BACKGROUND: Adolescent substance use poses a critical public health challenge, intertwined with risk-taking behavior, criminality, functional impairment, and comorbid mental and physical health issues. Adolescents with bipolar spectrum disorders (BSD) exhibit heightened susceptibility to substance use, necessitating a nuanced exploration of the bipolar-substance use relationship.
METHODS: This study addressed gaps in the literature by employing a prospective, longitudinal design with 443 Philadelphia-area adolescents, tracking BSD symptoms and substance use. We predicted that BSD symptoms would be associated with increases in substance use, and that these effects would be more pronounced for individuals with a BSD and those with high reward sensitivity.
RESULTS: Hypomanic symptoms predicted subsequent substance use, with a stronger association observed in individuals diagnosed with BSD. Contrary to expectations, depressive symptoms did not exhibit a similar relationship. Although the hypothesized moderating role of reward sensitivity was not supported, higher reward sensitivity predicted increased substance use.
CONCLUSIONS: Symptoms and substance use are only captured for the month prior to each session due to the assessment timeline. This highlights the benefits of frequent assessments over a shorter time frame to monitor real-time changes. Alternative classification methods for reward sensitivity, such as brain or behavior-based assessments, might yield different results.
CONCLUSIONS: This study\'s contributions include evaluating substance use broadly, utilizing a longitudinal design for temporal clarity, and shifting the focus from substance use predicting mood symptoms to the inverse. The findings underscore the need for continued exploration of mood symptom predictors of substance use, emphasizing the role of reward sensitivity.

UNASSIGNED: Elevated sensitivity to rewards prospectively predicts Bipolar Spectrum Disorder (BSD) onset; however, it is unclear whether volumetric abnormalities also reflect BSD risk. BSDs emerge when critical neurodevelopment in frontal and striatal regions occurs in sex-specific ways. The current paper examined the volume of frontal and striatal brain regions in both individuals with and at risk for a BSD with exploratory analyses examining sex-specificity.
UNASSIGNED: One hundred fourteen medication-free individuals ages 18-27 at low-risk for BSD (moderate-reward sensitivity; N = 37), at high-risk without a BSD (high-reward sensitivity; N = 47), or with a BSD (N = 30) completed a structural MRI scan of the brain. We examined group differences in gray matter volume in a priori medial orbitofrontal cortex (mOFC) and nucleus accumbens (NAcc) regions-of-interest.
UNASSIGNED: The BSD group had enlarged frontostriatal volumes (mOFC, NAcc) compared to low individuals (d = 1.01). The mOFC volume in BSD was larger than low-risk (d = 1.01) and the high-risk groups (d = 0.74). This effect was driven by males with a BSD, who showed an enlarged mOFC compared to low (d = 1.01) and high-risk males (d = 0.74). Males with a BSD also showed a greater NAcc volume compared to males at low-risk (d = 0.49), but not high-risk males.
UNASSIGNED: An enlarged frontostriatal volume (averaged mOFC, NAcc) is associated with the presence of a BSD, while subvolumes (mOFC vs. NAcc) showed unique patterning in relation to risk. We report preliminary evidence that sex moderates frontostriatal volume in BSD, highlighting the need for larger longitudinal risk studies examining the role of sex-specific neurodevelopmental trajectories in emerging BSDs.

Due to the significant impairment associated with subthreshold bipolar symptomatology and the harmful effects of delayed diagnosis, there is a great need for diagnostic tools that can facilitate early identification of bipolar spectrum disorders. The Mood Disorder Assessment Schedule (MDAS) is a newly developed measure that focuses on autonomous changes in mood and energy, a key indicator of bipolar spectrum problems which is not included in current diagnostic tools for bipolar disorders. The current study tested the ability of the MDAS to identify individuals at risk for bipolar spectrum disorders. In a cross-sectional sample of 396 inpatient adolescents, the MDAS identified a group of individuals with several bipolar spectrum disorder (BSD) indicators, including greater manic and depressive symptoms, affective lability, suicidal behavior, adverse reactions to antidepressants, and a family history of bipolar disorder and suicidal behavior. When compared to a standard diagnostic interview for bipolar disorders (i.e., Kiddie Schedule for Affective Disorders and Schizophrenia [KSADS]), the MDAS yielded stronger clinical utility in its ability to identify individuals with BSD indicators. Therefore, the MDAS appears to be a promising diagnostic tool for identifying adolescents at risk for BSDs and may help facilitate earlier diagnosis and prevent harmful effects of improper treatment.

The role of activation in the pathogenesis of bipolar spectrum disorders (BSD) is of growing interest. Physical activity is known to improve mood, but it is unclear whether low activity levels contribute to inter-episode depressive symptoms observed in BSD. This study examined whether sedentary and vigorous activity, as well as the timing of the activity, were differentially associated with next-day depressive symptoms for individuals at low risk for BSD, high-risk for BSD, and diagnosed with BSD.
Young adults (n = 111, ages 18-27) from three groups (low BSD risk, high BSD risk, and BSD diagnosis), participated in a 20-day ecological momentary assessment study. Physical activity was measured via wrist actigraphy counts. The percentage of time awake spent in sedentary, light, moderate, and vigorous activity states was calculated, as was the percentage of morning hours and evening hours in each activity state. Multilevel models examined whether the BSD risk group moderated associations between sedentary and vigorous activity and depressive symptoms, which were assessed three times daily.
There were no between-group differences in time spent in each activity state, nor were there main effects of sedentary or vigorous activity on depression. Increased time spent engaging in vigorous activity was associated with a greater reduction in subsequent depressive symptoms for the BSD group. An increase in the evening, but not morning, vigorous activity was significantly associated with a reduction in subsequent depressive symptoms for the BSD group after controlling for chronotype.
Interventions targeting physical activity may effectively help regulate inter-episode mood disturbances in BSD.

