivity, AIR, and severe mood symptoms showed faster response to emotional words, when compared to profiles with mild symptoms and depression. These analyses provide additional evidence for AIR being distinct from mood and attention problems. Profiles that include AIR symptoms possess unique characteristics, which may help differentiate them from other profiles.

Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior.

BackgroundThe serotonin 1A (5-HT1A) receptor has been implicated in depression and suicidal behavior. Lower resting cortisol levels are associated with higher 5-HT1A receptor binding, and both differentiate suicide attempters with depression. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to familial risk and resilience for suicidal behavior.Methods[11C]CUMI-101 positron emission tomography imaging to quantify regional brain 5-HT1A receptor binding was conducted in individuals considered to be at high risk for mood disorder or suicidal behavior on the basis of having a first- or second-degree relative(s) with an early onset mood disorder and history of suicidal behavior. These high-risk individuals were subdivided into the following groups: high risk resilient having no mood disorder or suicidal behavior (n = 29); high risk with mood disorder and no suicidal behavior history (n = 31); and high risk with mood disorder and suicidal behavior (n = 25). Groups were compared with healthy volunteers without a family history of mood disorder or suicidal behavior (n = 34). Participants underwent the Trier Social Stress Task (TSST). All participants were free from psychotropic medications at the time of the TSST and PET scanning.ResultsWe observed no group differences in 5-HT1A receptor binding considering all regions simultaneously, nor did we observe heterogeneity of the effect of group across regions. These results were similar across outcome measures (BPND for all participants and BPp in a subset of the sample) and definitions of regions of interest (ROIs; standard or serotonin system-specific ROIs). We also found no group differences on TSST outcomes. Within the high risk with mood disorder and suicidal behavior group, lower BPp binding (β = −0.084, SE = 0.038, P = .048) and higher cortisol reactivity to stress (β = 9.25, 95% CI [3.27,15.23], P = .004) were associated with higher lethality attempts. There were no significant relationships between 5-HT1A binding and cortisol outcomes.Conclusions5-HT1A receptor binding in ROIs was not linked to familial risk or resilience protecting against suicidal behavior or mood disorder although it may be related to lethality of suicide attempt. Future studies are needed to better understand the biological mechanisms implicated in familial risk for suicidal behavior and how hypothalamic-pituitary-adrenal axis function influences such risk.