Social, cultural, and structural factors are associated with delays in seeking help from mental health professionals and poor treatment adherence among patients with mood disorders. This qualitative study examined the perspectives on the services and response to treatments of individuals diagnosed with Bipolar Spectrum Disorder (BSD) in Iran through 37 in-depth semi-structured interviews with patients who had received BSD diagnosis and treatment (excluding Bipolar-I). Interviews explored two broad areas: 1) coping and help-seeking strategies; and 2) barriers to treatment and expectations of outcomes from treatment. Multiple factors influenced the help-seeking strategies and trajectories of patients with BSD diagnoses in Iran, including: structural limitations of the mental healthcare system; modes of practice of biological psychiatry; characteristics of the official psychology and counseling services permitted by Iran\'s government; popular psychology and consultation (offered through social media from the diaspora) by Iranian psychologists and counsellors in the diaspora; and alternative spiritual and cult-based groups. To improve the quality and accessibility of mental health services, it is essential to have structural changes in the healthcare system that prioritize human rights and individuals\' values over the political and ideological values of the state and changes in the professions that promote secular training of mental healthcare providers and an ecosocial model of care.

Bipolar affective disorder includes Bipolar Disease (BD) and Bipolar Spectrum Disorder (BSD). The prevalence of BSD, BD-I, BD-II, and subthreshold BD globally is estimated to be about 3.1%, 1.5%,0.03%, and 1.6%, respectively. BD is a multidimensional disease that exhibits a range of moods of mania, hypomania, and depression. The disease is chronic, complex, and fatal, with a high possibility of reappearance, infirmity, social incompetence, and felo-de-se. Managing emotional disruption, negative neuropsychology, physiology, and immunology is a challenge. This review focuses on therapeutic benefits, adverse drug reactions, and pharmacological intervention for BD and BSD, in particular lithium. Long-term management of BD with a single medication is ineffective and therefore, not recommended. It is advised to use multiple agents for treatment instead. Medications include mood stabilizers (lithium and anticonvulsants), atypical antipsychotics, and antidepressants. Along with medication provision, psychotherapy is of great significance for BD patients. The review was conducted on recent available scientific literature through the electronic database like Embase, ScienceDirect, Google Scholar, and PubMed using keywords like \'Bipolar Disease,\' \'Bipolar Disease Therapeutics,\' \'Bipolar Disease and Psychotherapy\' to highlight the possible effective means of management of this disease of mood instability.

Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.
We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children\'s Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.
This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.
These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.
ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.

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Bipolar spectrum disorders (BSDs) and substance use disorders (SUDs) are associated with neural reward dysfunction. However, it is unclear what pattern of neural reward function underlies pre-existing vulnerability to BSDs and SUDs, or whether neural reward function explains their high co-occurrence. The current paper provides an overview of the separate literatures on neural reward sensitivity in BSDs and SUDs. We provide a systematic review of 35 studies relevant to identifying neural reward function vulnerability to BSDs and SUDs. These studies include those examining neural reward processing on a monetary reward task with prospective designs predicting initial onset of SUDs, familial risk studies that examine unaffected offspring or first-degree relatives of family members with BSDs or SUDs, and studies that examine individuals with BSDs or SUDs who are not currently in an episode of the disorder. Findings from the review highlight that aberrant responding and connectivity across neural regions associated with reward and cognitive control confers risk for the development of BSDs and SUDs. Discussion focuses on limitations of the extant literature. We conclude with an integration and theoretical model for understanding how aberrant neural reward responding may constitute a vulnerability to the development of both BSDs and SUDs.

Purpose: Offspring of mothers with a bipolar disorder are at high-risk for impaired developmental outcomes and psychopathology (e. g., mood, anxiety, sleep disorders) later in life. This increased risk of psychopathology is not only because of genetic vulnerability, but environmental factors may play an important role as well. The often long and debilitating mood episodes of mothers with bipolar disorder might hamper their qualities as a caregiver and may impact the child. We examined early mother-to-infant bonding 1 year postpartum in mothers with bipolar spectrum disorder as compared to mothers of the general population. The association between mother-to-infant bonding and the type of bipolar spectrum diagnosis (bipolar I, bipolar II, bipolar Not Otherwise Specified) as well as relapse within 12 months postpartum was also assessed. Methods: In total, 75 pregnant women with a bipolar spectrum disorder participated in the current study. The participants were included in a longitudinal cohort study of women with bipolar spectrum disorder and were prospectively followed from pregnancy until 1 year postpartum. Mother-to-infant bonding was assessed using the Pre- and Postnatal Bonding Scale. A longitudinal population-based cohort of 1,419 pregnant women served as the control group. Multiple linear regression analyses were used to assess the association between bipolar spectrum disorder and mother-to-infant bonding scores, controlling for several confounders. Results: Women with bipolar spectrum disorder perceived the bonding with their child as less positive compared to the control group. The type of bipolar spectrum disorder was not associated with poorer bonding scores. Relapse during the 1st year after delivery also did not affect bonding scores in women with bipolar spectrum disorder. Conclusions: Our findings could imply that women with bipolar spectrum disorder are more vulnerable to impairments in bonding due to the nature of their psychopathology, regardless of the occurrence of postpartum relapse. Careful follow-up including monitoring of mother-to-infant bonding of pregnant women with a history of bipolar spectrum disorder should be a standard to this vulnerable group of women. In addition, regardless of severity and mood episode relapse, an intervention to improve bonding could be beneficial for all mothers with bipolar spectrum disorder and their newborns.